Diverse effects of bursectomy on humoral immune responses in the chicken. Chickens bursectomized hormonally or surgically at various ages in embryonic to postembryonic lives were immunized with a mixture of antigens, and the antibodies produced titrated. immune responses to Salmonella pullorum (SP), Brucella abortus (BA). Staphylococcus aureus (Staph) and ovalbumin (OA) were more markedly suppressed by the bursal deprivation than those to heterogenous erythrocytes, viruses and such bacteria as Pasteurella multocida (PM) and Escherichia coli B. The immune response to bovine serum albumin (BSA) was on a level between the two groups. Hormonal bursectomy in embryonic life permitted chickens immunized with sheep red blood cells (SRBC) to produce antibody of the IgM type but not of the IgG type. In surgically bursectomized chickens IgG but not IgM production was inhibited. Chickens hormonally bursectomized on the third day of egg incubation produced IgM to a level higher than the normal chickens in contrast with the suppressed IgG production. Such diversity in the bursal influences on antibody responses was discussed in relation to ontogeny of the humoral immune system.


Effects of roxarsone on pigmentation and coccidiosis in broilers. Roxarsone (0.005%) medicated chickens inoculated at seven weeks of age with Eimeria maxima oocysts had significantly higher pigment levels in blood plasma than did unmedicated controls. Unmedicated E. maxima infected birds had significantly lower pigment levels compared to uninoculated controls. Uninoculated roxarsone medicated controls showed no increase in pigment levels over uninoculated unmedicated birds. This experimental design demonstrates that the beneficial effect of roxarsone medication is due to anticoccidial action rather than an increase in pigmentation after feeding the yellow-colored roxarsone. Since uninoculated birds gained more rapidly if roxarsone (0.025%) was added to the diet, the drug also appears to stimulate growth as well as to protect against coccidial infection. In two floor-pen experiments roxarsone demonstrated anticoccidial activity as measured by higher pigment scores than unmedicated infected controls. The coccidial infection was induced after seeding the litter with oocysts from birds infected with E. acervulina, E. brunetti, E. hagani, E. maxima, E. mivati, E. necatrix, E. praecox, and E. tenella. Pigmentation levels were significantly higher in plasma and skin of roxarsone medicated chickens in two experiments and in shanks in one experiment. Similar protection against depigmentation was demonstrated by adding roxarsone to feed medicated with nequinate. These results involving addition of roxarsone may explain some equivocal reports on pigmentation, weight gains or feed conversion. Some previous investigators appear to have used an inadequate experimental design by omitting use of unmedicated uninoculated controls or to have made no attempt to monitor for presence or absence of coccidiosis.


Enzymes and electrolytes in the semen of Japanese quail. Japanese quail (Coturnix coturnix japonica) semen was collected at 10 a.m., 2 p.m., or 6 p.m. for four consecutive days during four consecutive weeks. All but the first day's collections were analyzed for sodium, potassium, chloride, carbon dioxide, H+ concentration, cell count, volume and total sperm number. A random sample was then collected for the analysis of amylase and another random sample was collected for the analysis of glutamic oxalacetic transaminase (GOT), creatine phosphokinase (CPK), and lactic dehydrogenase (LDH). The activities of GOT and LDH in quail semen were approximately ten times higher than those obtained for larger fowl (chickens and turkeys) and mammals. While CPK levels have not been measured in other animals, its activity in quail semen is probably also high. There was a significant difference between the enzyme activity of the sperm and seminal plasma for GOT and CPK. The parameters of sodium, potassium, chloride, carbon dioxide, H+ concentration, cell count, volume, and total sperm number did not show a significant variation at the hours of 10 a.m., 2 p.m., and 6 p.m. Three of these parameters (cell count, potassium, and chloride), however did show significant variation during collection over three consecutive days, the chloride decreasing and potassium and cell count first decreasing and then by the third day returning to levels of the first day. None of the parameters followed the sperm concentration closely enough to be of value as an index of quail fertility.


Activity of certain liver enzymes in fast- and slow-growing lines of chickens. The realtionship between growth rate and the metabolic activity of certain liver enzymes was studied using two strains of White Plymouth Rock chickens which had been selected in divergent directions for eight-week body weight. The activities of hexokinase, glucokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase, citrate synthase, glycogen synthetase, glutamate dehydrogenase and aspartate transaminase were measured at 4, 8 and 20 weeks of age. The mean percentage rate of growth of the birds selected for high eight-week body weight exceeded that of the birds selected for low eight-week body weight only during the early growth period. Thereafter, and until sexual maturity, the low-line birds grew at a faster rate, relative to body size. The mature body weight of the high-line birds exceeded that of the low-line birds by a factor of approximately 1.5. A close similarity was noted between the metabolic activity of certain liver enzymes and the growth rate (relative to body size) of the birds studied. At four and eight weeks of age, the faster-growing birds (whether high- or low-line) generally exhibited a greater capacity for glucose phosphorylation and glycolysis, but a poorer capacity for glycogen synthesis, than the slower-growing birds. At twenty weeks, growth rate and metabolic activity were similar in both strains.


Debeaking method for Bobwhite quail.

Debeaking method for Bobwhite quail. Four experiments were conducted to determine the suitability of various debeaking procedures for Bobwhite quail at hatching or at one week of age. Two experiments were conducted using a "precision" type debeaking method with the following treatments: control; debeaked at hatching with debeaker guide plate holes of 2.38 or 2.78 mm; debeaked at seven days of age using guide plate holes of 2.38, 2.78 or 3.18 mm. Two experiments tested a "touch-burn" method at hatching with the following treatments: control; burned 1/4 distance to nares; and burned 1/2 distance to nares. The "precision" type methods at hatching or seven days of aged reduced mortality from cannibalism; however, these methods were found to be relatively slow and difficult, and the birds lacked uniformity in beak and body size at five weeks of age. Burning 1/2 distance to nares was too severe, causing a reduction in body weight and poor feed efficiency. Burning 1/4 distanct to nares gave the most favorable results: growth and feed efficiency as good or better than controls, uniform birds and decreased cannibalism.


The effect of hypothalamic lesions on thyroid-stimulating hormone concentration in the chicken pituitary. Studies of thyroid activity following hypothalamic lesions have provided indirect evidence of TSH influence on the pars distalis of birds. The present study examined the influence of hypothalamic lesions on TSH assays of the rostral and caudal lobes of the pars distalis. Lesions of the septomesencephalic tract increased TSH levels in the rostral lobe but had no influence on the caudal lobe. Lesions of the supraoptic or ventrolateral nuclei neither stimulated nor depressed TSH in either lobe of the pars distalis.


Toxicity of dietary lead in Japanese quail. The toxicity of dietary lead in Japanese quail was investigated. The data indicated that dietary lead, in the form of lead acetate, was toxic to young quail at the level of 500 p.p.m. and this toxicity was evidenced by an inhibition of normal growth and by anemia. The anemic state in the lead toxic quail was more readily detected by reduced blood hemoglobin concentrations than by packed cell volumes. In addition, the data suggested that lead interfered with normal sexual development in the males. Lead at levels as high as 1000 p.p.m. did not prevent normal primary antibody responses to sheep erythrocytes.


The interaction of ochratoxin A with some environmental extremes. Presently, ochratoxin is the most potent mycotoxin studied in chickens. The possibility that ochratoxin can interact with environmental extremes was investigated by incorporating pure ochratoxin A (0, 0.5, 1.0, 2.0, 4.0, and 8.0 mug./g. feed) into the diet of 4 replicates of 10 birds from hatching until 3 weeks of age. There was a significant (P less than 0.05) decrease in the mean survival times of birds exposed to 4 degrees C. and 90% relative humidity at dose levels of 4.0 and 8.0 mug./g. However, birds exposed to 43 degrees C. and 45% relative humidity had a significantly (P less than 0.05) prolonged mean survival time at 8.0 mug./g. Birds given drinking water containing 2% NaCl had a significant (P less than 0.05) decrease in mean survival time at 8.0 mug./g. These data suggest that ochratoxin like aflatoxin can interact with other agents to produce syndromes not attributable to each alone.


Efficacy of D-, L- and DL-methionine for growth of chicks fed crystalline amino acid diets. Four assays employing young male chicks were conducted to evaluate the relative efficacy of D-, L- and DL-methionine and to estimate the requirement for D- and L-methionine when serving as the sole source of sulfur amino acids or when added to a diet containing 0.27% L-cystine. Crystalline amino acid diets containing 14.9% protein equivalent and 4200 kcal. M.E./kg. were used in all assays. L-methionine supported faster and more efficient gains than D- or L-methionine when fed at levels below thhe requirement. At levels of supplementation near the requirement, however, equal efficacy was attained. When serving as the sole source of sulfur amino acids, the requirement as estimated by least squares for optimal gain was 0.58% of the diet or 104 mg./day for L-methionine and 0.59% or 104 mg./day for D-methionine. In the presence of cystine, the requirements were estimated at 0.27% or 49 mg./day and 0.30% or 52 mg./day for L- and D-methionine respectively. The results indicate that at lower levels of supplementation, L-methionine is a better source of sulfur amino acids than D-methionine. On the other hand, L- and D-methionine appear to have equal efficacy when incorporated into diets that are only marginally deficient in sulfur-bearing amino acids.


Cadmium and the laying hen: apparent absorption, tissue distribution and virtual absence of transfer into eggs. After being given a single oral dose of 40 muCi. of 109CdCl2, laying hens were fed a practical type ration to which 0 or 60 p.p.m. cadmium (Cd, as CdCl2) was added. On the basis of 109Cd in excrement, apparent absorption of the isotope averaged less than 10% of the dose for both diets. Less than 4% of the dose was retained in total body tissue 23 days after dosing. Dietary Cd level did not significantly influence excretion of 109Cd by hens, but hens fed 60 p.p.m. Cd retained a significantly higher proportion of 109Cd dose in liver, kidneys and whole body than did control hens. 109Cd was only detected in blood 48 hours after dosing and more than 75% of radioactivity in the blood occurred in plasma. Hens fed 60 p.p.m. Cd consumed less feed and produced less eggs than control hens. 109Cd was found infrequently at very low levels in yolks of eggs produced by hens fed 60 p.p.m. Cd. No radioactivity was detected in any egg whites, or in yolks of eggs produced by control hens.


Reproductive performance of caged Beltsville Small White turkeys as affected by choline, bird density and forced molting. Reproductive performance was determined on Beltsville Small White hens housed 2 or 3 per cage for 10 weeks and then changed to 1 or 2 per cage for 10 additional weeks. Hens were then molted and data collected for a second production cycle of 18 weeks. Hens were fed a basal diet calculated to contain 1230 mg./kg. of choline, or supplemented with choline chloride to provide 1900, 2570 or 3240 mg. of choline per kg. of diet. Variations in production, fertility and hatch were observed between the first and second 10 week periods of the first laying cycle, but differences were affected more by two high choline levels than by number of hens per cage. When data was combined to show the effects of choline supplements for the entire 20 weeks, there were no significant differences in egg production or hatch of fertile eggs due to choline levels. However, significantly lower fertility resulted in groups fed choline at the level of 2570 or 3240 mg./kg. during this 20 wk. laying cycle. During the second production cycle (one hen per cage), choline supplements improved egg production, increased egg weight, depressed fertility and had no effect on hatch of fertile eggs. When data from the first and second production cycles were combined, there was no significant effect of choline on production or hatchability, but all groups supplemented with choline had significantly lower fertility than the basal group, indicating that 1230 mg./kg. of choline was adequate.


Deamination of amino acids in the small intestine of chickens fed meat meal. The loss of amino acids by bacterial deamination in the small intestine of chicks fed heated and unheated meat meal was studied by incubating the intestinal contents in vitro. The loss of amino acids by bacterial deamination was found to take place mainly in the lower small intestine. Deamination of amino acids was significantly higher in the contents of the small intestine of chicks fed a meat meal compared to the freeze-dried raw materials, and this deamination was reduced by the addition of 50 p.p.m. penicillin to the meat meal.


Attempted induction of gynogenesis in chickens. Dark Cornish and White Leghorn hens were divided into a virgin group and a group inseminated with semen that had been irradiated with 5,000r. of X rays. Two replicate trials were performed, one during winter and the second during summer. Two parthenogenetic embryos were found among 1,417 virgin eggs incubated for 24 hours. No other development was seen in eggs from this group. The three chicks produced by the inseminated group were not gynogenetic. Their heterozygous coloration showed them to be normal fertilization products. Fertility of 1,500 eggs was only about 5% and survival was almost nif for eggs from hens artificially inseminated with semen irradiated at 5,000 r. Most embryonic development consisted of membranous growth with occasional blood cells. The frequency of detectable embryonic development in abortive eggs was half as great after seven days incubation compared to the frequency after only 24 hours incubation.


Effect of turning and age of egg on hatchability in the pheasant, chukar, and Japanese quail. Eggs from pheasants, Chukar partridge and Japanese quail were stored 1 to 28 days in a cold box where temperature and relative humidity were maintained at approximately 16 degrees C. and 70 percent, respectively. Half the eggs from each species was turned once daily from a 45 degree angle from the verticle to the opposite angle. Turning eggs prior to incubation had no appreciable effect on hatchability of eggs stored up to 28 days. Length of storage for eggs from the pheasant and quail was critical, with significant declines in fertility in eggs stored beyond 14 days. Storage of Chukar eggs up to 28 days had little effect on subsequent hatchability, and their holding quality was comparable to that for commercial strains of chickens and turkeys.


Biotin deficiency as a possible cause of swelling and ulceration of foot pads. A high incidence of foot pad lesions and breast blisters were observed in broilers. Histological examination of foot pads indicated changes similar to those previously found when broilers were fed a biotin deficient diet. It is suggested that a marginal biotin deficiency in practical diets may be responsible for enlarged foot pads causing birds to rest on their breast resulting in increased breast blisters.


Dieldrin dilution in visceral fat of field-contaminated broilers. Broilers aged 4, 5 and 6 weeks were selected from 8 commercial flocks which had been accidentally exposed to dieldrin in feeds. The birds were given a dieldrin-free ration and were reared to 10 weeks of age. Dieldrin residues in visceral fat were determined weekly. Results indicated that dieldrin residues are rapidly diluted in the growing chick with a half-time for dilution of approximately 12 days.


The dietary-fecal relationship of calcium and phosphorus levels in White Leghorn hens. Fecal samples were collected from individually caged White Leghorn hens in two experiments to determine the relationship of dietary and fecal levels of calcium and phosphorus. Data indicated that fecal levels of both calcium and phosphorus increased with increased dietary levels and could be directly altered as their dietary counterparts were varied.


Inefficacy of carnitine as a substitute for choline for normal reproduction in Japanese quail. An experiment was conducted to determine if DL-carnitine could partially or completely substitute for choline for maintaining normal reproduction in Japanese quail. Adding 2800 mg. choline chloride per kg. to a purified diet significantly increased egg production and egg weight and improved hatchability, but adding a similar level of carnitine failed to improve any of the parameters measured. Likewise, performance of quail fed 1400 mg. carnitine per kg. in combination with 1400 mg. choline chloride was no better than that obtained with quail fed choline chloride (1400 mg./kg.) alone.


Adolescent pregnancy.

Adolescent pregnancy. The results of a retrospective study of adolescent pregnancy indicated that obstetric and perinatal complications were fewer than expected. The case histories of 178 pregnancies, all occurring in patients aged 15 years or less at the time of delivery, were reviewed. During the ten-year period 1963 to 1972 there were no maternal deaths, no stillbirths and no neonatal deaths. As expected, the majority of patients were primigravidae, but 35 patients (approximately 20 per cent) subsequently became pregnant for a second time before their sixteenth birthday. This emphasizes the need for improvement in contraceptive advice and follow-up for this age-group so that further illegitimate pregnancy or abortion can be avoided.


A combined procedure for preparation of plastocyanin, ferredoxin and CF1. Homogeneous preparations of ferredoxin, plastocyanin, and chloroplast coupling factor (CF1) have been isolated from spinach by a combined procedure in which supernatants from preparation of chloroplasts are used for isolation of ferredoxin and the chloroplasts serve as the source of plastocyanin. The proteins were purified by DEAE-cellulose chromatography and gel filtration, after precipitation with acetone in the case of ferredoxin or release from membranes in the case of plastocyanin. The proteins obtained by this procedure are pure, as evidenced by absorption ratios (ferredoxin, A420/A276 = 0.47-0.48; plastocyanin, A278/A597 = 1.2) and by the fact that both proteins migrate as single bands on polyacrylamide gels in the presence of sodium dodecyl sulfate.


Affinity chromatography of succinate dehydrogenase from the membranes of Micrococcus lysodeikticus. Isolated plasma membranes of Micrococcus lysodeikticus were subjected to extraction with n-butanol in a two-phase system. Succinate dehydrogenase obtained in the soluble aqueous phase after high-speed centrifugation was resolved by separation on calcium phosphate gel and affinity chromatography. The affinity ligand used was oxaloacetate and elution from the column was achieved with 0.5 M succinate. In the final product there was an eleven-fold reduction in the 32P-lipid to protein ratio and a fourteen-fold increase in specific activity relative to the high speed supernatant fraction following n-butanol extraction.


[Effect of the stereoisomers of glutamic acid on the vital activity of auxotrophic mutant producers of lysine]. Studies of L, D and DL-forms of glutamic acid as the sole nitrogen source or as a supplement to the major nitrogen source--ammonium sulphate have demonstrated that in the first case all forms of glutamic acid are assimilated by auxotrophic mutants--lysine producers. However, the lysine synthesis was very low, when L-glutamic acid was used as the only nitrogen source. Glutamic acid at a concentration of 0.01 M applied as a supplement to the major source of nitrogen acted as a stimulator of lysine synthesis, slightly inhibiting biomass increment. That was true of every form of glutamic acid, especially of DL-glutamic acid.


[Effect of furfural on the energy metabolism of fodder yeasts]. The effect of furfurol on the rate of oxygen uptake and carbon dioxide production by Candida tropicalis cells was studied. Furfurol was shown to inhibit significantly the yeast respiration, inducing aerobic glycolysis. Enhanced carbon dioxide production in the presence of furfurol was followed by an intensive degradation of trehalose and ethanol accumulation in the medium.


[Effect of certain substances on the biosynthesis of cellulase by the thermotolerant fungus, Aspergillus terreus I7P]. Different substrates which activate the enzyme synthesis were added to the natural medium for Asp. terreus 17P cultivation where wheat straw was used as the carbon source. Tween-80, oleic acid, sodium salts of ascorbic and acetic acid, potassium salt of indolyl acetic acid, sunflower seed oil, coreander seed oil, soapstock and sugars--glucose, sucrose, fructose and lactose were tested. An addition of Tween-80 at a concentration of 0.1% to the cultivation medium showed the most favourable effect on the synthesis of cellulolytic enzymes. Milk serum and cheese serum, malt shoots and protein-vitamin complex were examined as a substitute for corn extract. Dry malt shoots added at a concentration of 1.5% was a good substitute for corn extract.


[Formation of primary alcohols and palmitic acid in the microbiological oxidation of hexadecane]. Forty seven microbial strains oxidized hexadecane to form primary cetol and palmitic acid. The maximum quantitiy of the compounds was accumulated in the exponential phase of growing cultures (for 72 hours) and for 6 to 16 hours of incubation of resting cell suspensions. Candida yeast were shown by the gas-liquid chromatography method to be the most active producers of cetol.


[Isolation and some properties of a nonspecific extracellular ribonuclease of Aspergillus clavatus]. RNase has been isolated from the homogenate of the Aspergillus clavatus mycelium by gel filtration through Sephadex G-75, chromatography on CM-cellulose and DEAE-cellulose. By gel filtration and electrophoresis in polyacrylamide gel the preparation has been shown to be homogeneous. The enzyme is acid protein with the isoelectric point at pH 4.4 and molecular weight of 27,000. RNase has pH optimum at 6.0--6.2 and temperature optimum 60 degrees for RNA action. The enzyme splits RNA completely in the absence of metal ions. Ions Zn2+, Cu+2, Ag+1 and Ni+2 at a concentration of 10(-4) M are strong inhibitors of RNase activity.


[Change in the alpha-glucosidase activity of cattle muscle tissue during slow autolysis]. Changes in the alpha-glucosidase activity of the cattle muscular tissue (oxen eye muscle of loin) were evaluated during storage at 2 degrees. Under these conditions both lysosomal and extralysosomal alpha-glucosidase activities underwent no significant changes during a long period of time (12 days). Activity of lysosome-bound alpha-glucosidase was about 10% of total enzyme activity in the homogenate; the remaining part of alpha-glucosidase was contained outside lysosomes.


[2 methods of preparing solvent systems for the chromatographic separation of organic acids]. The solvent system of alcohol-acid-water gradually forms an equilibrated amount of ester which facilitates the separation of di- and tri-carboxylic acids on paper chromatograms. Using the system of n-butanol-formic acid-water (3:1:1) as an illustration, two methods of accelerating the system ageing are demonstrated: 1) butanol-acid mixture at a required ratio is kept for several hours before water is added and 2) butanol-acid mixture is passed through the KU-2 layer in the H-form. The effect identical to that achieved as a result of 5-day storage of the solvent system under usual conditions can be reached with the first scheme during 6 hours and with the second scheme during 20-30 min.


[Enzymatic decomposition of pectin in the presence of amino acids and proteins]. The influence of amino acids--glycine, alpha-alanine, lysine, phenylalanine, serine, methionine, cysteine, tryptophan, aspartic acid and asparagine--and proteins--chick egg albumin and autolysate of Aspergillus niger biomass--on the disintegration of beet pectine by the Asp. niger enzymic preparation was investigated. This process was shown to depend on the chemical composition and concentration of amino acids and the protein nature. All the tested amino acids, except tryptophan, at doses of 0.0001 to 0.5% stimulated the activity of pectolytic enzymes. The effect of proteins was different: Asp. niger autolysate showed no essential influence and egg albumin inhibited pectine disintegration.


Furosemide induced release of prostaglandin E to increase renal blood flow. Levels of PGE in renal venous blood were found to be significantly elevated at the time RBF was increased by furosemide. Following indomethacin, a second dose of furosemide failed to increase RBF and levels of PGE in renal venous blood were not elevated. Levels of PGF and PGA were not affected by furosemide. The increase of PGE in renal venous blood at the time of renal dilation supports the hypothesis that furosemide increases RBF by releasing PGE. An intrarenal action of the released PGE is implied by this mechanism.


An improved diffusion chamber (DC) for culture of hematopoietic cells. A DC with Nuclepore filter wall has been described. Recovery of in vitro incubated human nucleated peripheral blood cells and in vivo growth of mouse bone marrow cells in intraperitoneally implanted DCs were improved when compared to the growth obtained in the more commonly used Millipore filter chambers.


Effects of sugars on leucine and lysine uptake by intestinal cells from rats fed sucrose and stock diets. The effect of various dietary sugars on the uptake of 1 mM leucine and 1 mM lysine by intestinal cells isolated from stock-fed and sucrose-fed rats was determined. Leucine uptake was activated by 10 mM fructose and inhibited by 10 mM glucose or 20 mM sucrose on both diets. The major dietary effect noted was a significant increase in the inhibition of leucine by glucose in the sucrose-fed rats. The uptake of lysine was minimally affected by the sugars irrespective of the diet fed. These results demonstrate an important dichotomy in the properties of glucose and fructose transport in the intestine and suggest that dietary fructose may increase the transport of certain amino acids.


The incorporation of radioactive uridine into the hepatitis B antigen of a chimpanzee. Radioactive (3H) uridine was incorporated into RNA isolated from the HBsAg of a chimpanzee carrier. HBsAg was purified by precipitation as an immune complex with the IgG fraction of chimpanzee anti-HBs. RNA was extracted from the washed complex with buffered phenol precipitated with alcohol and four nucleotides were identified by thin layer chromatography after alkali degradation.


Vitamin K requirement and warfarin tolerance in the hamster. A dietary deficiency of vitamin K has been demonstrated in the Syrian hamster. This species has also been shown to be relatively resistant to the action of the indirect anticoagulant Warfarin, and very sensitive to the anticoagulant action of the vitamin K antagonist chloro-K. These observations, and the hamster's apparently high requirement for the vitamin, indicate that it responds to vitamin K and vitamin K antagonists in the same fashion as Warfarin-resistant strains of rats.


Unilateral luteotropic effect of uterine venous effluent of a gravid uterine horn in sheep. The involvement of the main uterine vein in the unilateral maintenance of CL was studied in bilaterally ovulating unilaterally pregnant ewes. Ewes were mated at estrus (Day 0) and bilaterally ovulating ewes were randomized into three groups at surgery on Day 5. In all ewes, the uterine horns were separated through the intercornual area and one was ligated and transected near the internal bifurcation to produce a nongravid horn. One group served as controls (five ewes). In the other two groups the main uterine vein on one side was surgically anastomosed (end to side) to the corresponding vein of the opposite side (gravid side to nongravid side in one group--three ewes, and nongravid side to gravid side in the other--three ewes). Necropsies were done on Day 20. Mean CL weight was less, (P less than .01) on the nongravid side in control ewes than on the gravid side in control ewes or for either side in the other two groups. There were no significant differences among mean weights of CL on the gravid side in control ewes and either side in the other two groups. The CL regressed when the ipsilateral uterine vein contained blood from only the nongravid horn whereas the CL was maintained when the ipsilateral uterine vein contained venous blood from a gravid horn, whether or not it also contained blood from a nongravid horn. Results indicate that the uterine venous effluent from a gravid uterine horn in sheep has a luteotropic effect on the ipsilateral CL.


Experimental pneumococcal meningitis: III. Chemotactic activity in cerebrospinal fluid. Chemotactic activity was assayed in CSF of rabbits with pneumococcal meningitis to further characterize the inflammatory response in this infection. CSF chemotactic activity was detected in increasing levels for 72 hr after infection. Activity was stable at 56 degrees and was inactivated by agents which denature proteins. Gel filtration demonstrated two chemotactically active fractions in infected CSF with mol wts of approximately 3000 and 11,000. Bacterial products appear to account for a portion of the observed CSF chemotactic activity, but the role of host factors remains to be clarified.


Alteration in tissue and serum concentrations of TSH, iodide, T4 and T3 induced by various dietary iodide levels. Isotopic equilibrium and radioimmunoassay methods were used to evaluate the effects of increases in iodide intake on tissue and serum concentrations of thyroid hormones. Within the range of iodide levels used total iodine in peripheral tissues and serum increase directly with iodide intake but this change is mainly due to an increase in inorganic iodide. It is concluded that increases in tissue thyroid hormone concentrations occur within a relatively narrow range of iodide intake and maximal concentration occurs at an iodide intake of 3-10 mug/day.


Salmon calcitonin and water and electrolyte transport in rabbit ileum. The administration of SCT, natural and synthetic, has no apparent effect on the ileal water and electrolyte transport in the rabbit. The failure of SCT to influence ileal transport of water and electrolytes in the rabbit, as it does in man, may be due to differences in the rabbit intestinal response to a foreign peptide hormone.


Depressed thymidine kinase activity in zinc-deficient rat embryos. The activity of thymidine kinase in 12-day fetuses taken from females exposed to a dietary zinc deficiency during pregnancy was significantly lower than in ad libitum (P less than .05) and restricted-intake (P less than .01) controls. Activity of the enzyme was not restored by in vitro addition of zinc at levels up to 0.075 mM but severe inhibition (approximately 50%) occurred at 0.75 mM. Enzyme activity was also severely reduced (approximately 44%) by 0.017 mM (0.96 mug/ml) of copper which raises the possibility that the reduction in thymidine kinase accompanying zinc deficiency may arise, at least in part, from an absolute or relative change in the intracellular level of copper.


Cell Na and K in the rat tail artery during the development of hypertension induced by desoxycorticosterone acetate. An increase in total Na, due in large part to an increase in cell Na, was measured in the freshly excised rat tail artery during the course of DOCA-saline treatment. Since this change was associated with a fall in cell K, was first observed at 2 weeks, coincident with the rise in blood pressure, and was not sustained during subsequent immersion of the artery at zero pressure, it probably reflects the high in vivo intravascular pressure. In the incubated artery, cell Na is significantly reduced early in the course of treatment, while cell K falls late. Thus, Na transport in the artery is under direct attack from the start, but it is suggested that this leads to hypertrophy rather than to vasoconstriction.


Characterization of rat liver cell plasma membranes. A method is described by which bile canalicular membranes (BCM) can be prepared, together with canaliculus-free plasma membrane (PM), both essentially free of contamination. The recovery of both fractions together was estimated to be 46%. The concentrations of total lipid, total phospholipid and cholesterol were substantially greater in the BCM, and polyacrylamide gel electrophoresis revealed differences in protein composition. The differences in lipid and protein composition of these two plasma membrane fractions are presumably related to their very different physiological functions.


The transmural distribution of coronary blood flow during maximal vasodilation. Experiments were performed to examine the transmural distribution of the coronary blood flow during maximal vasodilation and when intramyocardial pressures were either minimized (cardiac arrest) or maximized (tachycardia). The results reveal a gradient of vascular resistance across the ventricular wall that favors flow to the subendocardium in the presence of maximal vasodilation. Thus a flow gradient favoring the subendocardium was seen when intramyocardial pressures were minimized by cardiac arrest, but when tissue pressures were maximized through tachycardia this gradient of flow was reversed.


The preparation of membranes of some human T-mycoplasmas and the analysis of their carbohydrate content. Purified membranes were prepared from seven human T-mycoplasmas of which four are laboratory strains and three isolates from patients with nonspecific urethritis. The T-mycoplasmas were resistant to osmotic shock and sonication. Membranes were obtained only after lysing most of the T-mycoplasmas by four passes through a cell fractionator at 40,000 psi and separating the membranes from the unlysed cells by differential centrifugation. The membranes contained between 1 and 7% carbohydrates by dry weight. Mannose, galactose, and glucose were identified with glucose in the largest concentration.


Glucocorticoid-induced protection in circulatory shock: role of reticuloendotheilial system function. Experiments with rats indicate that: (i) hydrocortisone sodium succinate (HC) and methylprednisolone sodium succine (MP) enhance survival after hemorrhage; (ii) MP is approximately 10-times more potent than HC; (iii) both HC and MP are more efficacious if administered prior to hemorrhage; (iv) efficacy of postshock therapy with both steroids is not only time- but dose-dependent; and (v) HC and MP can ameliorate or completely prevent the early RES phagocytic depression observed in circulatory shock. Overall, these data could be used to suggest that: (i) the RES may play a pivotal role in the beneficial actions of synthetic adrenocorticosteroids in circulatory shock, and (ii) numerical RES phagocytic indices may be diagnostic and prognostic parameters in circulatory shock therapy.


Pituitary and serum concentrations of prolactin and GH in Snell dwarf mice. Secretions of prolactin and GH in dwarf mice were studied using homologous radioimmunoassays. Blood samples from adult male and femal dw/dw mice were collected by orbital puncture and by decapitation. Compared to related normals (+/?), pituitary concentrations of GH and prolactin were very low in dw/dw mice, the concentrations of prolactin being more scarce than those of GH. Prolactin and GH concentrations were also lower in sera of dw/dw mice, but the relative differences appeared sex-dependent: serum GH was more reduced in males than in females while serum prolactin was more depressed in females. The data confirm earlier indications of deficiencies in the circulating levels of prolactin and GH in dwarf mice and suggest that the hypoactivity of these hormones may be crucial to some of the anomalies found in this mutant.


Effects of spreading depression on stress-induced changes in plasma prolactin and LH. Female rats rendered "pseudopregnant" by treatment with PMS and hCG and ovariectomized rats injected with estradiol and progesterone (OVX-E2-P) were subjected to cortical spreading depression (SD). Within 7-10 min under ether anesthesia in a stereotaxic instrument a frontal craniotomy was performed and a cotton ball saturated with physiological saline (control) or 25% KCl was applied to the exposed dura, covered with dental cement and skin sutured. The animals were then placed in separate containers in an isolated room and decapitated for collection of trunk blood at 0, 15, 30, or 60 min after surgery. In PMS-hCH saline-treated control animals, prolactin levels had dropped by 15 and 30 min when compared with the zero-time values but by 60 min had increased significantly above the 30-min level. At that time (60 min), prolactin values in the KCl group were significantly lower than in the controls. Corticosterone levels were high at both 15 and 60 min in control and KCl groups. In OVX-E2-P control animals, plasma prolactin levels also rose at 60 min compared with 15- and 30-min samples and at 60 min were significantly higher than in the KCl group. In control animals, LH levels were lower at 15 and 60 min than at zero time, but they remained unchanged in the KCl group. The dato are interpreted as indicating that cortical SD suppresses the stress responses observed in saline-treated control animals.


Effects of dietary carbohydrate source on growth, plasma metabolites and lipogenesis in rats, pigs, and chicks. Rats, chicks, and pigs were fed diets containing fructose or glucose. Plasma triglyceride levels were elevated in rats but not in chicks or pigs fed diets containing fructose. The rate of fatty acid synthesis in rat liver but not in chick liver was elevated when fructose-containing diets were fed. Conversely, the rate of fatty acid synthesis in rat adipose tissue but not in pig adipose tissue tended to be depressed when fructose-containing diets were fed. These results indicate that there are species-specific as well as organ-specific metabolic responses to various dietary carbohydrates.


Spermatogenic arrest produced in the adult male rat by 19-norspiroxenone, a potent anti-estrogen. 19-Norspiroxenone, a potent anti-estrogen with no known estrogenic action, produces a striking arrest of spermatogenesis in the early stages of meiosis in the adult male rat with a complete block of fertility.


Effect of phenformin on the response of plasma intestinal glucagon-like immunoreactivity (GLI) to oral glucose in gastrectomized subjects. The effect of phenformin (DBI) on the plasma intestinal glucagon-like immunoreactivity (GLI) and pancreatic glucagon (IRG) responses to oral and intravenous glucose loads were studied in 26 gastrectomized subjects, using a cross-reacting and an IRG-specific anti-serum. The drug produced no significant changes in fasting GLI and IRG levels. Thirty minutes after oral glucose alone, the total GLI level rose to a peak of 1.55 +/- 0.17 ng/ml in the untreated subjects and to a maximum level of 1.67 +/- 0.18 ng/ml in the DBI-pretreated subjects. However, the mean GLI levels obtained 120 and 180 min after oral glucose were significantly higher after treatment with DBI. The blood sugar and IRI responses to oral glucose were lowered significantly by DBI pretreatment. DBI did not alter the glucose, IRI, IRG and GLI response to intravenous glucose. These results suggest that the release of intestinal GLI is not related to the intestinal absorption of glucose.


Ontogeny of Fc and complement receptors in mouse embryonic tissues. Mouse embryonic tissues were tested for their ability to form rosettes with EA and EAC. It was found that as early as the day after implantation (day 6) a small percentage of cells was able to bind both. After the 8th day of gestation the development of rosette-forming cells paralleled that of the immune system. However, the detection of Fc and C'3 receptors on cells at least 2 days prior to the earliest known demonstration of lymphoid stem cells suggests that they may be expressed on cells other than those of the immune and phagocytic series.


Effects of diazepam on the isolated chick embryo heart. Diazepam decreased the rate and amplitude of contraction in isolated embryonic chick hearts in a dose-dependent manner in both the noninnervated hearts obtained from 4-day-old embryos and the innervated hearts from 7-day-old embryos. The concentration of diazepam necessary to reduce the heart rate and contractile amplitude to 50% of the control values was about 1 X 10(-4) M. Concentrations less than 1.0 X 10(-5) M had no detectable depressant effects. Prior administration of atropine did not alter the depression induced by diazepam. Norepinephrine was able to stimulate the amplitude of contraction in the diazepam-depressed heart while atropine was without effect. The vehicle used in the clinical injectable preparation of diazepam had no depressant effects. The mechanism of action of the diazepam-induced depression on the isolated embryonic chick heart may be a direct depression of the myocardium.


Effects of triamcinolone and of desoxycorticosterone on renal function in sheep. Sheep were treated for 10 or 17 days with triamcinolone acetonide, 0.1 mg/kg body weight/day, or desoxycorticosterone acetate, 0.1 mg/kg body weight/day, and the results of renal function studies during hydropenia and mannitol diuresis were compared with respective control periods. GFR was increased and urine concentration was unimpaired by treatment with triamcinolone. A consistent decrease in mannitol-induced Na excretion was observed, but with large variations in the mean change, in triamcinolone treatment periods. Treatment with desoxycorticosterone resulted in an increased GFR but with impaired urine concentrating capacity. The hypokalemia produced by desoxycorticosterone was not accompanied by an increase in urinary K excretion. During mannitol diuresis in sheep treated with desoxycorticosterone, there was a significant decrease in Na excretion when compared with control periods.


Steroidogenesis of the fetal adrenal gland in vitro: influence of metopirone applied in vivo and in vitro. In vitro conversion of 4-14C-progesterone into corticosteroids in the adrenal glands of rat fetuses treated with Metopirone (Su 4885) on the last day of intrauterine development was studied. After a 1-hr incubation of the adrenal glands of fetuses injected with Metopirone, hydroxylation of progesterone into corticosterone (B), 18-hydroxycorticosterone (18-OH-B) and 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) decreased and the synthesis of 11-deoxycorticosterone increased. Following preincubation of the fetal adrenal glands and 1-hr incubation with Metopirone, hydroxylation of progesterone into DOC increased and the synthesis of B decreased. Preincubation and a 2-hr incubation with Metopirone caused a decrease in the synthesis of B, 18-OH-B and 18-OH-DOC and an increase in DOC. The results constitute direct evidence of the ability of the fetal adrenal glands to synthesize all corticoids and indicate that most probably corticoids are synthesized by the fetal adrenal glands in the same way as in the adrenals of adult animals.


Reversal of chronic renal hypertension: role of salt and water excretion. Rats with chronic one-kidney Goldlatt hypertension underwent an unclipping procedure with and without maintenance of body fluid volume through administration of iv salt solution. The blood pressure declined equally in the two groups. It is concluded that external loss of salt and water is not the mechanism for the reversal of this form of hypertension.


Effect of ouabain on adrenal potassium balance in sheep. A previous study revealed that ouabain caused a marked decrease in aldosterone secretion, but the adrenal K status was not clear from those data. The present study investigated the magnitude and time course of change in adrenal K balance when ouabain was administered into the adrenal arterial supply of the in situ adrenal of conscious sheep. Ouabain at an adrenal arterial plasma concentration of approximately 2.4 X 10(-4) M produced a striking negative adrenal K balance within 10 min of beginning the infusion. The adrenal continued to lose K during the 30-min infusion and for 30 min thereafter. The mean total K loss was 42.3 +/- 7.9 muequiv/adrenal (n = 11). Thirty minutes after ending the ouabain infusion, the adrenal began taking up K but had not recovered its normal K complement by 60 min.


Effects of proteolytic encymes on uremic serum inhibition of hepatic and renal transport functions. Dialysates of rat uremic serum were incubated with Pronase, Carboxypeptidase A, Leucine Aminopeptidase, or Trypsin to investigate whether these enzymes might destroy the inhibitory effects of the dialysates on the uptake of paraaminohippurate by rat renal cortical slices or the uptake of purines by rat liver slices. Of these enzymes, Pronase produced the greatest destruction (63.2 +/- 4.5%) of the inhibitory action on renal transport, with a much smaller destruction (17.8 +/- 2.1%) of the inhibitory effect on hepatic transport.


Spin label studies on rat liver plasma membrane: calcium effects on membrane fluidity. Spin-labeled stearic acid probes were incorporated into rat liver plasma membrane purified by a zonal centrifugation procedure. Temperature effects on the order parameter calculated from the spectra indicated the possible presence of a membrane phase transition at 20 degrees, in agreement with earlier studies in other systems. Addition of Ca2+ (1.96 mM) at 37 degrees increased the order parameter by 6.0 +/- 0.7%, suggesting a Ca2+-mediated decrease in membrane fluidity.


Effect of rifamycin and tilorone derivatives on Friend virus leukemia in mice. Several derivatives of rifamycin, and analogs of the tilorone-fluoranthene group were tested for inhibition of splenic enlargement in Friend virus leukemia. At least three members of the rifamycin group caused significant inhibition (31-49%) as did at least three members of the tilorone group (32-48%). These six compounds are among those found by others (6, 7) to be most inhibitory in vitro to the RNA-directed DNA polymerase of oncornaviruses. However our studies do not furnish direct evidence for or against a role of inhibition of the viral enzyme in the suppression of splenomegaly. None of the agents was as effective as methotrexate, which caused 90-92% inhibition. The activity of five of the agents was reduced, rather than enhanced by the injection of adjuvants (M. butyricum and pertussis vaccine). Three of the agents had a subtractive, rather than an additive effect on the inhibition caused by methotrexate alone.


Enhanced plutonium absorption in iron-deficient mice. The total body burden of plutonium 24 or 96 hr following a single gastric intubation was approximately fourfold greater in iron-deficient than in iron-replete mice. There was also a more rapid translocation of plutonium from soft tissues to bone in the iron-deficient mice by 96 hr after gavage. In the iron-replete group only liver concentrations of plutonium increased during the corresponding time period.


Actions of a leukocytic inflammatory substance on isolated tissue responses. LIS had no action on the mechanical activity of isolated cat vascular, intestinal smooth, or cardiac muscle. No effect on platelet aggregation was observed, and PGF2alpha activity was absent in LIS preparations. Isolated lysosomal enzyme release was increased significantly when LIS was added to the incubation medium. This action may help to explain the inflammatory action of this naturally occurring material found in the inflamed synovial fluid of the canine knee joint.


The response of blood flow to altered perfusion pressure in canine adipose tissue. It is concluded that subcutaneous adipose tissue autoregulates its blood flow only weakly or not at all in the range of perfusion pressures employed in our studies. Instead, these experiments demonstrate that when perfusion pressure is altered in the fat pad, vascular resistance must change in an opposite direction since there is little tendency for the flow to return to control values. Therefore, the vascular bed is responding passively. Furthermore, there was little evidence of autoregulation in denervated tissues indicating that the extrinsic neural control does not mask an underlying ability to modulate flow.


Renal function and metabolism after relief of unilateral ureteral obstruction. In summary, the present studies indicate the presence of both functional and structural abnormalities in the postobstructed kidney involving mitochondrial integrity and deranged intermediary metabolism. It is suggested that some of these metabolic changes may account in part for the functional abnormalities observed in vivo.


Utilization of yeast polyglutamate folates in man. Ingestion by healthy humans of small amounts of polyglutamate folates from yeast, equivalent to 300 mug of monoglutamate folate and containing 30 mug of "free folate," resulted in an appreciable elevation of the serum folate corresponding to 300 mug of synthetic pteroylmonoglutamate (PGA). Ingestion of higher amounts of polyglutamate folate did not result in higher serum folate elevations than did 300 mug. It is concluded that small amounts of polyglutamate folate from yeast are fully utilized, presumably by deconjugation in the gut prior to absorption. The relative ineffectiveness of larger doses of polyglutamate folates from yeast may be due to limiting conjugase activity in the gut, unfavorable conditions for its activity (such as unsuitable pH) or to an inhibitor of the enzyme present in impure preparations.


Resistance of W/Fu rats to adrenal regeneration hypertension. The procedure for producing adrenal regeneration hypertension did not cause an increase in the systolic blood pressure of W/Fu animals. The regenerating adrenal gland in W/Fu animals was not restored to normal; reduced numbers of mitochondrial cristae were seen and the mitochondria were smaller in size; regeneration was complete in Sprague-Dawley rats of the Holtzman strain and there was a severe form of hypertensive, cardiovascular disease.


Water diuresis from clonidine (catapres). The renal hemodynamic and excretory effects of clonidine were tested in two groups of dogs. In one group, the drug was given directly into the renal artery at a rate of 1.2 mug/min and resulted in a significant decrease of the effective renal plasma flow (ERPF) in both kidneys, an increase in filtration fraction (FF), urine volume (UV), and free water clearance (CH2O) and had no effect upon the glomerular filtration rate (GFR), osmolar clearance (Cosm) and the excretion of sodium (UNaV), chloride (UC1V), potassium (UKV), calcium (UCaV) and phosphorous (UPO4V). No unilateral effect was appreciated. In the second group of animals it was given intravenously at a rate of 12.0 mug/min and resulted in a significant decrease of ERPF, UNaV, UC1V, and increase in FF, UV, and CH2O) but had no effect upon GFR, Cosm, UKV, UCaV and UPO4V. Systemically it decreased heart rate (H.R.) and respiratory rate (R.R.) in both groups of animals; it increased blood pressure (BP) in Group 1 and had no effect on BP in Group 2.


N-hydroxy-2-fluorenylacetamide, an active intermediate of the mammary carcinogen N-hydroxy-2-fluorenylbenzenesulfonamide. The mechanism of mammary carcinogenesis by N-hydroxy-2-FBS, a highly potent mammary carcinogen for the female rat by ip administration, has been investigated. Previous work in vivo indicating hydrolytic cleavage of the nitrogen-sulfur bond has been confirmed with the use of sonicates of mammary gland. One of the products of the hydrolysis was N-hydroxy-2-FA identified by its conversion to 2-FA. Since carcinogenicity tests by local application showed that N-hydroxy-2-FA was not carcinogenic for the mammary gland, desulfonylation of N-hydroxy-2-FBS by mammary gland does not account for mammary carcinogenesis. N-Hydroxy-2-FBS applied directly to the mammary gland was not carcinogenic and 2-nitrosofluorene, the product of the spontaneous decomposition of N-hydroxy-2-FBS, exhibited only weak carcinogenicity upon local application. In contrast, N-hydroxy-2-FAA, a urinary metabolite of N-hydroxy-2-FBS, was highly carcinogenic by local application and very likely mediates the action of N-hydroxy-2-FBS. A metabolic pathway for the conversion of N-hydroxy-2-FBS to N-hydroxy-2-FAA is presented. This pathway involves the intermediate formation, by mammary gland or liver, of N-hydroxy-2-FA. The site of the subsequent acetylation of the hydroxylamine is unknown at present although the mammary gland appears to be excluded.


Maintenance of sexual behavior in castrate male SW mice using the anti-androgen, cyproterone acetate. The present study was designed to test the hypothesis that cyproterone acetate (C) might selectively block the actions of dihydrotestosterone (D) and via this action, function as an anti-androgen in male sexual behavior. Sexually experienced male SW mice, a strain previously shown to respond to D following castration, were divided randomly into six groups. Beginning on the day after castration, animals received SC injections for 21 days of either testosterone (T), (D), (C), (T+C), (D+C) or vehicle (V). C was found to significantly reduce seminal vesicle and body weights in all androgen treated groups. There was no evidence to support the contention that C selectively blocks the action of D. To the contrary, in sex tests C maintained palpations, thrust mounts, with intromissions and mounts with ejaculations. Indeed, only animals receiving C alone or in combination with T and D exhibited ejaculations throughout the testing. These results suggest that in the SW mouse, C can work like an androgen in the maintenance of male sexual behavior.


Effects of alpha methyl-para-tyrosine on the recall of a passive avoidance response. Treatment with alpha methyl-para-tyrosine 4 hr before training on a passive avoidance task altered recall in mice tested 24 hr after training. The observed alterations were dependent on the intensity of the footshock used during training. Retention of the avoidance habit was reduced by drug treatment when a footshock of 1.6 milliamperes (mA) was employed, while retention by drug-treated mice was enhanced when a footshock of 0.16 mA was used. No significant differences in retention were noted when a footshock of 0.8 mA or no footshock was employed. These results could not be explained on the basis of drug-induced changes in activity or sensitivity to footshock, of to state-dependent learning.


Alpha-methyltyptamine blocks facilitation of lordosis by progesterone in spayed, extrogen-primed rats. Alpha-methyltryptamine, a drug which stimulates serotonergic receptors in the central nervous system, inhibited the induction of sexual receptivity in spayed female rats by estradiol benzoate and progesterone. The drug had no effect on the sexual receptivity induced by estradiol benzoate alone. These data are consistent with the hypothesis that progesterone facilitates lordosis in estrogen-primed rats by inhibiting a serotonergic system in the brain. The data also suggest that estradiol and progesterone act on separate neurochemical systems to induce estrous behavior in rats.


Glucoprivic (2DG) eating in rats despite knife cut induced hyperphagia. Two weeks after parasagittal hypothalamic knife cuts, baseline eating was elevated and 300 mg/kg 2 deoxy-D-glucose (2DG) did not further stimulate food intake. Five weeks postoperatively the food intake baseline had fallen and an eating response to 300 mg/kg 2DG was now seen (p less than 0.005). In this delayed (static) phase intake was also stimulated by 150 mg/kg 2DG (p less than 0.005). 600 mg/kg did not stimulate intake in the lesioned rats at any time, although sham-operated rats always responded positively to this high dose. In conclusion, the neural substrate damaged in hypothalamic hyperphagic rats does not appear to mediate eating in response to glucopribation. The eating response is masked by high baseline intake in the dynamic phase, but reappears in the static phase.


Influence of apomorphine on brain serotonin turnover rate. Apomorphine (5.0 mg/kg) accelerated the disappearance of 5-HIAA from the brain of pargylinepretreated rats as well as depletion of brain 5-HT caused by inhibition of its synthesis. The latter effect has been abolished by spiroperidol. The results obtained suggest that apomorphine increases the 5-HT turnover rate, secondary to the stimulation of central dopamine receptors.


Suppression of conditioned drinking by taurine and related compounds. Mice were conditioned to respond for water reinforcements on a FR-5 schedule. Taurine, injected intraperitoneally at doses of 9.0, 13.8, and 21.3 mmole/kg 30 min prior to the experimental session, produced a dose-related decrease in both the initial response rate and total number of reinforcements received by mice deprived of water for 24 hr. The structural analogues of taurine (aminomethanesulfonic acid, 3-aminopropanesulfonic acid, beta-alanine, cysteamine, and glycine) also produced a hypodipsia. Doses of taurine which produced depression of responding for water reinforcements were used which produced no suppression of spontaneous motor activity, rotarod performance, Sidman avoidance, or shuttle-box avoidance. After intraperitoneal injection, the concentration of taurine increased in the hypothalamus and medulla, but not in other brain areas. We suggest that taurine might be acting by specifically depressing areas of the hypothalamus which stimulate drinking.


Disinhibitory effects of intrahippocampal of intrahypothalamic injections of anticholinergic compounds in the rat. The effects of intrahippocampal or intrahypothalamic injections of anticholinergic compounds on operant responding were observed in a multiple schedule paradigm consisting of reinforced, punished, and nonreinforced components and on a punished ingestive passive avoidance task. The pattern of results suggests that cholinergic components of the hippocampus and  hypothalamus mediate responding suppressed by nonreinforcement but not by punishment. The data are discussed with reference to Carlton's proposed central cholinergic inhibitory mechanisms.


Dissociation of disinhibitory effects of scopolamine: strain and task factors. In 3 experiments it was observed that 3 strains of mice (A/J, DBA/2J and C57BL/6J) differing in activity exhibited comparable levels of spontaneous alternation, and that scopolamine differentially affected activity in the strains, but uniformly eliminated shock-induced suppression and spontaneous alternation behavior. Data are discussed in terms of the relationship between activity and spontaneous alternation. It was suggested that scopolamine exerts its effects on spontaneous alternation via the effects on acetylcholine activity, independent of any effects on general activity levels.


Brain gangliosides: increased incorporation of (1- 3H) glucosamine during training. The incorporation of (1-3H)glucosamine into biochemical fractions of brain was studied in mice trained in a conditioned avoidance jump-up task, in mice yoked to the trained animals, and in undisturbed mice in their home cages. The (3H)glucosamine was injected subcutaneously 15 min before 15 min of training, and the mice killed after a total pulse time of one hour. There was a consistent and significant increase of about 21 percent of the incorporation of the 3H into the brain ganglioside fraction when trained mice were compared with quiet mice. This increase was not observed in any of the other chemical fractions studied, including the total chloroform-methanol-soluble compounds, the non-ganglioside lipids, and the chloroform-methanol-insoluble compounds (radioactivity principally in glycoprotein). Yoked mice showed an intermediate level of incorporation, exhibiting only a 12 percent increase in the ganglioside fraction. When the individual ganglioside species were analyzed by thin-layer chromatography the changed incorporation was not specific for any ganglioside species.


Intracranial alpha-methyl-P-tyrosine and response for electrical brain stimulation. Chemitrodes, allowing electrical stimulation of the brain at the same site, were implanted in 18 rats aimed at the medial forebrain bundle of the lateral hypothalamus. After these animals were trained to bar-press for electrical brain stimulation, the crystalline form of alpha-methyl-paratyrosine (AMPT), an inhibitor of catecholamine synthesis, was administered intracranially, and change in response rate was noted. Intracranial tyrosine administration was also tested as a control study. It was found that AMPT depressed rate of response of intracranial self-stimulation, whereas tyrosine administered intracranially exhibited no such effects. This result lends support to data reported in the literature on the use of AMPT administered intraperitoneally or orally, and suggests a noradrenergic or dopaminergic system of reward in the lateral hypothalamus.


d-Amphetamine: disruptive effects on the long-term store of memory and proactive facilitatory effects on learning in inbred mice. Male, C57BL/6J mice were given two daily trials on an appetitively-motivated successive brightness discrimination maze problem; they then received daily intraperitoneal injections of saline or d-amphetamine for 5 days. When trained again in the maze, mice in all d-amphetamine groups tended to display impaired retention: retention was significantly impaired in the 2.0 mg/kg group. Naive mice were treated exactly as were the pretrained mice except that they received no initial maze training prior to drug treatments. Mice in all naive d-amphetamine groups tended to display enhanced acquisition of the maze problem: acquisition was significantly enhanced in the 1.0 mg/kg groups. These results could not be explained as effects of d-amphetamine on attentional, motivational or other performance factors.


Propranolol, 14C-morphine accumulation and avoidance: peripheral and central variables. Pretreatment with propranolol HCI resulted in a substantial reduction in the amount of 14C-morphine found in blood plasma, neostriatum plus adjacent tissue, pons-medulla, midbrain, cerebral cortex and cerebellum 25 min after IP injection of the labelled morphine. Previous observations, demonstrating attenuation of behavioral effects of morphine following pretreatment with propranolol, might have been due to a decrease in peripheral and/or central levels of morphine. However, when morphine HCI (10-20 MUM) was administered via intraventricular cannulae following pretreatment with propranolol given intraperitoneally in rats performing free operant (sidman) avoidance, the anti-avoidance effects of the opiate were also attenuated. Hence, previous results cannot be attributed solely to reduced concentration of morphine at CNS site(s) of action.


Lesions in Guddesn's tegmental nuclei produce behavioral and 5-HT effects similar to those after raphe lesions. Lesions largely restricted to the dorsal and ventral tegmental nuclei of Gudden (GTN) produced several effects similar to those seen after midbrain raphe lesions. GTN lesions significantly reduced the 5-hydroxytryptamine (5-HT) concentration of the diencephalon (31 percent), hippocampus (59 percent), and remaining portion of the telencephalon (29 percent). Striatal 5-HT, however, was not affected. GTN lesions enhanced activity in an enclosed field and facilitated two-way avoidance acquisition. Pain sensitivity as measured by the flinch-jump method was not affected. These results suggest that the GTN may be the origin of ascending 5-HT fides and may be involved in the regulation of activity level and the adaptation of an animal to aversive situations. Thus, some of the behavioral and 5-HT effects of lesions in the midbrain raphe nuclei may be due to their involvement of the GTN and associated pathways.


Opposite effects of intraventricular serotonin and bufotenin on rat startle responses. Rat startle responses to air puffs were monitored in a stabilimeter during the intraventricular infusion of various doses of 5-hydroxytrptamine (5-HT) or the putative hallucinogenic congener of 5-HT, 5-hydroxy-N, N-dimethyltrytamine (5-HDMT) or saline. Qualitativity opposite effects were observed, with 5-HT producing a dose-dependent decrease in responsivity and 5-HDMT increasing the magnitude of startle responses. No specific effects of either compound could be demonstrated on the presumably separable processes of sensitization and habituation. The results are discussed in the context of a central serotonergic system which facilitates behavioral inhibition and which is antagonized by indoleamine hallucinogens.


Tolerance and cross-tolerance to the effects of amphetamine, methamphetamine and fenfluramine on milk consumption in the rat. It has been reported that rats develop tolerance to the milk intake suppressant effects of d-amphetamine, d-methamphetamine, and d, l-fenfluramine. However, it has been hypothesized that the mechanism of action of fenfluramine is different from that of the other two drugs. In the present experiment, rats were given one of these 3 phenylethylamine derivatives each day until tolerance developed to the suppression of milk intake. A second of these drug s was then substituted and milk intake measured. There was cross-tolerance to the drug-induced suppression between d-amphetamine and d-methamphetamine, but not between d-amphetamine and d,l-fenfluramine. The lack of cross tolerance suggests a different mechanism of action for these drugs.


Radioautographic localization of radioactivity in rat brain after intracarotid injection of 125I-alpha-melanocyte-stimulating hormone. 125I-alpha-melanocyte-stimulating hormone (MSH) was injected into the carotid artery of the rat and the radioactivity localized by radioautography. Radioactivity in the areas surrounding the ventricles and blood vessels after administration of 125I-alpha-MSH but not 125I-luteinizing hormone indicated passage of labeled material through the blood brain barrier. A specific concentration of radioactivity was found in the striatum and reticular nucleus of the thalamus. This localization, particularly in the thalamus, could be correlated with the previously reported effects of MSH on the brain of animals and man.


Cafeteria behavior in the rat after hypothalamic cholinergic and adrenergic stimulation. Norepinephrine, carbachol, or placebo was micro-injected into the perifornical region of the rat hypothalamus, via stereotaxically implanted cannulas. Ingestive behavior was observed in the hour after injection in a cafeteria situation in which water, milk, mash, powdered food, and lab chow were all freely available. After adrenergic stimulation, animals ingested significant amounts of mash only; after cholinergic stimulation, animals ingested significant amounts of water and milk, but water was significantly preferred to milk. These findings are seen as providing further support for the behavioral specificity of direct chemical stimulation of the brain, and as casting serious doubts on the interpretation of milk-ingestion as eating behavior.


Effect of daily saline, drug or blank injections on the susceptibility to the convulsant effect of drugs. The daily intraperitoneal injection to rats of doses of metrazol (30 mg/Kg), strychnin sulfate (1 mg/Kg) or picrotoxin (1.2 mg/Kg) that were initially subconvulsant, caused after a number of days which varied with the drug, clonic convulsions in a high percentage of the animals. However, after 18 daily injections of saline there was a similar increase of seizure susceptibility to the 3 drugs. The daily handling of rats as for injection, either followed or not by actual abdominal pricking (blank injection), had a similar though less pronounced effect. In animals that were housed in the same room where the others were tested, but which were not handled, the above mentioned doses of metrazol, strychnine and picrotoxin had no convulsant effect. These results indicate that the procedure of submitting rats to daily intraperitoneal injections is not as unconsequential as is usually thought to be, and that it may induce neurological changes.


A mild restraint and chronic venous catherization system for cats. An inexpensive and minimally restrictive restraint system for cats is described which protects any temporary connections to chronic physiological implants during recording sessions and permits free movement of the head and extremities for behavioral studies. Procedures for constructing and implanting a chronic indwelling venous catheter device are also described which allows, directly with a syringe of via a connector system, for intravenous drug infusions in cats. These catheters have remained intact and relatively free of infection for a period of months before tissue rejection begins at the site of the subcutaneous implant.


Effect of calcium chloride on some metabolic actions of certain antidiabetic drugs in normal and alloxanised rabbits. Calcium chloride increased the liver insulinase activity (LIA) in normal rabbits. No significant changes were noted in the plasma insulinlike activity (PILA), serum zinc level (SZ), and pancreatic zinc content (PZ). Insulin elevated PILA, SZ and PZ but did not affect LIA. Calcium chloride enhanced the effect of insulin on PILA, SZ and PZ. However, insulin did not affect the action of calcium chloride on LIA. Tolbutamide raised PILA, inhibited both LIA and SZ but did not affect PZ. Calcium chloride produced no change in the action of tolbutamide on PILA. On the other hand, tolbutamide prevented the rise of PILA obtained by calcium chloride. PZ was unaltered with calcium chloride and tolbutamide combination. Phenformin increased PILA, LIA, SZ and PZ. When it was given with calcium chloride no further changes in PILA and PZ were observed. The elevation of SZ was abolished but the rise of LIA was synergized. In alloxanized rabbits, LIA was decreased by calcium chloride. No changes were found in PILA, SZ and PZ. Insulin elevated PILA, LIA and SZ although it reduced PZ. Calcium chloride stimulated insulin effect on PILA, did not affect its action on SZ or PZ, and antagonized its effect on LIA. Tolbutamide increased LIA and SZ but did not affect PILA or PZ. Calcium chloride could not change the effect of tolbutamide on SZ or PILA although it could abolish the action of this drug on LIA and PZ. Phenformin significantly lowered PILA, LIA and PZ but raised SZ. Calcium chloride combination with phenformin produced a further decrease in LIA but no other changes in PIAL, SZ or PZ were recorded.


Reversal of the 6-hydroxydopamine-induced suppression of a CAR by drugs facilitating central catecholaminergic mechanisms. The intraventricular injection of 6-hydroxydopamine (200 mug) blocked a previously learned conditioned avoidance response (CAR) in rats. The administration of NE, DOPA, amphetamine, phenelzine, desipramine and clonidine induced the reappearance of the CAR. These results are in agreement with current hypotheses on the mechanism of action of 6-hydroxydopamine on the central nervous system.


Effects of delta9-tetrahydrocannabinol on active avoidance acquisition and passive avoidance retention in rats with amygdaloid lesions. Delta9-Tetrahydrocannabinol was administered to rats with basolateral amygdaloid lesions, control rats, and normal rats in doses of 0.75, 1.5, and 3.0 mg/kg i.v. They were trained in a one-session two-way active avoidance task. Delta9-Tetrahydrocannabinol increased the percentage of avoidance and the intertrial crossing rates in all groups, regardless of lesion treatment. Rats with basolateral amygdaloid lesions were not different from controls on any measure. In a second experiment, delta9-tetrahydrocannabinol was administered to rats with basolateral amygdaloid lesions and control rats in doses of 0.75 and 3.0 mg/kg 24 h after learning of a one-trial passive avoidance task, and retention was measured. No differences were found as a function of drug treatment or lesion condition. It was concluded that the basolateral amygdala is not a necessary condition for the action of delta9-tetrahydrocannabinol on active avoidance acquisition, that the drug has no effect on passive avoidance retention, and the basolateral amygdala is not necessary for two-way active avoidance acquisition or passive avoidance retention. Active avoidance results are discussed in terms of a possible relationship between delta9-tetrahydrocannabinol, ACTH, and avoidance learning.


Involvement of central dopamine in the hyperthermia in rats produced by d-amphetamine. The effect of amphetamine on the body temperature was studied in 6-hydroxydopamine and pimozide pretreated rats. Amphetamine alone (1, 2.5 and 5 mg/kg) produced a fairly dose-dependent increase in body temperature. The effect was almost totally antagonized by pimozide, and also reduced after pretreatment with 6-hydroxydopamine. These results are discussed with regard to the possible role of central dopamine in mediating amphetamine-induced hyperthermia in rats.


Quantitative measurement of delayed hypersensitivity in the guinea pig paw. To facilitate quantitative measurement of a delayed hypersensitivity reaction, a tuberculin reaction was produced in the paws of sensitized guinea pigs and the resulting edema estimated by one of the usual techniques. The edema formation was shown to be an expression of the delayed hypersensitivity reaction. Optimal conditions for this reaction were assessed. This model may be used for testing the influence of drugs on delayed hypersensitivity reactions.


Effect of prostaglandin-E2 on myoelectrical and mechanical activity of totally isolated, ex-vivo-perfused, canine stomach. This study was concerned with the effects of prostaglandin-E2 (PGE2) on myoelectrical and mechanical activity of the isolated, homologous perfused canine stomach. A flash injection of 25 mug of PGE2 into the gastric artery led to production of premature control potentials, uncoupling of electrical control activity (ECA) and to a weak mechanical response of short duration. After vagal stimulation of the nerve of Latarjet, or after flash injection of pentagastrin (2.5 mug) or of methacholine (5 mug), similar changes in ECA were observed, but mechanical response corresponding to antral contractions was very pronounced. Prolonged infusion of PGE2 (500 mug/h) induced a marked increase of ECA frequency. A similar effect on ECA frequency was observed during infusion of pentagastrin (32 mug/h). Infusion of PGE2 abolished, but infusion of pentagastrin stimulated, mechanical response. Effects of a flash injection of PGE2 on electrical activity were reduced by hexamethonium and abolished by tetrodotoxin and atropine. The action of the blocking agents on PGE2-induced changes in ECA was similar to the action of these blockers on gastric myoelectrical activity, stimulated vagally or by injection of pentagastrin and methacholine. Infusion of PGE2 induced a marked reduction in gastric peripheral vascular resistance, but no time-correlation between hemodynamic effects of PGE2 and its action of gastric musculature was noted.


Ethanol narcosis in mice: effects of L-dopa, its metabolites and other experimental variables. Ethanol-induced narcosis was studied in mice as a function of pretreatment with L-dopa and its metabolites administered alone or in conjunction with Ro-4-4602, an inhibitor of aromatic-L-amino acid decarboxylase. These studies suggest that L-dopa prolongation of ETOH narcosis in mice may be due to formation of one or more toxic metabolites rather than to a direct involvement of dopamine. Ethanol narcosis also was studied in mice as a function of age of animals, concentration of ETOH, ambient temperature and saline pretreatment. Since manipulation of these variables produced alterations in ETOH narcosis, the need for their rigid control is indicated.


Centrally induced hypotension by 2-(2,6-dichlorophenyl)-5,6-dihydroimidazo (2,1-b)-thiazole fumarate (compound 44-549). The experimental compound 44-549 = 2-(2,6-dichlorophenyl)-5,6-dihydroimidazo (2,1-b)-thiazole fumarate was tested in chloralose-anaesthetized cats. Low doses of compound 44-549 showed a much more pronounced hypotensive effect when injected into the left vertebral artery than upon intravenous administration. The compound possesses central hypotensive activity, which could be blocked by yohimbine, administered via the vertebral artery. Central alpha-adrenoreceptors are probably involved. Compound 44-549 resembles clonidine both pharmacologically and chemically. It is somewhat less potent.


Accumulation of norepinephrine (NE) by rat organs in vivo. In anesthetized rats intravenously infused, norepinephrine (NE) was accumulated by the heart, the spleen and the lung in a dose-related manner. With the lower dose of NE (2.5 mg/kg) the organ/blood ratios were more than unity and were generally greater than with higher doses (5 and 10 mg/kg), indicating that accumulation occurred by active uptake. Nialamide and pyrogallol treatment increased accumulation in the three organs. In animals receiving nialamide and pyrogallol treatment, normetanephrine (uptake2 inhibitor) and desmethylimipramine (uptake1 inhibitor) inhibited accumulation in all the organs and the entire accumulation of NE could be ascribed to uptake1 and uptake2 processes. In these animals, phenoxybenzamine and bilateral adrenalectomy inhibited and enhanced, respectively, the accumulation in the heart and the spleen only. NE accumulated in hearts of animals in vivo could be partly washed out by perfusion with NE-free medium in vitro. Washout was prevented by normetanephrine, indicating that this effect was not a passive diffusional leakage.


An intra-oral telemetry system for the continuous recording of vertical jaw movement. Continuous measurement of the separation between upper and lower dental arches, the so-called interocclusal distance (10D), is of interest in dentistry. Criteria for making such measurements by radio telemetry are discussed. It is concluded that a transmitter small enough to fit in a molar tooth gap is necessary in order to minimize interference with normal function; other design factors are related to obtaining adequate frequency stability, on which measurement accuracy depends. A transmitter fulfilling these requirements is described which sensed the instantaneous value of 10D by the frequency change produced when a metallic object (dental filling, gold crown, shorted turn of wire or piece of ferrite) in one dental arch moved relative to the transmitter in the other. Errors due to lateral and protrusive jaw movements were measured. Careful design and the use of high grade ceramic chip capacitors resulted in a transmitter of good frequency stability (+/- 0.03% in 10 h, +/- 0.02%/degrees c) and small size (10 X 7 X 5 mm). An example is given illustrating 10D movements due to swallowing, speech and respiration.


Skin temperature over an artificial heat source implanted in man. The medical application of infrared thermography makes use of the skin temperature as an indication of an underlying pathological process. In order to study the relation between the heat production from a source in living tissue and the overlying skin temperature, artificial heat sources were implanted subcutaneously in human volunteers. The experimental results show that a detectable surface temperature increase over the heat sources presupposes high power output or superficial implantation. The effect of forced convective heat loss from the skin surface and lowered ambient temperature was studied. Forced convection markedly decreased the temperature contrast. An implicit conclusion from experimental and theoretical work is that a localized 'hot spot' can only exceptionally be attributed to metabolic heat production conducted to the skin surface from a buried pathological process. The thermal pattern over a breast tumour, a septic or aseptic inflammation or a tissue injury mainly reflects the vascular reaction.


The simulation of skin temperature distributions by means of a relaxation method. To solve the differential equation for the heat in a two-layer, rectangular piece of skin tissue, a relaxation method, based on a finite difference technique, is used. The temperature distributions on the skin surface are calculated. The results are used to derive a criterion for the resolution for an infrared thermograph in a specific situation. A major limitation on the resolution in medical thermography is given. As an example of the power of the model, the sensitivity of the temperature profiles for variations of the layer thickness is determined.


The calculation of charged particle fluence and LET spectra for the irradiation of biologically significant materials by neutrons. As a preliminary step to evaluating recent theories concerning the biological effect of ionizing radiation, the charged particle fluence distributions and the dose distribution in linear energy transfer have been computed analytically for targets of biological and dosimetric interest irradiated by neutrons. Specifically, 14.7 MeV neutrons, the 252Cf neutron spectrum and a cyclotron generated neutron spectrum are considered to irradiate water, tissue-equivalent plastic and standard man tissue and results are given for all these cases. From a knowledge of the target composition, and the cross-sections and kinetics of all the possible neutron induced reactions in the elements hydrogen, carbon, nitrogen and oxygen, the secondary particle spectrum is calculated. By combining with stopping power data for the ions in the target, the charged particle fluence spectra and dose distribution in linear energy transfer are derived. Secondary quantities computed are kerma, energy expended as nuclear elastic scattering, specific ionization and mean quality factor. Stopping powers have been derived from published atomic stopping powers by summing according to the Bragg rule. A comparison between tissue-equivalent plastic and standard man tissue had been made for each of the neutron spectra.


RBE-dose relations for neutrons and pions. From cellular radiosensitivity parameters and theoretical particle-energy spectra in tissue, of the secondary particles from neutron and negative pion irradiations, RBE-Dose relations have been calculated. The theoretical results are compared with clinical and radiobiological data for normal tissue, tumours and cells in culture. Formulae for calculation, cellular parameters and the needed properties of equivalent 'track-segment bombardments' are given, for several mammalian cells irradiated with pions and with neutrons of several energies.


The response of the ferrous sulphate dosemeter to neutrons. A semi-empirical method of calculating G-values for the ferrous sulphate dosemeter irradiated by neutrons up to 18 MeV has been developed. It utilizes published charged particle G-values along with particle spectra calculated for mono-energetic neutron interactions with the dosemeter medium. All available G-value measurements with neutrons have been evaluated and compared with values predicted by this method. The agreement was excellent for DT generator and cyclotron neutron beams in which the neutron spectra had been accurately determined. However, the predictions could not be completely confirmed for lower energy neutrons becuase of the large experimental uncertainties in the measured G-values and the lack of detailed information on the neutron spectra.


A novel fast neutron dosemeter based on fission chambers. Part I: Principles of operation and theoretical response in neutron therapy radiation fields. A novel method is proposed of accurately measuring fast neutron doses of interest in radiotherapy. The technique, which utilizes calculated neutron fluence-to-kerma conversion factors, is based upon the combination of measurements with calibrated neptunium-237 and uranium-238 pulse fission chambers to obtain a response which matches the variation of kerma with neutron energy. The theoretical performance of a practical instrument has been assessed for a variety of neutron spectra to evaluate the spectrum dependence of the dosemeter. The overall systematic uncertainty using this absolute method of determining the neutron dose under charged particle equilibrium conditions is comparable to that encountered with ionization chamber techniques.


An experimental and calculated dose distribution in water around CDC K-type caesium-137 sources. The radiation distribution in water around caesium-137 K-type sources has been measured and the experimental results used to provide data for an expression for dose calculations which may be conveniently applied in computer programs. The calculated absorbed dose rate obtained in this manner is estimated to be within 3% of the actual dose rate for any point in water up to 8 cm from the source. It is also suggested that the strength of a brachytherapy source be expressed in terms of an experimental exposure rate at some well-defined distance since this quantity may be determined more precisely and with less ambiguity than source activity.


The validity of an equivalent point source (EPS) assumption used in quantitative scanning. Most methods used to estimate the absolute organ content of a gamma-emitting radionuclide from external counting measurements assume that the depth distribution of activity is equivalent to a point source of the same activity located at an 'effective' depth. A theoretical analysis is presented which shows that this assumption is not correct for a dual opposed detector system, because of self-attenuation of the photons by the organ (or source). Experimental varification is also given, and it indicates that the error caused by this assumption is normally less than 10%, although it can be very large in special cases.


Development and comparison of computer methods for organ motion correction in scintigraphy. The process of organ motion correction in scintigraphy is analysed in the frequency domain. The sequence of the chi- and gamma- coordinates registered during scintigraphic recording is converted to a frequency spectrum by a discrete Fourier transform. In the frequency domain motion correction is performed by linear filtering. Every convolution filter in the time domain corresponds to a linear filter in the frequency domain, and the filter form in the frequency domain is a good measure of the quality of the correction. With the aid of frequency analysis simple convolution filters in the time domain are developed. The usual centre of gravity method is not a convolution filter and has an unfavourable frequency behaviour. By means of phantom measurements the following correction methods are tested: the usual (non-convolutional) centre of gravity method, the convolutional centre of gravity method, a weighted convolutional centre of gravity method and the Fourier filtering method.


The use of precision thermoluminescence dosimetry for intercomparison of absorbed dose. A technique is described for making thermoluminescence measurements on phosphor powder with a relatively high degree of precision. Factors such as the rate of fading of TL response and extent of supralinearity for TLD-700 in the therapy-dose range have been measured in relation to its use for precise absorbed dose intercomparison studies in cobalt-60 beams. The results of such a trial intercomparison of six British radiotherapy centres are given, the performance of the TLD technique being matched against that of Fricke dosemeters. Factors involved in the extension of the technique to medium-energy X-rays are discussed including the possibility of determination of beam quality by employing TLD-700 and CaSO4: Dy 'in tandem'.


Digital reconstruction of point sources imaged by a zone plate camera. Zone plate cameras are used for high sensitivity imaging of X- and gamma-ray sources. The image thus obtained requires decoding and numerical techniques are devised for this purpose. The response function and the signal-to-noise ratio for a single point source have been evaluated for zone plates with varying numbers of zones. Autocorrelation is the best of the methods examined, and the results are in good aggreement with those obtained using Monte Carlo techniques. The autocorrelation method can give a gain of 50% in signal-to-noise for a single point source over the maximum obtainable with optical decoding. Criteria for the choice of number of zones are discussed.


Digital processing of images from a zone plate camera. A method for the digital decoding of data obtained with a gamma camera fitted with a zone plate aperture is described. Taking a line source as the object, computer simulations have been used to examine the effects of noise, solid angle variations, shape of detector and detector resolution and methods of dealing with these effects are considered. Using an Anger gamma camera and a zone plate aperture both a line source and a thyroid phantom containing 99Tcm have been well reconstructed. The behaviour of the system with regard to resolution, signal-to-noise ratio and tomographic capability is discussed.


A non-linear programming method for optimizing parallel-hole collimator design. A new method for optimizing the design of multi-aperture parallel-hole collimators for the gamma scintillation camera is presented. The method takes into account the frequency spectrum of a plane source object distribution as well as the energy of the radiation. A frequency dependent statistical figure of merit is calculated and combined with a weighted object distribution frequency spectrum to obtain an objective function which, when maximized, yields the optimum collimator design according to the chosen criteria. The optimization is performed by means of a sequential pattern search technique. The results show a positive correlation between te objective function and an experimental performance index evaluated for existing collimators. The optimal designs obtained by maximizing the objective function, under the assumption of no scatter within the source, exhibit somewhat higher sensitivity and lower resolution than the commercial low energy collimators tested. It is concluded that much of the resolution capability of very high resolution collimators is unused because of the limitation imposed by the intrinsic resolution of the detector assembly.


Correction functions for optimizing the reconstructed image in transverse section scan. Two correction functions are derived for one- and two-dimensional convolution methods for reconstructing a section image from multiple projections. The functions are optimized to yield a maximum 'signal-to-noise power ratio' for a given RMS resolution width, where 'signal power' is the integrated squared line spread function (signal power regarding one-dimensional position information per count) and 'noise power' is the variance of the image density at the centre of a locally uniform source. The point spread function of the reconstructed image is Gaussian, and the standard deivation of noise associated with a locally uniform image is found to be proportional to D-3/2, where D is the RMS resolution width. The autocovariance function for uniform noise is also given.


A spectral approach to ultrasonic scattering from human tissue: methods, objectives and backscattering measurements. The dearth of information on the physical processes involved in the propagation of ultrasound in tissue and the growing need for such information are discussed. The physical nature of the ultrasonic diagnostic process in considered in terms of a wave phenomenon and the limitations and advantages of frequency spectral analysis as a means of obtaining information are briefly analysed. A description is given of an experimental measuring system using a time-gate to select echoes scattered from a particular volume at a depth in soft tissues. The influence of attenuation by overlying tissue and the choice of the duration of the acceptance gate on the frequency spectra obtained are considered. The paper reports some backscattering measurements on formalin-fixed samples of human fat, liver and spleen in the frequency range 0-5-5-0 MHz. The results suggest that the approach may have diagnostic value in a clinical situation, in the characterization of structure in specific volumes of soft human tissue.


The interconversion of machine settings and size determinations between seven models of Coulter counter as illustrated by values for human spermatozoa. Calibration of the Coulter counter Models ZB Industrial, B Industrial D and D Industrial using 21 standard particles is reported using the same method as previously described for the Models B Medical, F and A. All the machines showed significant differences in design and sensitivity. The additional data allowed the relationship between the machine constant and the aperture diameter to be calculated and volume factors were calculated for each combination of settings on each machine. The general method of interconverting size data and machine settings between the instruments was demonstrated using human spermatozoa as an example.


Autoradiographic analysis of protein synthesis and measurements of nuclear volume in WISH cell cultures irradiated with 3 GHz electromagnetic radiation. WISH cell cultures were irradiated 24 h after passage with 3 GHz microwaves for 30 min at intensites of 5 or 20 mW cm-2. After times from exposure of 1, 4, 8, 12 and 24 h the cells were incubated with 5 muCi ml-2 of 3H-glycine and autoradiographs were made using stripping film. The incorporation of the amino acid was measured for four groups, 0-10, 10-20, 20-40 and above 40 grains per cell. Karyometric analysis of irradiated cell cultures was performed 1, 4, 8, 12, 24 and 48 h after exposure. In cultures irradiated at an intensity of 20 mW cm-2, inhibition of protein synthesis with lowering of nuclear volume and enlargement of nucleoli was found one hour after irradiation. This was followed by increase in glycine incorporation 12 and 24 h after irradiation, with enlargement of nuclei. In cultures irradiated at an intensity of 5mW cm-2 stimulation of protein synthesis and enlargement of nuclei were seen 24 h after irradiation. These results suggests that low intensity microwaves stimulate metabolism of cells grown in vitro, although at higher intensities the phase of stimulation is preceded by a short period of inhibition in the culture viability.


A mathematical model for the determination of cardiac regurgitant and ejection fractions from radioisotope angiocardiograms. A mathematical model taking into account the pulsatile pumping action of the heart has been developed which describes, in terms of a set of four recursive equations, the activity in the atrium and in the ventricle of the left or right heart at successive end-systoles and end-diastoles after bolus injection. The resulting closed form solutions permit calculations of chamber forward ejection fractions and valvular regurgitant fractions from computerized radioisotope angiocardiogram data. The method has been applied to a series of over thirty clinical studies with encouraging results.


Energy dependence of the response of lithium fluoride TLD rods in high energy electron fields. The energy dependence of lithium fluoride dosemeters is a complicated function of energy as well as of cavity size. In the application of TLD to charged particle dosimetry, a cavity perturbation effect may exist even though the ratios of the mass stopping powers are constant over the energies encountered. This effect was investigated for lithium fluoride rods in electron fields ranging in energy from 2-5 to 20 MeV. A 13% change of TL response per unit of absorbed dose was measured over that energy range. A semi-empirical theory was developed to account for the cavity effect, using Burlin cavity theory as a starting point. The agreement between theory and measurement is satisfactory.


An iterative computer algorithm for optimization of radionuclide subtraction studies. A new algorithm for off-line computer optimization of radionuclide subtraction studies is presented. Within the digitized image, any region of interest may be chosen for study. No prior knowledge is required concerning the position and extent of the principal and interfering objects, nor concerning their image intensities. Tests show that even when statistical fluctuations are relatively large, the intensity quotient calculated by this algorithm may be used to estimate a uniform background and correct for its contribution. The effect of smoothing the images prior to the use of the algorithm has been investigated. The method has also been used for pancreas imaging and one example of this application is presented.


The transformation method for the MIRD absorbed fraction as applied to various physiques. A transformation method was investigated for applying the MIRD absorbed fraction to internal dose calculations for an individual. The transformation method consists of two parts, transformation of the target organ mass, and of the distance between source and target organs. The variation of the specific absorbed fraction with distance in the human body was approximated with the traditional exponential form. To examine the transformation method, experiments were carried out for cobalt-60 gamma rays, using LiF-TLD, with the thyroid and ovaries as source organs. The transformed values of the MIRD absorbed fractions agreed well with the experimental values. Some results obtained from the MIRD values by these transformation methods were also compared with those for younger age groups calculated by Snyder.