Effect of diosgenin on lipid metabolism in rats. The purpose of this study was to determine whether diosgenin suppresses cholesterol absorption in rats, and to examine relevant changes in cholesterol and bile acid metabolism. Diosgenin fed with the diet for 1 week inhibited cholesterol absorption as determined by the serum isotope ratio technique, as well as by measuring in the feces the amount of unabsorbed radioactivity from orally administered [3H]cholesterol. In addition, diosgenin suppressed the serum and liver uptake of radioactivity from co-administered [3H]cholesterol as well as the accumulation of liver cholesterol in the cholesterol-fed rat; diosgenin was substantially more active than cholestyramine or beta-sitosterol. In vitro, diosgenin had no effect on the activity of rat pancreatic esterase. Diosgenin decreased the elevated cholesterol in serum LDL and elevated cholesterol in the HDL fraction of cholesterol-fed rats; diosgenin had no effect on serum cholesterol in normocholesterolemic rats. In contrast to cholestyramine, diosgenin markedly increased neutral sterol excretion without altering bile acid excretion; in vitro, diosgenin had no effect on bile acid binding. Diosgenin treatment increased hepatic and intestinal cholesterol synthesis as well as the activity of hepatic HMG CoA reductase. This was accompanied by increased biliary concentration of cholesterol, but not of bile acids. Diosgenin had no effect on cholesterol synthesis when added to normal rat liver homogenates. It was concluded that diosgenin interferes with the absorption of cholesterol of both exogenous and endogenous origin; such interference is accompanied by derepressed, i.e., increased, rates of hepatic and intestinal cholesterol synthesis. The increased unabsorbed cholesterol together with enhanced secretion of cholesterol into bile resulted in increased excretion of neutral sterols without affecting the biliary and fecal excretion of bile acids.


Norethindrone acetate inhibition of splanchnic triglyceride secretion in conscious glucose-fed siwne. The effects of conventional doses of two synthetic contraceptive steroids on the concentration and rate of secretion of plasma triglycerides from the splanchnic region were investigated. Studies were undertaken in miniature swine under steady state conditions produced by prolonged constant hypercaloric intravenous infusions of glucose. The steroids, alone or in combination, were administered with the high carbohydrate diet for at least 2 weeks prior to study of splanchnic metabolism and were also infused intravenously during the studies. Splanchnic triglyceride secretion was determined from measurements of plasma flow and transsplanchnic radiochemical gradients of plasma triglycerides. Compared with studies in the untreated animal, norethindrone acetate significantly reduced the arterial concentration (1.1 +/- 0.1 vs. 0.7 +/- 0.1 mM) and rate of splanchnic secretion of plasma triglyceride fatty acids (2.0 +/- 0.4 vs. 0.8 +/- 0.1 micro mol/min.kg body wt(0.75)) and decreased the percent of free fatty acids entering the splanchnic region that was converted to plasma triglycerides (22 +/- 5 vs. 13 +/- 3%, P < 0.05). Ethynylestradiol, in the dose employed, had no significant effect on these variables; however, ethynylestradiol and norethindrone acetate together gave responses similar to norethindrone acetate alone. When the glucose was given intraduodenally vs. intravenously, values for splanchnic metabolism of triglycerides were unchanged. The hypolipemic effect of norethindrone acetate in glucose-fed swine was attributable to inhibition of hepatic triglyceride secretion.-Wolfe, B. M., and D. M. Grace. Norethindrone acetate inhibition of splanchnic triglyceride secretion in conscious glucose-fed swine.


Interactions of cholesterol esters with phospholipids: cholesteryl myristate and dimyristoyl lecithin. The ternary phase diagram of cholesteryl myristate--dimyristoyl lecithin--water has been determined by polarizing light microscopy, scanning calorimetry, and x-ray diffraction. Hydrated dimyristoyl lecithin forms a lamellar liquid--crystalline phase (L alpha) at temperatures greater than 23 degrees C into which limited amounts of cholesteryl myristate (less than 5 wt. %) can be incorporated. The amount of cholesterol ester incorporated is dependent upon the degree of hydration of the L alpha phase. Below 23 degrees C dimyristoyl lecithin forms ordered hydrocarbon chain structures (L beta' and P beta') which do not  incorporate cholesterol ester. Comparison with other phospholipid--cholesterol ester--water phase diagrams suggests the following general principles: i) the incorporation of cholesterol ester occurs only into liquid crystalling phospholipid bilayers, ii) the extent of incorporation is temperature-dependent, with increasing amounts of cholesterol ester being incorporated at higher temperatures, and iii) unsaturated cholesterol esters induce increased disordering of the phospholipid bilayers.


Inhibition of epinephrine-induced lipolysis in isolated white adipocytes of aging rabbits by increased alpha-adrenergic responsiveness. The aim of this study was to explain the unresponsiveness of rabbit perirenal adipose tissue to epinephrine. The in vitro lipolytic response to isoproterenol and to epinephrine alone or associated with alpha- or beta-adrenergic blocking agents, was studied in the adipocytes of rabbits of various ages. Epinephrine induces a large glycerol release in young rabbit adipocytes whereas an increase in the rate of lipolysis cannot be shown with adult rabbit fat cells. Moreover, an antilipolytic effect can be shown for low concentrations of epinephrine when the basal rate of lipolysis is high in older rabbit adipocytes. Isoproterenol (beta-adrenomimetic) always exerts a strong adipokinetic effect, thus revealing functional beta-receptor sites. The blockade of alpha-adreneoceptor sites by phentolamine, which has no effect on young rabbits, abolishes the antilipolytic effect and unmasks strong lipolytic effect of epinephrine on aged and normal rabbit adipocytes. The loss of beta-adrenergic responsiveness towards epinephrine in the aging rabbit is linked to the involvement of an increased alpha-adrenergic responsiveness. The stimulation of alpha receptor sites by epinephrine leads to a depressive effect on lipolysis (lack of adipokinetic effect or antilipolytic action).


The stereochemical configuration of lysosomal phosphatidylcholine and phosphatidylethanolamine: comparison with lysobisphosphatidic acid. Lysosomal phosphatidylcholine and phosphatidylethanolamine were isolated from liver of rats treated with Triton WR 1339 and from cultured BHK-cells. Stereochemical analysis proved that these lipids, in contrast to the lysosomal lysobisphosphatidic acid, were derivatives of sn-glycero-3-phosphate.


12alpha-Hydroxysteroid dehydrogenase from Clostridium group P strain C48-50 ATCC No. 29733: partial purification and characterization. The growth of Clostridium group P strain C48-50 [an anaerobe that contains 12alpha-hydroxysteroid dehydrogenase (12alpha-HSDH) in the absence of other dehydrogenases active upon bile salts] is greatly enhanced by the addition of 2.0% d-fructose or d-glucose to the growth medium. Other sugars were less effective. The production of NADP-dependent 12alpha-HSDH paralleled the growth of the organism which was optimal at 72 hr. Growth (and enzyme production) were suppressed by the addition of bile salt to the medium; the order of suppression was deoxycholate > chenodeoxycholate >> cholate; 1 mM of either of the dihydroxy-bile salts inhibited 96% of the growth and 100% of the enzyme production. Kinetic studies on cell-free preparations of 12alpha-HSDH revealed a pH optimum of 7.8 with greater linearity of NADP evolution with time occurring only at more alkaline pH values (9-10). Lineweaver-Burke plots revealed Michaelis constant (K(m)) values in the range of 3-5 x 10(-4) M for deoxycholate and its glycine and taurine conjugates, while higher values were found for cholate and conjugates (K(m) value for taurocholate was 3 x 10(-3) M). Although there was no activity with NAD, 12alpha-HSDH was shown to bind onto both NAD- and NADP-Sepharose columns, with stronger binding on the latter. The enzyme was purified 20-fold by NAD-Sepharose chromatography. The molecular weight was estimated at 100,000 by Sephadex G-200 and a series of molecular weight markers. Substrate specificity studies showed that a variety of bile salts containing 12alpha-OH groups reacted; notably, the 3alpha-sulfates of cholate and deoxycholate were nonsubstrates.-Macdonald, I. A., J. F. Jellett and D. E. Mahony. 12alpha-Hydroxysteroid dehydrogenase from Clostridium Group P strain C48-50 #29733: partial purification and characterization.


Enzyme-linked immunoassay of ursodeoxycholic acid in serum. A sensitive and specific enzyme-linked immunoassay for the measurement of ursodeoxycholic acid in human serum was developed. Ursodeoxycholic acid conjugated to alkaline phosphatase (from calf intestine) was used as a tracer. An antiserum to ursodeoxycholic acid serum was raised in rabbits using ursodeoxycholic acid--bovine serum albumin conjugate as an antigen. The binding required 1 hr at 42 degrees C; separation of the bound tracer was achieved by addition of a second antibody, and alkaline phosphatase activity of this bound complex was measured colorimetrically. The ratio of bound to total enzyme activity decreased linearly with a logarithmic increase in ursodeoxycholic acid concentration from 20 to 900 pmol. The specificity and sensitivity of this enzyme-linked immunoassay were similar to those of a radioimmunoassay reported previously. The serum ursodeoxycholic acid levels measured by this method correlated well with those determined by gas--liquid chromatography and radioimmunoassay. Based on these findings, this enzyme-linked immunoassay of bile acid might be useful as a tool for the routine clinical analysis of serum bile acids.


Metabolism of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid by rat liver in vivo and in vitro. The metabolism of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid was studied in the bile fistula rats and in preparations from rat liver homogenates. In the bile fistula rats, the main products were chenodeoxycholic acid, alpha-muricholic acid, and beta-muricholic acid. Only small amounts of cholic acid were formed. Incubations of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid with microsomes and NADPH yielded as the main product 3 alpha, 6 beta, 7 alpha-trihydroxy-5 beta-cholestanoic acid. The formation of small amounts of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid was shown. The major product in incubations of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid with microsomes and the 100,000 g supernatant fluid fortified with ATP was identified as 3 alpha, 7 alpha, 24 xi-trihydroxy-5 beta-cholestanoic acid. This compound was converted into chenodeoxycholic acid and its metabolites in the bile fistula rat.


Synthesis of all-cis-1,3-diacylcyclopentane-1,2,3-triol-2-phosphate via acyl group migration in a cyclic diglyceride analog. The acid-catalyzed isomerization of the diglyceride analog (1,2,3/0)-1,2-dipalmitoylcyclopentane-1,2,3-triol has been used to generate syn-syn-1,3-diacyl-cyclopentane-1,2,3-triol, a required intermediate in the synthesis of a symmetrical all-cis-1,2,3/0-2P cyclopentanoid phosphatidic acid analog. The all-cis cyclo-phosphatidic acid analog has therefore been obtained in the free acid form and as the diphenyl ester, dimethyl ester, and dipotassium salt derivatives. The compounds have been characterized by microanalysis and spectroscopic methods. The 1,2,3/0-2P analog is now available for comparative studies with the corresponding all-trans cyclophosphatidic acid (1,3/2-2P).


An improved method for the covalent attachment of glycolipids to solid supports and macromolecules. A simplified method is presented for the oxidation of the olefinic bond of the sphingosine moiety of glycosphingolipids to a carboxyl group. Coupling of such "glycolipid acids" to glass beads, agarose gels, proteins, and polyacrylic hydrazide polymers is described. Solid supports and macromolecules that have been derivatized in this fashion are useful reagents for a variety of studies in cell biology and immunology.


Proton magnetic resonance identification and discrimination of stereoisomers of C27 steroids using lanthanide shift reagents. A simple proton magnetic resonance spectroscopic method is described for the identification and and confirmation of several stereoisomeric paris of C27 stanols as well as their keto and acetate derivatives related to cholesterol. The method, which involves the use of lanthanide shift reagents, is useful in distinguishing clearly between the isomeric pairs differing only in the geometry of a functional group and/or of the A/B-ring junction in the steroid skeleton.


Extraction of small amounts of oxytocin from biological fluids by means of agarose-bound neurophysin. The use of agarose-bound neurophysin for the extraction of oxytocin from biological fluids is described. Oxytocin can be extracted from plasma, urine and cerebrospinal fluid with a high rate of recovery and samples varying widely in volume and oxytocin concentration can be tested by the method. Columns can be used to extract and concentrate dilute samples, or to help identify small amounts of neurohypophysial hormones by affinity chromatography. The oxytocin can be eluted from the column directly into the buffer used for subsequent bioassay. The composition of the final extract is constant and independent of the composition of the sample. The specificity of the binding is high. It is suggested that the method has many advantages over others in current use.


Effects of cyproterone and cyproterone acetate on the adrenal gland in the rat: studies in vivo and in vitro. Male Wistar rats were treated for three weeks with cyproterone (1.7 or 5.1 mg/day) or cyproterone acetate (2 or 6 mg/day). The adrenal weights of animals treated with either dose of cyproterone acetate were significantly less (P less than 0.001) than those of untreated animals. In contrast, the adrenal weights of animals treated with cyproterone did not differ from those of the controls. The concentrations of corticosterone in the plasma were significantly less (P less than 0.001) in both groups treated with cyproterone acetate compared with those of the controls; only the higher dose of cyproterone reduced the plasma concentration of corticosterone (P less than 0.001). Cyproterone acetate inhibited the rat adrenal 3beta-hydroxysteroid dehydrogenase-5-ene,4-ene-isomerase complex in vitro, with both pregnenolone and dehydroepiandrosterone as substrates. Analysis of the reaction rates suggested an uncompetitive mode of inhibition. These results suggest that in rats the antiandrogens cyproterone and cyproterone acetate may provoke adrenal insufficiency by inhibition of steroid biosynthesis. Furthermore, indirect evidence from the mass and morphology of the adrenal suggests that cyproterone acetate may also suppress production or secretion of ACTH by the pituitary gland.


Involvement of prostaglandins in the inhibition of growth hormone production in cultured pituitary cells by insulin. The effect of insulin was tested on the rate of synthesis and release of growth hormone in cultured rat anterior pituitary cells. Concentrations of insulin between 10(-9) and 10(-7) mol/l (6--600 ng/ml or 0.15--15 mu./ml) inhibited synthesis of growth hormone; 10(-8) mol insulin/l was most effective. The effect was observed after a time-lag of at least 1 h. Insulin at concentrations between 3 x 10(-9) mol/l and 3 x 10(-7) mol/l also inhibited growth hormone secretion in 30 min incubations. The most effective insulin concentration in this case was 3 x 10(-8) mol/l. Insulin (10(-9)-10(-7) mol/l) also decreased the intracellular content of prostaglandins E and F. The effect was rapid, reaching a maximum after 30 min. Indomethacin, an inhibitor of prostaglandin synthetase, dramatically lowered the concentration of prostaglandins in the cells within 30 min; growth hormone synthesis was also decreased, but not until after 2 h of incubation. The results suggest that an initial response to insulin treatment is a lowering of intracellular levels of prostaglandins, which may then mediate a decrease in growth hormone synthesis, after a 1--2 h delay.


Interaction of ovarian tissues in the control of follicular steroidogenesis in culture. The interaction between developing antral follicles and other ovarian tissues in sheep was examined in vitro. Small follicles (2.0--2.9 mm in diameter) were co-cultured with a single ovarian component for 48 h, then separated and cultured singly for a further 72 h during which time changes in follicular steroidogenesis and structure were measured. Control follicles, cultured together for 48 h before separation, had a mean total daily steroid output during the 72 h test period of 180.4 +/- 12.6 (S.E.M.) pmol mg tissue-1 24 h-1; oestrogen (61.7 +/- 8.2 pmol mg-1 24 h-1) and testosterone (84.4 +/- 9.2 pmol mg-1 24 h-1) accounted for 81% of the steroid secreted by control follicles. The presence of stromal tissue during co-culture depressed (P less than 0.01) the subsequent output of total steroid by 22%, oestrogen by 81% and testosterone by 38%; progesterone output was, however, over twice that of the controls. There was no distinctive structural differences between follicles in the control and stromal groups. Luteal tissue enhanced (P less than 0.01) the output of total steroid by 51%, testosterone by 55% and progesterone by 242%; oestrogen output was similar to that in the controls. Follicles co-cultured with luteal tissue were characterized by extensive hypertrophy of the theca interna. Developing follicles co-cultured with large non-atretic follicles had a similar total steroid output, a slightly higher oestrogen output and more thecal hypertrophy than the controls. Follicles co-cultured with large atretic follicles differed from controls only with respect to their greater capacity to synthesize progesterone.


Unoccupied binding sites for oestradiol in nuclei from human breast carcinomatous tissue. The binding of oestradiol to a nuclear fraction extracted from human breast carcinomatous tissue was demonstrated. The material, which was extracted with KCl, sedimented at 3--4S and bound oestradiol with high affinity (dissociation constant approximately 2 X 10(-10) mol/l). Oestriol, diethylstilboestrol and 5 alpha-dihydrotestosterone (100-fold excesses) competed with [3H]oestradiol for the binding sites (binding inhibited by 89 +/- 8 (S.D.), 92 +/- 6 and 57 +/- 8% respectively), whereas progesterone and cortisol (100-fold excesses) did not (binding suppressed by 5 +/- 5 and 2 +/- 3% respectively). Similar competition patterns were found for cytoplasmic material which bound oestradiol. The binding occurred at 4 degrees C and was therefore considered to be a measure of the amount of binding material unoccupied by endogenous oestrogen, Unoccupied binding sites for oestradiol in the nucleus and cytoplasm were measured in 35 samples of breast carcinomatous tissue using sucrose gradient centrifugation. In 17 out of 35 tumorus, unoccupied nuclear and cytoplasmic 8S and 4S binding sites could be detected. Three out of 35 tumours contained unoccupied nuclear binding sites and 4S cytoplasmic binding sites. Nuclear binding sites only were found in two out of 35 tumours. Unoccupied nuclear binding sites were not detected in 13 out of 35 tumours and ten of these tumours also did not contain unoccupied cytoplasmic binding sites.


Adrenocortical function tests in dogs with hyperfunctioning adrenocortical tumours. The response has been studied in nine dogs with hyperadrenocorticism due to adrenocortical tumours to the administration of dexamethasone, insulin, lysine-vasopressin and tetracosactide by measuring the changes in plasma cortisol concentration. Administration of dexamethasone did not produce a decrease in the plasma concentration of cortisol in any of these dogs. Administration of insulin caused slight increases in the plasma concentration of cortisol in four out of eight dogs. Lysine-vasopressin increased the plasma concentration of cortisol in eight out of nine dogs, three responded supranomally. Eight out of the nine dogs responded to tetracosactide administration, three responded supranormally, It is concluded that in the dog, in contrast to man, the lysine-vasopressin test cannot be used to differentiate between pituitary-dependent hyperadrenocorticism and hyperadrenocorticism due to an adenocortical tumour. Apparently pituitary ACTH is not completely depleted in dogs with hyperfunctioning adrenocortical tumours.


Production of testosterone, 5 alpha-androstane-3 alpha, 17 beta-diol and androsterone by dispersed testicular interstitial cells and whole testes in vitro. The production of 5 alpha-androstane-3 alpha, 17 beta-diol (androstanediol), androsterone and testosterone by whole rat testes and testicular interstitial cells dispersed with collagenase was studied in vitro. Luteinizing hormone stimulated the production of each of the androgens by cells prepared from 31- to 34-day-old rats. Half maximum stimulation of the production of each androgen occurred with approximately 3.5 ng NIH-LH-B9/ml medium. Androstanediol was the predominant product then androsterone and then testosterone. Luteinizing hormone stimulated the production of testerone, but not androstanediol or androsterone by dispersed interstitial cells from 200-day-old rats. The time-course of production and the effect of the concentration of cells on the production of these androgens suggested that in dispersed testicular interstitial cells from immature animals androstanediol and androsterone are formed, at least partially, by the metabolism of testosterone. In these experiments LH-stimulated testosterone production increased during incubation for 15--60 min and then remained constant up to 180 min. The concentrations of androstanediol and androsterone increased in a linear manner during incubation for 60--180 min. Varying the number of cells incubated yielded a positive correlation between cell concentration and the ratio 5 alpha-reduced androgen : testosterone produced. Luteinizing hormone stimulated production of each androgen by whole tests obtained from rats at 30--175 days of age. The serum concentration of testosterone in these rats increased abruptly at 50 days of age. Significant changes in androgen production in vitro also observed at this age included: (1) increased production of the three steroids when incubated in either the presence or absence of LH and (2) testosterone production, either in the presence or absence of LH, which represented a greater percentage of the total production of the three androgens.


Alterations in adrenal growth and corticosteroid content in foetal and neonatal rats developing at high altitude. To study the effects of chronic maternal hypoxia on the growth and functional development of foetal and neonatal adrenal glands, Long-Evans rats were acclimatized to high altitude (3800 m) before mating and were maintained at this height throughout gestation. The body growth of the progeny at high altitude was essentially normal during the perinatal period, but adrenal weight and adrenocortical function showed marked differences from those of control rats maintained at sea level. The adrenal glands were larger in foetuses but smaller in neonates, compared with the adrenal glands of control animals maintained at sea level. Differences in the protein content of the adrenal glands between the two groups paralleled differences in adrenal weight. The concentration and content of corticosterone in the adrenal glands of both foetuses and neonates kept at high altitude were markedly lower than values in animals kept at sea level. The lower adrenal corticosterone content was not reflected in the concentration of the hormone in the peripheral plasma, since this was essentially the same at high altitude and at sea level in both mothers and perinatal animals. The reduction in the adrenal corticosterone content was accompanied by and may have resulted from, a reduction in the concentration of cytochrome P-450 in the adrenal tissue of foetuses maintained at high altitude. Possible explanations for the dichotomous results are discussed.


Mammary growth during pregnancy in hypophysectomized or bromocriptine-treated goats. Mammogenesis in primiparous hypophysectomized goats has been assessed between days 60 and 120 of gestation and compared with that found in untreated goats and goats treated with 5 mg bromocriptine/day. There were fivefold increases in the weight of lobulo-alveolar tissue in the hypophysectomized and bromocriptine-treated goats and a tenfold increase in the untreated goats. Histological examination of the mammary glands at 120 days showed normal structure, and determinations of lactose, lactose synthetase, cytosol enzymes, protein, DNA and RNA indicated qualitatively normal initiation of milk synthetic capabilities in both the hypophysectomized and bromocriptine-treated goats. Bromocriptine treatment lowered the plasma concentration of placental lactogen as well as that of prolactin. The results indicate that placental lactogen has important mammogenic effects during pregnancy.


Effects of exogenous cortisol on the uptake of corticosteroid by the isolated perfused guinea-pig mammary gland. Assay of corticosteroids in the plasma of guinea-pigs showed that concentrations were higher in lactating than in non-lactating and male animals. In five isolated perfused mammary gland experiments in which corticosteroids were at concentrations of 1,3--3,0 microgram/ml in the perfusate, equivalent to concentrations during lactation, the mean (+/- S.E.M.) uptake by the mammary gland was 900 +/- 210 ng g-1 h-1. In five experiments in which the concentrations of corticosteroid in the perfusate were 190--580 ng/ml, the uptake by the mammary gland was significantly lower (316 +/- 73 ng g-1 h-1; P less than 0.05). For the ten experiments there was a significant correlation between the concentration of corticosteroid in the perfusate and uptake by the mammary gland (P less than 0.05). No convincing evidence for a galactopoietic role of corticosteroids in the guinea-pig was obtained, although administration of cortisol signficantly stimulated the uptake of glutamine by the perfused gland.


Internal quality control of radioimmunoassays: monitoring of error. A cumulative sum technique has been specially designed to monitor the error between replicate determinations made on quality control plasma for consecutive batches of assays. This procedure has played a vital role in assessing assay performance. Special consideration has been given to small sample sizes (n = 2 or 3) which is generally the rule rather than the exception in many situations. This technique has been applied to numerous steroid radioimmunoassays and has ensured that both the mean value and the standard error of hormone levels of a quality control pool were under control. Data from routine assays of oestriol and testosterone in plasma from women are presented. Since this technique provides a sensitive measure of monitoring error, it assists the endocrinologist in elucidating statistical inferences which are a manifestation of assay performance.


Effects of pinealectomy on the secretion of luteinizing hormone, testosterone and prolactin in rams exposed to various lighting régimes. Two experiments were carried out to study the effects of controlled lighting régimes on plasma levels of LH were low in all groups of rams, which made the detection of significant effects of any treatment very unlikely. Pinealectomy reduced the effects of changes in the daily photoperiod on the patterns of secretion of testosterone and prolactin. These findings establish the pineal gland as an organ which influences the endocrine responses of rams to photoperiodic stimuli and it is concluded that the pineal gland is probably important as a mediator of seasonal reproductive changes in these animals.


Tissue distribution of immunoreactive somatostatin in the South African clawed toad (Xenopus laevis). Immunoreactive somatostatin is present in the brain, gut and pancreas of the South African clawed toad, but is absent from the skin, a rich source of many other brain-gut peptides.


Effect of the timing of perphenazine administration on pregnancy in the rat. Perphenazine in doses of 10--50 mg kg-1 day-1 given at the early stages of pregnancy delayed nidation up to day 8 of pregnancy. Once nidation had occurred the length of the rest of the gestation period was normal. Doses of up to 20 mg perphenazine kg-1 day-1, injected on days 1--7, prolonged gestation but the mothers and young were apparently normal; lower doses were effective only when treatment commenced soon after copulation. The delay in implantation of the ovum caused by perphenazine was corrected and and implantation was brought about immediately, by injection of 0.1 microgram oestradiol together with perphenazine. It is suggested that perphenazine delays and prevents implantation in rats by counteracting oestrogen release from the ovaries.


Effect of pregnancy on the collagen content of the oviduct in the lizard. It was shown experimentally that both the growth and total collagen content of the oviduct in the lizard Acanthodactylus scutellatus hardyi are mainly dependent on the number of eggs present. There was rapid formation of collagen if more than two eggs were present.


The electrical properties of a crustacean sensory dendrite. 1. The input properties and the response to stretch of a coxal receptor, the S fibre of the crab Scylla serrata, were studied using two and three intracellular microelectrodes. 2. In the relaxed receptor the transmembrane potential ranged from about -60 to -70 mV, and the input resistance, RT, from 1 to 3 M omega. The input IV relationship, studied by injecting slow-rising current ramps, was not linear either in the hyperpolarizing or in the depolarizing quadrants. 3. Low values of RT and linear IV relationship were associated with a large leakage of the microelectrodes. 4. The response to step stretches was complex, consisting of an initial depolarizing transient, Va, and a steady-state depolarizing plateau, Vs. Both Va and Vs propagated with decrement in the fibre which was about 9 mm long. The spatial decrement of Va and Vs was equal to that of the response to distally injected current pulses of comparable duration and amplitude. 5. On the basis of the spatial decrement of both Va and Vs the dendrite can be considered equivalent, for current flowing from its distal to its proximal end, to a semi-infinite cable having a length constant of between 4 and 6 cm. 6. The voltage transients recorded in response to long current pulses reached 84% of their final value in a time (t84%) ranging from 150 to 180 ms in fibres in which RT was 2 M omega or larger. t84% was smaller in fibres having a lower RT. 7. The time course of the transients recorded in response to injected current pulses deviated from the semi-infinite cable model in a manner suggesting the presence of a partial short-circuit. For this reason the membrane time constant of the fibre is considered larger (by an undetermined amount/ than t84%. 8. The fibre presented less resistance to current flowing from its proximal to its distal end than to current flowing in the opposite direction. For this reason, and also because of the time course of the voltage transient, it is concluded that the distal sensory endings of the fibre have the properties of a leaky end termination, even in the non-stimulated receptors.


Respiratory gas exchange in the resting starry flounder, Platichthys stellatus: a comparison with other teleosts. A wide range of respiratory, ventilatory, and cardiovascular parameters have been recorded under completely resting conditions in the starry flounder (Platichthys stellatus), a generally inactive benthic teleost. The results differ in a number of important respects from those of a previous study on the same species. The present data have also been compared with those reported for the active pelagic rainbow trout (Salmo gairdneri) and for other teleost species. Of particular note in the flounder, relative to the trout, are low arterial and venous PO2's, a low arterial-venous O2 content difference, a low transfer factor and high diffusion gradient for O2 across the gills, a high in vivo blood O2 affinity, a high cardiac output and stroke volume accompanied by a low peripheral vascular resistance, a low ventilation volume, a low ventilation-perfusion ratio, and a low capacity-rate ratio for O2 exchange at the gills. Parameters of CO2 transport and acid-base regulation appear conventional, though blood CO2 contents and lactate concentrations are low. The respiratory strategies of inactive versus active, and benthic versus pelagic teleosts are discussed.


A sliding microtubule model incorporating axonemal twist and compatible with three-dimensional ciliary bending. 1. Equations are developed to calculate the relative displacements of the doublet microtubules at the tip of a cilium when the microtubules twist about the axis of the organelle. 2. Displacements measured from electron micrographs show asymmetry (or skew) which can be matched quantitatively by the theoretical model with the appropriate selection of twist angle and orientation of the axoneme with respect to the plane of beat. 3. For Elliptio cilia the experimental results are consistent with a planar effective stroke and a recovery stroke involving a three-dimensional bend. The plane of the effective stroke is not normal to a surface containing the central pair of microtubules but contains microtubule 2 to produce the observed skew. 4. This model for the beat also explains the range of orientations of axoneme observed in sections through the metachronal wave.


Electrogenic Na+ transport in a crustacean coxal receptor. 1. The response of the coxal receptors of the crab Scylla serrata to step stretches consisted of a partial action potential, Va, followed by a steady-state depolarization, Vs. The input resistance of the fibre was reduced during Vs. 2. In the absence of stimulation, the dendrites of the receptors depolarized when external Na+ was substituted with choline or Li+, and when the external K+ concentration was increased or decreased. The dendrites also depolarized when ouabain was added to the saline. 3. The amplitude of both Va and Vs was dependent on external Na+. In cells which were depolarized by ouabain, the amplitude of Vs increased when the K+ concentration of the saline was reduced. 4. Vs was followed by a small, but long-lasting, after-potential which was depolarizing when the membrane potential was between -70 and -60 mV. In cells depolarized by ouabain or by low K+ saline, the after-potential became hyperpolarizing. 5. When trains of brief stretches (each 5 ms in duration) were used as stimuli, the cells responded with trains of Va responses. During this tetanic stimulation the cells hyperpolarized; cessation of the stimulus train was followed by a long-lasting hyperpolarization (PTH). 6. PTH was abolished in Li+ saline, in low K+ saline, and in the presence of ouabain. In control or in low K+ saline, PTH was not accompanied by a decrease in the input resistance of the fibres. 7. It is concluded that an electrogenic Na+ pump (or equivalent process) contributes a substantial fraction of the membrane potential of the unstimulated coxal receptors. Pump activity could be increased by Na+-loading the distal part of the cells with trains of Va responses. By contrast, during the steady-state response to stretch, the pump was not activated.


Fluorescence and luminescence of isolated photophores of Porichthys. 1. Isolated photophores of Porichthys exposed to u.v. light (365 nm) exhibit a green fluorescence localized in the photocytes and a bluish fluorescence originating from the lens-like body. 2. The luminescence of photophores evoked by epinephrine, nor-epinephrine or potassium cyanide decreases with the intensity of the green fluorescence of the photogenic tissue; the bluish fluorescence of the lens-like body does not change significantly. 3. The total amount of light emitted is a linear function of the decrease of the greenish fluorescence intensity. The slope of the regression line is maximal in response to epinephrine or nor-epinephrine 5.10(-4)M and potassium cyanide 10(-3)M. It decreases significantly for higher concentrations. 4. The decrease of fluorescence observed during the light emission is tentatively explained by oxidation of a luciferin present in a fluorescent form in a fresh photophore.


[Organ preservation by heavy water (D2O). Morphological and biochemical studies on heart and liver (author's transl)]. The tissue H2O of rabbit heart and rat liver was partially exchanged in situ with D2O. In rat liver, the loss of ATP, resulting from normothermic ischemia, was decreased after perfusion with D2O. The maximal protective effect was found when the proportion of D2O in the water of the liver tissue was 0.20. In both organs the protective effect of D2O could be correlated with a marked decrease in severe ischemic damage of cellular organelles, in particular mitochondria. D2O also increased the protective action of Mg-ions in the heart.


Selenium content and glutathione peroxidase activity in the plasma and erythrocytes of non-pregnant and pregnant women. Decreases in the glutathione peroxidase activity and in the selenium content were found in the plasma of pregnant women as compared with a control group. In the erythrocytes, both parameters remained unchanged. In both groups a fraction of about 0.90 of the glutathione peroxidase in the blood, was contained in the erythrocytes, whereas the selenium was nearly evenly distributed between plasma and red blood cells. A positive correlation existed between the total amount of selenium in the erythrocytes and that in the plasma.


Age related reference values for urinary free amino acids: a simple method of evaluation. The urinary excretion of free amino acids has been studied on 339 normal subjects, using ion exchange chromatography. Age related reference values were obtained. A simple method for their evaluation is discussed, and the application of the method to the detection of increased glycinuria, resulting from n-dipropyl acetate therapy, is described.


Arginase and free amino acids in hyperargininemia: leukocyte arginine as a diagnostic parameter for heterozygotes. Arginase activity and free amino acids were measured in plasma, erythrocytes and leukocytes of patients with hyperargininemia and in controls. There is no arginase activity in the leukocytes and erythrocytes of homozygous patients; in heterozygotes it is normal to low. The activity is 50 to 100 times higher in leukocytes than in erythrocytes. In controls as well as in patients and heterozygotes, the amino acid concentrations are higher in leukocytes than in plasma and erythrocytes. In addition to the increased arginine in the three blood compartments (the result of an arginase deficiency), there is also an obvious decrease of aspartic acid in the erythrocytes of the patients. The arginine concentration in leukocytes of heterozygotes is as high as in homozygotes and can therefore be used as a diagnostic parameter for heterozygotes.


Long-term observation of biochemical effects of lead in human experiments. In extension of two previous series of experiments, the results of which have been partially reported (1), further long-term tests were performed with daily oral doses of 5 mg Pb++ in 2 subjects. Lead in whole blood, free protoporphyrin 9 (III) and 5-aminolevulinate dehydratase activity in erythrocytes, hemoglobin, and urinary 5-aminolevulinic acid and coproporphyrin III excretion values were measured. From experiences with 8 human experiments, three compartmental phases of early detectable lead effect were postulated: 1. an "erythrocytic" reaction of 5-aminolevulinate dehydratase activity, 2. "hepatic" reactions of 5-aminolevulinic acid and coproporphyrin, and 3. an "erythropoietic" reaction of protoporphyrin.


A rapid enzymatic assay for methotrexate in serum. A kinetic enzymological assay for methotrexate in serum is described; the results are available after 1.5 hours. The lower limit of sensivity is 50 nmol/1; the day-to-day variation coefficients compare favourably with other procedures (about 7% in the 200-600 nmol/1 range). The method uses purified dihydrofolic acid reductase from bovine liver. The problem of its instability in the  assay is circumvented by several measures, e.g. the use of a reaction rate analyser.


[Computerized data processing for radioimmunoassay (author's transl)]. The computer programm of Marschner et al. ((1974), Arztl. Lab. 20, 184-191) for the calculation of radioimmunoassay data by spline functions was improved with regard to immediate availability of quality parameters. The existing programm was adapted to a computer Siemens 4004/151. Methods are reported for obtaining an exactly reproducible and objective smoothing of spline functions. The additional modifications enable even unskilled technicians to use the programm.


An automated microassay for blood ammonia. A microassay for blood ammonia has been developed. After dilution, blood is dialyzed by a continuous flow procedure, and the ammonium ions in the dialysate are assayed colorimetrically by the hypochlorite-phenol Berthelot reaction. Concentrations from 1 to 400 mumol/l NH+4 can be measured in a 50 mul whole blood sample. Using slight modifications, concentrations up to 800 mumol/l NH+4 can be determined. The precision, accuracy, sensitivity, and specificity of the method have been studied. In man, the usual values (mean +/- 2 SD) found are 27.4 +/- 10.2 mumol/l NH+4 in arterial blood, 20.9 +/- 9.8 mumol/l in venous blood. The usual values in rats and mice are very close to those given for man.


[Quantitative analysis of L-hydroxyproline in human biological material by gas-chromatography (author's transl)]. Quantitative amino acid analysis by gas chromatography was applied to the determination of 4-hydroxy-L-proline in biological material. After addition of a known amount of allo-4-hydroxy-D-proline, quantitative analysis of 4-hydroxy-L-proline can be performed by gas chromatographic separation of the amino acid enantiomers; since the standard and sample have identical chemical behaviour, they respond identically during derivatization. The accuracy, reproducibility, and sample requirement of this procedure are more advantageous than those of hitherto existing methods. This study is also an example of the application of chiral stationary phases, which permit the simultaneous separation of amino acids and amino acid enantiomers.


[Investigations on the utilization of D-gluconate and D-glucono-delta-lactone in the metabolism of the normal and alloxan diabetic rat (author's transl)]. Radioactivity was measured in the blood of normal and alloxan diabetic rats, after the oral administration of [U-14C]gluconate and [U-14C]glucono-delta-lactone, respectively. Radioactivity was also measured in the intestinal contents and feces 5 h after ingestion of the radioactive materials, It was concluded that the lactone is better absorbed from the intestine than the gluconate anion. According to this enhanced membrane permeation and the higher concentration reached in blood, the space of distribution of the lactone is larger than that of gluconate (50 and 41% of body weight, respectively); a higher retention in tissues and a greater loss in urine was also observed after administration of the lactone. Incorporation into liver glycogen is also higher from the lactone than from gluconate after oral administration, particularly in diabetic animals. The initial deficit in the oxidation of gluconate compared to that of the lactone, caused by a lag period of 7 and 4 h, respectively, is completely compensated during the following 8-9 h. The oxidative turnover of gluconolactone and of gluconate is significantly enhanced in diabetic animals. The better utilization in diabetic metabolism is in part explainable by a rise of glycolytic intermediates in the liver, which are decreased in starvation and diabetes. The limiting step of gluconate metabolism is the initial phosphorylation. Possibilities are discufor the dietetic use of gluconic acid in the form of an apolar derivative (lactone, ester).


Effects of an educational feedback strategy on physician utilization of thyroid function panels. Physician overutilization of clinical laboratory tests has been well documented, but previous attempts aimed at changing this behavior have met with limited success. An educational feedback strategy was used to try to change physician behavior in ordering thyroid function panels (TFPs) in the Duke-Watts Family Medicine group practice. The rate of TFP ordering significantly decreased for three months following the intervention but rose to the preintervention level within six months. Senior residents appeared to be more responsive to the educational feedback than junior residents. Results obtained in this and other studies suggest that other factors compete with educational approaches in motivating physician behavior, and these override rational decision making.


Some non-random views of statistical significance. Although research in family medicine is growing rapidly, few family physicians have had experience or training in statistical methods. Statistical significance and P values are often misunderstood and frequently misapplied. "Significance" is arbitrary; the actual P value is of greater interest than a significant/not significant statement; P values do not measure the strength of an association; statistical significance is not equivalent to "actual" significance; P values are largely dependent on sample size; and data "dredging" is guaranteed to yield spurious results. Competent statistical consultation, careful study planning, and recognition of statistical pitfalls are important to anyone who does research, and knowledge of these areas is useful as well to anyone reading the medical literature.


Inhospital family practice--a one year summary. A review of 914 medical records of patients hospitalized at the Polyclinic Medical Center of Harrisburg by members of the Department of Family Practice is presented. The age distribution of these patients was essentially bimodal, with peak numbers in the less than one year and greater than 65 years age groups. Physicians and physician groups which perform obstetrics rendered hospital care to a larger number of infants than those not performing obstetrics. The family physicians gave hospital care for a large number of different conditions. The family physicians frequently consulted other medical specialists, especially cardiologists and general surgeons. The consultation rate varied considerably among the physicians studied.


An analysis of returning patients in family practice. Morbidity records from eight practices participating for three years in the Virginia Family Practice Data System are analyzed with respect to two mutually exclusive groups of patients: those who return from one year to the next and those who do not return. Initially, substantial interpractice variation in patient return rates is presented, and age and sex characteristics of these patients are examined. The data indicate that approximately 40 percent of patients visiting the practice in one year return in the next, 25 percent return in each of two subsequent years, and only 12 percent return two years hence. Returning patients are found to be significantly older and more likely to be female than non-returning patients. These two groups of patients are then compared in terms of recorded morbidity and workload rates. Specific categories of problems, such as Diseases of the Circulatory System, are associated with returning patients. This paper thus presents empirical evidence which supports common assumptions concerning patients and problems seen in family practice.


Consultation and referral in a Vermont family practice: a study of utilization, specialty distribution, and outcome. Referral patterns and outcome were studied in an ambulatory family practice facility. One hundred eight referrals were initiated and studied during a period when 7,220 patients were seen--a 1.5 percent referral rate. Satisfactory outcomes occurred in 67 of the cases. Changing patterns of health care delivery may require new definitions of the consulation-referral process.


Suprapubic bladder needle aspiration in infants and children. Suprapubic needle aspiration of the bladder represents an excellent alternative to urethral catheterization to document bladder bacteriuria. Specific indications include documentation of bacteriuria in infants, in uncircumcised male children, in myelodysplastic children, and in children with abnormal genitalia.


Heparin and warfarin: use of anticoagulants in the prevention and treatment of venous thrombosis and pulmonary embolism. The physician frequently encounters the problems of deep vein thrombosis and pulmonary embolism. Recently, a number of studies have been published which are of considerable help in the management of these disorders. It has been shown that in many cases, low-dose heparin is effective in the prevention of both venous thrombosis and pulmonary embolism. However, once venous thrombosis has already occurred, it is necessary to use full-dose heparin, preferably by the continuous intravenous route, with maintenance of the partial thromboplastin time (PTT) at 1 1/2 times the control at all times. Although monitoring the PTT may not prevent hemorrhage, it will help prevent further thrombosis. Heparin is generally continued for seven to ten days. During this time warfarin is generally begun, and it is important to continue the patient on warfarin for five to seven days while the patient is receiving intravenous heparin therapy. After stopping heparin, oral anticoagulation with warfarin should be continued for six weeks. Then, in the absence of a previous history of venous thromboembolism or a known predisposing condition, it is safe to abruptly discontinue anticoagulation in most patients.


A multidisciplinary audit of diabetes mellitus. A multidisciplinary audit evaluating the quality of care of patients with a primary diagnosis of diabetes mellitus was performed at St. Mary's Hospital in Grand Rapids, Michigan. The audit served to evaluate the treatment and care of diabetic patients, in both the inpatient and ambulatory care settings, and also to identify interaction problems involving patient care among physicians, nurses, dieticians, and social workers. Analysis of the data indicated that each discipline rendered adequate patient care. As other published audits have also indicated, this multidisciplinary audit revealed that documentation of services is frequently lacking and that communication between the involved disciplines was less than desirable. The audit disclosed a need to educate the hospital staff (medical and nursing) as to the role and function of the Social Services Department. As a result of this audit, definite measures have been instituted in each participating department in an attempt to further upgrade the quality of medical care and improve interdepartmental communication and cooperation.


Management of grief in the hypochondriac. This paper illustrates the presentation and management of a grief reaction in a chronic hypochondriacal patient seen in a family medicine office. The manifestations of grief in the hypochondriacal patient are influenced by the unique characteristics of the chronic, somatic complainer in whom the grief reaction appeared as an intensification of the chronic complaints. The treatment of the grief reaction in these patients should take into account the techniques for managing the hypochondriacal patient.


Community medicine in the training of family physicians. Family practice residency programs are encouraged to include community medicine training in their curriculum, but there is little agreement as to what community medicine is or what would constitute appropriate training. Community medicine is most commonly defined as a discipline concerned with the identification and solution of health care problems of communities or other defined populations. The inclusion of training experiences in the identification and solution of health care problems of communities has two basic advantages for family practice residency programs: it fosters a contextual approach in the care of individual patients and it builds knowledge and skills for those who will work with communities in future practices. An example of curricular content is included. A survey was conducted in order to determine what residency programs teach in the field of community medicine. The results show that few of the responding programs include the areas which most clearly relate to community medicine. It is hoped that the report of these results, the rationale presented for including community medicine in the training of family physicians, and the suggested outline of curricular content will further encourage and assist family practice residency programs to incorporate such training in their curricula.


Continuity of care in a family practice residency program. Continuity of care, one of the basic characteristics of family medicine, was studied over a 12-month period in a family practice residency program. Continuity was measured in three contact areas; office hours, after hours, and on the inpatient service. The intensity of continuity was defined at three levels, from encounters with the personal physician to those with physicians on other medical teams. Continuity was further assessed in relation to family encounters. Third year residents averaged 83 percent continuity with their individual patients and 70 percent with their assigned families. Residents from other years were noted to have lower levels of continuity. Similar figures were noted for family practice inpatients. Continuity of care in private practice occurs in about 80 percent of patient encounters and it seems reasonable and feasible to expect residency training programs to come close to this figure.


Glucose effect on respiration: possible mechanism for capacitation in guinea pig spermatozoa. Guinea pig sperm respiration was determined in minimal capacitation medium (MCM) with different energy sources. The ZO2 observed for spermatozoa suspended in media containing pyruvate and lactate was 35.7 +/- 5.9, pyruvate alone, 27.9 +/- 3.8 and D-glucose alone 3.4 +/- 1.1. When D-glucose was added to spermatozoa rapidly respiring in media containing pyruvate as the only exogenous energy source, an immediate suppression in respiration was observed. Further reduction was caused by continued addition of D-glucose. Fructose and mannose also produced a suppression in respiratory rate. However, lactose, fucose, sucrose, L-glucose, and galactose did not alter the respiratory rate. The suppression of respiration by metabolizable sugars is paralleled by a suppression of acrosome reaction in guinea pig spermatozoa. The possibility that suppression of respiration is the mechanism for retardation of capacitation and the subsequent acrosome reaction by D-glucose and other metabolizable sugars is suggested.


Investigations into the degree of cell mixing that occurs between the 8-cell stage and the blastocyst stage of mouse development. This study was designed to assess the degree of cell mixing that occurs during the early development of the mouse embryo, and thus provide information which is important in relation to the current theories of differentiation. Previous studies of this nature have involved either chimeric composites, or have only followed a very limited number of cells in the embryo. Here the products of one of the 4-cell stage blastomeres have been labeled with tritiated thymidine, at a level which allows their descendants to be identified three or four cell divisions later, and recombined with the remaining blastomeres of the same embryo. After fixing and sectioning of the embryos at the blastocyst stage the locations of the labelled cells have been analyzed to assess the degree of clumping that they display. A significant tendency for the products of this one 4-cell stage blastomere to be confined to a single area in the blastocyst is demonstrated. This indicates that there is little marked cell movement during the observation period. The relevance of these results to current knowledge of blastocyst development is discussed.


Lactate dehydrogenase C4 in male sex accessory glands of normal mice and in testes of sex-reversed mice. Lactate dehydrogenase (LDH) C4 activity was observed in testis extracts of sex-reversed mice (Sxr) and in male sex accessory gland (seminal vesicle and prostate) extracts from C3H/He and C57BL/Go mice. These results reflect either (1) the presence of low concentrations of germinal cells in these tissues; or (2) the synthesis of LDH-C4 by somatic cells in Sxr testes and normal male sex accessory glands.


Dynamics of 9-aminoacridine block of sodium channels in squid axons. The interactions of 9-aminoacridine with ionic channels were studied in internally perfused squid axons. The kinetics of block of Na channels with 9-aminoacridine varies depending on the voltage-clamp pulses and the state of gating machinery of Na channels. In an axon with intact h gate, the block exhibits frequency- and voltage-dependent characteristics. However, in the pronase-perfused axon, the frequency-dependent block disappears, whereas the voltage-dependent block remains unchanged. A time-dependent decrease in Na currents indicative of direct block of Na channel by drug molecule follows a single exponential function with a time constant of 2.0 +/- 0.18 and 1.0 +/- 0.19 ms (at 10 degrees C and 80 m V) for 30 and 100 microM 9-aminoacridine, respectively. A steady-state block can be achieved during a single 8-ms depolarizing pulse when the h gate has been removed. The block in the h-gate intact axon can be achieved only with multiple conditioning pulses. The voltage-dependent block suggests that 9-aminoacridine binds to a site located halfway across the membrane with a dissociation constant of 62 microM at 0 m V. 9-Aminoacridine also blocks K channels, and the block is time- and voltage-dependent.


A common origin of voltage noise and generator potentials in statocyst hair cells. Voltage noise, generator potentials, and hair movements in the Hermissenda statocyst were analyzed. Motile hairs on the cyst's luminal surface moved as rods through +/- 10 degrees Hz when free and at 7 Hz when loaded with the weight of the statoconia (at 120 degrees C). For hair cells oriented opposite to a centrifugal force vector, rotation caused depolarization and increase of voltage noise variance. The depolarizing generator potential and the increase in voltage noise variance were similarly reduced by perfusion with zero external sodium or chloral hydrate. Cooling, perfusion with zero external sodium or chloral hydrate reduced the movement frequencies of the hairs but increased their range of motion. The same treatments reduced voltage noise variance and increased input resistance of the hair cell membrane. The results indicate that voltage noise and hair cell generator potential have a common origin: exertion of force on statocyst hairs by the weight of statoconia. The collision of statoconia with the motile hairs, not the hairs' bending, produces most of the voltage noise.


Heterogeneity in dog red blood cells: sodium and potassium transport. After incubation in isotonic KCl, dog red blood cells can be separated by centrifugation into subgroups which assume different cell volumes and possess different transport characteristics. Those red cells which swell in isotonic KCl exhibit a higher permeability to K and possess a greater volume dependence for transport of K than those red cells which shrink. A high Na permeability characterizes cells which shrink in isotonic KCl and these cells exhibit a larger volume-dependent Na flux than those red cells which swell. These two subgroups of red cells do not seem to represent two cell populations of different age. The results indicate that the population of normal cells is evidently heterogeneous in that the volume-dependent changes in Na and K permeability are distributed between differnt cell types rather than representing a single cell type which reciprocally changes its selectivity to Na and K.


Ionic mechanisms of two types of on-center bipolar cells in the carp retina. I. The responses to central illumination. Properties of the depolarizing response of on-center bipolar cells to a light spot stimulus were studied in the carp retina. On-center bipolar cells were classified into two types, cone-dominant and rod-dominant, according to their major input from cones and rods. Cone-dominant bipolar cells responded to spectral light with the maximum amplitude near 625 nm, suggesting major input from red cones. The response was accompanied by a resistance increase and showed a reversal potential at -63 +/- 21 mV when the membrane was hyperpolarized by current. The results suggest that the photoresponse of cone-dominant cells is due to a decrease of gK and/or gCl, membrane conductances to potassium and chloride, respectively. Rod-dominant bipolar cells responded to spectral light with the maximum amplitude near 525 nm under scotopic conditions and near 625 nm under photopic conditions, providing evidence that they receive input from rods and red cones. In the scoptopic condition their response was accompanied by a resistance decrease and showed a reversal potential at 29 +/- 13 mV, whereas in the photopic condition the response in most of them was accompanied by a resistance increase, at least in their part and showed a reversal at -53 +/- 11 mV. The results suggest that the photoresponse activated by rod input is due to an increase in gNa. In the mesopic condition rod-dominant cells showed complex electrical membrane properties as the result of electric interaction between the above two differnt ionic mechanisms activated by rod and cone inputs.


Calcium influx in internally dialyzed squid giant axons. A method has been developed to measure Ca influx in internally dialyzed squid axons. This was achieved by controlling the dialyzed segment of the axon exposed to the external radioactive medium. The capacity of EGTA to buffer all the Ca entering the fiber was explored by changing the free EGTA at constant [Ca++]i. At a free [EGTA]i greater than 200 microM, the measured resting Ca influx and the expected increment in Ca entry during electrical stimulation were independent of the axoplasmic free [EGTA]. To avoid Ca uptake by the mitochondrial system, cyanide, oligomycin, and FCCP were included in the perfusate. Axons dialyzed with a standard medium containing: [ATP] = 2 mM, [Ca++]i = 0.06 microM, [Ca++]o = 10 mM, [Na+]i = 70 mM, and [Na+]o = 465 mM, gave a mean Ca influx of 0.14 +/- 0.012 pmol.cm-2.s-1 (n = 12. Removal of ATP drops the Ca influx to 0.085 +/- 0.007 pmol.cm-2.s-1 (n = 12). Ca influx increased to 0.35 pmol.cm-2,s-1 when Nao was removed. The increment was completely abolished by removing Nai+ and (or) ATP from the dialysis medium. At nominal zero [Ca++]i, no Nai-dependent Ca influx was observed. In the presence of ATP and Nai [Ca++]i activates the Ca influx along a sigmoid curve without saturation up to 1 microM [Ca++]i. Removal of Nai+ always reduced the Ca influx to a value similar to that observed in the absence of [Ca++]i (0.087 +/- 0.008 pmol.cm-2.s-1; n = 11). Under the above standard conditions, 50-60% of the total Ca influx was found to be insensitive to Nai+, Cai++, and ATP, sensitive to membrane potential, and partially inhibited by external Co++.


Influence of chloride, potassium, and tetraethylammonium on the early outward current of sheep cardiac Purkinje fibers. In voltage clamp studies of cardiac Purkinje fibers, a large early outward current is consistently observed during depolarizations to voltages more positive than -20 mV. After the outward peak of the current, the total membrane current declines slowly. Dudel et al. (1967. Pfluegers Arch. Eur. J. Physiol. 294:197--212) reduced the extracellular chloride concentration and found that the outward peak and the decline of the current were abolished. They concluded that the total membrane current at these voltages was largely determined by a time- and voltage-dependent change in the membrane chloride conductance. We reinvestigated the chloride sensitivity of this current, taking care to minimize possible sources of error. When the extracellular chloride concentration was reduced to 8.6% of control, the principal effect was a 20% decrease in the peak amplitude of the outward current. This implies that the membrane chloride conductance is not the major determinant of the total current at these voltages. The reversal potential of current tails obtained after a short conditioning depolarization was not changed by alterations in the extracellular chloride or potassium concentrations. We suspect that the tail currents contain both inward and outward components, and that the apparent reversal potential of the net tail current largely reflects the kinetics of the outward component, so that this experiment does not rule out potassium as a possible charge carrier. The possibility that potassium carries much of the early outward current was further investigated using tetraethylammonium, which blocks potassium currents in nerve and skeletal muscle. This drug substantially reduced the early outward current, which suggests that much of the early outward current is carried by potassium ions.


Voltage clamp analysis of embryonic heart cell aggregates. The double-microelectrode voltage clamp technique was applied to small spheroidal aggregates of heart cells from 7-d chick embryos. A third intracellular electrode was sometimes used to monitor spatial homogeneity. On average, aggregates were found to deviate from isopotentiality by 12% during the first 3--5 ms of large depolarizing voltage steps, when inward current was maximal, and by less than 3% thereafter. Two components of inward current were recorded: (a) a fast, transient current associated with the rapid upstroke of the action potential, which was abolished by tetrodotoxin (TTX); and (b) a slower inward current related to the plateau, which was not affected by TTX but was blocked by D600. The magnitudes, kinetics, and voltage dependence of these two inward currents and a delayed outward current were similar to those reported for adult cardiac preparations. From a holding potential of -60 mV, the peak fast component at the point of maximal activation (-20 mV) was -185 microA/cm2. This value was about seven times greater than the maximal slow component which peaked at 0 mV. The ratio of rate constants for the decay of the two currents was between 10:1 and 30:1.


The effects of acidosis and bicarbonate on action potential repolarization in canine cardiac Purkinje fibers. Studies were performed on canine cardiac Purkinje fibers to evaluate the effects of acidosis and bicarbonate (HCO3) on action potential repolarization. Extracellular pH (pHe) was reduced from 7.4 to 6.8 by increasing carbon dioxide (CO2) concentration from 4 to 15% in a HCO3-buffered solution or by NaOH titration in a Hepes-buffered solution. Both types of acidosis produced a slowing of the rate of terminal repolarization (i.e., period of repolarization starting at about -60 mV and ending at the maximum diastolic potential) with an attendant increase in action potential duration of 10--20 ms. This was accompanied by a reduction in the maximum diastolic potential of 2--8 mV. In contrast, if the same pH change was made by keeping CO2 concentration constant and lowering extracellular HCO3 from 23.7 to 6.0 mM, in addition to the slowing of terminal repolarization, the plateau was markedly prolonged resulting in an additional 50- to 80-ms increase in action potential duration. If pHe was held constant at 7.4 and HCO3 reduced from 23.7 mM to 0 (Hepes-buffered solution), the changes in repolarization were nearly identical to those seen in 6.0 mM HCO3 except that terminal repolarization was unchanged. This response was unaltered by doubling the concentration of Hepes. Reducing HCO3 to 12.0 mM produced changes in repolarization of about one-half the magnitude of those in 6.0 mM HCO3. These findings suggest that in Purkinje fibers, HCO3 either acts as a current that slows repolarization or modulates the ionic currents responsible for repolarization.


The initiation of excitation and light adaptation in Limulus ventral photoreceptors. Two types of experiments indicate that light adaptation and excitation are initiated by the same, rather than different, populations of visual pigment. (a) The criterion action spectra of light adaptation and excitation are the same. (b) Increment-threshold curves were measured with a voltage-clamp technique under conditions of high and low concentration of plasma membrane rhodopsin (Rhpm). SD, the dark-adapted sensitivity, and 1/I2, the inverse of the background irradiance that desensitized by 0.3 log units, underwent the same fractional change when the rhodopsin concentration was changed. Both quantities appear to be linearly related to Rhpm. Reversible reductions in Rhpm were achieved by orange irradiation during a brief increase of extracellular pH from 7.8 to 10. This procedure would be unlikely to produce similar concentration changes in a hypothetical intracellular pigment because the concurrent change in intracellular pH, measured using the dye, phenol red, was only 0.45 pH units. It is thus unlikely that an intracellular pigment initiates light adaptation. On the assumption that light adaptation is mediated by a light-induced release of Ca++ from an intracellular store. the results reported here imply that an intracellular transmitter is needed to couple Rhpm to the intracellular store.


Synaptic inputs to the ganglion cells in the tiger salamander retina. The postsynaptic potentials (PSPs) that form the ganglion cell light response were isolated by polarizing the cell membrane with extrinsic currents while stimulating at either the center or surround of the cell's receptive field. The time-course and receptive field properties of the PSPs were correlated with those of the bipolar and amacrine cells. The tiger salamander retina contains four main types of ganglion cell: "on" center, "off" center, "on-off", and a "hybrid" cell that responds transiently to center, but sustainedly, to surround illumination. The results lead to these inferences. The on-ganglion cell receives excitatory synpatic input from the on bipolars and that synapse is "silent" in the dark. The off-ganglion cell receives excitatory synaptic input from the off bipolars with this synapse tonically active in the dark. The on-off and hybrid ganglion cells receive a transient excitatory input with narrow receptive field, not simply correlated with the activity of any presynaptic cell. All cell types receive a broad field transient inhibitory input, which apparently originates in the transient amacrine cells. Thus, most, but not all, ganglion cell responses can be explained in terms of synaptic inputs from bipolar and amacrine cells, integrated at the ganglion cell membrane.


Fluid transport and the dimensions of cells and interspaces of living Necturus gallbladder. The volume of the cells and lateral intercellular spaces were measured in living Necturus gallbladder epithelium. Under control conditions, the volume of the lateral spaces was 9% of the cell volume. Replacement of mucosal NaCl by sucrose or tetramethylammonium chloride (TMACl) caused intercellular spaces to collapse. During mucosal NaCl replacement, cell volume decreased to 79% of its control value. When NaCl was reintroduced into the mucosal bath, the intercellular spaces reopened and the cells returned to control volume. The NaCl active transport rate, calculated from the rate of cell volume decrease, was 266 pM/cm2.s, close to the observed rate of transepithelial salt transport. It was calculated from the decrease in cell volume that all of the intracellular NaCl was transported out of the cell during removal of mucosal NaCl. The flux of salt across the apical membrane, calculated from the rate of cell volume increase upon reintroducing mucosal NaCl, was 209 pM/cm2.s, in good agreement with estimates by other methods. The electrical resistance of the tight junctions was estimated to be 83.9% of the total tissue resistance in control conditions, suggesting that the lateral intercellular spaces normally offer only a small resistance to electrolyte movement.


Calcium content and net fluxes in squid giant axons. Axons freshly dissected from living specimens of the tropical squid Dorytheutis plei have a calcium content of 68 mumol/kg of axoplasm. Fibers stimulated at 100 impulses/s in 100 mM Ca seawater increase their Ca content by 150 mumol/kg.min; axons placed in 3 Ca (choline) seawater increase their Ca content by 12 mumol/kg.min. Axons loaded with 0.2--1.5 mmol Ca/kg of axoplasm extruded Ca with a half time of 15--30 min when allowed to recover in 3 Ca (Na) seawater. The half time for recovery of loaded axons poisoned with carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) and iodoacetic acid (IAA) is about the same as control axons. Axons placed in 40 mM Na choline seawater (to reduce chemical gradient for Na) or in 40 mM Na, 410 mM K seawater to reduce the electrochemical gradient for Na to near zero either fail to lose previously loaded Ca or gain further Ca.


Properties of chloride transport in barnacle muscle fibers. Unidirectional chloride-36 fluxes were measured in internally dialyzed barnacle giant muscle fibers. About 50--60% of the Cl efflux was irreversibly blocked by the amino-group reactive agent, 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulfonic acid (SITS), when it was applied either intra- or extracellularly. Similarly, Cl influx was also blocked by SITS. No significant effect on [Cl]i of SITS was noted in intact muscle fibers. However, the rate of net Cl efflux from muscle fibers which were Cl-loaded by overnight storage at 6 degrees C could be slowed by SITS treatment. Two classes of anions were defined based upon their effects on Cl efflux. Methanesulfonate and nitrate inhibited Cl efflux either when they replaced external chloride or when they were added to a constant external chloride concentration. The other group of anions (propionate, formate) stimulated both Cl efflux and influx and such stimulation could be blocked by SITS. Propionate influx was not nearly as large as the stimulated Cl efflux and was unaffected by SITS. Neither the effects of SITS nor those of the anion substitutes could be simply accounted for by changes in the membrane resting potential or conductance. These results suggest a mediated transport system for chloride across the barnacle sarcolemma.


The nature of arginine auxotrophy in cutaneous populations of staphylococci. L-Arginine was required for growth by a high percentage of strains of Staphylococcus species that were niche-specific and/or host-specific, but was usually not required for growth by species showing a wide host range. Growth stimulation patterns with arginine intermediates indicated that most of the auxotrophic strains had blocks in an early step(s) in arginine biosynthesis. These strains were designated phenotypically as Arg(CHG) according to the Salmonella typhimurium classification scheme. Staphylococcus simulans strains appeared to be either ArgA or Arg I. The ArgI strains of S. simulans and S. capitis had moderate to high ornithine carbamoyltransferase (EC 2.1.3.3) activities and therefore could not be designated as argI mutants. ArgI strains in other species had no or very low ornithine carbamoyltransferase activities. All of the natural Staphylococcus auxotrophs tested grew in the presence of L-citrulline and had moderate to high argininosuccinase (EC 4.3.2.1) activities. Arginine auxotrophs of species with a wide host range were often capable of reverting to arginine-independent or complete prototrophic growth, whereas auxotrophs of species that tended to be niche-specific and/or host-specific were incapable of reversion to arginine-independence, even in the presence of various mutagens. A relationship between the nature of arginine auxotrophy and habitat is suggested.


Simultaneous and successive cognitive processes in the Mueller-Lyer illusion. Performance in the Mueller-Lyer Illusion was analyzed for whole and partial presentations of the figure. S s were 120 third grade boys and girls. Four experimental groups were formed with the use of the human abilities model of simultaneous and successive syntheses, and the two types of presentation were given to each group. Results indicated that illusory effects in both presentations of the figure were significantly reduced by ability in simultaneous synthesis. Performance in the two presentations was also affected by successive ability, but these effects were in opposite directions for the two forms of presentation. The results did not support Piaget's theory of perceptual development, although they were consistent with the theory of simultaneous and successive syntheses. Suggestions are made for the design of future research.


Effects of alcohol on moral functioning in male social drinkers. The present study investigated the effect of alcohol consumption on both moral reasoning and moral values, cognitive variables which are likely to mediate moral behavior. Fifty-five male social drinkers (Mean age = 19.75 years) participated in a one-way pretest-posttest design incorporating two experimental (alcohol) and three control groups. Results showed that alcohol did not affect moral stage reasoning on the Defining Issues Test. However, the endorsement of meaningless items was significantly, but differentially, affected by the alcohol doses administered. No group differences were found in regard to moral values. These findings are related to previous research on alcohol and cognitive processes.


Predictive validity of the Rorschach Prognostic Rating Scale with schizophrenic patients. The prognostic validity of the Rorschach Rating Scale was assessed with schizophrenic patients. Through the use of a standardized structured interview and a diagnostic system for schizophrenia based on the use of discriminant function analysis with nonpathognomonic symptom combinations, a reliable and valid system was used to establish the criterion diagnosis. Outcome criteria used included a variety of measures of schizophrenic thought disorder. The results help to establish the practical utility of the PRS empirically with schizophrenic patients by demonstrating efficient prediction when other relevant demographic and nontest variables have been controlled. Furthermore, the concept of ego strength from which the PRS was developed does not appear to be too global a characteristic when the area for change is specifically delineated.


Is outcome for schizophrenia better in nonindustrial societies? The case of Sri Lanka. We now have evidence that the prognosis for schizophrenia is much better in nonindustrial than in industrial societies. This paper reports on a 5-year follow-up of schizophrenic patients living in the peasant society of Sri Lanka and shows that social adjustment and clinical state of a sample of first admission schizophrenic patients examined at the end of 5 years are remarkably good. Further, the 5-year outcome for these patients is consistent with WHO's samples followed in Nigeria and India, for example, and consistently different from outcome for schizophrenic patients followed in industrial societies such as Denmark, U.S.A., U.K., and U.S.S.R. Further, we have shown for the Sri Lanka schizophrenics that good outcome cannot be explained by artifacts of sampling or diagnostic methods, by type of treatment, or by the family's willingness to tolerate deviance. Instead, to explain cultural differences in prognosis, we propose a theoretical alternative to the medical model of disease, social labeling theory, that attributes good prognosis to cultural factors such as the traditional system of beliefs, structure of the treatment system, and family norms. In modern industrial societies, expectations and beliefs about mental illness and the operation of the treatment system serve largely to alienate schizophrenic patients from their normal roles and thus to prolong illness. In contrast, beliefs and practices in nonindustrial societies encourage short term illness and quick return to normality. Cultural differences in prognosis, then, may be the result of culturally based self-fulfilling prophecies.


Neurological soft signs and psychopathology. I. Findings in schizophrenia. Systematic, standardized evaluations for neurological soft signs were conducted on five psychiatric populations and a control group of medical inpatients. Soft signs were grouped according to their probable clinical association with cortical lobe dysfunction. Preliminary results indicated that schizophrenics, compared to other groups, showed significant increased presence of soft signs presumably related to frontal and parietal lobe dysfunction.


Quantification of the human orienting response to another human: lesioned and psychiatric patients compared to normals. A method for eliciting, controlling, and quantifying the alpha suppression response to a human "real-person" stimulus is presented. Improved control is achieved by a feedback from the EEG response to the presentation of the stimulus. Quantification is comprehensive in that initial response and subsequent habituation for both latency and duration are described. Patients who had suffered a focal lesion but who had recovered sufficiently to travel from one hospital to another by taxi were compared with hospitalized psychiatric patients and normal volunteers. Lesioned patients showed less EEG response to visual stimuli than did the other groups, even with an evocative, real-person stimulus. The differences among the three groups were most evident at the onset of stimulation and less so after habituation had occurred.


The diagnosis of Briquet's syndrome in a male population: the Veterans Administration revisited. Fifty psychiatric inpatients at a VA Hospital felt to be at high risk for the development of somatic complaints were surveyed for Briquet's syndrome. When criteria for the syndrome were strictly applied, no men were found with the disorder. If the criteria were minimally relaxed, two patients did have a sufficient number of symptoms in multiple areas to qualify for the diagnosis. However, they had alternative clinical and research diagnoses and none of the personality characteristics noted in previous populations of women surveyed for Briquet's syndrome.


Comparison of the clinical effectiveness of "short" versus "long" stay psychiatric hospitalization. IV. Predictors of differential benefit. One hundred seventy-three patients were randomly assigned to LT (long term, unlimited length of stay, mean 179 days) vs. ST (short term, 90-day limit) psychiatric hospitalization. Three-year follow-up results showed few between-group differences, although LT patients tended to be rehospitalized more and had superior relative ratings of psychopathology. Demographic and clinical data did not predict differential benefit from LT or ST hospitalization. Diagnosis did not generally predict differential benefit either, except that clinically diagnosed personality disorders, given LT as opposed to ST hospitalization, had poorer role functioning and less psychiatric treatments after discharge. Patients with a history of drug abuse did worse if given LT hospitalization in terms of role functioning and rehospitalization. Overall, this study agrees with other relevant studies in indicating that hospitalization should be kept as short as feasible.


Lithium toxicity with hypothyroidism as a possible determinant. A case of a woman with severe lithium toxicity and hypothyroidism with persistent hyponatremia and hypokalemia is presented. The mechanisms of the development of lithium toxicity by alterations in fluid and sodium metabolism, including those induced by lithium itself, are reviewed. The possibility that hypothyroidism may have been a significant determinant in the development of this case of lithium toxicity is considered and discussed. This is of special interest given that lithium can induce hypothyroidism. In addition, the safe reinstitution of lithium prophylaxis in this woman can be reported.


Frequency of depressive disorder in patients entering home hemodialysis. Fifty-eight patients were systematically interviewed at the time of their entry into a home hemodialysis training program. The social, demographic, medical, and psychological characteristics of the sample are described. On interview, 13 (22%) of the 58 patients were found to be experiencing rigorously defined depressive disorder. The importance of further study regarding the incidence of depressive illness in similar groups of patients and the need for further research in defining adequate therapy for these patients are emphasized.


Cerebral hemispheric lateralization of cognitive deficits due to alcoholism. Twenty chronic alcoholics and a group of matched control subjects were tested on verbal and visuospatial memory tasks in order to test directly the hypothesis that alcoholism disturbs cognitive functions subserved by the right hemisphere more than those subserved by the left hemisphere. The results provide some support for the hypothesis and indicate that information may be lost by pooling together test results from alcoholics which come from a mixture of verbal and nonverbal tasks.


Hypochondriasis and paranoia: similar delusional systems in an institutionalized geriatric population. Hypochondriasis and paranoia are common psychopathologies of aging. The former may be secondary to depression or organic brain syndrome, whereas the latter may be secondary to sensory impairment or organic brain syndrome. Paranoid schizophrenia, with delusions of grandeur, is rare in later life. The authors classified 273 institutionalized geriatric patients by means of staff ratings into categories such as lucid and alert, confused, hypochondriacal, paranoid, etc. Among confused patients there was a correlation of .45 (p less than .001) between hypochondriasis and paranoia. Even among nonconfused patients, there was a slight positive correlation. The authors concluded that geriatric paranoia and hypochrondriasis have similar structure (delusion) and functions (safeguarding self-esteem and manipulating others). An interpersonal perspective can also provide guidelines for when to treat these conditions.


Presentation of the steroid psychoses.

Presentation of the steroid psychoses. This study suggests that patients receiving daily doses of 40 mg of prednisone or its equivalent, are at greater risk for developing steroid psychosis. Psychotic reactions were twice as likely to occur during the first 5 days of treatment as subsequently. Premorbid personality, history of previous psychiatric disorder, and a history of previous steroid psychosis did not clearly increase the patient's risk of developing psychotic reaction during any given course of therapy. Steroid psychoses present as spectrum psychoses with symptoms ranging from affective through schizophreniform to those of an organic brain syndrome. No characteristic stable presentation was observed in these 14 cases reported here. The most prominent symptom constellation to appear some time during the course of the illness consisted of emotional lability, anxiety, distractibility, pressured speech, sensory flooding, insomnia, depression, perplexity, agitation, auditory and visual hallucinations, intermittent memory impairment, mutism, disturbances of body image, delusions, apathy, and hypomania. Phenothiazines administered in average daily doses of 212 mg produced excellent response in all patients studied. Of particular note was the fact that tricyclic antidepressants produced an exacerbation or worsening of the clinical state in all patients to whom they were administered.


Subclinical depression and performance expectations, evaluations of performance, and actual performance. Four hundred sixty-nine female and 311 male college students were administered a depression scale, an analogies test, and questions related to expectations and evaluations of performance. As predicted, significant negative correlations were found between subclinical depression and expectations and evaluations of performance. A significant negative correlation between depression and actual performance was apparent for females only. However, this correlation was much weaker than similar correlations previously reported for college student populations. It was concluded that low performance expectations constitute one dimension of subclinical depression. This suggests that Beck's theory of clinical depression, which holds that negative self-perceptions and other cognitions are importantly involved in depression, may be useful in understanding normal mood variation. The findings also suggest that some similarities exist between clinically and subclinically depressed groups in that both groups are reported to hold low performance expectations, but display minimal performance deficits.


The frequency and identification of false positive conversion reactions. The frequency with which conversion reaction diagnoses are inappropriately applied to persons with physical diseases was estimated in a sample of medical hospital patients diagnosed hysteric. This was accomplished by ratings based on file information available at the time of diagnosis and at a 10-year follow"up, and a count of patients whose "conversion" symptoms were later diagnosed as physical illnesses. The estimated false positive rate was 25%. The symptoms most characteristic of the false positives were degenerative diseases and structural failures affecting the spinal cord, peripheral nerves, bones, muscles, and connective tissues. An effort to identify psychological parameters capable of separating true conversion reactions from false positives with a variety of behavioral symptoms and Minnesota Multiphasic Personality Inventory scores was not productive.


A biphasic change in mood with a tricyclic antidepressant. Eight depressed patients received 150 mg of clomipramine for 4 weeks. They completed the Profile of Mood States five to seven times the first week of treatment and five to seven times at the end of treatment. Moods showing significant decrease from the beginning to the end of the first week were: tension-anxiety, depression, anger-hostility, and confusion. The only changes from the beginning to the end of the 4-week period were an increase in vigor and a decrease in fatigue. The occurrence of rapid and slow mood changes with antidepressants suggested that the former were due to sedative effects and the latter occurred at the rate of the improvement in the disease depression.


Cross-cultural differences in indicators of improvement from psychosis: the case of betel nut chewing. This paper uses a case from the Micronesian Island of Yap to illustrate that indicators of improvement from an episode of schizophrenic psychosis can vary tremendously from culture to culture. At times, the clinician must search diligently for such indicators since the patient will not verbalize any perception of improvement. A 39-year-old Yapese woman was evaluated by a psychiatrist and was found to have been psychotic for several years, suffering from gross delusions, and auditory hallucinations, flattened affect, and social isolation. In addition, she had discontinued chewing betel nut that was used daily by virtually all of her fellow islanders on Yap. Two months after beginning treatment with twice monthly injectable antipsychotic medication she was still delusional, with flat affect, and heard the same voices. She was slightly less socially withdrawn and she had interestingly resumed chewing betel nut. It seemed that she had given up betel nut chewing during the socially withdrawn phase of her illness and had resumed it as she improved and became less autistically preoccupied. In her culture, betel chewing was a main avenue of social intercourse and an intrinsic part of almost all social activities. In her particular case, the resumption of betel chewing was a primary indicator of her improvement from psychosis and reintegration into her social group.


Effects of 4-aminopyridine on the turnover of monoamines in the central nervous system of the rat. The effects of 4-aminopyridine (4-AP) on the turnovers of 5-hydroxytryptamine, dopamine and noradrenaline in the central nervous system of rats were studied by means of amine disappearance following inhibition of tryptophan or tyrosin hydroxylase. 4-AP (3 mg/kg i.p.) did not change the utilizations of 5-hydroxytryptamine or dopamine but it markedly accelerated that of noradrenaline in the brain and in the spinal cord. This stimulatory effect of 4-AP was completely dependent on nerve impulses since no effect was observed following an acute section of the noradrenaline nerves to the spinal cord. The effect of 4-AP was blocked by the alpha-adrenoreceptor stimulating agent clonidine. Pentylenetetrazole, at a dose producing similar behavioural changes as 4-AP, caused only a slight stimulation of the noradrenaline turnover. 4-AP might enhance the flux of calcium ions into nerve terminals during depolarization, and thus increase the release of noradrenaline, whereas this process might be of less importance in the dopamine and the 5-hydroxytryptamine nerves.


Effect of mazindol on brain dopamine turnover in spiperone-treated rats. Mazindol, an anorexic drug, caused a large increase in brain 3, 4-dihydroxyphenylacetic acid (DOPAC) concentration in spiperone-pretreated rats. The increase was dose-related over a 1--10 mg/kg dose range of mazindol and was maximum within 1 hour after maxzindol injection into rats pretreated 1 hour previously with spiperone. In spiperone-pretreated rats, mazindol accelerated the disappearance of dopamine after the inhibition of dopamine synthesis by alpha-methyltyrosine. Mazindol apparently resembles amfonelic acid, methylphenidate, and cocaine in facilitating the impulse-mediated release of dopamine.


Failure of anticholinergic drugs to antagonize the increase in dopamine seen after gammahydroxybutyric acid and axotomy. The increase in dopamine (DA) seen either 30 or 90 min after injection of gammahydroxybutyric acid or 90 min after axotomy of the nigrostriatal DA-fibers was not affected by i.p. injections of either atropine sulfate or atropine methyl nitrate or benztropine. These increases in DA are most probably due to feedback-mechanisms which do not involve cholinergic neurons.


d-Amphetamine-induced increase in catecholamine synthesis in the corpus striatum of the rat: persistence of the effect after tolerance. The effect of d-amphetamine on in vivo catecholamine synthesis in four regions of rat brain was determined by measuring the accumulation of dopa after inhibiton of dopa decarboxylase. In doses up to 2.5 mg/kg, d-amphetamine caused dose-dependent increases in striatal dopa accumulation to a maximum of 280% of control; further increases in dose resulted in smaller effects until 10 mg/kg d-amphetamine was not significantly different from control. d-Amphetamine did not alter dopa accumulation in telencephalon, in diencephalon-mesencephalon, or in pons-medulla oblongata. d-Amphetamine did not affect either dopamine levels in striatum or NE levels in pons-medulla oblongata; at high doses, d-amphetamine did reduce norepinephrine levels in telencephalon and in diencephalon-mesencephalon. Daily administration of pre-session but not of post-session d-amphetamine produced tolerance to the effects of d-amphetamine on milk consumption in rats. The ability of d-amphetamine to increase striatal catecholamine synthesis was not altered by the development of tolerance to d-amphetamine. These results suggest that tolerance to d-amphetamine is not related to its effect on catecholamine synthesis but instead occurs via changes in aspects of catecholamine metabolism other than synthesis via change in catecholamine release, reuptake, or receptor sensitivity, or via changes in non-catecholaminergic mechanisms.


Studies on the colour-change mechanism in a fresh-water teleost, Nandus nandus (Ham.). I. Neural control. The existence and nature of chromatic fibres controlling the colour-change mechanism in the teleost, Nandus nandus has been studied by means of spinal sectioning at various vertebral levels of the animal between vertebrae 3 to 10. Spinal sectioning at or anterior to 5th vertebra completely eliminated the neural control of colour-change. As a result, the animal darkened to its maximum and the neural responses of different backgrounds were abolished. Spinal sectioning at or posterior to vertebra 6 did not affect the melanophores and at the same time did not interfere with the normal background responses of the animal. This study clearly shows that the chromatic fibres in this species run in the spinal cord and leave the latter at 5/6th vertebral level. Effect of adrenaline in the chromatic spinal-sectioned fish shows that the fibres innervating the melanophores are aggregating in nature and adrenergic in character. The results also suggest that the dispersed condition of pigment in the melanophores represents the "resting state" of the melanophores when they are under no stimulation.