Study of the intestinal tyrosine metabolism using stable isotopes and gas chromatography-mass spectrometry.

Deuterated tyrosine, 4-hydroxyphenyllactic acid, 4-hydroxyphenylpropionic acid, 4-hydroxyphenylacetic acid and 4-hydroxybenzoic acid were incubated under anaerobic conditions with human faecal specimens for the in vitro study of their respective metabolisms. After 1 week, aromatic acids and phenols were extracted and analyzed by gas chromatography-mass spectrometry. [3',5'-2H2]Tyrosine produced 4-hydroxyphenyllactic acid, 4-hydroxyphenylpropionic acid and 4-hydroxyphenylacetic acid; [3',5'-2H2]-4'-hydroxyphenyllactic acid produced 4-hydroxyphenylpropionic acid, 3-hydroxyphenylpropionic acid, 4-hydroxyphenylacetic acid and phenylproionic acid; [3',5'-2H2]-4'-hydroxyphenyl-propionic acid produced 3-hydroxyphenylpropionic acid and phenylpropionic acid; [3',5',2,2-2H4]-4'-Hydroxyphenylacetic acid produced p-cresol; and [3',5'-2H2]-4'-hydroxybenzoic acid produced phenol. Thus the intestinal flora showed activities for decarboxylation leading to phenol and p-cresol, dehydroxylation leading to phenylpropionic acid and rearrangement leading to 3-hydroxyphenylpropionic acid. Rentention of both deuterium labels was observed in the rearrangement reaction.


Aldehyde condensation products as derivatives for the vapor phase analysis of biogenic amines.

The mass spectra of six tetrahydroisoquinolines and five tryptolines are surveyed. It is concluded that tryptolines are suitable for analysis of tryptamines, after condensation with aldehydes.


Applications of boronate derivatives in the study of ceramides by gas-liquid chromatography-mass spectrometry.

Methaneboronate derivatives of ceramides possess excellent gas-liquid chromatographic properties and give informative mass spectra. Molecular ions, present at high abundance where an unsaturated acyl substituent is present, are accompanied in the electron impact mass spectra by fragment ions which denote the acyl group and long-chain base. In the gas-liquid chromatographic-mass spectrometric analyses of natural ceramides, as methaneboronate derivatives, the properties of open-tubular columns are exploited to give good separations in moderate analysis times. An application is made to the analysis of ceramides derived from sphingomyelin of human arterial tissue.


Chemical ionization mass spectrometry for rapid assay of drugs in serum.

A rapid procedure has been devised for analyzing anti-epileptic drugs in serum by chemical ionization mass spectrometry. An internal standard, 5-(p-methylphenyl)-5-phenylhydantoin (MPPH), is added to serum diluted in buffer at pH 12. The mixture is washed with diethyl ether to remove neutral lipids, acidified, extracted with chloroform and the chloroform extract evaporated to dryness. The residue is then dissolved in methanol and an aliquot, corresponding to approximately 2% of the original mixture, is deposited in the glass capillary sample cup of the solid probe inlet of the mass spectrometer. The sample is then volatilized by heat into the ion source of the mass spectrometer, where it reacts with ionized methane reagent gas. As the temperature of the probe is increased, quasimolecular ion peaks of the protonated anticonvulsants appear, rise and fall on the oscilloscope tracing, indicating similar but not identical rates of volatilization. We recorded these peaks photographically by opening the shutter of the oscilloscope camera for the entire heating cycle. The concentrations of the anticonvulsants were estimated from the ratio of the height of the peaks of the drug to that of the internal standard on the photograph. The peak-height ratios were proportional to concentration within, above and below the therapeutic range. Other drugs, including barbiturates, carbamazepine, nicotine and caffeine, were readily identified when present. With one solid probe inlet, an assay could be performed every 2 min.


Structure-gas chromatographic electron capture sensitivity relationships of some substituted 17alpha-acetoxyprogesterones.

Structure-electron capture sensitivity relationships were established for underivatized 17alpha-acetoxyprogesterones. While progesterone was very insensitive, 17alpha-acetoxyprogesterone had a response of 4.8 X 10(2) C/mole. Methyl groups in the A or B ring of 17alpha-acetoxyprogesterone had no effect. A keto group at C-6 was 25 times more sensitive (1.2 X 10(4) C/mole). A double bond at C-6,7 enhanced the sensitivity sevenfold (3.5 X 10(3) C/mole), but double bonds at C-1,2 or C-9,11 had only slight effect. Substitution at C-16 was important. A methyl group at C-16 had two and three times the sensitivity in the 3-keto delta4 and 3-keto delta4,6 series (1.1 X 10(3) and 1.1 X 10(4) C/mole), respectively. A methylene group at C-16, in contrast showed a six-and twofold greater sensitivity over the C-16 methyl in the two series (7 X 10(3) and 2.2 X 10(4) C/mole), respectively. The most sensitive compound was 6-dehydro-6methyl-16-methylene-17alpha-acetoxyprogesterone (melengestrol acetate). Its sensitivity was 2.2 X 10(4) C/MOL, Comparable to the most sensitive halo esters of steroid alcohols reported in the literature. Its electron capture coefficient was 3-7.6X 10(10) 1/mole. The coef-icient was independent of the detector temperature, indicating low activation energy for electron absorpiton.


Application of gas-liquid chromatography and high-performance liquid chromatography to the analysis of trace amounts of salicylic acid, acetylsalicylic anhydride and acetylsalicylsalicylic acid in aspirin samples and aspirin formulations.

The gas-liquid chromatographic (GLC) determination of salicylic acid (SA) in 12 commercial acetylsalicylic acid (aspirin, ASA) samples and 12 ASA formulations is reported. The GLC determination of SA as an impurity in ASA, utilising methylation with methyl iodide in the presence of potassium carbonate, requires a column chromatographic separation of SA prior to derivatization. Trace amounts of SA in ASA have also been determined by high-performance liquid chromatography (HPLC) on a Sil-X-I adsorption column using light petroleum-ethyl acetate-acetic acid as the mobile phase. Acetylsalicylic anhydride (ASN) and acetylsalicylsalicylic acid (ASSA) were determined by HPLC on a reversed-phase C18 column with water-methanol mixtures as the mobile phase. GLC was also applied to the determination of ASN as an impurity in ASA formulations.


Post-column fluorescence derivatization of peptides. Problems and potential in high-performance liquid chromatography.

Some  critical parameters such as the pumping system, mixing devices and detector design in instrumentation for post-column derivatization in high-performance liquid chromatography are discussed. The derivatization was studied with pharmaceutically important nona-peptides containing primary amino groups which react with Fluram and reaction parameters such as pH, solvent and reagent concentration were investigated. Both adsorption systems and reversed-phase systems were used to separate the peptides prior to the post-column reaction. Reversed-phase chromatography has the advantage of simpler sample preparation, better reaction control and optimization of solvent conditions. As a result, detection limits of between 5 and 10 ng per injection can be obtained and the reproducibility of the results is better than +/- 2% (relative standard deviation). The method has been applied to the analysis of injection solutions (ampoules).


Evaluation of microparticle chemically bonded reversed-phase packings in the high-pressure liquid chromatographic analysis of nucleosides and their bases.

The reversed-phase partition mode of high-pressure liquid chromatography was used for the analysis of seven of the naturally occurring nucleosides and their bases. With microparticle chemically bonded packings, nucleosides and their bases can be quantitatively determined in the presence of nucleotides in 30 min with high sensitivity, accuracy, and reproducibility. Peaks in chromatograms of cell extracts were identified by absorbance ratios and enzymatic peak shift methods. Applications of this technique to biochemical studies are reported.


Selective liquid chromatographic isolation procedure for gas chromatographic-mass spectrometric analysis of 3-ketosteroids in biological materials.

A method for the isolation of 3-ketosteroids based on the positive charge of their oximes is described. The biological extract is filtered through a column of sulphoethyl Sephadex LH-20 (H+). Steroids in the filtrate are converted into oximes and the dried reaction mixture is filtered through a column of diethylaminohydroxypropyl Sephadex LH-20 (OH-) in methanol. After evaporation of the solvent and hydroxylamine, the oximes are taken up by and separated on a column of sulphoethyl Sephadex LH-20 (H+) in  methanol. Following elution of other steroids, the oximes of 3-ketosteroids are eluted as a group with methanol-pyridine (20:1, v/v), and are converted into trimethylsilyl ethers. Removal of reagents and further purification of the sample is achieved by rapid filtration through Lipidex 5000 in n-hexane-pyridine-hexamethyldisilazane-dimethoxypropane (97:1:2:10). The derivatives are then analyzed by computerized gas chromatography-mass spectrometry using open-tubular glass capillary columns. Recoveries of picogram amounts of 3H-labelled steroids carried through the entire isolation procedure are 80-90%. The purification achieved in analyses of plasma permits solid injection of the equivalent of 1-2 ml of plasma without overloading of the capillary column. The principle of the isolation procedure might be applicable to other groups of compounds that possess keto or aldehydo groups.


Analysis of benzoylecgonine in urine by high-performance liquid chromatography and gas chromatography-mass spectrometry.

Benzoylecgonine, a polar metabolite of cocaine, was extracted and purified from urine using a reversed-phase high-performance liquid chromatographic column. The portion of the eluent corresponding to elution of the drug was collected, derivatized, and quantified using gas chromatography-mass spectrometry with selected ion monitoring. Using this procedure, analysis of 1 ng/ml of benzoylecgonine in urine can be achieved.


Microdetermination of nitrates and nitrites in saliva, blood, water, and suspended particulates in air by gas chromatography.

A generally applicable method for the analysis of nitrates and nitrites  has been used for a wide variety of samples, including human saliva, blood, drinking water, and airborne particulates. Aqueous nitrate ion is first converted to nitrobenzene by reaction with benzene (or another aromatic reactant) in the presence of a catalyst. The nitrobenzene is then quantitated by electron capture gas chromatography (GC-ECD). Nitrite ion and gaseous oxides of nitrogen can be determined also if such samples are treated appropriately prior to CG-ECD analysis. Other reactants such as 1,3,5-trimethoxybenzene can also be used in the place of benzene. The high sensitivity of ECD allows the quantitation of as little as 0.1 ppm (w/w) nitrate in a single drop of saliva or blood.


Evaluation of organic pollutants in the open air and atmospheres in industrial sites using graphitized carbon black traps and gas chromatographic-mass spectrometric analysis with specific detectors.

A method for evaluating the organic content of the atmosphere, involving the use of personal samplers, is described. A comparison of the performances of Tenax GC and Carbopack B is given in terms of sample recovery. Apparatus including selective columns, specific detectors and combined gas chromatography-mass spectrometry is also described. Practical examples of the analysis of organic air pollutants trapped in the open air and the atmosphere in a chemical plant are discussed. A comparison of the results of complete gas chromatography and of the total hydrocarbon content is also made.


Gas chromatographic-mass spectrometric evaluation of exhaled tobacco smoke.

The impact of cigarette smoking on the distribution of organic substances in ambient air has been determined for the intermediate volatility range. A simple sampling procedure was employed, involving gas-solid adsorption onto an organic polymer followed by direct thermal elution onto a glass capillary column. Aliphatic and substituted aromatic hydrocarbons are predominant in urban atmospheres. Depending on location and weather conditions the total concentration of such volatiles can differ by as much as a factor of 20. This high background variation makes it difficult to analyze for trace substances with low odor threshold values, such as encountered in cigarette smoke. Standard cigarettes were smoked in a relatively small room, having no air filtration system. Air samples of approximately 3.51 were taken. The amount of volatiles added to air by cigarette smoking is unsignificant. Substances were analyzed and identified by gas chromatography and gas chromatography-mass spectrometry with glass capillary columns. Many compounds reported in cigarette smoke condensate have been confirmed.


Application of high-speed liquid chromatography to the analysis of polyoxyethylene surfactants and their decomposition products in industrial process waters.

Complementary high-speed liquid chromatographic techniques have been combined with infrared spectroscopy for the characterization and analysis of polyoxyethylene fatty acid surfactants and their decomposition products in industrial process waters. The combination of molecular sieve chromatography and infrared spectroscopy offers a selective and simple method for the analysis of trace concentrations (detection limit approx. 0.05-0.1 ppm) of these surfactants. Liquid-solid and reversed-phase chromatography have proven useful for the characterization and analysis of free fatty acids. Some of the parameters that affect the reversed-phase separation of fatty acids are discussed.


Gas chromatographic determination of hydrazoic acid.

A gas chromatographic procedure was developed for the determination of hydrazoic acid. Two possible columns were evaluated. The limits of detectability were 1.5 ng, or approximately 0.05%, in aqueous solution (w/v) and 2 mg per liter in air.


Determination of aminophenol isomers by high-speed liquid chromatography.

The simultaneous quantitation of aminophenol isomers (p-, m- and o-aminophenol) and anilline, which with previously reported methods was difficult and/or complicated, has been performed using a high-speed liquid chromatographic method. The resolutions of chromatograms were appropriate for separation and quantitation, when analysis times were 20 minutes. Since the method is applicable in aqueous media, a successful quantitation of p- and o-aminophenol formed by cytochrome P-450 model systems was carried out.


Theophylline and dyphylline levels in serum by liquid chromatography.

The widespread use of theophylline and dyphylline as bronchodilators in the treatment of acute and chronic obstructive airway disease, and recognition of the need to control the therapeutic drug level has created a demand for fast accurate measurement techniques. Measurement of theophylline levels by ultraviolet spectrophotometric techniques is hindered by interferences from barbiturates and caffeine, and thermal lability of the drug necessitates derivatization if gas chromatography is to be used. Because of these factors, a liquid chromatographic method has been developed which allows separation of the underviatized drug from interfering compounds, and quantitation of the theophylline in a single operation. In addition, the drug-containing fraction can be readily collected and subjected to mass spectral examination if there is any question as to its identify. The latter feature has particular significance in medico-legal cases.


The separation, identification, and quantitation of cannabinoids and their tau=butyldimethylsilyl, trimethylsilylacetate, and diethylphosphate derivatives using high-pressure liquid chromatography, gas-liquid chromatography, and mass spectrometry.

Methods for the separation, identification, and quantitation, of cannabinoids present in hashish have been developed. These methods include high-pressure liquid chromatographic and gas-liquid chromatographic separation of cannabinol, delta 9-tetrahydrocannabinol, delta 8-tetrahydrocannabinol, and cannabidiol as well as their tau-butyidimethylsilyl either and trimethylsilylacetate derivatives. The necessity for internal standards; the sensitivity of the HPLC method; and some mass spectral fragmentation pathways for the tau-butyldimethylsily, trimethylsilylacetate, and diethylphosphate derivatives are discussed.


Studies of human diploid fibroblast growth. I. Responses of normal and hypopituitary cells to fibroblast growth factor, insulin, and serum.

We have assayed the growth stimulating activity of bovine insulin, fibroblast growth factor (FGF), and fetal bovine serum (FBS) in diploid human fibroblasts from normal and idiopathic hypopituitary donors. All three factors stimulated DNA synthesis in cells arrested by serum starvation. FGF was active at concentrations as low as 5 ng/ml with maximum effect at 100 ng/ml. FGF stimualted DNA synthesis at lower concentrations than did insulin and also produced a greater maximum response. Only serum was capable of supporting cell division and growth, but FGF accellerated this growth rate when it was added to serum-containing medium. Hydrocortisone, actinomycin D, and cycloheximide inhibit FGF stimulation. There was no significant difference between fibroblasts from normal and hypopituitary donors.


Thyrotoxic periodic paralysis: a peculiar case with unusual dystonic behavior and variable relations of paralysis to serum potassium levels.

This report describes a male patient, aged 49, with tyrotoxic periodic paralysis. The patient had had episodes of main d'accoucheur for eight years. Since thyrotoxicosis had affected the patient last year, he had had attacks of flaccid paralysis of the limbs associated with main d'accoucheur. While the spontaneous attack was normokalemic and responded favorably to potassium, attacks similar to the spontaneous one were provoked not only by glucose infusion, carbohydrate feeding, and NaCl infusion, but also by oral KCl administration. Transition from hypokalemic to hyperkalemic type of paralysis occurred during potassium treatment of a sodium-induced attack, and that from hyperkalemic to hypokalemic type of paralysis occurred after glucose infusion given during a potassium-induced attack. Intra-arterial epinephrine injection caused prompt paralysis of the perfused hand. A main d'accoucheur was induced in one hand by cooling it in chilled water. The spontaneous attacks of flaccid paralysis disappeared after the patient returned to the euthyroid state, but reappeared when he was treated with high doses of desiccated thyroid. Even when the patient was relieved from thyrotoxicosis,  he still experienced stiffness in his hands. The administration of glucose, insulin, and KCl also provoked attacks of paralysis with main d'accoucheur or main d'accoucheur. The disease could be of the normokalemic variety of periodic paralysis with fluctations in the potassium levels depending on the provocative tests employed. It seems that the unusual dystonic behavior of this patient is due not to myotonia, but to muscle spasm resulting from metabolic abnormalities. It could also be suggested that excess thyroid hormones have adverse effects on the development and syndrome of periodic paralysis by abetting a latent hereditary abnormality.


Aromatization of androstenedione by cultured human fibroblasts.

The conversion of (1, 2, 6, 7-3H)androstenedione to (3H)estrone was measured in fibroblast monolayers grown from biopsies of genital and nongenital skins obtained from 15 control subjects, 9 males with developmental defects of the urogenital tract, and 8 patients with hereditary male pseudohermaphroditism. Under the standardized conditions utilized in this study, the rate of estrone formation in the fibroblasts from normal controls varied from less than 0.2 to 5.5 pmol/100 mg protein/h, and these rates were enhanced by incubation of intact monolayers with choleragen, theophylline, or dexamethasone. Rates of estrone formation were higher in some foreskin strains grown from subjects with developmental defects of the urogenital tract and in strains from scrotum and foreskin  of patients with familial incomplete male pseudohermaphroditism, types 1 and 2 than in normal strains or strains from patients with testicular feminization. The meaning of these apparent high rates of estrone formation is unclear.


Propionic acidemia and hyperlysinemia in a case with ornithine transcarbamylase (OTC) deficiency.

A female infant with episodic hyperammonemia due to a disorder of the urea cycle and who had hyperlysinemia and an unusual elevation of short chain fatty acids, mainly propionate, is described. Both occurred apparently only during attacks of hyperammonemia. Propionic acidemia was ruled out by enzyme studies. OTC deficiency was diagnosed on the basis of: 1) decreased enzyme activity in leukocytes;2) hyperammonemia in response to protein intakes in excess of 2.0 g/kg/day; 3) orotic aciduria in the patient and her asymptomatic mother; 4) suggestive evidence of x-linked dominant inheritance; and 5) exclusion of citrullinemia, argininosuccinic aciduria, argininemia, and disorders of lysine metabolism that are associated with hyperammonemia. Homocitrullinuria, presence of epsilon-N-acetyl-l-lysine in urine, and absence of saccharopine indicate deficiency of the saccharopine pathway of lysine degradation. However, alpha-ketoglutarate reductase was normal in fibroblasts. Since these metabolites were observed only in conjunction with hyperammonemia but not after a lysine load, we suggest that there was competition between ammonia and lysine for alpha-ketoglutarate. The link between disorders of the urea cycle and short chain fatty acid metabolism remains unexplained..


Improving the diagnostic reliability of rapidly fluctuating plasma hormone levels by optimized multiple-sampling techniques.

When plasma hormone levels undergo rapid and large oscillations, as in the case of testosterone, FSH, and LH, a single random sample is likely to yield a result within +/-20% of the true mean value only 68%, 54%, and 30% of the time, respectively. Multiple sampling increases reliability, and computer analysis demonstrates that three equally-spaced samples taken at 6 to 18 min intervals provide the optimum schedule, given certain practical considerations. Pooling of the three plasma samples prior to radioimmunoassay avoids an increased laboratory workload.


Dose-response of prolactin and thyrotropin to N3im-methyl-thyrotropin releasing hormone in euthyroid men.

The synthetic N3im-methyl analogue of thyrotropin releasing hormone (methyl-TRH) was administered intravenously to 15 euthyroid men, ages 36-62, in graded doses from 6.25 mug to 500 mug in order to establish the range of response of prolactin (PRL), TSH, T3 and T4 to various doses of methyl-TRH. There was a dose-related rise in serum TSH, PRL, T3, and T4 which gave a nearly linear relationship when the integrated area of response was used as an index of response to the various doses of methyl-TRH. All 15 men had a clear elevation in TSH, PRL, T3 and T4 following the lowest dose of methyl-TRH TESTED (6.25 mug). There was considerable variability in the response to methyl-TRH among the individuals. One hundred mug of methyl-TRH gave a maximum TSH response; a 25 mug dose elicited a maximum PRL response.


Serum lipid changes during contraceptive administration in obese women: relation to serum insulin levels.

Previous reports agree that estrogen and estrogen-containing contraceptives increase serum triglyceride levels of normal women, but disagree on their effect on serum cholesterol levels. Since obesity is often accompanied by hyperinsulinemia and since hyperinsulinemia may participate in production of hypertriglyceridemia, we investigated the effect of oral contraceptives on the serum lipids of obese women. Serum triglycerides and cholesterol were measured before and after 3 months administration of the contraceptives. The mean triglyceride level increased 23% in the obese and 21% in the normal women. The mean cholesterol level increased 6% (P less than 0.05) in the obese and did not change in the normal women. The increase in cholesterol occurred mostly in those with initial levels less than 225 mg/100 ml; in those with initial levels above 250 mg/100 ml the level usually decreased with treatment. The serum lipid changes were not related to the serum insulin levels.


Endogenous estrogen modulates phenothiazine stimulated prolactin secretion.

The role of endogenous estrogen in the regulation of serum prolactin concentration in man is controversial. To evaluate the possible effect of endogenous fluctuations in serum estrogen on the regulation of prolactin secretion, the authors determined phenothiazine stimulated prolactin secretion in 12 women in the early follicular phase of the menstrual cycle when estrogen levels were low (mean +/- SE E1 + E2 = 82 +/- 7 pg/ml) and compared it to the response during the late follicular phase when estrogen levels were higher (mean E1 + E2 = 320 +/- 63 pg/ml). Mean basal serum prolactin concentrations were similar in the early and late follicular phases of the cylcle (17 +/- 4 and 20 +/- 2 ng/ml, respectively). The integrated prolactin response following phenothiazine administration was significantly higher at mid-cycle (402 +/- 46 ng-hr/ml) than in the early follicular phase (317 +/0 46 ng-hr/ml, P less than .02). Thus, these studies suggest that endogenous estrogen secretion may play a role in the regulation of serum prolactin concentration in man.


Partial characterization of somatomedin bioactivity in term human amniotic fluid.

Somatomedin (SM) activity in human amniotic fluid (AF) was partially characterized. Aliquots of pooled AF, obtained at term gestation, were acidified to pH 2.3 and sequentially studied by ultrafiltration on various membranes, Sephadex gel filtration, and starch gel electrophoresis (SGE). SM activity was measured by a rat cartilage bioassay. SM activity in AF, under these conditions, was present in several stable indicated molecular size (IMS) forms; large (greater than 45,000) and small (near 10,000). The small SM was found in basic and acidic forms after SGE. These studies suggest that SM activity in term human AF is somewhat similar to SM in unextracted plasma. In addition, immunoreactive GH and insulin were measured in AF but at lower concentrations than usually found in plasma. After chromatography of AF, GH was found in large and small IMS forms, whereas most of the insulin was found in the monomer insulin IMS area.


Suppression of luteinizing hormone in castrated women by the administration of human chorionic gonadotropin.

The suppressive effect of human chorionic gonadotropin (hCG) on luteinizing hormone (LH) and/or LH-beta was studied by specific LH-beta radioimmunoassay following hCG administration. Eight castrated women were each administered 10,000 IU of hCG in a single intramuscular injection and five women in the control group were injected with saline. The serum level of hCG increased after the injection, reaching 217.6 mIU/ml after 8 h. There was a significant suppression of LH levels as compared to those of the control group and the pre-injection levels: 68.2% 1 h after injection, 64.7% after 2h, 65.5% after 4 h, 77.0% after 8 h, 78.6% after 12 h, and 78.2% after 24 h. There was no significant suppression of the follicle-stimulating hormone (FSH) as compared to the preinjection and control values. Serum concentration of estradiol1 was not detectable either before or after the hCG injection. We conclude that hCG has a suppressive effect on LH and/or LH-beta secretion not mediated by estradiol.


Methylphenidate increases serum growth hormone concentrations.

Serum growth hormone (GH) and cortisol concentrations were measured in 12 healthy, young men following oral administration of methylphenidate (20 mgm ) or a placebo. Methylphenidate elicited unequivocal GH elevations in 9 of 12 subjects while only 2 subjects showed GH elevation following placebo. Cortisol concentrations were not affected by methylphenidate.


Biological activity of des-Asp1-,Ileu8-angiotensin II (Ileu8-angiotensin III) in man.

Biological activity of ileu8-angiotensin III (AIIIA) was studied in man. In 5 normal men intravenous infusion of 200 ng/kg/min of AIIIA for 30 minutes from 0900 h had no effect on blood pressure (BP) but caused a decrease in plasma renin activity (PRA) and an increase in plasma aldosterone (PA). This dose did not inhibit pressor and steroidogenic actions of angiotensin II (AII) infused into the normal men at a rate of 20 ng/kg/min for 30 minutes. In 3 patients with Bartter's syndrome 260-1,200 ng/kg/ min of AIIIA infusion for 30 minutes from 0900 h had no effect on BP but caused decreases in PRA and PA. These results indicate that in man AIIIA has no pressor action and no antagonistic effect on pressor action of AII but has PRA-lowering and aldosterone-stimulating effects. Antagonistic effect of AIIIA on steroidogenic action of AII was also shown in patients with Bartter's syndrome but not in AII-treated normal men. This may be due to the difference of administered dose of AIIIA.


Study on the relationship between plasma prolactin levels and androgen metabolism in man.

The purpose of the study was to investigate the effect of hyperprolactinemia on the metabolism of androgens in man. A group of 6 normal men was treated for 4 consecutive days, on separate periods, with Sulpiride which is known to raise plasma prolactin (PRL) concentration. The effect of the treatment on plasma steroids was verified in basal conditions and under stimulation by HCG. In the controls, a parallel rise in testosterone (T) and dihydrotestosterone (DHT) was observed in response to HCG stimulation. In experimental hyperprolactinemia, the rise in T in response to HCG, similar to that of the controls, was accompanied by a markedly diminished rise in DHT. Similar results were observed in a patient with hyperprolactinemia following apparent accidental section of the pituitary stalk. These data demonstrate the interference of increased levels of PRL in the metabolism of testosterone into the active DHT form by 5alpha-reductase. They suggest that this mechanism could possibly impair the gonadal function in man.


Quantitative and bacteriological studies of urine specimens from canine and feline urinary tract infections.

The most prevalent microorganisms isolated from urine specimens of dogs (385) and cats (132) with clinical signs of urinary tract infections were Escherichia coli, Proteus spp., and Staphylococcus aureus. The results of quantitative urine-culturing methods showed 48.6% of the canine and 12.1% of the feline specimens had more than 10(5) organisms per ml of urine. The bacteria isolated appear to have a greater resistance to antibacterial agents than previously reported.


Growth requirements of some small-colony-forming variants of Staphylococcus aureus.

Nine stable, auxotrophic, small-colony-forming variants of Staphylococcus aureus were isolated. They were of two types. One type, from broth cultures containing varying concentrations of gentamicin or kanamycin, required heme for normal growth. The second type, from the blood culture of a patient who had been treated with penicillin and oxacillin, required long-chain unsaturated fatty acids for normal growth. These small-colony-forming variants differed from their parents with respect to specific metabolic activities, many of which may be attributed to an impaired electron transport system and related functions. A laboratory procedure for detecting possible small-colony variants in clinical specimens was proposed.


Evaluation of commercial Salmonella O polyvalent and Vi antisera.

Salmonella somatic polyvalent antisera for groups A through E or A through I with or without Vi and Salmonella Vi antisera were purchased from four commercial producers and evaluated. Center for Disease Control (CDC) methods and specifications were used. The four polyvalent and two of the four Vi antisera did not meet CDC performance specifications. Suggestions are made for improving the laboratory usefulness of the reagents and the product labeling.


A new approach to psychopathology.

A new approach to psychopathology based on the psychology of integration as applied to psychological states is outlined. Because all raw behavior occurs only in the form of psychological states, all formulations of psychopathology must refer to integrative disorders that are postulated to underlie all pathological or defective behaviors. Disintegration is the one common factor found in all mental disorders. Lack of integration underlies most inadaptability. The classical field of psychopathology, which formerly was limited to the consideration of formal psychiatric disorders, now is expanded to include deficits, imbalances and disintegrations of acute or chornic nature that result in erroneous or less than perfect judgments. Judgment is considered to reflect the quality of underlying integrative processes. Judgmental defects that lead to maladaptive decisions inevitably must result in maladjustment and/or less than perfect performance. It is necessary to differentiate between (a) integrative disorders per se, and (b) the personal-social effects of positive or negative integrations organized by healthy or unhealthy factors. Criminals may be well integrated in their asocial activities, but socially undesirable because organized about the criminal ethic. Postulates are presented that outline the theoretical assumptions upon which integrative psychopathology is based. This approach utilizes classic theories such as the Freudian psychopathology of everyday life when valid and relevant within the larger framework of integrative psychology. A differentiation is made between hierarchical levels of increasingly complex factors that may organize integration.


Recall of parental behaviors in female neurotic depressives.

Twenty-four neurotic depressive females and 24 female anxiety neurotics were compared on a 90-item questionnaire that concerned recall of parental behavior. Relative to anxiety neurotics, the neurotic depressives recalled fathers as unloving disciplinarians and recalled mothers as difficult to please, intrusive and controlling, and possibly more concerned with their own than with their children's needs. Previous findings that parents of depressives are recalled as depriving were supported, and a methodology for differentiating neurotic depressives from anxiety neurotics was described.


The relationship of self-disclosure to personality, adjustment and self-actualization.

This study tested the hypothesis that a high level of self-disclosure is indicative of psychological adjustment and self-actualization. The self-disclosure scale, Social Avoidance and Distress, Fear of Negative Evaluation, Alienation and Repression-Sensitization scales were administered to 60 Ss. The results for all scales indicated that a high level of disclosure was associated with adjustment as measured by these scales. A second group of 94 Ss completed the self-disclosure scale and the Personal Orientation Inventory, a measure of self-actualization. The results indicated that high disclosers compared to low disclosers had achieved a higher level of self-actualization. That is, there were significant correlations between self-disclosure and measures of self-actualization such as Time Competence, Internal Support, Existentiality, Self-Acceptance and Capacity for Intimate Contact.


The influence of interviewer self-disclosure and verbal reinforcement on personality tests.

The effects of prior interview experiences on subsequent test responding were examined by comparing the influence of three interviewer behaviors: interviewer self-disclosure, interviewer verbal reinforcement of self-referent statements, and direct instructions to be self-disclosive. Performance was contrasted with a control interview condition characterized by no interviewer self-disclosure or self-referent reinforcement and with a no-interview condition. Responses on measures of self-disclosure and anxiety indicated that female Ss tended to be more self-disclosive than males in general, but were relatively uninfluenced by experimental condition. For male Ss, verbal reinforcement increased self-disclosure relative to the interviewer seld-disclosure condition. Interviewer self-disclosure was shown to result in more favorable perceptions of the self and the interviewer, particularly for males, and greater social evaluative anxiety for females. Both these factors are discussed as possibly counteracting the modelling effects of interviewer self-disclosure. An interpretation of the results in terms of interactions between S sex, interviewer sex, and experimental condition is proposed and implications for related research discussed.


Normalizing the MMPI.

Effective psychological services require recognition of a client's strengths as well as weaknesses. Personality tests such as the MMPI, however, focus attention upon the abnormal and deviant attributes of personality. Therefore, a psychologist should have an understanding of various adaptive behaviors that may be indicated by moderately elevated MMPI scale scores. Because most of the literature deals with the pathological ramifications of scale elevations, the authors developed a conceptual perspective of counterpart descriptors for each MMPI clinical scale. These descriptors are presented so that apparently contradictory sets of behaviors for elevated scores on any given scale can be viewed on a continuum from adaptive to maladaptive behavior. An armamentarium of MMPI personality traits should include positive as well as negative considerations to provide a fully comprehensive basis for the formulation of realistic assessments of human potentialities.


Relationships between Spielberger trait anxiety and Lykken social and physical trait anxiety.

To determine the relationship between Spielberger's measure of trait anxiety and social-interpersonal vs. physical danger trait anxiety, Ss were administered and trait scale of the State-Trait Anxiety Inventory (STAI) and Lykken's Activity Preference Questionnaire (APQ). Results of correlative analyses indicated that the STAI-Trait measure correlated significantly with APQ-Social Anxiety, but not with APQ-Physical Anxiety. Results were discussed in terms of the implications for predicting state anxiety in different situations by the use of unidimensional vs. multidimensional trait anxiety measures.


Personality patterns among correctional officer applicants.

The MMPI profiles of 359 correctional officer applicant were cluster analyzed, which resulted in the identification of five relatively homogeneous subgroups. While MMPI performance was not related to later events in the correctional careers of the Ss, certain similarities were noted between the officer group and two samples of inmates previously studied in a comparable fashion. In this respect, although the officers manifested generally lower profile elevations than inmates, configural similarities were noted between the average inmate and the officer profiles, and partial overlap was seen between the profile types identified in the two groups. The implications of the findings for occupationally adaptive and maladaptive correctional officer behavior were discussed.


Correspondence of the MMPI and Mini-Mult among female reformatory inmates.

Comparison of the MMPI and Mini-Mult scales yielded significant scale-by-scale correlations. However, the group means were different in 6 of the 11 possible scales, and there was a general tendency for the Mini-Mult to over-estimate MMPI scales. The Mini-Mult proved to be highly ineffective to detect MMPI invalid profiles. In addition, agreement on profile configurations or high points and degree of pathology as indicated by number of significant clinical scale elevations was very poor. The results of this investigation are similar to the findings of Rybolt and Lambert (1975), as well as those of Platt and Scura (1972), and lead one to recommend that the Mini-Mult not be employed as a clonical assessment instrument with incarcerated adult female populations. Its multiple deficits make clinical use hazardous.


Relationship of internal-external control and United States suicide rates, 1966-1973.

The annual variations in scores obtained on the Rotter Internal-External (I-E) control scale by United States college students between the years 1966 and 1973 were related to the concomitant annual variations in suicide rates for the total United States population and for eight separate age groups. The I-E scores increased substantially during this time period and were correlated positively with the concomitantly increasing suicide rates among relatively young persons (in and below the 35-44 year age group). However, the suicide rates among older persons generally decreased during this time period and thus were correlated negatively with the I-E scores. These results suggest that perception of internal-external control did not change among older persons as they did among younger persons, perhaps because older persons might be less susceptible to the cultural influences that affect the perceived control of younger persons. Results of this and earlier research suggest that cultural characteristics that foster high perceptions of external control also foster suicidal behavior and suggest the value of attempts to convey perceptions of internal control to psychotherapy clients.


The effects of videotape models on the behavior of chronic schizophrenics.

The effects of "good" and "poor" peer models on the task performance of 45 chronic schizophrenic males were investigated. The findings revealed that patients who viewed a good peer model did significantly better on a subsequent task than patients who viewed either a poor model or no model. The use of peer models in the treatment of chronic schizophrenics was suggested.


Using the MMPI 168 with medical inpatients.

The potential utility of the MMPI 168 with two inpatient medical populations was explored in the present study. Correlations and clinically relevant comparisons suggested that the MMPI 168 predicted the standard MMPI with a high degree of accuracy.


Personality characteristics of high and low aggressive adolescents in residential treatment.

Variables related to aggression were explored in a population of psychiatrically disturbed male adolescents in a residential treatment setting. The Marlowe-Crowne Social Desirability Scale, Daydreaming Questionaire, Byrne Repression-Sensitization Scale, and the Buss-Durkee Hostility Inventory were administered to high and low aggressive patients. Multivariate analyses of the data indicated that high aggressors were significantly lower in their social desirability needs and significantly higher in their daydreaming, hostile, attitudes and sensitization than were low aggressive patients. These findings were discussed relative to a greater understanding of aggression in emotionally disturbed adolescents and implications for treatment.


The identification of brain damage by an abbreviated form of the Halstead-Reitan Neuropsychological Battery.

In recent years there has been an increased interest in the development of neuropsychological tests that can diagnose accurately brain damage. The most successful of these test are represented in the Halstead-Reitan Neuropsychological Battery, which has been shown to be 90% or more effective in the diagnosis of brain damage. However, this battery is not available to many psychologists or clients because of its length, cost, and the considerable background required to use it properly. The present study tested 121 Ss (30 normal, 91 brain-damaged) to develop an abbreviated version of the battery that is relatively brief (1 hour) and inexpensive, but accurate. It was found by discriminant analysis that the abbreviated battery is capable of diagnosing brain damage equally as well as the full battery 93% of the time. The limitations and advantages of the abbreviated battery are discussed.


The effects of verbal and nonverbal contingent reinforcement upon the intelligence test performance of black adults.

This study examined the effects of contingent verbal and nonverbal reinforcement upon the intelligence test performance of bladk adults. Thirty-six Ss (half male and half female) were pretested on the Quick Test and then administered the complete WAIS under one of three treatment conditions: verbal reinforcement, nonverbal reinforcement or no reinforcement (control condition). Verbal reinforcement was administered as statements of "good" or "fine" by the E, while nonverbal reinforcement took the form of a nod of the head or a statement of "Mmhm." The primary analysis of the data indicated no significant differences between the treatment conditions.


Bender Gestalt recall: memory measure or intelligence estimate.

WAIS subtest standard scores, IQ scores, and factorial deviation quotients were correlated with Bender Gestalt recall scores for 111 vocational rehabilitation clients. The number of Bender designs recalled was associated significantly with intellectual measures, with the strength of association somewhat stronger with nonverbal than with verbal scores. Bender recall scores were correlated more highly with Perceptual Organization DQs than with Memory-Freedom from Distractibility DQs, but that difference only approached significance. Despite the relationships between Bender recall scores and intelligence scores, the Bender recall task could not classify Ss as to general intelligence level with greater accuracy than could be obtained with the WAIS Vocabulary subtest alone.


Curative factors in psychotherapeutic and growth groups.

A 60-item Q-sort that represented 12 "curative factors" regarded as crucial to the efficacy of psychotherapeutic groups by Yalom (1970) was administered to volunteer undergraduate participants after the end of 20-hour (2 hours weekly) personal growth groups. The Q-sort items were ranked very similarly for Helpfulness in the group experience by the growth groupers and by Yalom's successful group psychotherapy outpatients. Members of both kinds of groups linked Helpfulness strongly with Yalom's Interpersonal Input and Catharsis measures. The content of these variables' salient items closely resembled two broader dimensions of interpersonal behavior, Acceptance vs. Rejection of Others and Self-Acceptance vs. Rejection, which appear prepotent (Hurley, 1976) in a wide variety of group settings.


Comparison of verbal reinforcement with information feedback in analogue psychotherapy.

Thirty Ss were assigned randomly to one of the two experimental analogue psychotherapy groups and a control group. In the experimental psychotherapy groups two different psychotherapy techniques were used for eight sessions. The two psychotherapy techniques employed were one-word verbal reinforcement (VR) and lengthy verbal information feedback (IF). Three therapists each demonstrated significant differences (P less than .001) in their verbal interactions with the Ss when they used the two different psychotherapy techniques. The results indicated that both treatment techniques were significantly effective (p less than .05) in improving self-ratings of self-concept. However, the two psychotherapy techniques were differentially effective in improving social skills as measured by behavioral ratings.


Suicidal age and childhood onychophagia among psychotic veterans.

The relationship between childhood onychophagia (fingernail biting) and the suicidal and nonsuicidal mean age among 150 hospitalized psychotic veterans was investigated. The results show that the suicidal mean age is significantly younger than the nonsuicidal mean age and that the childhood onychophagia variable "focal suicide" significantly lowers the mean age of suicidal veterans, but does not significantly lower the mean age of nonsuicidal veterans.


The effect of relocation on the satisfaction of psychiatric inpatients.

Fifty-one psychiatric inpatients were tested on a 36-item satisfaction scale before and after a reorganization at Harlem Valley Psychiatric Center. Patients were divided into three groups (Low, Medium, and High Stress) on the basis of whether they experienced no change as a result of the reorganization, environmental change only (different building), or environmental and social change (different building, different staff, different fellow patients). Patients in the three groups were matched on the basis of chronological age, length of hospitalization, and sex. Results indicated that there were no reliable differences among the satisfaction scores of the groups as a result of the relocation. This finding supports the hypothesis that the involuntary relocation of chronic psychiatric patients to another institutional treatment environment results in few demonstrable effects.


The effect of structured and unstructured leader roles on internal and external group participants.

This study assessed the impact of structured and unstructured leader roles on measures of outcome for Ss who differed on the pretest dimension "locus of control." On the basis of their pretest locus of control scores, Ss were assigned to a structured or an unstructured marathon group. The treatment in the two 16-hour -arathons consisted of a defined series of exercises; the only difference between the two groups was the degree of leader control over member participation. As predicted, internal Ss in the unstructured group rated the leader and the group more psoitively than did external Ss, while the reverse responsivity occured in the structured group. Significant Locus of Control X Treatment interactions indicated that internal and external Ss reflected differential shifts in general anxiety, general depression, and locus of control as a function of treatment. The relationship between changes in self-actualization and locus of control and changes in conflict-handling styles and negative affects differed as a function of locus of control and treatment condition. The overall results coupled with prior findings tentatively support the appropriateness of an unstructured leader role for internal scores and a structured leader role for external scorers.


The impact of differential shifts in leader structure on the outcome of internal and external group participants.

This study investigated the interaction between locus of control and high and low degrees of structure of leader role as related to outcome. On the basis of their pretreatment locus of control score, college students were assigned randomly to one of five groups: a group that began unstructured and shifted to a structured format at the midpoint of the group, a group that began structured and shifted to an unstructured format at the midpoint, a group that was structured throughout, group that was unstructured throughout, and a no-treatment control group. Treatment in the 23-hour marathon groups consisted of the same sequence of planned group exercises; the leader varied his structure in accordance with the experimental design. The results indicated that an initial highly structured leader role followed by a relatively unstructured leader role presented at the midpoint of treatment fostered the greatest gains in self-actualization in both internal and external Ss.


Affection for patients as a factor in therapists' outcome judgements.

This study was concerned with psychotherapists' evaluations of the outcome of therapy. Staff and resident psychiatrists employed in 23-item questionnaire to rate the seccess of psychotherapy with 85 of their inpatients. These were patients for whom psychotherapy constituted a significant part of the treatment that they received in the hospital. The therapists' responses to the questionnaire items were intercorrelated. The results indicated that a major aspect of a psychotherapist's judgment of the success of treatment-as these judgments usually are employed in current psychotherapy research-is the therapist's affective reaction to the patient, Better-liked patients were viewed as having improved more. However, when the therapists' responses were subjected to factor analysis, independent Improvement and Affection factors emerged. It is suggested that when therapists' ratings of success are used in psychotherapy research they should be treated or refined statistically to minimize potential confounding with their affection for patients.


The validity of the Rorschach Prognostic Rating Scale with incarcerated offenders.

Previous research has shown that the Rorschach Prognostic Rating Scale reliably predicts the adjustment capacity of various S types to a variety of situations. The present study investigated the efficacy of the RPRS to suggest the adjustment capacity of prisoners to various aspects of their institutional environment. Twenty-five male inmates of the Petersburg Federal Reformatory served as Ss. Group therapy, dormitory behavior, work progress adjustment ratings, and RPRS scores were obtained for each S. Intercorrelations among the adjustment measures and the RPRS total and component scores revealed no significant correlations between the adjustment measures and the RPRS total score. However, in employing a moximum R stepwise multiple correlation procedure with the RPRS compontnts, significant multiple Rs resulted for two of the three criterion measures. These results were discussed in terms of the earlier research with the RPRS, and suggestions for future research were made.


Sex guilt and preferences for illegal drugs among drug abusers.

This study investigated the relationship between sex guilt and drug preferences. Seventy polydrug users completed a drug preference inventory and the Mosher Forced-Choice Sex Guilt Subscale. Results indicated that individuals who prefer sedatives are higher in sex guilt than either individuals who prefer stimulants or individuals with no definite preference.


Evidence that suggests a negative association between cigarette smoking and learning performance.

The results of this study indicate that tobacco smoking may have a deleterious effect on the learning process. One hundred and fifteen male volunteers were assessed on four learning tasks. Those Ss who smoked in excess of 12 cigarettes per day did significantly less well, as a group, than nonsmokers and light smokers on three of the four learning tests.


Relationship between psychopathology, experienced control and perceived locus of control: in search of alcoholic subtypes.

Alcoholic Ss were categorized into four subtypes based upon differential levels of perceived locus of control and experienced control. The relationship between generalized psychopathology, as measured by the MMPI, and subtype classification was investigated. Alcoholics with an internal locus of control and high levels of experienced control exhibited the least psychopathology. The greatest degree of psychopathology was found among Ss with an external locus of control and minimal levels of experienced control. The implications of these results with respect to psychosocial functioning and drinking behavior among alcoholic subgroups were discussed.


Serial liver biopsies in blood donors with persistent HBs antigenaemia.

Initial liver biopsies from asymptomatic HBs antigen positive blood donors showed a range of histological abnormalities ranging from minor parenchymal lesions to cirrhosis. Twenty of these have now been followed up for periods of up to four years and during that time have had at least two liver biopsies. Throughout the period of study all the donors have remained carriers of HBs Ag, and there was no significant variation in the titers of antigen or the electron microscopic appearances of the serum in individual donors. The histological appearances of subsequent liver biopsies were not always the same as those seen initially, and while there appeared to be some improvement in three cases, there were nine in which the histological appearances were worse.


Immunoglobulins and complement in pleural effusions associated with bronchogenic carcinoma.

Levels of IgG, IgA, IgM, the total haemolytic complement (CH50), and the individual components C1q, C3, C4, C6, and C7 were measured in 29 pleural effusions. Of these, 18 were associated with carcinoma of the bronchus and 11 were non-malignant effusions including empyemas. The level of IgG was significantly lower in the malignant group when compared with non-malignant effusions. The usefulness of measurements of IgG with respect to malignant effusions associated with carcinoma of the bronchus requires an expanded study to show whether it has any real diagnostic value. There were no significant differences in other immunoglobulins, the CH50, and individual complement components between the two groups. The identification of total haemolytic activity in the majority of effusions in both groups indicates that all nine components of the classical pathway of complement, including macromolecules such as C1, can be present in pleural fluids.


Hyperfibrinogenaemia and hyperviscosity in sickle-cell crisis.

Plasma fibrinogen concentration and whole-blood viscosity, the latter measured at two shear rates (23 and 230 sec-1), were estimated during eight episodes of sickle-cell crisis and compared with values in 26 sickle-cell anaemia patients who were not in crisis. Painful crisis was associated with a significant increase in both plasma fibrinogen and whole-blood viscosity. Increased fibrinogen-erythrocyte interaction in vivo may be a significant contributory factor to raising blood viscosity and precipitating vaso-occlusive crisis in sickle-cell disease.


Erroneous values for the total white cell count and ESR in patients with cryoglobulinaemia.

Temperature dependent fluctuations in the erythrocyte sedimentation rate were noted during the assessment of one patient with symptomatic cryoglobulinaemia. Two patients with this condition were found to have erroneously high leucocyte counts when estimated by the Model S Coulter Counter. The artefact was directly related to the degree of exposure to cold before the estimation was performed and appeared to be due to the formation of microaggregates of cryoglobulin and fibrinogen.


Changing blood picture in sickle-cell anaemia from shortly after birth to adolescence.

The blood picture of children with sickle-cell anaemia was found to change with age. The changes were most marked in the first year but the mean level of haemoglobin, haemoglobin F, and target cells fell until adolescence, and irreversibly sickled cells rose. Reticulocytes, Howell Jolly bodies, and normablasts altered little after one year. The fall in haemoglobin F suggested a delayed changeover from fetal to adult haemoglobin production. It was concluded that the blood changes in sickle-cell anaemia were progressive throughout childhood.


Radioimmunoassay kits for thyroid hormones.

Characteristics of the T4 and T3 radioimmunoassay kits that are commercially available in the UK are described. Useful comparative data and criticism are given about many of these kits. Some unacceptable variation in accuracy is demonstrated.


Stabilization of bromthymol blue colour in lecithin-sphingomyelin ratio determinations in amniotic fluid.

Amniotic fluid lecithin and sphingomyelin areas after extraction and chromatography are rendered permanently visible by the use of bromthymol blue dye buffered to a pH of 11-3.


A critique and case study of nodular sclerosing Hodgkin's disease.

This paper presents a critique of the present concepts of the pathology of nodular sclerosing Hodgkin's disease and particularly of the criteria required for diagnosis for the condition and its separation from other types of Hodgkin's disease. In addition, the natural history and histopathology of the condition have been studied among 104 cases of Hodgkin's disease presenting at The London Hospital, and the significance of the appearance is discussed.


Cellular infiltrate of the jejunum after re-introduction of dietary gluten in children with treated coeliac disease.

Jejunal lamina propria plasma cells and eosinophils and intraepithelial lymphocytes were raised in coeliac children on gluten-containing diets, but only intraepithelial lymphocytes were increased in patients on gluten-free diets. In contrast, lamina propria lymphocytes were reduced in children with coeliad disease on gluten-containing diets but were normal in paitents on gluten-free diets. In children with coeliac disease who were studied serially, lamina propria plasma cells and eosinophils and intraepithelial lymphocytes increased, and lamina propria lymphocytes decreased, within three months of the reintroduction of gluten to the diet. These observations are essentially similar to those made in the adult form of the disease and suggest that more than one type of immunological reaction is involved in the pathogenesis of the jejunal lesion.


Serum lysozyme in inflammatory bowel and coeliac disease.

Serum lysozyme levels were determined by a turbidometric method using egg white lysozyme as standard in 100 patients with Crohn's disease, 86 with ulcerative colitis, 31 with coeliac disease, and in 38 normal control subjects. Though the levels in Crohn's disease were significantly higher than those in ulcerative colitis and in coeliac disease, there was marked overlap between the disorders and control subjects, and so they were of no value in differential diagnosis. There was some evidence that serum lysozyme levels reflected disease activity in Crohn's disease but not in ulcerative colitis.


Morphological basis of radiological band shadows on chest radiographs.

Lungs of unselected cadavers were fixed at necropsy using a formalin vapour technique. "Band shadows" were identified in the excised lungs and these were correlated with in vivo radiographs and with the morphological changes in the lung. Persistent shadows were produced by pulmonary infarction, subsegmental atelectasis, and septal fibrosis singly and in combination. Potentially transient shadows were seen in association with atelectasis and pulmonary oedema.


An evaluation of automatic coding of surgical pathology reports.

The use of the Systematised Nomenclature of Pathology as the basis of an indexing system to histopathological data is outlined. Two computer programs which perform the task of producing codes from free English summaries are compared. It is concluded that a simple system has a great deal to offer the pathologist who is prepared to accept a set of constraints.


Sea-blue histiocytosis associated with hyperlipidaemia.

A patient with sea-blue histiocytosis in spleen and bone marrow with an accompanying hyperlipidaemia is described. The hyperlipidaemia was due to an increase in "free" cholesterol, lecithin, and triglycerides. Despite these findings lecithin-cholesterol acyl transferase activity was normal. Although the precise biochemical defect was not identified, there was a failure of transport of cholesterol from chylomicrons in vitro. We propose that the sea-blue histiocyte is a marker, in some cases, of abnormal lipid metabolism.


Serum triiodothyronine determination in clinical use.

Two radioimmunassays for the determination of serum triiodothyronine (T3) were developed. The assay of T3 in unextracted serum had several advantages over the assay on extracted serum and was chosen for the routine determination of T3 in serum from 117 patients requiring assessment of their thyroid status. In 53 subjects considered retrospectively not to have thyroid dysfunction nor to have been on steroid contraceptives or therapy, the pooled mean serum T3 concentration was 1-92 (actual range 0-88-2-62) nmol/l. A significant inverse relationship was observed between the serum T3 level and the age of the subject. Serum total T3 levels discriminate clearly between hypo-,eu- and hyperthyroid patients and provide a rather more sensitive index of hyperthyroid function than total serum T4. In the face of normal serum T4 the T3 level was depressed in five patients with marked hypoproteinaemia and elevated in two patients taking heroin.


Severe selective IgM deficiency.

Among the primary antibody deficiency syndromes, severe selective IgM deficiency (also previously known as type V dysgammaglobulinaemia) is rare, and the majority of previous reports have indicated a fatal outcome. Three adult patients who were found to have a persistently low serum IgM are described. This deficiency was not obviously related to their presenting illness; in two of the patients, who were investigated in detail, it appeared to be of no immediate consequence.


Polyacrylamide gel disc electrophoresis of alkaline phosphatase isoenzymes in bone and liver disease.

Acrylamide gel disc electrophoresis provides a reliable and reasonably rapid method of differentiating the raised serum alkaline phosphatase (AP) of bone origin from that of liver origin. The technique has been placed for the first time on a semiquantitative basis. Measurement of both band width and band position effectively distinguishes the bone from the liver isoenzyme, but band width provides superior discrimination. An origin band was seen in none of the normal subjects and in only 7% of patients with bone disease but was present in 78% of patients with liver disease, a highly significant increase. Fifty percent of normal individuals had a small-intestinal band in serum taken two hours after a meal, as did 35% of patients with liver disease, but the incidence of intestinal bands in bone disease was only 11%, significantly less than in the other two groups. The genetic control of small-intestinal AP in serum has been confirmed, but it has been demonstrated that the decrease of intestinal AP in bone disorders is not genetically determined.


A case of veno-occlusive disease of the liver in Britain associated with herbal tea consumption.

Veno-occlusive disease of the liver with clinical and pathological features similar to those of the condition occurring in the Caribbean is described in a young woman resident in Britain. The diagnosis was made from liver biopsies and hepatic venography and was confirmed at necropsy. Small amounts of pyrroliziding alkaloids were recovered from a sample of mate (Paraguay) tea, owned by the patient, to which she was addicted. It seems probable that the consumption of large amounts of this tea over a period of years was the cause of the hepatic disease.


Papillary tumours of the minor salivary glands.

The clinical and histological features of oncocytic adenomatous hyperplasia, papillary adenoma, and papillary adenocarcinoma of the oral cavity are described, and the literature is reviewed. Histological features which may be of value in distinguishing between benign and malignant variants are described, and in view of the slow growth rate of most of these tumours, the importance of long-term follow-up is stressed.


Pseudotumour of the lung caused by infection with Bacillus sphaericus.

A patient is described who suffered from severe chronic asthma complicated by repeated chest infections. She developed a large gelatinous pseudotumour of the lung which was found to be caused by Bacillus sphaericus.


Flavobacterium meningosepticum in the hospital environment.

Ten strains of Flavobacterium meningosepticum were isolated from routine clinical material during a period of two years. Of a number of antibiotics tested, clindamycin was the only one to which they were fully sensitive. The organism was found in chlorhexidine gluconate (Hibitane) solutions in use on the wards for the storage of thermometers and for routine disinfection.


An assessment of inositol fermentation by Klebsiellae and its implication in screening media.

Four patterns of inositol fermentation by different isolates of Klebsiellae are described. Inositol fermentation by some isolates may be modified by medium incorporation of acetoin and diacetyl. An inositol--hydrogen sulphide--motility medium, modified by reducing the pH value, increasing the inositol concentration, and the incorporation of acetoin, is described and evaluated as a means of detecting acid production by isolates showing different inositol fermentation patterns.


Detection of staphylococcal enterotoxin in gastric juice.

The gastric juice of a patient showing symptoms of staphylococcal food poisoning was examined by a radioimmunoassay for the presence of enterotoxins. Assays gave markedly higher results at 35 degrees than at 5 degrees. The source for this discrepancy was attributed to interference due to trypsin activity on the basis of (1) the demonstration of hydrolysis of p-toluenesulfonyl-L-arginine methyl ester by the specimen, (2) inhibition of this activity by trypsin inhibitor from lima bean, and (3) lowered values produced for enterotoxins in gastric juice when the inhibitor was included in the assay system.


Rate of clearance by the spleen of heat-damaged erythrocytes.

The rate of uptake in the spleen of heat-damaged red blood cells labelled with 99mTc has been measured by radioisotope scanning in 38 patients. The values obtained for the half-clearance time into the spleen using this method have been compared with the values obtained simultaneously by blood sampling for the rate of loss of radioactivity from the circulation. It was found that the uptake into the spleen was approximately three times faster than the measured rate of loss of radioactivity from the blood. The reasons for this are discussed and it is suggested that the scanning technique is more reliable as a measure of this aspect of splenic function.


A comparison of the bioavailability of digoxin in capsule, tablet, and solution taken orally with intravenous digoxin.

Six healthy volunteers were given five single-dose treatments of 0.40 mg digoxin either intravenously, in liquid form, in conventional tablet form (dissolution rate 76 per cent in 1-hour), or in new capsule preparations containing 0.05, 0.10, or 0.20 mg digoxin per capsule. Serum levels, area under the concentration-time curve, and daily urinary digoxin excretion were measured for six days. Higher serum digoxin levels were seen after ingestion of the capsules than after the tablets, with peak levels for the former being 2.2-2.8 times higher than after tablet digoxin. Bioavailability was assessed further by comparing the area under a six-hour concentration-time curve, and again the capsules gave a consistently higher value than the tablets. In addition, the absorption of 0.40 mg digoxin from any of the capsule preparations was much greater than 0.50 mg digoxin in commercially available tablets. The six-day cumulative urinary digoxin excretion was also greater for the capsules than for the 0.20-mg tablets. In comparison with intravenous digoxin, tablets provide 75 per cent maximum bioavailability, whereas the capsule preparations of digoxin improve the bioavailability of digoxin and the 0.20-mg digoxin capsule is absorbed better than 0.25-mg digoxin tablet.


Influence of renal dysfunction on warfarin plasma protein binding.

The in vitro plasma protein binding of warfarin was evaluated by ultrafiltration in plasma from seven normal subjects and seven patients with varying degrees of renal dysfunction. The unbound, or free, warfarin fraction was twice as high in the plasma samples withdrawn from patients with renal impairment than in the samples obtained from normal volunteers. Furthermore, there was a positive correlation between the extent of renal dysfunction and the magnitude of the free warfarin fraction when either creatinine clearance, plasma creatinine, or BUN was used to estimate renal function.


The effects of chlordesmethyldiazepam on behavioral performance and subjective judgment in normal subjects.

Eight normal subjects were tested on a battery of subjective and psychological tests 12 hours after a hypnotic dose of chlordesmethyldiazepam (1 or 2 mg), amylobarbitone sodium (100 mg), and a placebo. The tests included self-ratings of hypnotic effects and alertness; reactiontime, card-sorting, coding and cancellation tasks; arithmetic; and tapping. Before each task, test anxiety and performance expectation was self-rated; and after the task, judgment of performance was self-rated. Residual effects were definitely detectable after the 2-mg dose of benzodiazepine with both behavioral impairment and subjective hangover. Both the 1-mg dose and the barbiturate were almost devoid of such effects. Very few drug effects on test anxiety and performance judgment were discerned. Plasma concentrations of amylobarbitone were related to decreases in test anxiety and of chlordesmethyldiazepam with ratings of sleepiness.


The utility of pharmacokinetics to the pharmaceutical industry.

Pharmacokinetic studies done early in the course of drug development can favorably influence the course of research by suggesting optimum dosage regimens, drug delivery methods, and fixed-ratio combinations and by alerting the clinical pharmacologist to potential problems. Pharmacokinetic data can be useful in the design of rational clinical drug research and thereby expedite clinical trials and save research costs. Thus, in addition to their value in the area of comparative bio-availability, pharmacokinetic studies carried out by the pharmaceutical industry are useful economically as well as scientifically.


Comparison of hospital admissions for cerebrovascular disease in Michigan and North Carolina.

Hospital admission rates and death rates for cerebrovascular disease differ markedly between states. Hospital admission data were analyzed: (a) to ascertain why death rates from this disease group are lower in Michigan than in North Carolina and (b) to clarify whether hospital care in either state has inadequacies that can be corrected quickly. Among both whites and blacks of the same age, case-fatality ratios were higher in North Carolina than in Michigan. Subarachnoid and cerebral hemorrhages were diagnosed more often in the southern state. For both areas, the records showed a marked underreporting of hypertension and diabetes mellitus as secondary conditions in the hospital admissions; elevated blood pressures were about equally common in each state but were treated more vigorously in Michigan. Secondary diagnoses of respiratory disease and use of anti-infective agents were reported more frequently in North Carolina. In contrast, diabetes mellitus was more prevalent in Michigan admissions. Some reasons for these findings are advanced, particularly as they relate to diagnostic and treatment patterns. Finally, the need for more detailed research is emphasized to create guidelines for better hospital care of cerebrovascular disease.


Does level of professional training make a difference in crisis intervention counseling?

This study tests the concept that crisis intervention using a multilevel trained staff is more effective, because a staff with less education might better reach clients from diverse socioeconomic and cultural backgrounds. The Client-Post Rating Scale (Revised) was administered to a sample of clients served by a multilevel crisis intervention team located in a large midwestern metropolitan area to determine the efficacy of worker intervention. It was found that level of training was unrelated to counselor effectiveness and that less well-educated staff more frequently worked with less economically advantaged populations.


The policy effectiveness of health services research: a reconsideration.

It has often been asserted that health services research (HSR) has been either epiphenomenal or entirely ineffectual in influencing the formation of policy. In this examination of the HSR-policy relationship that assertion is contested; the authors conclude that there has been a relationship between HSR and policy, at least public policy. A diagrammatic framework is presented to describe the HSR-policy nexus in an attempt to facilitate an understanding of how future efforts in the conduct of HSR might be most effective.


The role of the health facilitator in community health education.

A community health education program has been established by the Department of Community Health Sciences of Duke University Medical Center in two target areas of Durham County, North Carolina. The program trains unpaid lay people, "health facilitators", to whom others already turn for help, to increase their competency for advising and referring community residents to appropriate community resources. Several methods for identifying potential health facilitators have been developed. Evaluation of the role of health facilitators hinges upon designing measures to demonstrate their existence in the community and the impact that they make. To be successful, the training of health facilitators should result in improving the quality of the advice they give their fellows. It is also important to assess the cultural acceptability of the facilitators' advice and to ensure that their helping role in the community is not disturbed by the possible professionalization of their role due to the training program.


Problems in the development of a rural primary care center.

For 18 months between July 1973 and December 1974, the development of a primary care center for a rural Appalacian county engaged the efforts of local community leaders and the Department of Community Medicine of the University of Kentucky College of Medicine. This case study discusses some of the major events and factors contributing to this unsuccessful endeavor. The local cultural and sociomedical circumstances, including economic and political forces, and the errors in institutional relations and communication are analyzed. Many of the community problems encountered, at both the local and regional levels, are common to various rural areas. Considerations discussed in some detail include medical care payment mechanisms, rural economics, and local sociocultural systems. These community health problems, and the broader health policy issues that they represent, must be addressed before any significant changes or advances can be made in health care in rural America.


The localization of cholinesterase in the retina of the fetal and newborn guinea pig.

Retinae of guinea pigs from the fortieth day of gestation to one day postnatally were processed for the localization of cholinesterases in the electron microscope according to the method of Lewis and Shute ('66). Selective inhibition served to distinguish acetylcholinesterase from non-specific cholinesterase activity. Acetylcholinesterase activity was found initially in small amounts in some regions of the outer plexiform layer at the fortieth day of gestation. At later stages it increased in distribution being observed at some photoreceptor terminals and in non-synaptic regions of the layer. Activity was less intense initially in the inner plexiform layer but increased rapidly so that by birth it encompassed a majority of processes. Perikarya of horizontal and some amacrine and ganglion cells possessed acetylcholinesterase activity in their nuclear envelope and rough endoplasmic reticulum. The possible role of the enzyme in inhibitory circuits of the fetal retina is discussed.


The development of the cerebellar cortex of the Syrian hamster, Mesocricetus auratus. Foliation, cytoarchitectonic, Golgi, and electron microscopic studies.

Although a number of investigations of abnormalities of cerebellar development have been carried out in the hamster, no detailed Golgi or ultrastructural studies of cerebellar development in this species have been reported. This report describes the development of the hamster cerebellar cortex from birth (day 0) through postnatal day 78, as studied by light, Golgi, and electron microscopic methods. Foliation patterns correlate with the expansion of the cerebellar layers and of total cerebellar area. Cytologic and morphologic development of the major cerebellar cell types--Purkinje, Golgi, basket, stellate, granule, and Bergmann glial cells--correlate with those of other species, such as the rat and mouse. Electron microscopic observations at selected developmental ages allow identification and classification of synapses in the early postnatal hamster. Parallel fiber and climbing fiber synapses are already present at birth. Although synaptogenesis probably continues through the first two postnatal months, all major cell types have developed initial synapses by postnatal day 6, at a time when little cellular maturation has occurred. By using gestational rather than natal age, close developmental correlations between hamsters and rat and mouse are possible. Since the gestational period of the hamster is only 16 days, the hamster cerebellum is less mature at birth than that of either the rat or mouse. Thus, the hamster is a convenient animal in which to investigate the effects of various procedures on early cerebellar development.


The structural maturation of the stato-acoustic nerve in the cat.

The maturation of the stato-acoustic nerve in the cat was studied by light and electron microscopy from the fetal stage to the adult. Measurement of the outer diameter of the fibers and the study of the myelination process revealed that myelination begins earlier for the vestibular nerve than for the cochlear nerve: by the fifty-third day of gestation 64% of the vestibular fibres have already passed the promyelin stage whereas for the cochlear nerve this promyelin stage begins for the majority of fibers on the fifty-seventh gestation day. Afterward, maturation proceeds more rapidly for the cochlear nerve. In the case of both nerves, maturation is still incomplete at two months of age. Concerning the relationship between the thickness of the myelin sheath and the axoplasmic diameter, there is already a good correlation by the fifty-seventh day of gestation in the vestibular nerve, whereas it appears several days after birth in the cochlear nerve.


Evidence that at least some of the motor nerve cells that die during development have first made peripheral connections.

The paper sets out to determine whether the spinal motoneurons that die during the normal development of Xenopus tadpoles have been peripherally connected before death. The numbers of cells in the control ventral horns were compared with the numbers remaining after early (stage 50 or 52/53) amputation of the limb bud. Up to stage 52, there was no difference between the two sides, but thereafter the numbers on the amputated side fell away until at stage 57 none were left. Thus, as neurons mature, they become dependent for survival on contacting the limb. During this time, there was no difference between amputees and controls in the numbers of mitoses in that part of the ventricular layer that gives rise to ventral horn cells, indicating no change in proliferation. Thus, the numbers of ventral horn cells remaining after early amputation is a measure of the numbers of cells in the normal animal that are still independent of the limb (Phase I cells) and hence by subtraction, the other cells (post-Phase I cells) are those that only survive by virtue of having contacted the limn. A graph of numbers of post-Phase I cells shows a peak at stage 54 and thereafter declines as metamorphosis approaches. This is interpreted to indicate that a number of cells that survive at stage 54 by reason of peripheral contacts or connections in the limb subsequently themselves die, that is, that al least some of the cells that die during normal development have previously made contacts within the limb.


Areal changes in mouse cortical barrels following vibrissal damage at different postnatal ages.

The normal cytoarchitectonic pattern of barrels in layer IV of mouse SmI face cortex is altered by early damage to the mystacial vibrissae (Van der Loos and Woolsey, '73). In the present study, the middle row of vibrissae (row-C) on one side of the face in groups of Swiss mice was cauterized on the day of birth (postnatal day [PND] -1)or on PND's - 2, 3, 4, 5, 7, 10, 12, 15, 20 and 30; littermates in each group served as controls. All animals were perfused on PND-60 and the brains sectioned parallel to SmI layer IV. For each specimen, the posteromedial barrel subfields (PMBSF) of the two hemispheres were reconstructed with a camera lucida and the cross-sectional areas of individual barrels measured using a small computer. The findings are: (1) The hemispheres ipsilateral to the vibrissal damage are quantitatively indistinguishable from the littermate controls indicating that the ipsilateral hemispheres in lesioned animals can serve as controls for observations of the type reported in this paper. (2) There are no consistent differences in the cross-sectional areas of the PMBSF's as a whole in the hemispheres ipsi- and contralateral to the peripheral damage, suggesting that there is no net loss of cortex as a result of the lesions. (3) The contralateral row-C barrels are reduced in size. Expressed as a percentage of normal values; row-C is reduced to 17% for animals lesioned on PND-1, 16% on PND-2, 38% on PND-3, 52% on PND-4 and 79% on PND-5; on PND-7 and later the cross-sectional areas of row-C barrels are normal. This implies that the barrel field of the SmI face cortex becomes progressively refractory to the effects of peripheral damage during the first postnatal week and in the period prior to PND-6, an intact periphery is necessary for normal cortical development. (4) In every case, the decreased cross-sectional area of row-C is accompanied by precisely increased cross-sectional areas of the barrels in adjacent rows-B and D. in the case of the restricted peripheral damage which we produced, there is a "compensation" in the contralateral hemisphere, which can be correlated with patterns of the specific thalamocortical projections.


Single unit studies on the dorsal and intermediate acoustic striae.

Studies were made of the fiber compositon and of single unit dischage characteristics in the dorsal and intermediate acoustic straie. Counts of fibers and cells revealed more than twice as many fibers as cochlear nucleus cells of the types known to contribute axons to these tracts. Recordings were made in the striae to confirm the classes of discharge patterns which are transmitted from the posterior cochlear nucleus to more central structures and to seek evidence for descending activity entering the cochlear nucleus through the striae. Discharge patterns of the majority of units resembled those seen in previous studies when recordings were made from regions of the cochlear nucleus which are known to contribute fibers to the striae. Some patterns, however, were unlike any which have been reported in the cochlear nucleus on the same side as the recording site, but resembled activity of other auditory structures, suggesting that these were descending inputs. To confirm the presence of descending activity, recordings were made in the dorsal acoustic stria at a point medial to where the stria had been completely severed. Recordings made under these conditions demonstrated the presence of descending activity. The physiological findings help explain the disparity between the counts of fibers and cells, and point out a need for more detailed descriptions of the origins of descending inputs through the striae.


Mechanisms of efferent neuronal control of the reflex nicitating membrane response in rabbit (Oryctolagus cuniculus)

Efferent mechanisms controlling the nicitating membrane (NM) reflex response to air puff in the albino rabbit were analyzed using stimulation, lesions, and recording techniques. In brief, stimulation of the sixth nerve (abducens) yields short-latency NM extension. Stimulation of the fourth and seventh nerves and the superior cervical ganglion has essentially no effect on the NM. Stimulation of the third nerve causes short-latency retraction of the NM. Lesions and recording data are consistent with this result - the sole efferent neuronal control of NM extension is the sixth cranial nerve and of NM retraction is the third cranial nerve. The NM extension response appears to be mediated by mechanical actions via retraction of the eyeball by the retractor bulbi muscle, and NM retraction appears to result from direct activation of muscle fibers in the NM by the third nerve. The superior cervical ganglion appears to play no role in reflex NM retraction in the rabbit, in contrast to its action in the cat.


Tone-induced changes in excitability of abducens motoneurons and of the reflex path of nictitating membrane response in rabbit (Oryctolagus cuniculus).

Excitability of the reflex nicitating membrane (NM) response to air puff and of the abducens motoneurons (final common path) to direct electrical stimulation (measured as amplitude of the evoked NM response) in rabbit was tested at various times after onset and offset of a 350-msec tone. Excitability to air puff showed a substantial increase during tone on a gradual decrease following tone off, in agreement with Ison and Leonard. Excitability of motoneurons showed a similar marked increase during tone on a transient decrease immediately following tone off, and then a gradual decrease. It is suggested that these excitability changes, which parallel closely the interstimulus-interval conditionability function reported by Gormezano for the same preparation, may provide an independent measure of the "molar stimulus trace". Excitability of abducens motoneurons tested in the intertrial intervals during subsequent tone-air puff conditioning showed no consistent changes. Surprisingly, animals given tone-abducens nucleus shock testing developed conditioned responses. In subsequent conditioning, using standard tone-air puff training, they showed 85% savings in acquisition relative to nonstimulated controls.


Peripheral heat as a reward for heart rate response in the curarized rat.

It is generally assumed that the mechanical perception of shivering is necessary for the perception of cold discomfort. Shivering of rats in a cool environment was eliminated by curarization. The rats were kept alive by artificial respiration. Heart rate was proportional to rectal temperature in a group of controls. One group of rats was conditioned to increase heart rate to trigger an infrared lamp; another group was conditioned to decrease heart rate to obtain heat. When compared with the results of the control group without infrared heat reward, the results obtained from the two heart-rate-modifying groups show that shivering is not a necessary signal to determine thermoregulatory behavior in rats and, presumably, cold discomfort in man.


Bait shyness: avoidance of the taste without escape from the illness in rats.

Thirsty rats habituated to drinking .12 M sodium chloride accepted .12 M lithium chloride for 5 min on the first trial but stopped short of their sodium baseline. With repeated trials they reduced consumption of the toxin by either (a) detecting subtle oral (conditioned stimulus, CS) differences, thus avoiding toxicosis (unconditioned stimulus, US) or (b) detecting earlier signs of malaise (US), thus escaping further distress. When both solutions were masked with saccharin, the discrimination was more difficult but still possible. When both solutions were mixed in a solution masking all four taste qualities, the discrimination was severely disrupted. When oral sensors were bypassed with nasopharyngeal tubes, intragastric pumping rats were unable to use postingestional cues to escape, even though such cues were proximal to the ultimate malaise. Oral cues at the distal end of the consummatory chain were extremely effective.


Role of mate's previous experience in ring dove hormone-induced incubation.

Progesterone-induced incubation was examined in 40 pairs of adult ring doves, differing in their previous reproductive experience (courtship vs. nest building) and the previous reproductive experience of their mates (courtship vs. nest building) during testing. Only the previous experience of the experimental subject significantly affected the establishment of incubation during the 24-hr test period. More doves experienced with nest building established incubation than did courtship-experienced doves. The latency to enter the nest area and the latency to stand on the nest were affected by both the previous breeding experience of the subject and the previous breeding experience of its mate. Nest-building-experienced mates decreased the latencies of courtship-experienced subjects, and courtship-experienced mates increased the latencies of nest-building-experienced doves. Males were not more affected by their mates' experience than were females. Time spent on the nest was affected only by the subject's previous experience and sex. While the hypothesis that the behavior of the mate can affect a dove's progesterone-induced incubation was not confirmed, the mate's behavior can affect some of the components of nest responsiveness.


Hormonal control of female sexual attractiveness proceptivity, and receptivity in rhesus monkeys.

The sexual behavior of 18 female and 11 male rhesus monkeys was observed in pair tests, in two experiments. In one experiment the females controlled the occurrence of pair tests. The females were ovariectomized and treated with estradiol, two dosages of testosterone, estradiol plus testosterone, estradiol plus dexamethasone, or no hormone; and the effects of the treatment on female attractiveness, proceptivity, and receptivity were examined. Sexual attractiveness of females to males (the effectiveness of the female as a sexual stimulus) was affected by estrogen and androgen. Estrogen enhanced attractiveness, but the effect of androgen depended on the dose. Female sexual proceptivity (the extent to which the female seeks out the male and elicits sexual behavior) was heightened by estrogen and androgen. Female sexual receptivity (willingness to receive a male in copulation was somewhat stimulated by estradiol, but not by testosterone. Both estradiol and testosterone had a greater effect on attractiveness and proceptivity than on receptivity. The hypothesis that testosterone is the "libidinal hormone" in female primates was not supported.


Ventromedial hypothalamus and short-term feeding suppression by caerulein in male rats.

A series of six experiments examined the neural loci responsible for caerulein's suppression of eating. Caerulein is a decapeptide chemically and physiologically similar to cholecystokinin, a naturally occurring gut hormone in rats. Rats with lesions in the ventromedial hypothalamus (VMH) showed reduced sensitivity to caerulein (1 mug/kg); rats with lateral hypothalamic (LH) destruction showed heightened sensitivity. Microinjections of caerulein into the VMH, but not into the LH, limited feeding. Finally, tritiated caerulein was selectively bound to tissue in the VMH. The results are discussed in terms of the hypothesis that the VMH manages postprandial inhibition in the rat.


Molecular weights of three mouse milk caseins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and kappa-like characteristics of a fourth casein.

Caseins of mouse milk are phosphoproteins which precipitate at pH 4.6, stain blue with "Stains-all," and stain red with "Stains-all" following alkaline phosphatase digestion. Four caseins were separated electrophoretically in sodium dodecyl sulfate-polyacrylamide gels varying from 8.5 to 15% acrylamide. Molecular weights for three of these proteins were 43,200, 27,700, and 25,900. The molecular weights determined for bovine alphas1 and beta caseins by this method were similar to those previously obtained by other methods. A fourth mouse casein contained carbohydrate, phosphorus, and sialic acid. This protein was rennin-sensitive and behaved anomalously on sodium dodecyl sulfate polyacrylamide gels, as did bovine kappa-casein. Because of similarities with bovine kappa-casein, it was designated with "kappa-casein" of mouse milk.


Optimum amino acid complement for protein synthesis by rat mammary cells in tissue culture.

The amino acid requirement of rat mammary cells for milk protein synthesis was investigated in dispersed cell culture. A three-dimensional central composite design utilizing three variables (X1 = lysine; X2= methionine, valine, and arginine; X3 = isoleucine, tryptophan, threonine, phenylalanine, and histidine) at five concentrations each, was duplicated twice with mammary cells from lactating Sprague-Dawley rats. The optimum combination of amino acids for maximum milk protein synthesis from multiple regression models was X1 15.0-, X2 4.5-, and X3 1.5-fold their quantities in Eagle's minimal essential medium with leucine, tyrosine, cystine, and glutamine at the base 1-fold in the medium.


Effects of zinc, copper, and manganese supplementation of high-concentrate ration on gastrointestinal absorption of copper and manganese in Holstein calves.

Sixteen Holstein bull calves were fed a high-concentrate ratio supplemented with zinc, copper, and manganese, alone or in combination, for 10 wk. After 6 days of preliminary feeding of chromic oxide, fecal grab-samples were collected for 6 days. Calves were slaughtered, and samples of the contents of the reticulo-rumen, omasum, abomasum, small intestine, cecum, and large intestine were analyzed for chromic oxide, copper, and manganese. Absorption along the gastrointestinal tract, measured by comparison of one segment with the previous segment, indicated net secretion of copper in the abomasum but net absorption from the rest of the tract. The exception was that net secretion into the reticulo-rumen was associated with low dietary copper. Net secretion of manganese was mainly in the small intestine and cecum in all treatments. A higher proportion of copper apparently was absorbed when this mineral was supplemented in the ration. However, absorption of manganese was decreased slightly when manganese was supplemented in the ration. Reabsorption of manganese in the large intestine was probably greater than that of copper.