Onset of puberty and duration of fertility in rats fed a restricted diet. Chronic dietary restriction such that the body weight of CFY Sprague-Dawley female rats was 50% that of animals fed ad libitum resulted in enhanced longevity (LD 50 of 1090 days compared to 704 days). All the experimental females had reached puberty by 227 days and 80% were able to conceive and wean young at 510 days, an age beyond that at which the control rats had ceased to breed (450 days). Some (25%) of the experimental rats were able to breed at over 800 days of age.


Changes in ovine cervical mucus in response to oestrogen treatment. After 10 days pretreatment with 10 mg progesterone daily, ovariectomized ewes were injected i.m. with 12.5, 25, 50 or 100 micrograms oestradiol benzoate (OB) and cervical mucus was collected 16, 24, 32, 40 and 48 h later (Exp. 1), or were injected with 12.5, 40 or 100 micrograms OB daily, and the mucus examined, for 9 days (Exp. 2). The Spinnbarkeit was affected by the dose of OB over 9 days, but at all doses it increased over the first 3 days of treatment (Exp. 2). The wet weight of the mucus, the amount and proportion of water, and therefore the degree of arborization, increased with the dose of OB but decreased after 3 days in Exp. 2. The amount of dry matter, protein or carbohydrate did not have any clear relationship to dose or duration of OB treatment.


Serum concentrations of oestradiol and progesterone during the normal oestrous cycle and early pregnancy in the lion (Panthera leo). During a 6-month study period weekly serum samples demonstrated 9 oestradiol surges above 14 pg/ml (range 19-108 pg/ml) among 3 lionesses isolated from male lions. Intervals between peaks ranged from 3 to 8 weeks. Progesterone surges of more than 17 ng/ml (range 17-282 ng/ml) and lasting for 2-6 weeks were recorded after 7 of the oestradiol peaks. Sexual behaviour correlated well with the oestradiol peaks. Except for cornification following oestradiol peaks, there was no obvious vaginal cytology pattern at other times of the cycle. Pregnancy occurred after a 12-h contact with a male during behavioural oestrus. During gestation (108 days) oestradiol values remained low, while progesterone was elevated to 49 ng/ml within 12 h after mating, reaching a peak of 143 ng/ml at the 4th week, and remaining elevated during the next 2 months.


Effects of various lighting regimens and pinealectomy on semen production in Romney rams. Sixteen Romney rams were utilized in a 2 x 2 factorial experiment designed to evaluate the effects on semen production of (i) contrasting lighting regimens, and (ii) pinealectomy or sham-operation. Reversal of the annual photoperiodic cycle advanced the seasonal peak of fructose levels in semen by 4 months and also reduced percentages of unstained and morphologically normal spermatozoa. Pinealectomy abolished this advancement of peak fructose production and reduced overall concentrations and motility of spermatozoa. Moreover, towards the end of the study pinealectomized rams had higher ejaculate volumes than did sham-operated rams. Testicular and accessory sex gland data obtained after the rams were killed showed a marked influence of the lighting regimen: high values from sham-operated rams in short daily photoperiods contrasted with depressed values from those in long daily photoperiods. Pinealectomized rams provided values midway between these extremes, a finding which suggested both anti- and pro-gonadotrophic roles for the pineal gland in rams.


Gonadotrophin-inhibiting activity in seminal plasma from intact and vasectomized bulls. Bull seminal plasma administered to male rats at the time of castration inhibited the rise in the levels of FSH and LH otherwise seen in the serum 24 h later. That the gonadotrophin-inhibiting activity was also present in the seminal plasma from vasectomized bulls suggests that it was not of testicular origin. Although the substance with gonadotrophin-inhibiting activity was a protein, it may be chemically distinct from inhibin.


Evidence of the origin of the gelatinous masses in the oviducts of mares. The gelatinous masses known to occur in the mare oviduct were examined by light and scanning electron microscopy. Many (44%) of the masses which occurred in 16 of the 24 oviducts studied were connected with the mucosa of the ampulla near the ampullary-isthmic junction. The masses consisted of lobules of fine fibres probably derived from the fibrous connective tissue of the lamina propria in the oviductal mucosa.


The location of eggs retained in the oviducts of mares. The oviducts of 24 mares were examined to determine the site of retention of unfertilized eggs. The ampullary-isthmic junction regions of 42 of the 48 oviducts were serially sectioned and examined histologically. The remaining parts of the oviducts were flushed and the flushings searched microscopically. Of 45 eggs located, 40 were in the sectioned segments of 24 oviducts and only 5 were in the flushings. All but one of the sectioned segments contained prominent masses of material obstructing the lumen, but these were apparently not the direct cause of egg retention since eggs were found on both sides of them.


Short- and long-term effects of hypophysectomy and unilateral ovariectomy on ovarian follicular populations in sheep. The effects of hypophysectomy and unilateral ovariectomy on the total number of follicles with greater than 3 layers of granulosa cells were determined at 4 and 70 days following treatment. The population of preantral follicles (less than 0.23 min diam.) was found to be under the control of gonadotrophins but such control was only evident on a long-term basis. At 70 days after unilateral ovariectomy there was a large increase in the number of preantral follicles but at 70 days after hypophysectomy there was a large decrease. The population of antral follicles (greater than 0.23 mm diam.) was under the immediate control of gonadotrophins. By 4 days after hypophysectomy all large antral follicles had become atretic and the number of antral follicles was further decreased at 70 days after treatment. At 70 days after unilateral ovariectomy there was an increase in the number of antral follicles. The follicular growth rates at 70 days following treatment were decreased in hypophysectomized ewes but increased in ewes after unilateral ovariectomy.


Selecting a mammalian species for the separation of X- and Y-chromosome-bearing spermatozoa. All (524) male karyotypes in An Atlas of Mammalian Chromosomes (Hsu & Benirschke, 1967-1977) were visually estimated for the chromatin difference between the X- and Y-chromosome-bearing spermatozoa. After more exact measurement of axial chromatid length for 100 karotypes, 24 species were found in which the difference between X and Y chromosomes was greater than 6.2%. It is suggested that such species would be the best for attempts to separate the X- and Y-bearing spermatozoa.


Morphological characteristics of male germ cells of rats in contact with Sertoli cells in vitro. Fragments of seminiferous epithelium were prepared from 3-week-old rats. Although the Sertoli cells formed a monolayer, germ cells (spermatogonia and early spermatocytes) remained in association with them and were of normal ultrastructural appearance. Germ cells became completely separated from Sertoli cells after 3 weeks of culture in a chemically defined medium. The contact areas between Sertoli and germ cells were characterized by desmosome-like junctions while those between germ cells appeared to be pentalaminar.


A cytogenetic study of the Caspian pony. The group of Caspian ponies studied contained some animals with 65 chromosomes and others with 64 chromosomes. The morphology and G-banding pattern of the chromosomes resembled those of Equus caballus and E. przewalskii. The karyogram of animals with 65 chromosomes was identical to that of the cross between E. caballus and E. przewalskii. It is suggested that the Caspian pony is the product of natural hybridization between E. caballus and E. prezwalskii. Low reproductive effeciency of the Caspian pony is suggested as the cause of decline in the population of these animals.


Effect of the fetal placenta and of a rabbit pituitary extract on plasma progesterone in fetectomized rabbits. When fetuses and placentas were removed on Day 18 in normal pregnant rabbits, plasma progesterone levels declined rapidly to non-pregnant values within 48 h. This decline was largely prevented if only fetectomy was performed, leaving the placentas in situ, but not when the fetal components of the placentas were also removed. These results suggested that ovarian progesterone production was dependent upon trophic influences emanating from the fetal portions of the placentas. Ovarian progesterone production was maintained by an extract of rabbit pituitaries for at least 72 h after removal of fetuses and placentas.


Fetal and placental weight relationships in the rat at days 13 and 17 of gestation. Mean fetal and placental weights were, respectively, 0.018 and 0.051 g on Day 13 and 0.376 and 0.250 g on Day 17. Fetal and placental weights within litters were weakly correlated on Day 13 (r = 0.322) but not on Day 17. Litter size was negatively correlated with placental weight on Day 17 (r = -0.485) but not with fetal weight. Male fetuses were heavier than female fetuses on Day 17 but their placentas were not significantly different. Fetuses and placentas were lighter at the ovarian end of the uterine horn on both days examined, revealing an early influence of local environmental factors on their growth.


Cytogenetics and reproduction of sheep with multiple centric fusions (Robertsonian translocations). The significance of centric fusions (Robertsonian translocations) in domestic animals, with special reference to sheep, is reviewed. The mating is described of a further 856 ewes with either a normal chromosome number 2n = 54 or carrying one or more of the three different translocations (centric fusions) t1, t2 and t3 in various heterozygous and homozygous arrangements. Rams which were used in the matings were homozygous for one of the translocation chromosomes (2n = 52), double heterozygotes (2n = 52), triple heterozygotes (2n = 51) or were carriers of 4 translocation chromosomes (2n = 50) and 5 translocation chromosomes (2n = 49). A remarkably even distribution of segregation products was recorded in the progeny of all combinations of translocation ewes x translocation rams in those groups in which sufficient animals were available for statistical analysis. Forty-eight chromosomally different groups of animals were mated. Further, the overall fertility of the translocation sheep, measured by conception rate to first service, lambing percentage and number of ewes which did not breed a lamb, was not significantly different from New Zealand national sheep breeding data. In some groups the poorer reproductive performance could be explained by the age structure of the flock and inbreeding depression, which probably affected the performance of some animals. Sheep with progressively decreasing chromosome numbers, due to centric fusion, 2n = 50, 2n = 49 and 2n = 48, are reported. The 2n = 48 category represents a triple homozygous ewe and a triple homozygous ram and is the first report of the viable evolution of such domestic animals. Less than 1% of phenotypically abnormal lambs were recorded in a total of 1995 progeny born over 10 years. It is now considered that there is little or no evidence to suggest that centric fusions in a variety of combinations affect the total productive fitness of domestic sheep. It is suggested that future research should be more actively directed to understanding their genetic significance.


Detection of induced death of embryos in sheep by the rosette inhibition test. The rosette inhibition test has been used to monitor the decrease of an 'early pregnancy factor' in 2 groups of pregnant sheep (19-21 days) in which embryos were removed surgically or by induction of luteolysis with cloprostenol. The rosette inhibition titres of sera taken from sheep of each group declined from high (16-18) to low (8-10) levels within 48 h of treatment. Surgical removal of embryos caused little change in serum progesterone concentration whereas cloprostenol prompted a rapid decrease over the same period. Death of the embryo can therefore be detected by the rosette inhibition test within 48 h of occurrence, but not necessarily by the measurement of progesterone in blood within this period.


Within-subject variability of human semen in regard to sperm count, volume, total number of spermatozoa and length of abstinence. The within-subject variability of the semen sperm count (n), volume (v) and the total number of spermatozoa (N) was studied on 220 ejaculates from 36 normal subjects after an abstinence of 7 days or less. For each of the three variables, the within-subject standard deviation, sigma, was practically proportional to the mean, mu; the common value of the coefficient of variation sigma/mu for all subjects was very high: 0.39 for n, 0.28 for v and 0.55 for N. The 95% confidence intervals based on a single ejaculate were asymmetrical and very large, the lower and upper limits being respectively 0.5 x n and 2.3 x n; 0.7 x v and 1.8 x v; 0.4 x N and 2.9 x N. The three semen characteristics for a given subject were highly correlated with length of abstinence: for an increase in abstinence of 1 day there were mean increments of 13 x 10(6)/ml for n, 0.4 ml for v, and 87 x 10(6) for N.


Detection of anti-Müllerian activity in boar rete testis fluid. Boar rete testis fluid was tested for its capacity to induce Müllerian regression in 14.5-day-old rat Müllerian ducts. Weak activity was present in crude RTF, but after gel filtration 5-fold concentration, greater activity was detected in 1 our of 7 pools of the eluted fractions. The biologically active fraction (mol. wt 160 000-310 000) coincided with the elution of authentic labelled anti-Müllerian hormone, obtained from bovine fetal testes. These results indicate that a small amount of anti-Müllerian hormone is still synthesized in post-natal life.


Exteroceptive factors and pregnancy block in the Mongolian gerbil, Meriones unguiculatus. A series of experiments based on 150 newly mated, uni- and multi-parous Mongolian gerbils provided no evidence for the existence of pregnancy blocking due to a strangle male effect. The reduced level of fertility observed was attributed to stressful factors at critical times in the pregnancy. Treatment with 10 i.u. PMSG on the day following mating interrupted pregnancy and the majority of females mated again within 4 days.


Increase of total protein synthesis during mouse oocyte growth. Quantitative changes of mouse oocyte protein synthesis during oogenesis have been studied by determining the rate of leucine incorporation into total cell protein. The leucine intracellular poor was artificially expanded by exposing the isolated oocytes to different concentrations of radiolabelled leucine, and leucine incorporation was followed as a function of the time. Protein synthesis by mouse oocytes increases linearly with the increase of the cell volume, and such increase is constant throughout the entire period of oocyte growth.


Spontaneous electrical activity of the rat epididymis in vitro. Smooth muscle electrical activity was recorded with suction electrodes from the partly or completely uncoiled epididymal duct of the rat in vitro. The electrical activity of the cauda epididymidis consisted of one or few spikes followed by a plateau of 1-2 sec. The frequency of electrical activity declined from the thicker-walled initial segment of the thin-walled initial segment, was increased to the level seen in the initial segment in the thicker, major portion of the caput epididymidis, declined in the corpus and fell steeply in the cauda epididymidis towards the vas deferens. Electrical activity spread over long distances in the distal cauda and epididymal vas. Elsewhere in the epididymis activity remained synchronous only for a short period in short segments.


Electrical activity and intraluminal pressure of the cauda epididymidis of the rat. Smooth muscle electrical activity was recorded simultaneously with intraluminal pressure in the cauda epididymidis and epididymal vas of the rat in vitro. Spontaneous electrical activity spread over distances of several centimetres and was associated with a pressure wave recorded through an open-ended catheter in the distal cauda and epididymal vas. Transmission of pressure wave was gradually damped by filling of the catheter with spermatozoa.


A high molecular weight antifertility factor from human seminal plasma. The presence of a high molecular weight antifertility factor in human seminal plasma was established. The factor can be precipitated by centrifugation at 104 000 g. Its activity is maximal when the protein concentration reaches 150 micrograms/10(5) spermatozoa using the mouse in-vitro fertilization assay as the test system. The factor is heat labile but its activity is not affected by dialysis. It prevents the penetration of the spermatozoa through the layers surrounding the egg but has no effect on the fusion of the spermatozoa with the vitelline membrane. The factor is only partly removed from spermatozoa by washing but is completely dispersed when the spermatozoa are incubated in capacitation medium. The pellet that is precipitated from the seminal plasma does not contain any particles or vesicles. However, it is significantly contaminated with low molecular weight material. This material includes the acrosin inhibitor which is present in large enough quantities to hinder fertilization. Washing the pellet twice with H2O removes these low molecular weight compounds, as indicated by the absence of the acrosin inhibitor, but has no effect on the antifertility properties of the pellet. Therefore, before further study or purification of the factor, it is essential that the pellet is washed such low molecular weight material. The washed pellet consists of at least 7 components as judged by disc gel electrophoresis.


Effect on gonadotrophin secretion of blockage of the ductuli efferentes in the normal and androgen-deprived rat. Serum LH and FSH concentrations were measured in adult male rats. Blockage of the ductuli efferentes by surgical ligation or treatment with the anti-fertility drug alpha-chlorohydrin did not produce any changes in serum LH or androgen-dependent organ weights. Serum FSH in both groups was significantly raised by 4 days after treatment and remained so throughout most of the experimental period (42 days) but did not attain the values obtained in castrates. The gonadotrophin changes were accompanied by an initial increase in the weight and turgidity of the testes which then became flaccid and atrophied. These changes were similar but not identical after both treatments. Androgen secretion was impaired in adult rats treated with ethylene dimethane sulphonate; serum LH values were similar to those of 14-day castrates, and serum FSH was also elevated but not to the level found in the castrates. Ligation of the ductuli efferentes did not produce any further changes in concentrations of either hormone in spite of the retention of the testicular products within the testes as reflected by an increase in weight. The results are consistent with the view that changes in serum FSH after blockage of the ductuli efferentes are related to disturbances in the production of inhibin from the seminiferous epithelium rather than retention of inhibin with the testicular tubules.


Determination ob biologically active LH in the serum of male rheusus monkeys (Macaca mulatta). The in-vitro bioassay for LH, using mouse Leydig cells, has been modified for the direct measurement of serum LH in the male rhesus monkey. Validation of the assay demonstrated good reliability in terms of accuracy, precision and sensitivity (1.5 mi.u./ml). Basal LH concentrations in laboratory-maintained monkeys with and without anaesthesia were not significantly different from those in free-ranging, feral monkeys. LH-RH (50 micrograms i.v.) elicited a 30-fold increase in LH concentrations after 30 min. LH levels in castrated adult monkeys were approximately 50 times the normal levels. Intact and castrated juvenile males had only very low LH levels. LH from the serum of an adult male castrate was further characterized by Sephadex G100 column chromatography. The in-vitro bioassay provides a preferable alternative to the heterologous radioimmunoassay method for the routine determination of LH in the rhesus monkey.


Nutrient requirements of rat embryos undergoing organogenesis in vitro. Rat embryos at the head-fold stage were cultured in rotating bottles for 2 days in rat serum extensively dialysed against glucose-free BSS, and to which various energy sources and nutrients were added. Optimum growth and differentiation, virtually indentical with that obtained in while serum and to that seen during the corresponding period in vivo, were obtained with the addition of glucose and certain vitamins: pantothenic acid and riboflavin had a general beneficial effect on development, i-inositol suppressed neural tube defects, and folic acid significantly improved growth of the embryos.


Elemental composition of rabbit antral fluid during preovulatory follicular swelling. Electron probe microanalysis was used to determine the concentrations of Na, Cl, K Ca, Mg, S and P in samples of follicular fluid, ovarian vein serum and peripheral venous serum obtained from virgin rabbits at 2-h intervals up to 10 h after injection of hCG. Throughout this 10-h period the elemental composition of follicular fluid was essentially the same as that of blood serum. However, there was a significant drop in follicular fluid Ca relative to blood during the 10-h period which may reflect Ca involvement in the regulation of oocyte maturation. Significant differences were also found between follicles within rabbits for K and P concentrations.


Changes in body weight, blood glucose and serum proteins in relation to the appearance of post-partum oestrus in Gir cows. Of 16 cows, 9 did not exhibit oestrus within 90 days of parturition. These 9 cows had significantly lower body weights, blood glucose and serum protein concentrations than did the 7 cows which exhibited a fertile oestrus. It is suggested that these differences could be used to identify those cows which will not show an early post-partum oestrus.


Clinical use of plasma total estriol measurements in late pregnancy. A critical review of the clinical use of measurements of plasma total estriol concentration in late pregnancy was done on the basis of one year's experience with the test at one institution which provides tertiary-level care to high-risk obstetric patients. The overall efficiency of the test in discriminating patients at risk was 59%. It appears to be most useful when a negative result provides some reassurance that the status of the fetus is satisfactory.


Results of the intensive perinatal management of very-low-birth-weight infants (501 to 1,500 grams). In January 1975 at the University of Colorado Medical Center, a program of intensive intrapartum and neonatal care went into effect for all infants with expected birth weights of over 600 gm. Data are presented on the 187 infants weighing 501 to 1,000 gm born in 1975 to 1976. The 70 infants weighing 501 to 1,000 gm had a perinatal mortality of 65% and a neonatal mortality of 55%. The perinatal mortality of the 117 infants weighing 1,001 to 1,500 gm was 25% and the neonatal mortality 20%. Among the 501- to 1,000-gm infants, cesarean section for delivery of abnormal presentations resulted in a lower perinatal mortality than did vaginal delivery. Apgar scores were predictive of an improved chance of survival, but scores of three or less even at five minutes were associated with a 25% survival rate. Of those infants who did not survive the neonatal period, over 70% had died by 48 hours of life. These results were achieved without the use of beta-mimetic tocolytic agents to inhibit labor or long-acting corticosteroids to enhance pulmonary maturation. The improved survival of the infants weighing 1,500 gm or less when compared with infants of similar weights in preceding years is attributed to more intensive perinatal management of these mothers and their very-low-birth-weight infants.


4-Anilidopiperidine analgesics. 2. A study of the conformational aspects of the analgesic activity of the 4-anilidopiperidines utilizing isomeric N-substituted 3-(propananilido)nortropane analogues. Relatively little information is available concerning the influence of conformational factors on the potent analgesic actions of the 4-anilidopiperidines. A series of N-substituted 3 alpha- and 3 beta-(propananilido)nortropanes have been designed, synthesized, and stereochemically characterized as semirigid analogues of the 4-anilidopiperidine analgesics in an attempt to study the influence of certain stereochemical factors on analgesia in this class of compounds. Conformational analysis of 3 alpha-propananilides (4) reveals a boat conformation for the preferred conformation of the piperidine ring of these tropane analogues. Evaluation of the analgesic potencies of the isomeric N-substituted 3-(propananilido)nortropanes of this study indicates greater potency for the 3 beta-(propananilido) isomers (5) with N-benzyl and N-phenethyl substitution as compared to the corresponding N-substituted 3 alpha-propananilides. Analysis of relative solubility differences among these isomers suggests that both structural and stereochemical influences predominate in affecting analgesic potency.


New antiarrhythmic agents. 1. Primary alpha-amino anilides. Thirty-two alpha-amino anilides with various substituents in the aromatic ring and in the alpha position are described. Their abilities to protect mice against chloroform-induced fibrillation and to elicit toxicity were determined. Substitution of an alkyl or aryl group in the alpha position enhanced the antifibrillatory activity. In most cases, increased potency was accompanied by increased toxicity. Eleven compounds were tested in dogs with surgically induced myocardial infarction; most showed antiarrhythmic activity. 2-Aminopropiono-2',6'-xylidide, tocainide, was chosen for clinical investigation.


New antiarrhythmic agents. 2. Amide alkyl alpha-amino xylidides. The synthesis of a series of N-alkyl 2-amino 2',6'-xylidides is described. The method involved coupling of the N-alkyl-2',6'-xylidine with the appropriate 2-haloacyl halide, followed by ammonolysis. Alternatively, alkylation of the 2-phthalimido 2',6'-xylidide with NaH and the alkyl halide followed by hydrazinolysis was used. All compounds were evaluated for their ability to protect mice against chloroform-induced ventricular fibrillation. The compounds were generally more potent antifibrillatory agents than the corresponding secondary amides. All were more potent than tocainide and several showed less CNS toxicity. Five compounds were further evaluated in dogs with ventricular arrhythmias resulting from myocardial infarction. N-Ethyl-2-aminoaceto-4'-propoxy-2',6'-xylidide was as potent as lidocaine and produced less CNS toxicity.


New antiarrhythmic agents. 3. Primary beta-amino anilides. The synthesis and pharmacologic evaluation of primary beta-amino anilides, as well as comparisons with tocainide, lidocaine, and its beta homologue, are described. Substituted anilines were acylated with 3-bromoacyl chlorides and converted to the title compounds by direct amination or via 3-phthalimido anilides and subsequent hydrazinolysis. Alternatively, anilines were acylated with substituted acryloyl chlorides and the amines prepared by addition of ammonia to the double bond. The target compounds were evaluated for their ability to protect against chloroform-induced fibrillation in mice. All were found to have some antifibrillatory activity; several were more potent than tocainide, a compound in clinical trials as an oral antiarrhythmic drug. Four compounds were tested for their effects against ventricular arrhythmias in dogs with myocardial infarction. 3-Amino-2',6'-butyroxylidide (38) was found to be more potent and less CNS toxic than tocainide.


Reactions of 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in aqueous solution. Products formed from the reaction of two chloroethylnitrosoureas in neutral aqueous solution have been identified and quantified. Mixture components recovered after a 1-h incubation period accounted for 75--85% of the starting nitrosourea. Approximately 65--85% of the reaction products were formed by an initial cleavage of the nitrosourea to the proposed intermediates 2-chloroethyl azohydroxide and an isocyanate and by subsequent hydrolytic reactions. A minor pathway, 5--10% of products, involves denitrosation of the nitrosourea with oxazoline formation. Stable isotope labeling and mass spectrometry have been used to determine the reaction sequence and product origins. Reaction product identification has been made using high-performance LC isolation and comparison with synthetic material.


Comparative cytotoxic and biochemical effects of ligands and metal complexes of alpha-N-heterocyclic carboxaldehyde thiosemicarbazones. Several alpha-N-heterocyclic carboxaldehyde thiosemicarbazones and their iron and copper complexes have been tested for their cytotoxicity and inhibiting activity against DNA synthesis under controlled metal conditions. No ligands show cytotoxicity against Ehrlich cells at the concentrations tested, while some iron and copper complexes are active. In contrast, the ligands inhibit DNA synthesis at much lower concentrations than used above. Similarly, the metal complexes are effective inhibitors at concentrations much below those necessary to demonstrate cytotoxicity. In addition, the iron complexes of 1-formylisoquinoline thiosemicarbazone, 2-formylpyridine thiosemicarbazone, and 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone were shown to be three- to sixfold more active than their free ligands as inhibitors of partially purified ribonucleotide reductase to which no iron has been added. The copper complex of 2-formylpyridine thiosemicarbazone was slightly more active than the free ligand against the reductase.


Potential antitumor agents. 31. Quantitative structure-activity relationships for the antileukemic bis(guanylhydrazones). Certain L1210-active bis(guanylhydrazones) have structural and biological properties in common with the DNA minor groove binding, antileukemic, bisquaternary ammonium heterocycles. Monitoring of the DNA binding of the bis(guanylhydrazones), by fluorimetric quantitation of drug displacement of DNA-bound ethidium, shows that, like the bisquaternary salts, these agents bind more strongly to poly[d(A-T)] than poly[d(G-C)]. The drug concentrations necessary to inhibit L1210 DNA-dependent DNA polymerase in vitro by 50% (IC50) are linearly related to measures of drug-DNA binding with no preference for a particular primary sequence of DNA being evident. Mammalian toxicity of the bis(guanylhydrazones) is effectively modeled by a regression equation containing binomial terms in Rm values, used as a measure of agent lipophilic-hydrophilic balance, and the logarithms of the IC50 values.


Chance factors in studies of quantitative structure-activity relationships. Multiple regression analysis is a basic statistical tool used for QSAR studies in drug design. However, there is a risk or arriving at fortuitous correlations when too many variables are screened relative to the number of available observations. In this regard, a critical distinction must be made between the number of variables screened for possible correlation and the number which actually appear in the regression equation. Using a modified Fortran stepwise multiple-regression analysis program, simulated QSAR studies employing random numbers were run for many different combinations of screened variables and observations. Under certain conditions, a substantial incidence of correlations with high r2 values were found, although the overall degree of chance correlation noted was less than that reported in a previous study. Analysis of the results has provided a basis for making judgements concerning the level of risk of encountering chance correlations for a wide range of combinations of observations and screened variables in QSAR studies using multiple-regression analysis. For illustrative purposes, some examples involving published QSAR studies have been considered and the reported correlations shown to be less significant than originally presented through the influence of unrecognized chance factors.


A preliminary structure-activity study of the mixed-function oxidase inhibitor 7,8-benzoflavone. A series of substituted and structural analogues of 7,8-benzoflavone were examined for their ability to inhibit benzo[a]pyrene oxidation by the mixed-function oxidases found in hepatic microsomes prepared from 3-methylcholanthrene- and phenobarbital-induced rats. Of all the benzoflavones tested, only 6-amino-7,8-benzoflavone possessed significant inhibitory activity toward both classes of induced mixed-function oxidases. Parameters which were found to be necessary for maximal inhibitory activity were the maintenance of an unsubstituted or specifically substituted exocyclic phenyl group on position 2, the preservation of the pyran-4-one ring, and a 6 position which is either unsubstituted or substituted with an oxidizable moiety.


Syntheses and biological activities of 7 beta-methyl steroids. The preparation of 7 beta-methyl-5 alpha-dihydrotestosterone acetate and its 2-thia-A-nor analogue is described. Biological evaluation shows that a 7 beta-Me largely decreases myotrophic-androgenic activity in both 5 alpha-dihydrotestosterone and the 2-thia-A nor analogue. Testing for antitumor activity shows that the reduction in breast tumor weight was not significant for either compound, but the final tumor size in the animals treated with 7 beta-methyl-2-thia-A nor steroid at 10 (mg/kg)/day was significantly reduced. The effects of 7 beta-Me steroids on the various organ weights are also described. The influence of 7 beta-Me substituent on the biological activities of androgens may be mediated through direct interaction of the substituent with the receptor surface in contact with the third dimension of the steroid molecule.


Steric effects of substituents on phenethylamine hallucinogens. 3,4-(Methylenedioxy)amphetamine analogues alkylated on the dioxole ring. The compounds 1-(2-methyl-1,3-benzodioxol-5-yl)-2-aminopropane and 1-(2,2-dimethyl-1,3-benzodioxol-5-yl)-2-aminopropane were synthesized and evaluated for pharmacologic effects in mice. These can be viewed as analogues of the known psychotomimetic agent 3,4-(methylenedioxy)amphetamine (MDA). Their hydrochloride salts were compared with MDA for their ability to increase spontaneous motor activity and to elicit behavioral effects. The former compounds was MDA-like in action, while the latter was not. The results suggest that one face of the molecule must be free of steric bulk to possess activity.


Structure-activity relationship of aniline mustards acting against B-16 melanoma in mice. A set of 23 aniline mustards [X-C6H4N(CH2CH2Cl)2] have been tested for their activity against B-16 melanoma in mice. The following quantitative structure-activity relationship (QSAR) correlates the data well: log 1/C = -2.06 sigma - 0.15 pi - 0.13 pi2 + 4.13 (r = 0.936). When this equation is compared with those formulated for aniline mustards acting against leukemia, it is found that log P0 (ideal lipophilicity) is higher for solid tumors. The QSAR brings out the unique activity of phenylalanine aniline mustard.


Allylic esters as potential antitumor agents. Derivatives and analogues of 2,3-bis(hydroxymethyl)-7-oxabicyclo[2.2.1]hept-2-ene. Derivatives and analogues of 2,3-bis(hydroxymethyl)-7-oxabicyclo[2.2.1]hept-2-ene were synthesized. Of the compounds prepared, dimethyl 2,3-bis(acetoxymethyl)-7-oxabicyclo[2.2.1]hepta-2,5-diene-5,6-dicarboxylate (5) was the most potent in a leukemia L1210 tissue culture assay (93% inhibition at 10(-6) M). None of the compounds showed significant reproducible in vivo antileukemic activity.


Autosomal recessive sudden unexpected death in children probably caused by a cardiomyopathy associated with myopathy. The propositus, who died suddenly at the age of 22 months, was investigated because of an unusual myopathy. Family history revealed two sisters and four cousins who had also died suddenly and unexpectedly. The finding of asymmetric septal hypertrophy by echocardiography in the propositus suggested that the cause of the sudden death in the relatives was an undetected cardiomyopathy accompanying a mild and often subclinical myopathy. The affected children were in two sibships and both sets of parents were first cousins. The mother of one sibship was the sister of the father of the other. It is suggested that a gene causes a mild autosomal recessive myopathy with cardiomyopathy that is often undiagnosed and usually ends in sudden unexpected death in the second year of life. The same gene may manifest on echocardiogram in some heterozygotes as asymmetric septal hypertrophy.


Heterochromatic polymorphism in spontaneous abortions. Since the advent of C-banding as a routine diagnostic procedure, the significance of heterochromatic polymorphism has been questioned. Some workers have considered variations in heterochromatin in chromosomes 1 and 9 to be associated with fetal wastage, recurrent abortions, and abnormal phenotypes. Over a 15-month period, this laboratory made a study of the diagnostic significance of heterochromatic variants in 50 couples with a history of recurrent abortions. A control group of 50 couples with at least two normal children and no miscarriages was investigated simultaneously. The results indicated no significant difference in the heterochromatic regions between aborting and non-aborting couples.


Alpha-thalassaemia in Cyprus.

Alpha-thalassaemia in Cyprus. The frequency of alpha-thalassaemia in Cyprus was determined with studies of haemoglobin Bart's in 1200 Greek Cypriot and 132 Turkish Cypriot newborn babies. Of the Greek newborns, 12.4%, and of the Turkish newborns, 6.8% had raised Hb Bart's (from 0.6% to 12.9% of the total haemoglobin) suggesting that they were carriers of either alpha-thalassaemia-1 or alpha-thalassaemia-2 genes. The findings suggest that the population of Cyprus has the highest frequencies of alpha-thalassaemia among Caucasian people.


Prenatal diagnosis of beta-thalassaemia by fetal red cell concentration with anti-AB serum. Prenatal diagnosis by globin chain synthesis analysis on fetal blood samples obtained by placental aspiration was performed in two pregnancies at risk for beta-thalassaemia. Since both fathers had blood group AB, and both mothers had group O, fetal red cell concentration from maternal-fetal mixtures was obtained with the aid of anti-AB serum. With this approach it was possible to carry out globin chain synthesis analysis with very small amounts of fetal blood. Heterozygous and normal genotypes were ascertained and confirmed after birth.


Benign familial haematuria in children from the Jewish communities of Israel: clinical and genetic studies. Over 7 years, 130 children were referred for prolonged isolated haematuria of unknown cause. In 34 instances, haematuria was also found in one or more family members. In 23 of these families (18% of all referrals for isolated haematuria), investigation and follow-up, for periods of 5 to 10 years, of the index cases and of 56 haematuric relatives showed no evidence of renal disease and no other pathological findings. These subjects were diagnosed as having benign familial haematuria. The gene for benign familial haematuria is apparently transmitted as an autosomal dominant with reduced penetrance and variable expressivity. In Israel, the disorder seems to be more frequent among Jews of non-Ashkenazi descent than among those of European ancestry (Ashkenazim).


Non-progressive cerebellar ataxia, aplasia of pupillary zone of iris, and mental subnormality (Gillespie's syndrome) affecting 3 members of a non-consanguineous family in 2 generations. A family is reported in which a brother and sister both showed non-progressive cerebellar ataxia, aplasia of the pupillary zone of the iris, and mild mental subnormality. These clinical findings were similar to those in two previous case reports. Despite the birth of an affected son to the affected sister, this family is considered to confirm autosomal recessive inheritance of this syndrome. The paternity of the mother's husband is supported by blood groups and biochemical markers and it is presumed that the husband is a heterozygote, even though no consanguinity could be detected.


Muscular dystrophy in an X; 1 translocation female suggests that Duchenne locus is on X chromosome short arm. A unique combination of a Duchenne-like muscular dystrophy in a girl with a translocation-inversion rearrangement involving an X chromosome and a no 1 chromosome appeared as a result of both gene mutation and chromosome mutation in the mother. The X-autosome rearrangement would permit full expression of an X-linked recessive gene, such as that for Duchenne muscular dystrophy, in a female, and this would satisfactorily explain the characteristic Duchenne-like course of our patient's illness. The simultaneous de novo appearance of the Duchenne mutation and the X;1 rearrange suggests possible sites for the Duchenne locus on the X chromosome short arm (at Xp1106 or Xp2107).


Duchenne type muscular dystrophy and consanguinity: difficulties in pedigree analysis. We report the case of a 2-year-old girl who had signs of Duchenne type muscular dystrophy on clinical, electromyographic, laboratory, and pathological examination. The parents of the child are first cousins. A brother and nephew of the mother also had Duchenne type muscular dystrophy. Karyotype analysis in the proband showed both X chromosomes to be morphologically normal. The mother had very high plasma CK levels, equivalent to those observed in carriers of the disease. We discuss different hypothetical mechanisms designed to account for the family pedigree.


A case of partial trisomy 17 resulting from X-autosomal translocation. A case of partial trisomy 17 with partial monosomy X resulting from a maternal X-autosomal translocation t(X;17)(q13;q21) is presented. Three previously reported cases are reviewed and the phenotypic features of trisomy 17 are discussed.


18p--syndrome resulting from translocation (13a;18q) in a mildly affected adult male. The patient was a 27-year-old male with short stature, borderline mental deficiency, strabismus, and a short fourth metacarpal. His karyotype showed deletion of the short arm of a chromosome 18 as the result of de novo fusion centric translocation between chromosomes 13 and 18 (45,XY, --13, --18, +t(13;18) (13qter yields cen yields 18qter).


Brachydactyly and polydactyly with dermal ridge dissociation and ridge hypoplasia. A child with brachymesophalangy and postaxial postminimal polydactyly was found also to have dermal ridge dissociation and ridge hypoplasia. She was the second child of unaffected, unrelated parents and was born after a normal pregnancy and delivery. No previous report of a similar combination has been traced.


Relationships between performance in medical school and first postgraduate year. Data from a longitudinal study of Jefferson Medical College graduates were analyzed to determine levels of clinical competence in the first postgraduate year and relationships between postgraduate ratings and performance during medical school. Ratings were obtained on knowledge, data-gathering skills, clinical judgement, and professional attitudes from the hospitals in which the graduates received their training. Significant relationships were found among three levels of performance in medical school and postgraduate ratings and in all four competence areas. Relationships were strongest at the highest and lowest performance levels. It is concluded that in a substantial number of cases good and poor performance in the first postgraduate year can be predicted on the basis of information already available to the medical school faculty.


Augmentation of clinical services in rural areas by health sciences students. Over a five-year period 230 senior-level students in medicine, nursing, and pharmacy served in clinics located throughout five rural communities. Students participated in the development of the clinics and in the organization of services that otherwise would not have been delivered. Community-based preceptors helped integrate the students' learning about community processes. The project provided experiential learning and interdisciplinary interactions that were enthusiastically received by the students. Follow-up surveys suggested that the experience reinforced interest in eventual practice in rural areas and in interdisciplinary settings. The project demonstrated that students were able to provide clinical services which were useful and acceptable to the communities and which were supported by local practitioners.


Prison health and medical education.

Prison health and medical education. Prison health has long been neglected as an area of serivice by organized medicine and a site for clinical education by health science centers. The University of New Mexico Health Science Center offers an elective, weekly clinical experience for preclinical medical students, senior nursing students, and senior pharmacy students at a prison facility in need of medical services. Students' reaction to the prison experience was strongly positive. Most developed empathy toward the inmates and a greater understanding of prison health problems. Inmates rated the student service highly and requested its continuation. This community health education experience has provided a noncontractual model of a university-prison health alliance.


The volunteer patient as an educational resource. In this article the authors describe the contribution to health science teaching made by volunteer patients in a purely educational setting. Patients with documented illnesses volunteer to give their own history, to be examined, and frequently to provide feedback to students. The over 2,500 such volunteer patients who have participated in this program in a six-year period are enthusiastic and highly motivated. Significant educational benefits are achieved, including the assumption of teaching responsibilities by nonprofessionals. The fact that this large number of ambulatory patients is available suggests that the majority of patients in active treatment settings may also appreciate their opportunity to cooperate in the education of health science students.


Student performance in internal medicine: the effect of previous clerkship experience. To test the assumption that students who have completed other clerkships are likely to perform better in internal medicine, the authors undertook a prospective study of 160 senior students from two classes. Groups of students with little or no senior clerkship experience before their internal medicine clerkship were compared with groups of students who had extensive clerkship experience in disciplines other than medicine. Groups were compared with respect to ward-performance scores and scores on identical multiple-choice examinations. Neither ward-performance nor multiple-choice scores revealed differences attributable to previous clerkship experience. It is concluded that despite areas of instruction and experience which overlap between medicine and other disciplines, previous clerkship experience apparently does not have a beneficial effect on student performance in internal medicine, as measured by these two commonly used methods of evaluation.


Chemical and biological properties of a purified lymphoreticular-stimulating fraction of Corynebacterium parvum (Propionibacterium acnes type I). A method is described in which washed whole cells of Corynebacterium parvum were chemically and enzymatically extracted to remove cytoplasm and cell-wall lipids. The resultant insoluble cell-wall residue possessed lympho-reticular stimulating properties as measured by their ability to increase spleen weight and protect against tumour-cell challenge. Analysis of the final product by chromatography and infrared spectroscopy has shown it to consist of carbohydrate and peptidoglycan, both of which appear to be necessary for the activities measured.


Radioimmunoassay for antibodies to rubella virus and its ribonucleoprotein component. IgA and IgG antibodies to the ribonucleoprotein component of rubella virus have been demonstrated by radioimmune precipitation in sera from patients with recent but not remote rubella infection. This observation suggests that a test for antibodies to the ribonucleoprotein component may provide additional evidence in the diagnosis of recent rubella infection.


Electron microscopy of the L-cycle in Bacillus licheniformis var. Endoparasiticus (Benedek). Electronmicrographs of sections show that the L-phases of Bacillus licheniformis var. endoparasiticus (Benedek) simulate the various types of micro-organism described by previous workers as associated with ostensibly noninfective conditions, notably cancer and arthritis; e.g., mycoplasmas, mycobacteria, corynebacteria and actinomycetes. The stages of the L-cycle, from spheroplasts through smaller and larger 'diphtheroid' bacteria to the fully reverted sporogenous bacillus, differ from one another mainly in their degree of reconstitution of the cell envelopes. Occurrence in 'diphtheroids' of nonresistant, cell-wall-deficient spore-like bodies, confirms their relationship with the true sporing bacillus stage. Large, swollen forms appear to be mother cells of minute stages.


Relationship between sexual intercourse and urinary-tract infection in women attending a clinic for sexually transmitted diseases. The prevalence of urinary-tract infection (UTI), diagnosed by examination of a single midstream urine from sexually active women was found to be 6.4%. Significant bacteriuria was most common in women who presented within 24 h of coitus but was not related to the number of sexual partners. UTI occurred significantly more often in women who presented within 4 days of intercourse than in women seen after a longer interval. Whether frequency of intercourse affects the prevalence of UTI remains to be determined.


Oerskovia species: rare opportunistic pathogens. The second documented instance of opportunistic infection by member of the genus Oerskovia is reported. There is some evidence to suggest that this group of bacteria, which is extensively distributed in the soil, may be more closely associated with man than has hitherto been supposed.


A binding site model of membrane transport: binary and cooperative flows. The flows of solute molecules in a membrane under the influence of concentration gradients are considered within the framework of classical physical theories. A lattice model is constructed in which the binding sites represent potential minima and the flows are regarded as a result of molecules' making discrete transitions between the binding sites. Expressions for two-component currents are derived from certain descriptions for the transition mechanism. Where the molecular movement is given the crudest description, permeability coefficients are identical for both components and there is no current coupling. Where the molecular movement is given some finer detail, the permeability coefficients differ and positive coupling of flows appears. Our result applies to a combination of flows of tracer and abundant species as well as, more generally, to any combination of flows of two components which are distinguishable yet kinetically similar. Also considered are binary currents whose transport mechanism is further controlled by allosteric cooperativity. Whether the cooperative control is short or long ranged, permeability coefficients and fluxes differ appreciably from those without cooperative control. Thus, unlike in the case of channel flow, current coupling here may be either positive or negative, depending on the strength and nature of cooperative coupling. Numerical evidence suggests that the permeability and coupling may have discontinuous behavior, possibly indicating the existence of phase transitions. Our lattice model, from which the formulations for the flows are obtained, is compatible with current concepts of membrane structure.


Hypertonic cryohemolysis of human red blood cells. Hypertonic cryohemolysis of human erythrocytes is caused by incubation of the cells in hypertonic medium at a temperature of 20--50 degrees C (stage 1), with subsequent cooling to 0 degrees C (stage 2). In 0.86 M sucrose hemolysis increases, with increasing stage 1 temperature, whereas in 1 M NaCl cryohemolysis has a temperature optimum at a stage 1 temperature of about 30 degrees C. Cryohmeolysis is inhibited by preceding ATP depletion of the cells and by preincubation of the cells in hypertonic medium at 0 degrees C. In general, anesthetics inhibit cryohemolysis strongly. Only in 1 M NaCl at stage 1 temperatures in the range of 40--50 degrees C is cryohemolysis stimulated by these drugs, if present during the entire incubation period. This effect is abolished, however, when the anesthetic is added after prior incubation of the cells at 40--50 degrees C in 1 M NaCl. Ghost-bound ANS fluorescence indicates complicated conformation changes in the membrane structure during the various experimental stages leading to cryohemolysis. Some of the experimental results can be considered as examples of molecular hysteresis, thus indicating several different metastable structures of the membrane, under various experimental conditions. The described results support the working hypothesis of Green and Jung that the experimental procedure results in membrane protein damage, preventing normal adaptation of the membrane during cooling.


Anionic detergents as divalent cation ionophores across black lipid membranes. Three ionic detergents commonly used in membrane-bound protein isolation and reconstitution experiments, SDS, cholate, and DOC, are shown to act as divalent cation ionophores when incorporated into black lipid membranes made from either oxidized cholesterol or a mixture of phosphatidylcholine and cholesterol (PC/cholesterol = 5:1 mg). At a concentration greater than or equal to 1 microM, SDS shows large selectivity differences between cations and anions and among the different cations tested (Ba2+, Ca2+, Sr2+, Mg2+, and Mn2+). Deoxycholate and cholate at concentrations greater than 4 X 10(-4) M and 10(-3) M, respectively, also act as divalent cation ionophores. The selectivity sequence measured for these two detergents is evidence for a strong ionic interaction between the divalent cation and the anionic charged groups on the detergent. In the case of cholate, the conductance depends on the third or fourth power of the cholate concentration and shows a linear dependence on CaCl2 concentration. The conductance for deoxycholate depends onthe sixth or seventh power of the DOC concentration and is also linearly dependent on the CaCl2 concentration. In an oxidized cholesterol black lipid membrane in the presence of 5 mM CaCl2, small concentrations of LaCl3 (less then 1 microM) inhibit the ionophoric activity of each of the detergents tested. Evidence is presented to show that this inhibitory effect is a nonspecific effect on oxidized cholesterol BLM's, and is not due to a direct effect of La3+ on detergent-mediated transport.


Saxitoxin binding to synaptosomes, membranes, and solubilized binding sites from rat brain. Binding of 3H-saxitoxin to Na+ channels was studied in subcellular fractions prepared from rat brain homogenates. Saxitoxin binding to synaptosomes was saturable with an apparent dissociation constant of about 1 nM; about 1 pmol/mg protein was bound at saturating saxitoxin concentrations. A linear, nonsaturable component of saxitoxin binding accounted for less than 3% of the total binding at 30 nM. Saxitoxin binding to synaptosomes was unaffected by depolarization with elevated K+ concentrations, or by activation of the Na+ channels with batrachotoxin plus a purified polypeptide toxin from the scorpion Leiurus quinquestriatus. A procedure is described for preparing a membrane fraction that contains 70--80% of the total saxitoxin binding activity of the crude homogenate. The specific activity of this fraction was about 4 to 6 pmol/mg protein. About 60--70% of the saxitoxin binding sites were solubilized by incubating these membranes with the nonionic detergent Triton X-100; the detergent-solubilized binding sites eluted at a position corresponding to a mol wt of about 700,000 on gel filtration chromatography. Both membrane-bound and solubilized saxitoxin binding were assayed by a new cation exchange column method. The binding of saxitoxin to both membrane-bound and detergent-solubilized binding sites was saturable with an apparent dissociation constant of about 2 nM. Dissociation of the saxitoxin-receptor complex followed a single exponential decay with a rate constant at 0 degrees of 0.1 min-1 for membrane bound and 0.2 min-1 for detergent-solubilized binding sites. The measured association rate constant was 6 X 10(8) M-1 min-1 at 0 degrees for membrane-bound saxitoxin binding sites.


Intracellular chloride activities and active chloride absorption in the intestinal epithelium of the winter flounder. Intracellular chloride activities, (Cl)c, and the electrical potential difference across the mucosal membrane, psimc, were determined in the isolated small intestine of the winter flounder, using Cl-selective and conventional (KCl-filled) microelectrodes. In the presence of a Na-containing buffer psimc averages -69 mV and (Cl)c averages 24 mM, a value that is 3.4 times that predicted for an equilibrium distribution across the mucosal membrane. On the other hand, when the tissue is then perfused with Na-free buffer, (Cl)c slowly falls to a value that does not differ significantly from that predicted for an equilibrium distribution, and psimc depolarizes significantly. Finally, when the tissue is again bathed in the Na-containing buffer, (Cl)c rapidly returns to a value well above equilibrium. These results, together with those of Frizzell et al. (J. Membrane Biol. 46:27, 1979), provide direct evidence that: (1) Cl is accumulated against its electrochemical potential difference (32 mV) by this tissue, and (2) this accumulation is coupled to and energized by the entry of Na down its steep electrochemical potential difference.


Highly purified basal lateral plasma membranes from rat duodenum. Physical criteria for purity. Preparations of intestinal epithelial cell basal lateral plasma membranes were analyzed with free flow electrophoresis and density perturbation with digitonin. The initial basal lateral membrane preparations were obtained by equilibrium density gradient centrifugation after two different schemes of homogenization and differential sedimentation (A.K. Mircheff, C.H. van Os, and E.M. Wright. 1978. Membr. Biochem. 1:177, and A.K. Mircheff, S.D. Hanna, M.W. Walling, and E.M. Wright. 1979. Prep. Biochem. 9:33. In these preparations, Na,K-ATPase, a marker for the basal lateral mambrane, was purified 16- to 18-fold over the initial homogenate. The preparations were also enriched in NADPH-cytochrome c reductase, alkaline phosphatase, acid phosphatase, and galactosyltransferase. Both free-flow electrophoresis, which separates on the basis of surface charge, and density perturbation with digitonin, which depends on a specific interaction of digitonin with cholesterol-rich membranes, resolved the preparation into three populations of particles. The major population, which represented basal lateral membranes purified 20- to 32-fold with respect to the initial homogenate, contained Na,K-ATPase, alkaline phosphatase, adenylate cyclase, and acid phosphatase. A second population was defined by its content of NADPH-cytochrome c reductase, and the third was defined by its content of galactosyltransferase. Guanylate cyclase appeared to be partitioned between the Na,K-ATPase-rich and NADPH-cytochrome c reductase-rich populations. Galactosyltransferase is also present in fractions which contain the Na,K-ATPase-rich membranes, but the present data cannot exclude the possibility of spillover by the adjacent, galactosyltransferase-rich population. This work emphasizes the importance of multiple, physical criteria for purity in the isolation of subcellular components.


Effect of amiloride on the apical cell membrane cation channels of a sodium-absorbing, potassium-secreting renal epithelium. The effect of the K-sparing diuretic amiloride was assessed electrophysiologically in the isolated cortical collecting tubule of the rabbit, a segment which absorbs Na and secretes K. Low concentrations of amiloride in the perfusate caused a rapid, reversible, decrease in the magnitude of the lumen negative transepithelial potential difference, Vte, transepithelial conductance Gte, and equivalent short-circuit current, Isc, with an apparent K1/2 of approximately 7 X 10(-8) M. The effects of a maximum inhibitory concentration of amiloride (10(-5) M) were identical to those observed upon Na removal from lumen and bath (Na removal from the bath alone has no effect). Removal of Na in the presence of 10(-5) M amiloride had no affect on Vte, Gte, or Isc, and is consistent with the view that amiloride blocks the Na conductive pathways of the apical cell membrane. Further, in the absence of Na, the subsequent addition of amiloride had no influence. In tubules where active Na absorption was either spontaneously low, or abolished by removal of Na from lumen and bath, the elevation of K from 5 to 155 meq/liter in the perfusate caused a marked change of the Vte in the negative direction and an increase in the Gte. These effects could be attributed to a high K permeability of the apical cell membrane and not of the tight junctions. Amiloride (10(-5) M) had no effect on these responses to K. It is concluded that amiloride selectively blocks the apical cell membrane Na channels but has no effect on the K conductive pathway(s). This selective nature of amiloride may indicate that Na and K are transported across the apical cell membrane via separate conductive pathways.


Reduction of stereotyped body-rocking using variable time reinforcement: practical and theoretical implications. The first experiment assessed the effectiveness of two schedules of reinforcement in reducing stereotypy engaged in profoundly retarded patients in ward environments. These schedules were the differential reinforcement of other behaviour (DRO) and variable time reinforcement (VT). This experiment was terminated prematurely because of problems in implementing the DRO contingencies. However, the VT contingency appeared to reduce stereotypy. The second experiment evaluated the VT schedule of reinforcement alone. Significant decreases in amounts of stereotypy from baseline measures were observed in all five profoundly retarded female subjects. It is tentatively concluded that stereotypies in ward and laboratory environments differ in function. This has implications for the treatment of patients who engage in stereotyped behaviour.


Experimental hyperglycinaemia--an evaluation of the efficacy of strychnine therapy in nonketotic hyperglycinaemia. A hyperglycinaemic state resembling the human disease nonketotic hyperglycinaemia (NKH) was created in male adult albino rabbits by injecting subcutaneously a ten  percent aqueous glycine solution. A single dose of 300 mg./kg. caused a transient rise of plasma glycine level, but CSF glycine concentration began to rise only after an injection of 1,000 mg./kg. glycine. Repetition of the latter dose every four hours for twenty-four hours caused a gradual rise of both plasma and CSF glycine. Progressive neurological symptoms, highly resembling the early stages of NKH, developed during this prolonged loading. Numerous therapeutic approaches have been made to NKH which, if not fatal during the neonatal period, leads to severe psychomotor retardation, but only strychnine treatment (100--200 micrograms./kg/. day) has resulted in some improvement of the clinical condition of these patients. However, even the highest tolerated dose of strychnine (1 mg./kg./day) did not significantly alter the progression of neurological symptoms during glycine loading in the present study. All but one of twenty-nine rabbits succumbed during glycine loading, and only three of twenty-one survived when the glucine-antagonist strychnine was administered during glycine loading. Therefore, it seems probable that the protective effect of strychnine in a hyperglycinaemic state is of limited value. Glycine loading influenced intermediate amino acid metabolism in several ways, plasma alpha-amino-N and ammonia level rose and moderate metabolic acidosis developed during the last phase of the experiment. Profound alterations of levels of amino acids involved in glycine metabolism occurred in both blood plasma and cerebropinal fluid.


The effects of institutionalisation on retardates social independence. Subjects were grouped into eight experimental groups to control for mental age (MA) and chronological age (CA) and at the same time to allow the examination of the effects due to the proportion of lifetime spent institutionalised on an objective measure of social dependency. The results suggest that the longer proportion of life-time institutionalised, the more likely the retardate is to be socially dependent. The implications of this finding for retardates in institutional settings is discussed.


Post-maturation of the plastid ribosomal RNA in the plant kingdom. The in vivo fragmentation of the plastid rRNA from plants situated at different places in the evolutionary sclae, with the exception of Algae, was analysed by electrophoresis using fully denaturing conditions. This fragmentation corresponds to an in vivo post-maturation. It exists only in some bacteria and is not random. Five main groups of fragments with the following real molecular weights (Mr) are found in 23 S: ca 0.9 x 10(6); 0.7 x 10(6); 0.45 x 10(6); 0.35 x 10(6) and 0.15 x 10(6). The existence of a large fragment (Mr = 0.9 x 10(6)) corresponds to a primitive type of fragmentation found in some archaic plants. Dicotyledons and several other groups have the same pattern of 23 S fragmentation, often comprising all the fragments mentioned above, whilst Graminaceae (Monocotyledons) constitute a special group with a very predominant 0.35 x 10(6) dalton fragment and the absence of the 0.45 x 10(6) dalton fragment. The plastid 16 S rRNA in all plants studied here has a Mr of 0.54 x 10(6) which is smaller than the 16 S of Escherichia coli taken as reference (0.56 x 10(6) dalton).


The role of metal ions in chemical evolution: polymerization of alanine and glycine in a cation-exchanged clay environment. The effect of the exchangeable cation on the condensation of glycine and alanine was investigated using a series of homoinic bentonites. A cycling procedure of drying, warming and wetting was employed. Peptide bond formation was observed, and the effectiveness of metal ions to catalyze the condensation was Cu2+ greater than Ni2+ approximately Zn2+ greater than Na+. Glycine showed 6% of the monomer incorporated into oligomers with the largest detected being the pentamer. Alanine showed less peptide bond formation (a maximum of 2%) and only the dimer was observed.


Geometry of the dry-state oligomerization of 2',3'-cyclic phosphates. Evaporation of a solution of thymidine plus either the exo or the endo diastereomer of uridine cyclic 2',3'-O, O-phosphorothioate (U greater than p(S) in 1,2-diaminoethane hydrochloride buffer gave the 2',5' and 3',5' isomers of (P-thio) uridylylthymidine (Up(S)dT) in a ratio of 1:2 with a combined yield of about 20%. These isomers were re-converted to U greater than p(S) and dT by a reaction that is known to proceed by an in-line mechanism. Both the 2',5' and 3',5' isomers gave as product the same diasteromer of U greater than p(S) that had been used originally in their formation. These dry-state 'prebiotic' reactions (Verlander, Lohrmann, and Orgel 1973) are thus shown to be stereospecific, and both the 2',5' and 3',5' internucleotide bonds are formed by an in-line mechanism.


Primary structure of pronghorn pancreatic ribonuclease: close relationship between giraffe and pronghorn. Pancreatic ribonuclease from pronghorn (Antilocapra americana) was isolated and its amino acid sequence was determined from a tryptic digest of the performic acid-oxidized protein. Peptides were positioned by homology with other ribonucleases. Only peptides that differed in amino acid composition from the corresponding peptides of ox or goat ribonucleases were sequenced. In a most parsimonius tree of pancreatic ribonucleases, pronghorn and giraffe were placed together and these two were placed with the bovids, leaving the deer as a taxon separate from the other ruminants. The amino acid replacements that determine this tree topology are three rarely occurring replacements shared by pronghorn and giraffe. Notwithstanding their close phylogenetic relationship, both ribonucleases differ strongly in extent of glycosidation, net charge and antigenic properties.


The assessment of sexual function and marital interaction. The increasing need expressed by clinicians and researchers alike for valid and reliable psychological measures of sexual behavior and adjustment contrast with the limited available information on the assessment of human sexual functioning. The aim of this article is to present relevant data on the psychometric characteristics of scales designed to measure one or more aspects of human sexual activity and marital interaction. This list is by no means exhaustive but covers most assessments of either individuals or dyads, mainly in a heterosexual context. Under the title of the scales, which have been arranged by alphabetical order according to the first author's name, the information provided may permit a preliminary judgment concerning the potential applicability of the instrument to the reader's need.


Assessing sexual behavior in couples.

Assessing sexual behavior in couples. The role of formal assessment in the practice of sex therapy with couples is discussed. A case is made for the use of behaviorally oriented paper-and-pencil tests of the self-report variety, in clinical settings, at two points in time: prior to any therapist-client contact and following completion of therapy. Such procedures are both efficient and effective, yielding information relevant to diagnosis, treatment planning, and development of clinical skills. Assessment procedures used routinely at the Stony Brook Sex Therapy Center are described and illustrated using sample cases. The authors suggest that behavioral assessment approaches have considerable clinical potential which has yet to be fully realized.


The DSFI: a multidimensional measure of sexual functioning. The present report summarizes work to date on the Derogatis Sexual Functioning Inventory (DSFI), a multidimensional measure of human sexual functioning. We discuss the rationale for the test as well as the selection of the primary domains of measurement. Reliability coefficients for the various subtests are given, and a review section on validation studies is provided, including a factor analysis, predictive validation, and discriminant function analyses. Prototypic clinical profiles are also provided for several of the major types of sexual dysfunction.


The Sex Knowledge and Attitude Test (SKAT). The Sex Knowledge and Attitude Test (SKAT) was designed to measure knowledge, attitudes and degree of experience in a variety of sexual behaviors, and to be used as a teaching and research instrument. The SKAT has been administered to over 35,000 students, approximately two-thirds of whom have been medical students. SKAT has served two major objectives: to measure changes in knowledge and attitudes after a course or program in human sexuality and to demonstrate the deficiencies of medical and nursing education in preparing health professionals to aid patients with sexual problems. Additional types of research using the SKAT are suggested.


The measurement of marital quality.

The measurement of marital quality. The quality of marital relationships is the most studied topic pertaining to marriage and family life. Moreover, clinicians have become increasingly interested in this variable as divorce rates have climbed and as services for counseling and therapy have become more readily available and more widely accepted. These research and clinical needs necessitate the availability of measures of variables which assess marital quality (e.g., marital adjustment, satisfaction, and happiness). This article discusses the need for such measures, reviews the history of measurements in this area, identifies some conceptual and methodological issues of relevance, and then focuses most specifically on the Dyadic Adjustment Scale developed by Spanier. Some cautions for clinicians are noted, and a discussion of future measurement needs is presented.


Partial hepatectomy reduces both metabolism and toxicity of benzene. Removal of 70--80% of the liver reduced both the metabolism and the toxicity of benzene in rats. Metabolism was evaluated by measuring the levels of urinary metabolites in both sham-operated and partially hepatectomized rats given 2200 mg/kg [3H]benzene sc. Toxicity was evaluated by measuring the incorporation of 59Fe into circulating erythrocytes according to the method of Lee et al. The observation that partial hepatectomy decreases benzene metabolism and protects against benzene toxicity indicates that the liver may play a primary role in the development of benzene-induced bone marrow toxicity. The fact that benzene administration also reduces the ability of the liver to regenerate after partial hepatectomy suggests that the regenerating liver may serve as a model system in lieu of the bone marrow for studying the mechanism by which benzene inhibits cell proliferation.


A new in vitro method for testing plant metabolism in mutagenicity studies. A rapid method was proposed to detect whether a harmless agricultural chemical can be converted into a mutagenic one by plant metabolism. The method is based on the use of Nicotiana alata cell cultures. Results obtained with five pesticides (atrazine, dichlorvos, tetrachlorvinphos, Kelevan, and maleic hydrazide) suggest that the proposed method simulates the metabolism of the whole plant. This procedure was also successfully applied to the genetic system of Aspergillus nidulans. One pesticide, atrazine, induced mutations and somatic segregation only after metabolism during cocultivation with N. alata cells.


Perinatal toxicity of maneb, ethylene thiourea, and ethylenebisisothiocyanate sulfide in rodents. The potential of the fungicide maneb and two of  its metabolites, ethylenebisisothiocyanate sulfide (EBIS) and ethylene thiourea (ETU), to induce perinatal toxicity in four species of rodents was investigated. The compounds were admininistered to rats and mice during the period of organogenesis, and ETU was also administered to rats and mice during the period of organogenesis, and ETU was also administered by oral gavage for a similar period to hamsters and guinea pigs. Treatment also continued through the lactational period in groups of rats that were allowed to give birth. Fetuses were examined for signs of toxicity, including terata, and neonates for reflex developement and open-field behavior. Maneb produced hydrocephalus in fetuses in litters of rats receiving 480 mg/kg . d. No fetotoxic effects were noted in litters of rats receiving EBIS at doses at high as 30 mg/kg . d. ETU proved to be a potent teratogen in the rat. Among the effects seen at doses of 40 mg/kg . d or greater were hydrocephalus, encephalocele, kyphosis, and various defects of the digits. Neither maneb (up to 1500 mg/kg . d), ETU (up to 200 mg/kg . d), nor EBIS (up to 200 mg/kg . d) elicited signs of fetal toxicity in the mouse. ETU also failed to result in fetal toxicity when administered to the hamster (100 mg/kg . d) or the guinea pig (100 mg/kg . d). Neither maneb nor EBIS produced significant dose-related alterations in the behavioral development of perinatally exposed rat neonates. At doses that also produced neonatal hydrocephalus, ETU produced significant increases in the open-field activity of the neonates. In addition to the perinatal effects noted above, both maneb and EBIS caused maternal limb paralysis in the rat, an effect not noted in the mouse at much higher doses.


Embryotoxic and teratogenic effects of petroleum hydrocarbons in mallards (Anas platyrhynchos). Egg surface applications of microliter quantities of crude and refined oils of high aromatic content are embryotoxic to mallards (Anas platyrhynchos) and other avian species; applications of aliphatic hydrocarbons have virtually no effect. Mallard eggs at 72 h of development were exposed to a mixture of aromatic hydrocarbons or to aromatic compounds representative to those present in crude oil to assess their toxicity. The class composition of the mixture was similar to that of South Louisiana crude oil, an American Petroleum Institute reference oil. Application of 20 microliter of the mixture reduced embryonic survival by nearly 70%. The temporal pattern of embryonic death was similar to that after exposure to South Louisiana crude oil. Embryonic growth was stunted, as reflected by weight, crown-rump length, and bill length, and there was a significant increase in the incidence of abnormal survivors. When individual classes of aromatic hydrocarbons were tested, tetracyclics caused some embryonic death at the concentrations in the mixture. When classes were tested in all possible combinations of two, no combination appeared to be as toxic as the entire mixture. Addition of the tetracyclic compound chrysene to the aromatic mixture considerably enhanced embryotoxicity, but could not completely account for the toxicity of the crude oil. The presence of additional unidentified polycyclic aromatic hydrocarbons as well as methylated derivatives of polycyclic aromatic compounds such as chrysene may further account for the embryotoxicity of the crude oil.


Accumulation and excretion of [1-14C]bis(tri-n-butyltin) oxide in mice. Laboratory COBS strain albino mice were administered [1-14C]bis(tri-n-butyltin) oxide in dilute aqueous solutions. Test solutions were prepared by using an elastomeric controlled-release formulations that emitted the agent at a constant rate. Tissue and excreta were periodically analyzed for 14C by standard liquid scintillation counting methods. Assuming that the label was not cleaved from the tin, 90--96% of the ingested agent was excreted, predominantly in the feces. Of the remainder, kidney levels were high, possibly indicating metabolism; tissue accumulation was diffuse, with liver, spleen, and fat predominating. Blood levels were low. Termination of organotin ingestion led to rapid clearance of storage sites.


Variation of corneal glycosaminoglycan values of hares in relation to environmental pollution by industrial emissions. In localities contaminated by industrial emissions a significant decrease in keratan sulfate and chondroitin 4-sulfate occurs in the cornea of the hare. The changes also occur in hares living near small emission sources with a local emission zone; therefore they should not be neglected, especially if the area is used for recreation, as in the case reported here. The decrease in glycosaminoglycan values is more pronounced in adults than in juveniles, because of the length of exposure. Relatively large amounts of keratan sulfate in the glycosaminoglycan fraction correspond to changes expected in a prematurely senescent tissue. Because of the painstaking laboratory work required, assessment of glycosaminoglycans could be used for special bioindication purposes but would not be suitable for routine monitoring.


Nickel(II)-binding constituents of human blood serum. Studies were undertaken to investigate the Ni(II)-binding properties of human blood serum and to identify the low-molecular-weight Ni(II)-binding constitutents in the serum. Three Ni(II)-binding fractions were obtained when labeled nickel chloride (63NiCl2) was added to the native serum. Of the total Ni(II), 95.7% was associated with albumin, 4.2% was bound to low-molecular-weight components, and a small fraction, usually less than 0.1% was associated with a high-molecular-weight protein that was eluted in the void volume of Sephadex G-150. Amino acids were shown to be responsible for the low-molecular-weight Ni(II)-binding fraction and L-histidine was found to be the main (Ni(II)-binding amino acid in human blood serum. Compared with albumin, L-histidine was shown to possess a greater affinity for Ni(II). Ni(II)-binding to human albumin became evident only when no more L-histidine was available. Since the concentration of albumin is much higher than the concentration of L-histidine in normal serum, most of the added Ni(II) was associated with albumin. The equilibria between Ni(II)-L-histidine and Ni(II)-albumin may facilitate the transport of Ni(ii) between blood and tissues.


Inorganic mercury(II)-binding components in normal human blood serum. The interaction of Hg(II) with human blood serum was studied at physiological pH. Most of the Hg(II) was found to be associated with the proteins, and only a small fraction was associated with the low-molecular-weight substances in serum. Albumin is the major Hg(II)-binding protein (greater than or equal to 90%) in serum. Among the amino acids, L-cysteine has the highest affinity for Hg(II). In dialyzed serum having equimolar concentrations of Hg(II), albumin, and L-cysteine, the amount of Hg(II) found in the supernatant after ultracentrifugation was about 6--7%. There are preferential Hg(II)-binding sites on the albumin molecule. However, no significant change in the circular dichroism spectrum of albumin was detected until at least two equivalents of Hg(II) were present. Hg(II) can mediate the formation of the albumin dimer as well as a ternary complex of the type albumin-Hg(II)-L-cysteine. The latter presumably plays an important role in the transport of Hg(II) between blood and various tissues.


Proliferation of lung and airway cells induced by nitrogen dioxide. Proliferation of lung cells of Chinese hamsters was examined in several regions of the lung parenchyma and ciliated airway epithelium after a 24-h exposure to 28.2 mg/m3 (15 ppm) nitrogen dioxide (NO2). Label was retained 3 wk after the injection of [3H]thymidine, and autoradiographic methods were used to localize the site of retention. By 24 h after administration of [3H]thymidine, parenchymal areas, exclusive of airways, showed an increased labeling index, indicative of cell death and replacement. This increase in the number of labeled cells persisted for 3 wk. Type II cells were labeled twice as frequently in regions of the terminal bronchiole than in other alveolar areas. Type II cell cycle time was reduced from 26 to 3 d after NO2 exposure. Alveolar macrophages were significantly labeled in the alveolar areas during the thymidine pulse at the end of the exposure episode and retained label for 3 wk. Airway epithelia showed no labeling in the trachea and progressively greater labeling in increasingly small er airways. Epithelial cells lining the small airways and alveoli showed greater susceptibility to NO2 injury than cells lining the bronchi or trachea. Nonciliated or basal cells serve as a precursor of ciliated cells in the epithelium of small airways (0.35 mm) and bronchi.


Effect of styrene and fiber glass on small airways of mice. Three groups of 20 mice each were exposed to respirable glass fibers, to 300 ppm styrene vapor, and to glass fibers plus 300 ppm styrene. The glass fiber concentration was congruent to 1070/cm3; fiber diameters were under 3 micron and fiber lenths under 10 microns. The 5 h/d, 5 d/wk inhalation experiment lasted 6 wk. Glass fibers did not cause any lung damage when inhaled separately but combined styrene and glass fibers induced a change in the cellularity of the bronchiolar lining, where aprocrine-type cells became predominant. The same type of bronchiolar epithelial change was found in 10% of the styrene-exposed mice, while most of the styrene-exposed animals (90%) presented thickened bronchiolar walls becasue of stratification of the bronchiolar epithelium.


Residue studies with [14C]fosamine ammonium in channel catfish. The active ingredient in du Pont Krenite brush control agent is ammonium ethyl carbamoylphosphonate (fosamine ammonium salt, formerly known as DPX-1108). Residues in channel catfish exposed to 1.1 ppm 14C-carbonyl-labeled fosamine ammonium in water for 4 wk were found to plateau in 2-3 wk with an accumulation factor (ratio of residue in fish to residue in water) of less than 1. In a separate experiment channel catfish were placed for 4 wk in a tank containing [14C]fosamine ammonium-treated soil (15 ppm) that had been aged for 30 d prior to flooding and initiation of fish exposure. The residue levels in this latter group of catfish also plateaued in 2-3 wk with an accumulation factor of less than 1. In both experiments, after the 4-wk exposures, the fish were transferred to fresh water for 2-wk depuration periods, during which residue levels dropped 50--90%. No effects on the fish were observed during these experiments.


In vitro formation of neuroglial synapses. Neuroglial synapses have been systematically observed in histotypical cerebellar rotary tissue cultures. These axoglial contacts appear as excitatory-like synapses in which the presynaptic element contains rounded synaptic vesicles accumulated at the presynaptic active zone. The post-synaptic structures were always the somata as well as processes of astrocytic glial cells. The axoglial contacts appear in these cultures when they are prepared from 16-day-old chick embryos cerebellum and cultivated during 6 days. To explain these neuroglial interrelationship it has been suggested as a working hypothesis that glial and nerve cells develop plastic capacities in order to establish synaptic contact in the in vitro conditions.


Uptake of 2-deoxy-D-glucose by cortical synaptosomes from the Long-Evans rat. Uptake of 2-deoxy-D-glucose (2-DG) has been studied in synaptosomes from the Long-Evans rat. Although there are some differences, the results are generally similar to those reported for Sprague--Dawley rats. Both D-glucose and 2-DG are taken up by the same carrier, since D-glucose was found to inhibit uptake of 2-DG. Uptake is highly dependent on a source of metabolic energy, since incubation at 0 degrees C completely eliminated uptake, while 10(-3) M 2,4-dinitrophenol (DNP) inhibited uptake by 76.5%. Uptake has also been measured as a function of both 2-DG and sodium concentration and the data fitted to a model. Sodium is found to inhibit uptake. A model assuming noncompetitive inhibition by sodium gives best fit to the data. Thus both Kt and apparent Vm are dependent on the sodium concentration. Although these effects are small, Kt increases with [Na], while apparent Vm declines.


Cerebral uptake of nicotine and of amino acids. Nicotine is among the compounds that enter the brain very rapidly (blood-flow-limited). It also leaves the brain rapidly; by five minutes, 90% exits, an exit somewhat slower than that of water. In spite of rapid exit, brain levels remain higher than levels in blood over a wide range of blood concentrations. Nicotine enters the fetal circulation from the maternal blood; it enters fetal brain but to a smaller extent than adult brain. Nicotine entry is different from that of amino acid: No interaction of amino acid transport and nicotine could be detected. Most close analogs have no effect on nicotine uptake, but at higher concentrations nicotine uptake is saturable. Nicotine and morphine mutually inhibit each other's uptake. The results suggest an uptake compartment (lipid space) for nicotine shared by morphine.


The effect of morphine tolerance on the incorporation of 3H-leucine into proteins of rat synaptic membranes. The rate of incorporation of 3H-leucine into proteins of the synaptic junctional and nonjunctional membranes and synaptic vesicles of rat brain has been examined in control and morphine-tolerant rats. There are no discernible differences between control and tolerant animals in amount of protein as measured by densitometric tracings of dye-stained proteins separated by acrylamide gel electrophoresis from the three membrane fractions of whole brain areas. However, there are differences in the turnover of membrane protein: three vesicle protein bands and one junctional-membrane protein band are significantly more highly labeled, and one junctional-membrane protein is significantly less highly labeled by 3H-leucine in samples from tolerant rats. Of these, the two junctional-membrane proteins can be tentatively identified as components of the post synaptic densities, and one of the vesicle proteins as tubulin.


Pediatric pelvic fractures: review of 52 patients. Fifty-two patients (ages 1 to 16 years) with pelvic fractures were hospitalized at an urban medical center during a 5-year period. All patients with acetabular fractures had adjacent hemipelvis fractures. None were seen to develop symptomatic acetabular dysplasia. Stable breaks in the ring (anterior ring fracture) were encountered most frequently. While many patients were discharged ambulating within a short time, over 50% had prolonged hospitalizations due to associated truma. Only one child had serious urologic trauma, demonstrating that isolated anterior ring fractures in children are not as treacherous in terms of pelvic content injury as those one might encounter in adults. Unstable breaks (anterior and posterior ring fractures) pose acute and chronic management problems and associated injuries are often fatal. Life-threatening complications may overshadow proper fracture management. It is critical to maintain a symmetrical pelvis in order to prevent either cephalad translation or anterior-posterior hemipelvis rotation. A child with the latter problem is presented in detail.


Filtration of debris from banked blood.

Filtration of debris from banked blood. Commercially available filters will effectively remove microaggregates from stored blood. The combined results of screen filtration pressure (SFP), debris weight, and particle size analysis offer a reproducible means of evaluating different filters. The effectiveness of three blood filters (Fenwal, Bentley, and Pall) is evaluated using SFP, debris weight measurement, particle size analysis, and determinations of filter capacity. Of the filters studied the Fenwal filter provides the most efficient means of removing debris while maintaining adquate flow rates for relatively large volumes of blood. The filter appears comparable to the Swank filter in overall effectiveness and flow characteristics.


Adenylate cyclase after burn injury: resistance to desensitization by catecholamines. In vivo injection of isoproterenol(IPR) (4 mg/kg) in normal rats caused fat cell adenylate cyclase to become desensitized to stimulation by IPR in vitro. In contrast, adenylate cyclase from tissues of burn-injured rats (20% body surface, full-thickness scald) remained fully responsive to stimulation by IPR for several days after injury even though catecholamine excretion was elevated more than twofold. Furthermore, fat cell adenylate cyclase from burn-injured animals was not desensitized after acute in vivo IPR injections, whereas adenylate cyclase from the shams did become desensitized after acute IPR injections. To determine whether the apparent resistance to desensitization in burn-injured rats might be an adaptation to the chronic elevation of catecholamines that follows burn injury, two other rat models in which catecholamines are chronically elevated were studied: one was produced by a twice daily schedule or IPR (1 mg/kg) injections for 3 weeks; the other by 3 weeks' cold exposure (0--4 degrees C). As had been observed in burn injury, adenylate cyclase remained fully responsive to IPR in both models, and adenylate cyclase from the cold-acclimated rats was resistant to desensitization by acute injections of IPR. It therefore seems likely that chronic elevations of catecholamines evoke regulatory mechanisms in target cells to circumvent the desensitizationwhich would otherwise occur consequent to acute exposures to catecholamines. In burn injury this  may result in an inadvertent adaptation which contributes to hypermetabolism.


Effects of reserpine upon thermal stress-induced cardiovascular changes. The cardiovascular changes induced by 15% total body surface area third-degree burn have been studied in anesthetized dogs. The responses observed were a decrease in plasma volume, a decrease in cardiac output, and a slight but insignificant fall in mean arterial pressure. Graded doses of reserpine ranging from 0.1 to 1.0 mg/kg were administered preceding thermal trauma, and produced a reduction in plasma volume loss. The most effective dose of reserpine was 0.2 mg/kg. Despite the significant reduction (approximately 50%) of plasma volume loss in this dosage group, there were no significant alterations in either cardiac output or mean arterial pressure. These results demonstrate that reserpine is effective in reducing plasma volume loss but ineffective in altering the other cardiovascular parameters observed. Based upon the size of the maximally effective dose in reducing plasma volume loss and the failure of this dose to alter the other cardiovascular responses, it is postulated that the plasma loss reduction may be due to some action of reserpine other than its release of catecholamines and reduction in catecholamine stores.


Clinical implications of blood gas analysis of chest tube drainage. Blood gas analysis of chest tube drainage following thoracostomy for experimental and clinical penetrating chest injuries was evaluated to determine its usefulness in predicting the etiology of the injury. Twenty dogs were divided into four groups and sustained right chest injury as follows: Group I--closed chest lung laceration; Group II--open chest lung laceration; Group IIII-gunshot wounds; Group IV--thoracotomy and injection of autologous, mixed venous blood. All animals and 14 patients who sustained penetrating chest injury were made simultaneously from chest tube draininage, systemic artery, and central vein in all dogs and patients. Eight patients (Group A) had pneumothorax; six patients (Group B) did not. Mean control canine aortic PO2 and pulmonary arterial PO2 values in Group I did not differ significantly from those in the other three canine groups, nor from the two human groups. Group II dogs exhibited chest tube PO2 which was significantly (p less than 0.01) above aortic PO2. In Group IV, chest tube PO2 was increased significantly above pulmonary arterial blood. Patients without pneumothorax had values for PO2 in chest tube drainage and aorta which were not significantly different, whereas when pneumothorax was present, PO2 of chest tube drainage was significantly higher than that of aortic PO2. Thus blood gas determinations on chest tube drainage may reflect the nature of the injury; however, the presence of air in the pleural space can result in oxygenation of contained blood well above systemic arterial levels.


Injury patterns in motorcycle accidents. A retrospective study of 260 cases of motorcycle accidents which occurred over a 4 1/2 year period is reported. Approximately 8% died of their injuries. The vulnerability of the tibia to open fractures is noted, and the frequent association of these open injuries with severe contamination and devitalization of tissues resulting in a high complication rate. Severely comminuted intraarticular fractures of the distal tibia and radius were numerous, and one is tempted to name the injury the "motorcycle radius." Traumatic amputations were few and all involved the lower extremity. Fractures of the cervical and thoracic spine numbered only one each, but in each instance severe neurologic sequelae ensued. A plea is made for more accident prevention measures including protective equipment and driver education specific for the motorcyclist.


Complete sensorimotor paralysis after cord injury: mortality, recovery, and therapeutic implications. In 273 completely paralyzed cord injured patients, the 1-year mortality was 34% in the patients with cervical fractures and 7% in the patients with thoracic and thoracolumbar fractures. Recovery of useful motor function return occurred in 6.7% of the cervical and 11% of the thoracic and thoracolumbar patients; only 1% of the patient population became completely normal. No specific treatment could be singled out as aiding recovery. A case with recovery from complete paralysis after C5--6 fracture-dislocation is presented.


Ayptical lumbar spine injury from a two-point seatbelt. A case of atypical lumbar spine injury of a 20-year-old man is described. Injury resulted from a car crash while the man was wearing a two-point safety belt. The characteristics of injuries caused by seatbelts are described. In previous cases displacement fractures were usually at the same level. The patient reported is unusual in that a longitudinal fracture of L3 and injury at two different levels occurred. Recovery was uneventful.