[Selective phytotoxic activity of N,N-di,sec.butylamides of aminobenzoic acids mono-, di- and tri-substituted on the nucleus]. N,N-di,sec.butylaminobenzamides, mono-, di- or trisubstituted on the nucleus with methyl and/or halogen groups were prepared and tested for phytotoxicity. The corresponding benzoic acids and series of N-alkyl- and N,N-dialkylamides of 2-amino-3-bromo-5-methyl-, 2-amino-3,5-dibromo, 2-amino-3,5-dichloro- and 3-amino-2,5-dichlorobenzoic acids were studied in parallel. Both pre- and post-emergence phytotoxicity tests were carried out with doses of 6 kg/ha or less on seven representative weeds and some plants of agricultural interest. The series of N,N-di,sec.butylamides studied proved to be effectively phytotoxic on absorption through either the roots or the foliage. As regards the effect of substitution in the nucleus on the phytotoxicity of these amides, 3,5-dihalogenation proved important. The results also showed: 1) the importance of two sec.butyl groups on the amide nitrogen for the appearance of selective phytotoxicity against two grass weeds; 2) the different behaviour of the two acids (XXIa) and (XXIIa) in comparison with the corresponding di,sec.butylamides (XXI) and (XXII); 3) the importance of derivative (IL) which was highly active against graminaceous weeds but showed low phytotoxicity against crop plants, graminaceous ones included.


[Research on substances with antiblastic activity. LXI. Synthesis of 6-amino- and 7-amino-9-keto-9H-pyrrolo[1,2-a]indole derivatives]. Intramolecular cyclization of 1-(2-carboxy-4-nitrophenyl)pyrrole afforded 7-nitro-9-oxo-9H-pyrrolo[1,2-a]indole, which was then reduced to 7-amino-9-oxo-9H-pyrrolo[1,2-a]indole. The same procedure was adopted for the synthesis of 6-amino-9-oxo-9H-pyrrolo[1,2-a]indole starting from 1-(2-carboxy-5-nitrophenyl)pyrrole. The preparation of some N-acylderivatives of the above cited aminoketones is reported. These compounds shall be subjected to biological screening against Leukemia L 1210 as a simple analogues of Mitomycin C.


[2-amino-3,5-dichloro-benzoic acid and 3-amino-2,5-dichloro-benzoic acid derivatives with phytotoxic action]. Derivatives of 2-amino-3,5-dichloro- and 3-amino-2,5-dichlorobenzoic acids have been prepared in order to extend previous research regarding the phytotoxicity of these two acids and of the corresponding N,N-di,sec.butylamides. The methyl esters of the two acids, the corresponding acids acetylated on the amino group and their respective methyl esters, and the N,N-di,sec.butylamides acetylated or formylated on the amino group were prepared. All these compounds were subjected to pre- and post-emergence tests using seven representative weeds, using doses of 6 kg/ha and, where substances proved active, at lower doses also. The results showed the importance of the N,N-di,sec.butylamide of 2-amino-3,5-dichlorobenzoic acid which, in contrast to the other derivatives tested, shows selective activity. For 3-amino-2,5-dichlorobenzoic acids and the amides tested, it was confirmed that only the acid shows marked generic phytotoxic activity in both pre- and post-emergence tests. It should be noted that the methyl ester of 3-acetylamino-2,5-dichlorobenzoic acid shows selective phytotoxicity activity.


[Structure-activity relationship in reactivators of acetylcholinesterase inhibited by phosphoric esters. XII. Hydroxyiminomethylalkylpyridine iodomethylate]. 2-Hydroxyiminomethyl-4-alkylpyridine methiodides were prepared and tested for their in vitro reactivating potency on phosphorylated electric eel cholinesterase. They were also tested as in vivo protecting agents: only one of the compounds, 4-methyl-2-hydroxyiminopyridine, offered a greater protection from DFP than 2-PAM, the others had little to no effect.


[Cardiovascular action of 1,2,4-benzothiadiazine-1,1-dioxide derivatives. VII]. A series of dimethylamino-, diethylamino-, pyrrolidyl- and morpholylalkyl derivatives of 3-amino-1,2,4-benzothiadiazine-1,1-dioxide (compounds I leads to XX) was prepared and tested for cardiovascular activity. It was found that substitution of the alkyl group with the above mentioned groups in 3-amino-1,2,4-benzothiadiazine-1,1-dioxide derivatives in most cases causes marked dissociation of hypotensive activity from bradycardial activity and also disappearance or great reduction in the effect on differential pressure. It was also found that hypotensive activity is particularly dependent on the nature of the basic chain in the two components: length of the carbon chain between the two nitrogens and nature of the basic grouping. For the first component a chain of three carbon atoms seems the most effective and for the second the diethylamino group seems the most favourable. In addition, substituents in the benzene ring influence hypotensive activity, often positively, and 6,7-dichlorosubstitution in some compounds also affects the increase of differential pressure.


[Reaction of ortho-ortho-dimethylphenacyl-halides with formamide. Formation of 4(5)-(ortho-ortho-dimethylbenzoyl)imidazoles]. Reaction of 2,3,5,6-tetramethylphenacyl halides with formamide did not produce the expected 4(5)-(2,3,5,6-tetramethylphenyl)imidazole, but 4(5)-(2,3,5,6-tetramethylbenzoyl)imidazole (VII) was isolated as the major product together with 5-(2,3,5,6-tetramethylphenyl)oxazole (III), alpha-formylamino-2,3,5,6-tetramethylacetophenone (IV) and alpha-chloro-beta-amino-vinyl 2,3,5,6-tetramethylphenyl ketone (IX) as by-products. The corresponding mesitylene derivatives gave analogous results, whereas 4(5)-(2-methylphenyl)imidazole was obtained from 2-methylphenacyl bromide as expected according to the Bredereck's reaction. The structure of the isolated compounds were elucidated by element analysis, mass, I.R., U.V. and N.M.R. spectra, and by chemical reactivity.


[Correlative analysis in the study of enzyme-ligand interactions]. A comprehensive study on enzyme ligand interactions by QSAR techniques is discussed. Thirteen correlation equations are presented which relate activity of 1086 ligands of isolated chloroplasts, chymotrypsin, dihydrofolate reductase, xanthine oxidase and guanine deaminase to their chemical structures. Two kinds of space within and on the surface of an enzyme are defined by means of pi and MR constants. Emphasis is put on the use of indicator variables as a means of rationalizing special enzyme-ligand interactions. The use of such studies for drug development is discussed.


[Bicyclic piperazine homologues XIV (1). Synthesis and analgesic activity of 3,8-diaza-bicyclo[3.2.1.] octane derivatives]. The synthesis of two new series of 3,8-diazabicyclo [3.2.1] octane derivatives is described. The first series includes some 3-(or 8)-allyl and 3-(or 8)-(3,3-dimethylallyl) derivatives of 3,8-diazabicyclo [3.2.1] octane and 3,8-diazabicyclo [3.2.1] octane-2-one. The second series includes some esters and carbamates of 3-(3-hydroxy-3-methyl)butyl-3,8-diazabicyclo [3.2.1] octane. Two new 3,8-diazabicyclo [3.2.1] octane derivatives structurally related to propoxyphene are also described. Some pharmacological data of these compounds are reported.


[Alkylation of delta 6-octalone-1].

[Alkylation of delta 6-octalone-1]. In connection with the synthesis of shwarone (II), a sesquiterpinoid with interesting pharmacological properties, some results on the alkylation in the 9-position of the model substance delta6-octalone-1 (VI) are reported. Methylation, especially if carried out in polar aprotic solvents, gives mainly the trans derivative, this being the type needed for synthesis of compound (II); alkylation with allylbromides and propargyl gives mainly the cis isomer.


[Bromination of 3-amino-1,2,4-benzothiadiazine-1,1-dioxide]. The bromination of 3-amino-1,2,4-benzothiadiazine-1,1-dioxide (1) in N,N-dimethylformamide has been studied. Depending on the operating conditions the reaction produces 7-bromo-3-amino-1,2,4-benzothiadiazine-1,1-dioxide (II) or 5,7-diabromo-3-amino-1,2,4-benzothiadiazine-1,1-dioxide (III). Derivatives halogenated at the nitrogen were not isolated in any of the experiments.


[Reactions of potassium salts and methyl esters of some aroylhydrazino-carbodithioic acids]. In continuation of previous research designed to obtain compounds of pharmacological interest, the following substances were prepared, from the potassium salts (I-III) and from the methyl esters (IV-VI) of some aroylhydrazinocarbodithioic acids, derivatives of 1,3,4-oxadiazole (VII-XV), of 3-aminorhodanine (XVI-XVIII), of 1,2,4-triazole (XIX-XXI), of 7H-(1,2,4)-triazol[3,4-b] [1,3,4] thiadiazine (XXII-XXIV) and of 1,3,4-thiadiazole (XXV-XXX). The compounds have present in the molecule a nucleus and radical which have produced marked biological activity in other series of compounds. To date some of the above compounds have shown antibacterial, antimycotic and antimitotic activity.


What will 1984 be like? Socioeconomic implications of recent twists in age structure. Since 1940, under conditions of restricted immigration and high and sustained growth in aggregate demand, shifts in the relative number of younger versus older adults have had a pervasive impact on American life. Before 1960, younger males were in increasingly short supply and their relative economic position substantially improved; after 1960, the opposite was true. Since the early sixties, as the relative condition of young adults has deteriorated, marriage has been increasingly deferred and fertility reduced. The labor force participation of young women has risen at above average rates, and that of older women has risen at below average rates. Changes in the age structure of the working age population have also contributed to a combination of rising unemployment and accelerating inflation. Cohort divorce rates, suicide among young males, crime rates, and political alienation have worsened. The rise in college enrollment rates has been interrupted, and SAT scores have declined. In contrast, in the period 1940-1960, changes in these various magnitudes were typically of a more favorable sort. The United States is now at the start of a new period of growing scarcity of young adults as a result of the birth rate decline that set in after 1960. This implies that the 1980s will see a turnaround or amelioration in a wide variety of these social, political, and economic conditions, some of which have been taken as symptomatic of a hardening social malaise.


A model of fertility by planning status. Data from the 1965 and 1970 National Fertility Studies are used to produce classifications of births and exposure to births by planning status for real and synthetic marriage cohorts, covering the experience of the 1940s, 1950s, and 1960s. Indices of reproductive input (three ends, three means, and three conditions) and of conventional reproductive output (such as the mean number of unintended births) are derived from these observations. The outputs are expressed as deterministic equations in terms of the inputs; this permits the study of the structure of fertility determination. The model provides a parsimonious description of the sources of change in fertility and an instrument of possible use in policy.


The malleability of fertility-related attitudes and behavior in a Filipino migrant sample. The malleability of fertility-related attitudes and behavior was studied by analyzing data collected from cross-sectional groups of Filipino migrants who had lived in the United States for varying lengths of time, in conjunction with data from a comparison group of Caucasians from the Filipinos' neighborhoods. With increasing number of years lived in the United States, Filipino migrants' fertility-related knowledge, attitudes, and desires became increasingly similar to those of the Caucasian group, but their contraceptive behavior did not. While approximately equal numbers of Filipinos and Caucasians were contracepting, Filipino couples regardless of duration of stay in the United States were using less effective methods with less regularity. Despite these contraceptive behavior patterns, Filipino migrants perceived that they would have 0.32 fewer children in the United States than they would have had had they remained in the Philippines. By far the most predominant reason given by Filipino respondents for changing fertility patterns in the United States was the difficulty of obtaining child care in the new environment.


The relationship between apartment living and fertility for blacks, Mexican-Americans, and other Americans in Racine, Wisconsin. Recently published data from a sample of Bogotá, Colombia public housing residents  show that apartment dwellers, but not house dwellers, reduced their fertility in a tight housing market. We propose that the utility-cost theory of fertility accounts for this finding, and, using this theory, we predict that (a) apartment residents will not decrease their fertility in an open housing market and (b) higher fertility will be associated with larger dwellings. Longitudinal data from a sample of Midwest urban blacks, Mexican-Americans, and other Americans support both predictions. The substantive implications are discussed.


Age, biological factors, and socioeconomic determinants of fertility: a new measure of cumulative fertility for use in the empirical analysis of family size. To influence the number of children ever born to a woman, socioeconomic variables must operate through behavioral and biological mechanisms such as the age at marriage, the level of fertility in the absence of deliberate fertility control, and the level of control exerted to reduce fertility within marriage. In this paper, we propose a new measure of cumulative fertility which is standardized for the age-fecundity relationship and for exposure to the risk of conception associated with duration of marriage. A simple model of fertility behavior which incorporates some of the mechanisms through which socioeconomic factors may affect fertility is developed and applied to data from the United States to demonstrate the properties of alternative measures of family size. The results indicate that use of the new measure allows more precise estimates of socioeconomic fertility relationships than would be obtained with children ever born or by sample stratification.


Estimating the intrinsic rate of increase of a population from the average numbers of younger and older sisters. Based on stable population theory, a mathematical relationship is developed between the intrinsic rate of increase (r) of a population and the ratio (Z) of the average number of younger sisters ever born to the average number of older sisters ever born, for a random sample of women in the population. This mathematical formula is then converted into a technique for estimating r from data on numbers of sisters. The extent to which the technique may be generalizable to actual populations is discussed.


The Demeny-Shorter and three-census methods for correcting age data. This paper presents, tests, applies, and compares methods that utilize age data collected at consecutive censuses to examine and adjust for age and coverage errors. The Demeny-Shorter method, for example, was devised for this purpose, and its flexibility in regard to census coverage errors is examined. The Demeny-Shorter method is found difficult to apply directly, so a method based on the same idea as the Demeny-Shorter method  but utilizing age data from three, instead of two, successive censuses is presented and discussed as a possible alternative. This three-census method is applied to data from Turkey's censuses and, in some cases, found to be better than the Demeny-Shorter method, because the former allows for and estimates the likely changes in census coverage and different patterns of age errors in successive censuses. Unfortunately, the three-census method cannot be applied to data from most developing countries on account of a lack of the requisite series of censuses.


Adjustment of rates using multiplicative models. By the conception of an underlying multiplicative model for cross-classified data, a statistical method for the adjustment of rates is suggested. This method rests upon the multiplicative definition of interaction in cross-classifications and can lead to results different from those obtained from the more usual methods (e.g., Kitagawa, 1964). Comparisons with alternative approaches are made, and illustrative applications to data are provided.


An evaluation of Brass mortality estimates under conditions of declining mortality. An evaluation of the Brass childhood mortality estimates under conditions of declining mortality shows them to overestimate current mortality. Error increases as the rate of mortality decline increases, as the childhood age up to which cumulative mortality is being estimated increases, and as age at onset of childbearing decreases. We use the results to develop a method for correcting the Brass estimates for the effects of quasistability. The method requires an estimate of the rate of mortality decline within the population in addition to information on the pattern of childbearing in the population.


Dynamics of some special populations with NRR = 1. We discuss two special cases of population dynamics with changing vital rates subject to the constraint NRR = 1 and consider the specifics of ergodicity and stationarity. By restricting the number of age groups to two, we can make explicit the way weak ergodicity works. When mortality is constant and the period NRR = 1, a life-table stationary population eventually results; everything of demographic interest (except age-specific fertility and the cohort NRR) is asymptotically constant. With changing mortality, but both period and cohort NRR = 1, only weak ergodicity holds, and everything changes over time.


Population movement and city-suburb redistribution: an analytic framework. This paper introduces an analytic framework that can be used to assess the relationships between individual movement differentials and place characteristics, on the one hand, and aggregate mobility levels and city-suburb population change (in size or composition), on the other. Application of this framework using census data for individual metropolitan areas allows the analyst to decompose population changes due to net migration into contributing mobility streams and their component rates which are subject to unique community and individual influences. The paper provides both theoretical and empirical rationale for the framework, illustrates its use with 1970 census data, and discusses its implications for empirical research on city-suburb population redistribution.


Metropolitan deconcentration: subareal in-migration and central city to ring mobility patterns among southern SMSAs. The analysis of in-migration streams and subareal residential mobility patterns for moves made between 1965 and 1970 in SMSAs in the East South Central and South Atlantic census divisions indicates that, despite their historical contexts, these metropolitan areas now show spatial differentiation patterns similar to those of the great cities of the Northeast. The white population has increased in ring areas primarily because of in-migration rates; the black population in the central cities has increased primarily because of in-migration rates to those subareas. Little variation in these patterns across SMSA size categories was apparent.


Population trends of nonmetropolitan cities and villages in subregions of the United States. This is a comparison of the 1950-1970 trends in population size of U.S. nonmetropolitan cities and villages among 26 homogeneous subregions. There are wide variations in the proportion of the nonmetropolitan population in incorporated places, and, though this proportion generally increased over the 1950-1970 period, decentralizing tendencies also are evident. There was most often a decline in the differential between the growth rate of incorporated places and of open country over the two decades. The positive association between initial size of place and growth, present in half of the subregions in the 1950s and indicative of population centralization, was found only in the Corn Belt, Great Plains, and Rocky Mountain subregions in the 1960s. There were regionally distinctive differences in all variables considered; most notably, the percent of places growing ranged 50 percentage points over the 26 subregions. The extent of subregional variation revealed by this analysis indicates how differences in physiography, climate, history, and economy continue to be reflected in settlement trends which are obscured when larger regional groupings are used.


A short note on the Taeuber paradox.

A short note on the Taeuber paradox. When the force of mortality is reduced by a constant fraction delta at every age, the relative increase in life expectancy e(0) can be measured by deltaH, where H is determined by the l(a) values of the life table. Although H is not easily reducible in terms of the well-known life table parameters, it has been shown that it can be approximately estimated by 2 - e(0)/a in which a is the average age of the stationary population. It has been found that, for a given value of delta, the relative gain in life expectancy is less appreciable in countries with larger values of e(0).


Calculating life tables by estimating Chiang's a from observed rates. A simple, accurate method of life table construction is advanced based upon a new way to estimate Chiang's nax (the average number of years lived in the x to x + n age interval by those dying  in the interval). The estimate for nax leads immediately to an expression for  lx+n (the survivors to age x + n) in terms of lx and the known mortality rates for the interval x to x+n and the two adjacent intervals. The complete solution for the basic life table is given. The proposed method and five other easily applied methods are then compared against the standard provided by the U.S. life tables for 1969-1971. The results attest to the excellent performance and high degree of accuracy of the proposed method. Finally, extensions of the method to multiple decrement and associated single decrement life tables are briefly described.


Indigenous labor supply, sustenance organization, and population redistribution in nonmetropolitan America: an extension of the ecological theory of migration. The ecological theory of migration asserts that change in sustenance organization, to the extent that it produces changes in the opportunities for living, necessitates a change in population size. Migration may thus be viewed as a demographic response to the populations's need to reestablish a balance between its size and sustenance organization, thus attaining its best possible living standard. However, the levels of net in- or out-migration needed to restore the balance should be affected by the degree of positive or negative growth of the indigenous labor force population. We thus test the hypothesis that changes in opportunities for living will be balanced by net changes in the number of persons in the labor force, where this is a function of both indigenous labor supply and net migration.


Evidence for a role of endorphins in stress- and suckling-induced prolactin release in the rat. Injection of the opiate antagonist naloxone completely prevented the rise of serum prolactin induced by ether stress in intact male rats. Naloxone also led to a 50--95% inhibition of the marked elevation of plasma prolactin levels induced by suckling. These data suggest that endogenous opiates (endorphins) are involved in the stimulation of prolactin release induced by both stress and suckling in the rat.


Effect of several androgens, cyproterone acetate or estrogen-progesterone on the prolactin-releasing activity of arginine vasotocin in castrated male rats. Intravenous (iv) administration of 5 microgram of arginine vasotocin (AVT) into urethane-anesthetized, castrated male rats had no effect on plasma prolactin titers as compared to the rise in prolactin levels observed in intact AVT-treated rats. However, when castrated rats were first treated for two days with 2.5 mg/day of testosterone propionate and then challenged with a 5-microgram dose of AVT, the prolactin surge values obtained were comparable to those seen in intact AVT-treated rats. Conversely, treatment of intact rats for two days with 25 mg/day of the anti-androgen, cyproterone acetate, blocked the prolactin-releasing activity of AVT. In a separate experiment, treatment of castrated rats for two days with 2.5 mg/day of testosterone, androsterone or 50 microgram of estradiol benzoate and 25 mg progesterone, completely restored the prolactin-releasing activity of AVT. Similar treatment with 2.5 mg/day of androstenedione or dihydrotestosterone was without effect in restoring this response to AVT. It is concluded that the presence of gonadal steroids is essential to the action of AVT in provoking the release of prolactin in urethane-anesthetized male rats.


Interations of gonadotropins with corpus luteum membranes. VII. Association of hCG-binding and adenylate cyclase activities with rabbit corpus luteum plasma-membranes. Previous studies with rat luteal cell plasma membranes indicated a dissociation of hCG binding sites and adenylate cyclase activity. The hormone binding sites were associated with a light membrane (d 1.13) fraction derived from the microvillous surface while the cyclase enzyme was associated with a heavy membrane (d 1.17) fraction derived from the basolateral surface of the cell. In this study of plasma membranes from 8-day pseudopregnant rabbit corpora lutea both hCG binding and adenylate cyclase activity were associated with a light membrane (d 1.13) fraction. No heavy membrane material was detected.


Prolactin secretion in nonalcoholic liver cirrhosis. Serum prolactin levels were determined following stimulation by sulpiride in 20 patients with nonalcoholic liver cirrhosis and 10 normal controls. Prolactin response was essentially the same in the two groups. Only 5 cirrhotics, all with ascites, showed a lower prolactin response after sulpiride stimulation. This was interpreted as a consequence of a rapid prolactin escape from blood into the ascitic fluid, as it was shown to be the case in 2 of these patients. It is concluded that prolactin secretion in nonalcoholic liver cirrhosis is essentially normal. The higher prolactin levels found by others in alcoholic cirrhosis could be the result of a direct effect of alcohol on hypothalamic structures involved in prolactin secretion.


A stereological and biochemical study of the human liver in uncomplicated cholelithiasis. A quantitative analysis of needle liver biopsies of patients with untreated, uncomplicated cholelithiasis has been performed to better evaluate eventual changes occurring under medical therapy of gallstones. With the light microscope, the intensity of parenchymal steatosis was variable among the patients but the mean volume density of lipid droplets was significantly increased as compared to normal subjects. In addition, there was a significant increase in the volume density of lipocytes (fat-storing cells) without an increase in the number per square area, suggesting a hypertrophy of individual cells. The data obtained by ultrastructural morphometry show a significant increase in the surface density of the rough endoplasmic reticulum in the hepatocytes, a significant increase of the mitochondrial volume density together with the presence of curled mitochondrial cristae and a slight, inconstant intracellular and intracanalicular bile retention. No qualitative or quantitative changes were observed at the level of the smooth endoplasmic reticulum. The activity of the microsomal enzyme NADPH-cytochrome c reductase as evaluated on liver biopsy material was in the normal range. Some of the features observed in this group of patients are reminiscent of alterations previously described in human or experimental cholestasis and suggest that they might depend on a common underlying disturbance in cholesterol and bile salt metabolism.


The role of bile acids in determining ileal flow rates in normal subjects and following ileostomy. The possibility that intraluminal bile acid concentrations contribute to fluid and electrolyte movement in the normal ileum, and that alterations following ileostomy aid ileostomy adaptation, has been investigated. A significant correlation between the concentration of chenodeoxycholic acid plus deoxycholic acid, and volume flow through the normal ileum and ileostomy effluent volume was found. However, the regression lines relating bile acid concentrations to volume flow in the two groups were clearly separated, indication that factors besides altered bile acid metabolism are predominant in ileostomy adaptation.


Inhibition of human colonic adenylate cyclase by RMI 12330 A. RMI 12330 A, a compound of the lactamamide series, is a potent inhibitor of vasoactive intestinal polypeptide(VIP)- and prostaglandin (PG)-stimulated colonic secretion in the rat. This substance was tested on the adenylate cyclase system in human colonic mucosa. RMI 12330 A inhibited PGE2-, 16,16-dimethyl-PGE2- as well as VIP-sensitive adenylate cyclases in a dose-related manner. Half-maximal inhibition of hormone-stimulated enzyme activities occurred at a lactamimide concentration of about 0.15 mM. Lactamimide inhibition was non-competitive. Our results are compatible with the concept of RMI 12330 A acting as an inhibitor of colonic secretion via inhibition of hormone-sensitive adenylate cyclase. Since basal, NaF- and guanylyl-imidodiphosphate-stimulated enzyme activities were also affected by this compound, we may conclude that RMI 12330 A is a non-specific inhibitor of the human colonic adenylate cyclase system.


The effect of L-amino acids given intravenously on gastric secretion stimulated by pentagastrin in dogs. L-Amino acid solution given intravenously in Heidenhain pouch dogs resulted in marked changes of both basal and pentagastrin-stimulated gastric secretions. During a 1-hour amino acid infusion, a significant augmentation of pentagastrin-induced secretion was observed. A significant increase of secretion during amino acid infusion was also found in dogs not infused with pentagastrin. Absolute values of HCl output were much higher in dogs in which secretion was stimulated by a combination of pentagastrin and amino acids than by amino acids alone. This increase was followed by a fall of gastric secretion in response to pentagastrin.


Acute gastritis in cats. Effect of water lavage and local hypothermia on gastric blood flow. In the present investigation gastric blood flow was determined in cat stomachs with acute inflammation during continuous local irrigation with ice water (4 degrees C) or water at body temperature (37 degrees C). Acute gastritis was induced by a 10% acetic acid solution and gastric mucosal and muscularis blood flow were measured by means of gamma-labelled microspheres. The mucosa and muscularis blood flow remained essentially unchanged during irrigation either with ice water or warm water during the observation time of 2 h. The difference in gastric blood flow between the ice-water and warm-water-irrigated groups was not significant.


Induction of colonic adenocarcinomas by 1,2-dimethylhydrazine intrarectally administered in rats. Multiple colorectal adenocarcinomas were found in Sprague-Dawley rats after intrarectal injection of 1,2-dimethylhydrazine (DMH). These lesions along with mild hyperplasia of the surrounding mucosa developed within 34 weeks after either 3 or 8 injections of 250 mg DMH/kg body weight.


Development of exocrine cells of the pancreas and parotid gland in rats. Relation between morphological and biochemical changes. Electron microphotographs showed that pancreatic acinar cells contain many dense zymogen granules in the fetal stage (day 21 of gestation), both dense and less dense granules in the infant stage (day 10 after birth) and again only dense granules in the adult stage. Injection of dexamethasone in the infant stage greatly increased the number of dense granules, and slightly increased the total number of granules, whereas its injection in the weanling stage (day 24 after birth) did not increase the total number of zymogen granules or their density. Parotid acinar cells contain many zymogen granules of low density in the weanling stage (day 24 after birth), and granules of low density with dense spots in the adult stage. Injection of dexamethasone in the weanling stage increased the number of adult-type zymogen granules, but did not increase the total number of granules. The developmental change in amylase activity was parallel with the change in the high-density areas in zymogen granules, and the latter seemed to be influenced by the serum glucocorticoid level.


Acute and chronic pancreatitis in the rat caused by a closed duodenal loop. A closed duodenal loop was created by the obstruction of the duodenum on either side of the common bile duct. Acute haemorrhagic pancreatitis developed within 24 h with interlobular oedema, marked acinar cell necrosis, intra-abdominal fat necrosis and ascites. Plasma amylase activity was greatly increased together with a marked decrease in albumin. There was a temporary abnormality of liver function tests due to obstruction of bile. When the duodenal obstruction was released and the animals allowed to survive there was at 3 weeks a marked reduction in the pancreatic acinar cells with fibrosis and areas of necrosis and chronic inflammatory cell infiltration. Plasma amylase activity was normal but there was an increase in total plasma protein at 3 weeks. This technique of a closed duodenal loop in the rat gives a simple, reliable and economic experimental model for studies on acute and chronic fibrotic pancreatitis.


Protein digestion and jejunal dipeptidase activity in rats fed a normal protein alcohol diet during 6 months. Protein digestion was studied in pair-fed rats receiving an adequate (protein 12% and alcohol 35% of calories) diet during 24 weeks. No differences in fecal nitrogen excretion were observed between the alcohol-treated and control rats. At the 24th week the rats were sacrificed and jejunal mucosa dipeptidase activity was studied. No differences were found either between controls and alcohol-treated animals.


The endocrine pancreas of the fetus from diabetic pregnant rat. Diabetes was induced in female rats by streptozotocin administration prior to mating. Pregnant rats were divided into "severe diabetics" (blood glucose concentration above 300 mg/100 ml) and "mild diabetics" (blood glucose ranging from 100 to 200 mg/100 ml). When compared to control fetuses, fetuses from severely diabetic mothers showed a slight decrease of body weight on days 20.5 and 21.5. Fetal pancreatic insulin stores and plasma insulin concentrations were decreased at 19.5, 20.5 and 21.5 days. The insulin response to glucose was impaired both in vivo and in vitro. In contrast, fetuses from mildly diabetic females showed no change in body weight. Pancreatic and plasma insulin concentrations were increased at 19.5, 20.5 and 21.5 days. The response of the beta cells of term fetuses of mild diabetics to glucose stimulation was enhanced in vitro. These results are consistent with the hyperglycaemia-hyperinsulinaemia theory with regard to the fetuses from mildly diabetic rats and with an impairment of insulin biosynthesis and release in fetuses from severely diabetic females.


In vitro bioactivity of insulin analogues: lipogenic and anti-lipolytic potency and their interaction with the effect of native insulin. This paper presents a survey of the biological potencies of a variety of naturally-occurring and semi-synthetic insulin analogues and a study of the joint biological action of some of these materials with native insulin. Biological activity was tested on isolated rat fat cells using lipogenesis from glucose as the metabolic index. A brief comparison using inhibition of fat cell lipolysis was included. The results indicated: 1. Analogue potencies varied considerably (0.4-100% insulin activity). Values obtained were mainly confirmatory but included two further B1-modified materials and a tricarbamylated insulin. The results supported previous indications on the relative roles of the A1, B1, and B29 residues of insulin for hormone activity. 2. Analogue bioactivities, whether assessed by stimulation of lipogenesis or inhibition of lipolysis, were similar for the four materials tested in both systems. The response of fat cells with respect to both metabolic indices occurred over a comparable range of insulin concentrations, with half maximal effects at 30-35 pmol 1(-1) insulin. 3. The presence of modified insulins appeared to alter the biological action of native insulin in vitro. Small effects of both potentiation and antagonism were identified.


[Correlations between studies with plain radiography and with cineventriculography in subjects with prior myocardial infarct]. In 86 subjects wiht healed myocardial infarction the reliability of cardiothoracic ratio (C/T), of the left half-diameter (EDTS/m2) and of the overall subjective evaluation of a standard chest X-Ray plate has been tested by comparison to quantitative data drawn by selective cineventriculography. C/T and EDTS/m2 are scarcely reliable, whereas subjective evaluation allowed a separation among different groups of patients, though with wide overlap. Right anterior oblique and lateral views, and the evaluation of the third aortic arch were more useful than left anterior oblique and lowered apex.


[The oxygen pulse for evaluation of the response to exercise in rehabilitation of patients with myocardial infarct]. A program of physical conditioning for the rehabilitation of the patients affected by myocardial infarction is founded on a preliminary ergometric evaluation and on following examinations of the effects of the prescribed treatment. Submaximal ergometric stress tests utilizing non invasive methods which contain sufficient information about the cardiocirculatory response to the physical effort are required.  Sixteen patients underwent hemodynamic evaluation, during ergometric stress test, two months after myocardial infarction. A statistical analysis of the results shows a significant correlation between stroke volume and oxygen pulse. The oxygen pulse, under an increasing effort, describes a curve; the end of its ascending limb may be regarded as the point of the maximal stroke volume. The workload where the curve of oxygen pulse changes the slope can be used as the caloric expense which should be safely attained during the physical conditioning.


[Electrophysiological aspects of ectopic atrial tachycardia (author's transl)]. In 10 patients with supraventricular tachycardia who underwent an electrophysiological study the ectopic atrial origin of the tachycardia could be demonstrated by the intracavitary localization of the earliest depolarized point (six cases in the right atrium and four cases in the left). Vagal stimulation and/or the i.v. infection of ATP induced or increased the degree of AV block during tachycardia; in five cases ATP interrupted the tachycardia. On the basis of their clinical and electrophysiological behavior, the patients were divided into two groups. In the first one (6 patients) tachycardia was persistent, started following late atrial beats with the same morphology of the subsequent and showed a progressive initial rate increase (warm-up phenomenon); programmed atrial stimulation failed to start and interrupt it. In the second group (4 patients) tachycardia was paroxysmal or repetitive, started following early atrial beats and could be induced and interrupted by programmed atrial stimulation. With respect to the electrophysiological characteristics of each group the authors try to define the possible mechanism responsible for the tachycardia (automaticity and micro-reentry).


[Electrophysiological evaluation of ventricular tachycardia by right and left ventricle endocardial mapping (author's transl)]. Eight patients with ventricular tachycardia (VT) have been studied by unipolar recordings of 7 endocardial points of the left ventricle (LV) and 6 endocardial points of the right ventricle (RV) in order to record if possible: 1) where the VT arose; 2) a continuous electrical activity during the sistodiastolic phase of the intracardiac ECG [late potentials (LP)], suggesting the reciprocating mechanism of VT. All the patients underwent cardiac catheterization with left and/or right ventriculography. A coronary arteriography was performed in four cases. Four patients had no evidence of heart disease; one patient had aortic stenosis; one patient had two vessels coronary disease and extensive ipo-akinesis of the LV; two patients had dyskinetic areas of the RV. In all the cases it was possible to identify where the VT arose by means of recordings during spontaneous VT episodes (the sites of origin of the VTs were stated in the points where the intracardiac QRS began with an intrinsic deflection), or by means of asyncronous ventricular stimulation (the sites of origin of the VTs were stated in the points where the ventricular stimulation reproduced a surface ECG similar to the one recorded during spontaneous VT). The fact that the site of origin of the VT is never in the same point of the earliest endocardial activation during sinus rhythm and the fact that this site is located in a zone with rich terminations of the conduction system, suggest the reciprocating VT may develop in a circuit, with both conduction and myocardial tissue.


[Ventricular pre-excitation in old age associated with severe troubles of a-v conduction (author's transl)]. The Authors describe two cases of old people with syncopal crises in which the appearance of ventricular pre-excitement (WPW) is a new phenomenon associated with the progressing of severe troubles in A-V conduction, sometimes only shown by endocavitary electrophysiologic test. The appearance of accessory pathways latent or functionally dumb up to that time might be a substitutive mechanism in the attempt of counterbalacing serious deficiences of A-V conduction. In these patients special care is necessary in the use of antiarrhythmic drugs and in the interpretation of syncopal troubles in order to prescribe a correct therapy.


[Segmental anatomic diagnosis in congenital cardiac anomalies. I. Anatomic criteria for the identification of the cardiac cavities (author's transl)]. Anatomical features are illustrated for the identification of the cardiac chambers. Essential and accessory morphological structures are recognized. The identification of the atrial cavities is based upon the anatomy of the free walls (crista terminalis, size and shape of the atrial appendages). On the contrary, the identification of the ventricles is founded on the septal morphology (trabecula septo-marginalis on the morphological right side, smooth basal septum on the morphological left side, presence or absence of septal insertions of the atrio-ventricular value apparatus). Finally, no essential feature can be applied to the identification of the great arteries.


[The estimated risk of coronary heart disease in four working population groups: the Rome Project of Coronary Heart Disease Prevention (author's transl)]. Within four middle-aged population groups enrolled in the Rome Project of Coronary Heart Disease Prevention, a theoretic estimation of coronary heart disease (CHD) incidence in 5 years has been made on the basis of some risk factors (age, systolic blood pressure, serum cholesterol, smoking habit, physical activity at work, body mass index), employing four different solutions of the multiple longistic function (MLF) derived from previous population studies and a simple risk score adopted by the WHO European Collaborative Group to which this study belongs. The use of different MLF solutions provides rather different levels of estimated incidence, but the ranking and the relative risk between population groups are substancially constant and little dependent on the different solutions. Moreover, an acceptable similarity has been found in terms of estimated risk between the pool of the treatment and that of the control population groups (ratio between 0.97 and 1.09). A reasonable hypothesis indicates that in the absence of preventive action the annual incidence of severe CHD (hard criteria) should be around 6 per 1,000. The estimation of the relative risk within single population groups allows to identify strata of people with different risk, which suggests, again in the absence of any preventive action, a concentration of 25-30% of all new cases of disease in a 10% of the population and about 40-45% in a 20% of the same.


[Coronary collateral circulation in coronary atherosclerosis (author's transl)]. The coronary collateral circulation of 162 patients suffering from atherosclerosis and coronary insufficiency (coronary artery disease) was studied. It was found to be present in 44 patients, or 27.1%; homocoronary in 9%, intercoronary in 90.9%. As other Authors have previously reported, anastomotic circulation is more developed when the coronary occlusion exceeds 75%. Not one of the 44 cases with normal coronary arteries or occlusion inferior to 75% presented collateral circulation. In addition, it was found to be present more frequently in cases with three branch lesions. The time of insurgence of coronary insufficiency seems to condition the development of anastomotic circulation which appears more frequently when the symptoms have been present for more than 5 years (43.9%). Anastomotic circulation is also found more frequently (48.4%) in patients who have suffered myocardial infarction and who have angina. Collateral circulation was not found in any of the 46 patients with unstable isolated angina; this seems to show the importance, in its pathogenesis, of the functional factor (spasm). In conclusion, we may say that anastomotic circulation is more developed: 1) in cases of severe occlusive lesions (in severe coronary occlusive disease/atherosclerosis) (85%);2) in three branch lesions; 3) in cases of long standing symptomatology; 4) in stable angina and in angina  t infarction.


[Left ventricular-right atrial communication. Diagnostic and therapeutic aspects: report of 16 cases (author's transl)]. 16 cases of left ventricular-right atrial communication are reported. The most consistent clinical features, suggestive of this condition, were: auscultatory findings of V.S.D., electrocardiographic patterns of right atrial enlargement and biventricular hypertrophy, considerable right atrial enlargement coexisting with signs of left-sided cardiac enlargement and increased polmonary vascularity to Xray examination, echocardiographic fluttering of the tricuspid valve. Cardiac catheterization revealed an increased oxygen content in the right atrial or ventricular blood without the passage of the catheter through an A.S.D. The definitive diagnosis was established by left ventricular angiocardiography which demonstrated immediate opacification of a dilated right atrium through a septal defect; the location of the septal defect in the cardiac septum was attempted. In patients who suffered from a large left to right shunt were recommended for surgical treatment also in view of the relatively bad tolerance of this defect and low operative risk. There were two deaths: one baby died of early congestive failure. 9 cases were operated upon with one immediate postoperative death. The remaining, controlled by clinic follow-up, had good results.


[Hemodynamic effects of disopyramide and procainamide in open-chest animals]. Hemodynamic effects of two antiarrhythmic agents, disopyramide and procainamide, have been evaluated in anesthetized open-chest healthy pigs after random administration. At therapeutic plasma concentrations none of these agents proved to have deleterious hemodynamic effects. The most important action was observed after disopyramide infusion and consisted in significant bradycardia which confirmed the known effect on sinus node automaticity of the drug. Left ventricular dp/dt, an index of cardiac contractility, was unchanged after infusion of both drugs. On the ECG intervals, only procainamide provoked a significant prolongation of QTc. It is concluded that at therapeutic dosage disopyramide does not present deleterious hemodynamic effects in animals and proves to be a valid alternative to other traditional antiarrhythmic agents.


[Presence of bites in VCGrams of a high coronary risk population (author's transl)]. The association between the presence of areas of myocardial fibrosis and the appearance of unexpected DEVIATIONS OF THE QRS loop-outline on the vectorcardiographic tracing (bites) has been reported. In order to re-evaluate the correlation between the presence of bites and the possible existence of scars we have studied 511 patients. On the basis of clinical data, laboratory data, rest and exercise electrocardiograms, the subjects have been divided into four groups; 195 normal subjects; 267 with ischemic heart disease, 16 with arterial hypertension and 33 with diabetes mellitus (the last two groups as representative of subjects with higher risk for myocardial ischemia). Bites in at least one plane were detected in 9.7% of normal subjects, 27.8% of ischemic patients, 56.3% of hypertensive patients and 18.2% of diabetics (less than 0.001). The genesis of bites and reliability of the diagnostic criteria are discussed. With more restrictive criteria the frequency in the normal subjects falls to 1%, while in the other three groups it remains much higher (10.1%-12.5%-6.1%).


[Conventional echocardiography in the differential diagnosis between rupture of the ventricular septum and mitral regurgitation complicating myocardial infarction (author's transl)]. In three patients with myocardial infarction complicated by rupture of the ventricular septum the AA. looked for characteristic echocardiographic signs, to be used in a  differential diagnosis with mitralic insufficiency from the dysfunction of the papillary muscles. The partial disagreement between the facts ascertained (slight increase in the dimensions of the left atrium, inconstant behaviour of the dimension of the right ventricle), and those observed by other authors can be explained considering the multiplicity of the pathophysiological moments capable of influencing the echocardiographical picture: from the location and extension of the myocardial necrosis to the entity of the left-right shunt, from the coexistance of a hypertensive cardiomyopathy or of a pregressive myocardial infarction to the modalities of intraventricular diffusion of the electric stimulus, from the type of treatment (cardioactive supportive) to the time intervals between myocardial infaction -- rupture of the septum -- echocardiographic examination. The AA. conclude that M-mode echocardiodiography is not very helpful to the physician who must interpret a systolic murmur from punctal and/or mesocardial regurgitation in a subject with myocardial infarction.


[Disturbancies of iron utilization: chronic anaemia, sideroblastic anaemia, and residual endothelial siderosis (author's transl)]. Knowledge of disturbancies of iron utilization has been considerably extended by histochemical-ultrastructural findings and the results of immunoradiometric assays for serum ferritin. -- In chronic anaemia due to infections or neoplastic diseases hyposideraemia and normal unsaturated iron binding capacity were associated with increased iron retention in macrophages and slightly to highly increased serum ferritin (500--4000 ng/ml). -- 117 patients with sideroblastic anaemia formed a heterogenous group of diverse aetiology. The iron granules of ringed sideroblasts contained nonferritin iron in mitochondria. At diagnosis, a normal iron status was found in single cases. More frequently, praelatent and latent iron overload with ferritin levels up to more than 2000 ng/ml were observed. Manifest iron overload with tissue damage was mostly the result of numerous transfusions (ferritin 4700 bis 9500 ng/ml). -- After i.v. application of colloidal iron endothelial siderosis was a regular finding. The typical uniform granules representing nonferritin-iron in lysosomes disappeared in the course of 1--3 years completely. In contrast, the colloidal iron taken up simultaneously by the macrophages was rapidly transformed into ferritin and easily used up for haemoglobin synthesis when required. The corresponding increase of serum ferritin up to maximal 4000 mg/ml was dose related. Continued blood losses lead to residual endothelial siderosis after exhaustion of macrophageal iron and recurrence of iron deficiency anaemia. The serum ferritin fell to low levels (0--12 ng/ml) as observed in untreated cases.


Effect of estrogen treatment on coagulation and fibrinolysis in postmenopausal women. With special reference to cold activation of factor VII. Estriol (E3) and estradiol (E2) was given to 81 women with perimenopausal complaints. Venous blood was sampled before and after 2 weeks' treatment. In plasma coagulation and fibrinolysis the most marked estrogen effects were seen within the extrinsic coagulation system, with increased Thrombotest and Normotest activities. The incidence of cold activation of factor VII showed a marked increase after treatment with 6 mg of E2 or 8 mg of E3. The cold activation of factor VII was correlated to an activation of the plasma kallikrein system, as revealed by the peptidase activity of plasma kallikrein. The treatment with E2 and E3 induced changes also in the plasma proteolytic capacity, and in some proteinase inhibitors (antithrombin III, Cl inactivator). Like the effects within the plasma coagulation and kallikrein systems, these effects were similar to those reported after treatment with ethinyl estradiol, mestranol, and diethylstilbestrol, and in pregnancy. The conclusion is drawn, therefore, that the coagulation and fibrinolytic effects of E2 and E3 are basically similar to those of other estrogens, the differences between the various estrogens being more of a quantitative than of a qualitative nature. For the changes described, no absolute dose dependency could be found. Thus, treatment with E2 and E3 should be submitted to the same precautions as treatment with other estrogens.


Metronidazole and facultative anaerobes. The influence of metronidazole on some strains of facultatively anaerobic bacteria was studied. In high doses similar to those used for local treatment the growth of some strains was clearly suppressed, moreover there was an inhibition of hemolysis in hemolytic strains even when they were found to be resistant to the drug. Results are of particular importance for clinical problems as they might explain a number of alterations in the microbial flora of the vagina during and after therapy with metronidazole.


The 'LH/HCG test', a valuable aid in the diagnosis of tubal pregnancy. 174 patients with suspected tubal pregnancy were thoroughly examined. The diagnosis was confirmed in 102 women. As the usual noninvasive and invasive examination methods proved to be rather inaccurate, a new procedure, the 'LH/HCG test', was evaluated. Results were positive in all our cases. It was therefore concluded that this assay should receive primary consideration when tubal pregnancy is in question.


The assessment of digital vessel disease by dynamic hand scanning. A method of assessing hand and digital vessel perfusion is described. It involves an intravenous injection of Tc99m pertechnetate with monitoring of the isotope uptake in the hands and fingers by a gamma camera equipped with a small computer. The technique allows visual evaluation of the arterial supply and a means of quantifying digital perfusion. An evaluation of the technique in normal hands, in patients with digital vessel disease from vibration trauma, Raynaud's and embolism from an ulnar artery aneurysm is described. The potential of the technique in quantifying response to treatment is illustrated by sequential isotope hand scans in a patient treated for obliterative disease of the fingers.


Observations on the joints of the hand.

Observations on the joints of the hand. Thirty-two hands (sixty-eighty years) were dissected to study configuration and spatial setting of the articular surfaces of the joints of the thumb in order to note the features which are associated with deviation, torsion and rotatory movements. Four varieties of the trapezial surface were encountered in the carpometacarpal joint: saddle-shaped, triangular, ovoid and semicylindrical. The last exhibited marked osteoarthrosis with formation of osteophytes.


Simultaneous double toe transfer for severely disabled hands. Two cases are presented in which a severely damaged hand was reconstructed by the simultaneous transfer of two toes using microvascular techniques. A two year evaluation of the functional result is made in both cases. Conventional reconstructive methods have little place in the reconstruction of these severe disabilities.


Repair of the established post traumatic boutonnière deformity. A technique is described for the repair of the chronic, post traumatic, uncomplicated boutonnière deformity which has given consistently good results. The fundamental steps are: Mobilisation and reefing of the lengthened middle slip; Kirschner wire fixation of the proximal joint in full extension and replacement of the mobilised lateral slips with the distal joint flexed approximately 45 degrees.


The A.O. small fragment set in hand fractures. The use of the A.O. small fragment set in fractures of the hand is discussed. Problems in phalangeal fractures have been encountered but the equipment has been valuable in certain diaphyseal and articular fractures of the metacarpals. The advantages and disadvantages have been weighed.


Biodegradable cuff an adjunct to peripheral nerve repair: a study in dogs. This is a report of a study in which cuffs of biodegradable copolymers were placed about ulnar and peroneal nerves in legs of ten adult mongrel dogs. The results were evaluated by clinical response, electromyographic observations, nerve conduction studies, and light microscopic examination.


Some results using triamcinolone on immobilized joints. The frequency and causes of joint stiffness are reviewed. The most sophisticated repair may be for naught if the joints stiffen. Treatment of the established condition leaves much to be desired. Since mobility cannot be maintained during many postoperative periods and during the treatment of many conditions, any aid to prophylaxis is desirable especially if the side effects are negligible. Steroids have been chosen because of their influence on collagen metabolism and because much is known of their toxicity and side effects. The drug was first given into the knee joints of rats where it was found effective in preventing joint stiffness in joints immobilized three weeks. In view of the animal success, fourteen patients with thenar pedicles have had a single dose of triamcinolone injected into the peri-articular tissues of their proximal interphalangeal joints at the time of construction of the pedicle. Follow up observation shows all patients to have complete proximal interphalangeal joint extension and flexion to 95 degrees. Side effects were minimal.


Tuberculosis of the hand.

Tuberculosis of the hand. Eleven cases of tuberculous infection affecting the hand are presented. The age incidence, clinical presentations and investigations are discussed. Treatment includes chemotherapy, radical synovectomy and early mobilisation. Hand function after surgery in the follow-up period of three to twenty-one months was very satisfactory with the exception of three cases which presented at a very late stage with secondary involvement of the wrists. The confusion that exists while using such terms as "Tuberculous Dactylitis" and "Tuberculous Tenosynovitis" is discussed. An alternative suggestion is made that "Tuberculosis of the Hand" be used.


Maffucci's syndrome.

Maffucci's syndrome. A case is reported of Maffucci's Syndrome with multiple enchondromata involving the left ring finger and subcutaneous haemangiomata in the left thenar eminence, treated by surgical excision.


Soft tissue stretching with magnets.

Soft tissue stretching with magnets. Various clinical conditions require soft tissue elongation that can later host a bone graft. The possibility of stretching the soft tissues by magnetic force was tested on the forearm of dogs. The results are encouraging, provided certain precautions are taken and the pull exerted is not too great.


Subcutaneous ring anaesthesia in the prevention of tourniquet pain in hand surgery. A simple method for achieving satisfactory regional anaesthesia for a wide range of hand surgery is presented. It entails separate attention to the two aims of regional anaesthesia, namely analgesia of the tourniquet and of the operative site. This study of 149 patients indicated that (a) subcutaneous ring anaesthesia produced excellent tourniquet analgesia, both in the forearm as well as the upper arm; (b) a tourniquet applied to the forearm provided excellent regional ischaemia in 98% of our cases, contrary to what has been previously accepted. The advantages of this method are its safety and simplicity even for the relatively untrained surgeon. It also obviates the need for brachial plexus blocks, intravenous regional or general anaesthesia with all their drawbacks.


Cerebral massive hemorrhage in congophilic angiopathy and its medicolegal significance. The principles of a special type of senile cerebromeningeal angiopathy, these days usually named "congophilic angiopathy", are demonstrated on the basis of eight cases, complicated by spontaneous massive intracranial hemorrhages in seven and late traumatic hemorrhage in one of them. The occurrence of massive hemorrhages associated with congophilic angiopathy has until now only rarely been reported. The medicolegal significance of this vascular disease is emphasized by the eighth, traumatic, case, which became forensically relevant; the late massive hemorrhage had to be regarded as significantly favoured by amyloid angionecrosis, which is the main feature of congophilic angiopathy.


[Early prognosis in patients with recent myocardial infarct]. Hemodynamic studies were performed in a total of 50 patients suffering from acute transmural myocardial infarction. The aim of these studies was to find hemodynamic parameters permitting at an early stage a reliable prognosis. Our results show that only by combining hemodynamic parameters an accurate prognosis can be made before the onset of cardiogenic shock. The most reliable statement can be made by means of cardiac work index and cardiac work.


The role of the forensic pathologist in the investigation of fatal traffic accidents--the Finnish system. In Finland about one-half of the fatal traffic accidents are investigated by special Boards of Inquiry. The cumulating data serves multidisciplinary sciences, juridical and insurance purposes and legislation. The participating physicians benefit from the systematic work of the Boards in many ways. As an example of the results a list of causes of accidents is shown.


Ninety-five percent probability of paternity with HLA, ABO and haptoglobins. Using HLA tissue typing as the basic genetic test along with ABO and haptoglobin typing, it is generally possible either to exclude a putative father conclusively or, in nonexclusion cases, to assign a greater than 95% probability of paternity. In 22 of 53 nonexclusion cases, the putative father had a probability of paternity above 99% based on these genetic tests.


Carboxyhaemoglobin and methaemoglobin findings in burnt bodies. The often observed absence of carboxyhaemoglobin in burnt (charred) bodies is re-discussed in the light of two new cases in which the inhalation of very hot gases obviously led to reflex breathing and circulation arrest. (Macro and microscopic evaluations of the upper respiratory tract can give significant information as to whether a person was still alive at the time of the fire outbreak.) In the cadaver blood of people who survived a given period after a fire, high methaemoglobin values (up to 37%) were found. This was caused by the inhalation of nitrogen oxides that were produced by burning plastic.


[Transcervical extraamniotic Rivanol instillation as a method of avoiding complications in pregnancy interruption]. The number of abortions performed is steadily increasing. According to information available to date from the Federal Statistics Office in the Federal Republic of Germany, pregnancies are still largely terminated by means of cervical dilatation with Hegar dilatators and subsequent curettage. Almost half of all abortions are performed in young women who have not yet given birth. In a great number of cases these patients have a gracile, rigid cervical os which has to be opened abruptly in a few minutes with Hegar's dilatators, often under asserting quite some force. This can result in lacerations of the cervix, cervical insufficiency, inflammation and cicatrization. The transcervical extraamnial Rivanol instillation seems to be a method for avoiding these early and the serious late complications ensuing. Using this method--an alternative to the Prostaglandine application, with its even more serious secondary effects and contraindications--the highest possible degree of success can be achieved in avoiding cervical injuries and in reducing inflammation in the pelvis minor to a minimum, which could later on lead to sterility.


[Extraamniotic induction of abortion with a new prostaglandin E-2 derivative]. First clinical results are reported of a new prostaglandin-E2-derivative (16-phenoxy-prostaglandin-E2-methylsulfonylamide = SHB 286) as abortifacient using the extraamniotic route of application. Upon investigation in animals this prostaglandin-E2-derivative proved to be more tissue-selective and more potent in inducing abortion than the naturally occurring prostaglandins. Prostaglandin SHB 286(50 or 100 microgram) was applicated to 31 patients for legal abortion and to 7 patients with a missed abortion. The mean instillation-abortion time was 14.2 and 13.7 h respectively. 96% of the patients had a complete or incomplete abortion after 24 hours. Severe local or systemic side effects did not occur and the patients did not need any further medication.


[Treatment of motor dysfunction of the urinary bladder]. Symptoms and objective characteristics of 86 female patients with bladder instability and uninhibited detrusor contractions suffering from urgency incontinence were analyzed. The subjective and objective response to a six week-parasympathicolytic treatment with Emepronium-Bromide (Cetiprin) was examined and the results are discussed.


[Side-reactions in peptide synthesis, III. Synthesis and characterization of Nin-tert-butylated tryptophan derivatives (author's transl)]. It was possible to elucidate a side reaction which had long been assumed to occur during the acidolytic cleavage of protecting groups based on a ter-butyl moiety, by synthesizing Nin-tert-butyltryptophan in different ways. It was found to be absolutely identical with a "modified tryptophan" which was isolated after the total synthesis of a gastrin analogue; Nin-tert-butyl-tryptophan peptides are formed as the main products of a tert-butylation reaction, the mechanism of which is not very clear yet. The proof for a Nin-tert-butylation of tryptophan was obtained by spectroscopic methods, in particular mass spectrometry and nuclear magnetic resonance spectroscopy.


[Side-reactions in peptide synthesis, IV. Charactertzation of C- and C,N-teri-butylated tryptophan derivatives (author's transl)]. Besides Nin-tert-butylated tryptophan derivatives, other tert-butyl-tryptophan analoga are also found as a result of side-reactions accurring during the acidolytic cleavage of protecting groups being based on a tert-butyl moiety. C-mono-substitution could be detected as well as di- and tri-substitution. All these tert-butylated tryptophans could be isolated in a pure form from the tert-butylation mixture either free or as derivatives and could unequivocally be identified in particular by means of mass spectrometry and nuclear magnetic resonance spectroscopy.


[Direct tert-butylation of tryptophan: preparation of 2,5,7-tri-tert-butyltryptophan (author's transl)]. The tert-butylation of free tryptophan under simulated conditions of acidolytic cleavage of protecting groups being based on a tert-butyl moiety does finally yield the tri-substituted amino acid as a main product, namely 2,5,7-tri-tert-butyltryptophan. The structural elucidation of this substance and other tert-butylated products, which were isolated mostly in a pure form, was achieved by means of spectroscopic methods, in particular mass spectrometry and nuclear magnetic resonance spectroscopy.


[tert-Butylation of the tryptophan indole ring during the removal of the tert-butyloxycarbonyl group (author's transl)]. The tert-butylation of the tryptophan indole ring during the removal of tert-butyloxycarbonyl groups under different conditions was studied. The incorporation of tert-butyl groups was measured by a 1H-NMR technique. It was established, that the rate and specificity of the tert-butylation is highly dependent on the character of the cleaving reagents used and on the environment of the tryptophan residue in the peptide chain.


Secretin/cholecystokinin-stimulated secretion of trypsinogen and trypsin inhibitor in pure human pancreatic juice collected by endoscopic retrograde catheterization. Pure pancreatic juice was collected by endoscopic retrograde catheterization of the papilla of Vater from 10 fasting patients without known pancreatic disease. Secretin was given intravenously as a bolus dose at the beginning of the examination and cholecystokinin was given in the same way 15 min later. The juice was siphoned for 25 min and collected in 1-min fractions. Pancreatic secretory trypsin inhibitor, PSTI, and trypsinogen were measured by an immunochemical method. Secretin produced an increase in hydrogencarbonate and a decrease in chloride secretion. Cholecystokinin caused a prompt increase in the concentration of both PSTI and trypsinogen. The ratio between these was constant, suggesting a strictly parallel secretion. The effect of cholecystokinin on secretion of total protein when given as bolus dose was of short duration, with a half-life of action of about 3.5 min.


Peptide esters and nitroanilides as substrates for the assay of human urinary kallikrein. Ac-Phe-ArgOMe is hydrolyzed much faster than are Bz-ArgOEt, Z-ArgOMe, or Ac-Gly-ArgOMe by the kallikrein from human urine. The synthesis of Ac-Phe-ArgOEt is described. Hydrolysis of this substrate can be conveniently monitored by a coupled spectrophotometric procedure. Increase in absorbance is linear with time and proportional to the amount of kallikrein up to a deltaA366 of at least 0.22/10 min. This assay for human urinary kallikrein is 46-fold more sensitive than that based on Bz-ArgOEt and 38-fold more sensitive than that with D-Val-Leu-Arg-p-nitroanilide. A number of other arginine p-nitroanilides are hydrolyzed by this enzyme at still lower rates. The assay of human urinary kallikrein with D-Val-Leu-ArgOEt is about a factor of two less sensitive than the assay with Ac-Phe-ArgOEt. This also holds for Z-TyrONp, which displays a rapid spontaneous hydrolysis. Furthermore, the rate of the enzymic reaction with Z-TyrONp drops off rapidly.


Disulfide bridges in the middle part of human fibrinogen. Human fibrinogen contains 29 disulfide bridges per molecule. The amino acid sequences around all half-cystine residues are known. When fibrinogen is cleaved by cyanogen bromide five disulfide-containing fragments are formed. The second-largest of them is derived from the middle part of all three peptide chains, it is monomeric and contains 345 amino acid residues, 12 of which are half-cystines. The arrangement of the six disulfide bonds was determined by analysing sequences and amino acid compositions of subfragments isolated after cleavage with trypsin, thermolysin and staphylococcal protease and after clearage of the disulfide bonds. All half-cystine residues were found to be linked in unique pairs. Six half-cystine residues, two in each of the three peptide chains and forming the -Cys-X-X-X-Cys- sequences, were shown to connect the chains in a ring-like structure, similar to the one in the N-terminal part of the molecule. The remaining six half-cystine residues were found to connect two sections of the gamma-chain in a loop-like structure and four sections of the beta-chain in a loop-inside-a-loop-like structure, the inner beta-chain loop being homologous to the gamma-chain loop.


Purification and properties of 3-cis-2-trans-enoyl-CoA isomerase (dodecenoyl-CoA delta-isomerase) from rat liver mitochondria. The mitochondrial enzyme 3-cis-2-trans-enoyl-CoA isomerase, responsible for the positional and geometric isomerization of beta,gamma-unsaturated fatty acyl-CoA intermediates arising during beta-oxidation of unsaturated long chain fatty acids, has been isolated from rat liver, purified to homogeneity by a heat step and a combination of gel filtration and ion-exchange chromatographic procedures. The enzyme has a molecular weight of 30,000, as determined by dodecylsulfate polyacrylamide gel electrophoresis. The isomerase has a strong tendency to form a dimer. It elutes from a calibrated Sephadex G-200 column with an apparent Mr = 60000. The basic isoelectric point, pI 9.0-9.2, is due to its high content in basic amino acids. The amino acid composition determined by the ninhydrin and o-phthalaldehyde detection method is presented.


Preparation and properties of acetylcholinesterase from the sea mussel Mytilus edulis. The large-scale isolation of an acetylcholinesterase from the haemolymph of the sea mussel mytilus edulis by means of fractional (NH4)2SO4 precipitation, affinity chromatography and isoelectric focusing is described. The yield is about 20% of the initial enzyme activity with a specific activity of 1727 nkat/mg protein. Purification steps are followed by disc electrophoresis, analytical isoelectric focusing and immunoelectrophoresis, showing the enzyme to be homogeneous with an isoelectric point of 4.81 +/- 0.02 and to have an apparent molecular weight of 245,000, which is composed by six equal subunits as judged by C- and N-terminal amino acid analysis. The acetylcholinesterase is a metalloprotein containing three Fe2 ions per subunit (molecular weight 40625); this consists of 351 amino acid and six sugar residues, but contains no sialic acid. As calculated from CD data, the enzyme has about 55% helical structure.


Cytoplasmic control of histone messenger RNA translation is not mediated through protein phosphorylation. It was investigated whether the cytoplasmic control of histone synthesis, i.e. the selective and rapid degradation of histone mRNA following interruption of DNA replication, is linked to the phosphorylation of specific proteins of the translational apparatus or other cytoplasmic proteins. No specific protein phosphorylation was observed when synchronized HeLa cells in the S-phase were blocked with hydroxyurea or cytosine arabinoside and pulse-labeled simultaneously with [32P]orthophosphate. Protein phosphorylation was also studied in cell-free protein-synthesizing systems (S16 extracts) from blocked and unblocked S-phase cells under a variety of conditions. No protein could be detected that becomes specifically phosphorylated with [gamma-32P]ATP in a cell-free system derived from S-phase cells in which DNA replication and histone mRNA translation was interrupted with hydroxyurea.


The pathophysiology of sodium balance.

The pathophysiology of sodium balance. Whether deficit or surfeit, sodium imbalance responds best to management based on an understanding of the underlying mechanisms that have gone awry. A review of the kidney's role in normal sodium homeostasis lays the groundwork for rational therapeutic approaches to correcting the pathophysiology of the major depletion and retention states. Clinical implications and management principles of various disease entities are discussed.


Familial mediterranean fever: a status report. The recent discovery that an age-old drug, colchicine, can control this enigmatic, often unrecognized, recurrent disease means that most affected individuals can now lead virtually normal lives. The research leading to this advance is described, as are the essentials of diagnosis, colchicine's possible mechanisms of action, and the relative merits of chronic vs intermittent colchicine therapy in the abortion of impending attacks.


Differential diagnosis of osteopenia.

Differential diagnosis of osteopenia. Differentiating the demineralizing bone diseases, especially osteoporosis from osteomalacia, is difficult but clinically rewarding, since the latter is highly treatable. Bone biopsy can detect the 20% of osteoporotic patients who also have osteomalacia.


Electroshock therapy: myths and realities. The methodology of the 1940s provided the data base for the myths that grew up around electroshock therapy. Since then indications have been refined and techniques drastically revised--as with many other medical treatments. When administered for carefully defined indications, in the proper setting by an experienced team, and with appropriate safeguards, EST is safe, effective, and often the treatment of choice.


Chromosomal and histological changes in the reproductive organs of infertile men. The chromosomal changes in the process of spermatogenesis in 27 infertile men have been examined. Normal chromosomal meiotic activity was found in 44% of cases, various chromosomal anomalies were seen in 18%, and no cells in meiosis were detected in 37% of cases.


Recombinant chromosome as a result of pericentric inversion of X chromosome. A structural X chromosome abnormality was found in the karyotype of a tall patient with gonadal dysgenesis and with no extragenital anomalies. Based on her mother's karyotype, which showed a pericentric inversion of the X chromosome: 46,X,inv(X)(p22q24), as well as from G and R banding, we concluded that the abnormal X chromosome of our patient was a recombinant chromosome that had originated as a result of one crossing over in the inversion loop during gametogenesis in her mother. The recombinant X chromosome had a partial delection of Xq and a partial duplication of Xp: 46,X,rec(S),dup p,inv(X)(p22q24). After BUDR incorporation, the abnormal X chromosome of the patient and that of her mother showed a late replication. The karyotype-phenotype correlation and the nonrandom inactivation of the inverted X chromosome in the mother are discussed.


Familial pericentric inversion of chromosome 1 with a note on reproductive risks. An inversion of chromosome 1 was found in three normal members of a two generation family. G- and C-banding studies revealed inv(1)(p13q23). The problems encountered in counseling such normal carriers are discussed.


Quantitative analysis of high-resolution trypsin-giemsa bands on human prometaphase chromosomes. We have constructed ideograms of human prometaphase chromosomes from synchronized and from standard 72-h lymphocyte cultures. G banding was achieved by a trypsin-Giemsa (or Wright's stain) method. In addition to light (white) and dark (black) bands, we have distinguished three different shades of grey. This distinction is essential for proper identification of the increasing number of bands displayed by high-resolution chromosomes. The relative amount of chromatin in each category of staining intensity has been calculated and expressed as 'light value.' The ideograms represent the maximal number of bands discernible with some consistency on prometaphase chromosomes, i.e., 721 euchromatic and 62 'variable' heterochromatic or heteromorphic bands. The ideograms are based on measurements. On selected printed copies of each chromosome derived from different cells and different individuals, the relative width of each band was measured in relation to the length of the respective chromosome arm. The measurements per chromosome were averaged and used for construction of the ideograms. The distance of each border between bands or sub-bands from the centromere has been calculated on a relative scale, with positions 0 at the centromere and 1.0 at the p terminus of q terminus. The numbering system for bands and sub-bands follows the Paris Conference (1971) recommendations.


PGM1 subtyping by means of acid starch gel electrophoresis. 'PGM1 subtyping' can be clearly demonstrated by horizontal electrophoresis in acid starch gel. Because of the different cathodal mobilities of PGM1-gene products, the allelic superscripts for PGM1 were designated as 1F, 1S, and 2F, 2S, respectively. Gene frequencies of a population sample from Southwestern Germany are presented. They fit in well with other, previously published data on this matter.


Cytogenetic effects of influenza virus infection on male germ cells of mice. Swiss albino male mice were administered two doses (1 and 2 HA units) of influenza A2 Hong Kong/68 virus IP. The incidence of chromosomal anomalies in spermatocytes was analysed at various times post infection and was found to be significantly higher than in controls, indicating that the influenza virus had induced these anomalies.


Polymorphism of human salivary amylase: a preliminary communication. Variation of human salivary amylase isoenzymes was investigated by isoelectric focusing on thin-layer polyacrylamide gel. Preliminary studies indicate a genetic polymorphism.


Isochromosome 17q in two cases of acute blast transformation in myeloproliferative disorders. Two cases of acute blast cell transformation in myeloproliferative disorders associated with a dicentric 17q isochromosome are reported. In both cases, the karyotypes also included a Philadelphia 9q;22q translocation, and in one case, an additional chromosome 8 (trisomy 8).


A case of trisomy 22 with a probable Robertsonian translocation 21/22. A 2-year-old girl with a prabable trisomy-22 translocation is described. The principal clinical symptoms described by the authors who have reported cases with proved trisomy 22 are presented. A probable 46,XX,-21,+t(21q;22q) karyotype was established in the patient. The proband's clinical picture is compared with other trisomy 22 cases described in the literature. The incidence of this trisomy among the human population is discussed.


Partial trisomy 2q and familial translocation t(2;18)(q31;p11). This report describes a malformed infant with distal 2q trisomy/distal 18p monosomy due to adjacent segregation of a familial t(2;18). The rearrangement was present in four generations, and linkage studies were performed.


10p- syndrome associated with multiple chromosomal abnormalities. A karyotype with six de novo autosomal abnormalities in chromosomes 2,4,9,10,12, and 13 was identified in a 7-year-old boy with mental retardation and other minor malformations. The G- and C-banding techniques revealed an equilibrated translocation between autosomes 2 and 4 and between autosomes 9 and 13. One chromosome 10 has lost genetic material from its short arms, probably because of an interstitial deletion. An unidentified chromosomal fragment has become inserted in the long arms of an autosome 12. The G bands demonstrate that genetic material inserted in the autosome 12 is not the genetic material deleted from the autosome 10. The propositus presents clinical features similar to the reported cases with 10p- syndrome. Nevertheless it is not possible to establish the influence of the genetic material inserted in autosome 12 on the propositus' phenotype.


Cytogenetic and histologic analyses of spontaneous abortions. In a study of spontaneous abortions the correlations between karyotype (166 cases), anamnestic data, and macroscopic and histologic findings in placentas (107 cases) and embryos (73 cases) were analyzed. The main results were: 1. The rate of chromosomal aberrations was 39%. Trisomies predominated (60%), followed by monosomy X (20%), triploidies (14%), and structural aberrations (6%). 2. In trisomies a clear prevalence of female sex constitution (2:1) was observed. In normal karyotypes a slight prevalence of females was seen (1.2:1). 3. With increasing maternal age, more trisomies were found in the abortions. 4. Women whose index abortion had a normal karyotype had a history of fewer births but more abortions. 5. Trisomies of acrocentric chromosomes were mainly chorionic sacs with an embryo, while trisomies of the other autosomes resulted in intact empty sacs. 6. The average developmental stage of the embryos was 5 weeks, with a mean gestational age of 14 weeks. Gross malformations were found in 58% of the embryos.


Systematic analysis of 95 reciprocal translocations of autosomes. The statistical analysis of 95 cases of reciprocal translocations involving autosomes detected among about 10,000 patients studied with the R-banding technique gives the following information: 1. An excess of break points exists for chromosome arms 4p,9p, 10q, 21q, and 22q and a deficiency for 1p, 2p, and 6q. Furthermore, there are relatively more break points in the small arms than in the large arms, when the translocation is ascertained through an unbalanced translocation carrier. Except for chromosome 22, an ascertainment bias explain this non random distribution. 2. An excess of telomeric break points exists in all cases of translocations ascertained through unbalanced carriers, and an excess of centromeric break point exists in the case of 3:1 and 1:3 segregations only. These excesses are also explained by an ascertainment bias. 3. The break points are located usually at the junction of the bands (interfaces). 4. The size of the chromosomal imbalance varies in the ascertainment classes. It is very large in cases ascertained through balanced carriers (at least one break point is far from the telomere), large in cases ascertained through abortion, and relatively moderate in cases ascertained through unbalanced translocation carriers (at least one break point is juxta telomeric). 5. An excess of balanced reciprocal translocations exists in our sample of mentally retarded and malformed children (position effect?). 6. An excess of balanced reciprocal translocations (not involving chromosome 21) exists among the trisomics 21 and their parents (interchromosomal effect?). 7. A large excess of maternal transmission exists in cases of 3:1 segregation of reciprocal translocation.


Studies on H-Y antigen in different cell fractions of the testis during pubescence: immature germ cells are H-Y antigen negative. Various cell types of the rat testis during pubescence, including germ, Sertoli, and Leydig cells, were partially enriched. The fractions were tested for the presence, binding, and secretion of H-Y antigen. The main results are: Immature germ cells are H-Y antigen-negative until the late diploid stages, and late primary spermatocytes or spermatids become positive; the somatic cells of the gonad are positive at all ages examined (18 days old to adulthood). Secretion of H-Y antigen is restricted to the Sertoli cell fraction. Binding of externally supplied antigen takes place on Leydig cells; the Sertoli cell surface will be saturated because of active secretion; there is no binding to germ cells. Thus, immature germ cells seem to be the only H-Y antigen-negative cells of the male organism, and the Sertoli cells seem to be the only ones to secrete H-Y antigen.


A genetic study of two French Guiana Amerindian populations. I. Serum proteins and red cell enzymes. Phenotypes and gene frequencies are presented for 20 serum and erythrocyte proteins in two Amerindian populations of inner French Guiana. No genetic variability was detected in 12 of these systems. Heterozygosity was calculated for the others and the reasons for its variation are discussed.


XO/XY mosaicism and non-fluorescing Y chromosome in a male. An adult male of short stature and with underdeveloped external genitalia is described, who carried out a number of sexual assaults on young women. He proved to have XO/XY mosaicism and a non-fluorescing Y chromosome. It was considered to be a terminal deletion on morphological grounds. It is suggested, on the evidence of the small number of XO/XY mosaics examined by appropriate staining methods, that an abnormal Y chromosome, whether terminally deleted or non-fluorescing owing to an altered chemical state, predisposes to anaphase lagging and non-disjunction. Of eleven reported cases of XO/XY mosaicism with a non-fluorescing Y chromosome, this is the fifth of male phenotype. The severe behaviour disturbance of early onset is considered to be probably causally associated with the chromosome anomaly.


Partial trisomy of the long arm of chromosome 1 due to a familial translocation t(1;10) (q32;q26). A new case of partial trisomy for the long arm of chromosome 1 was observed in a newborn female, who died at age 26 days. The father was a proven carrier of a balanced translocation involving chromosomes 1 and 10.


Partial distal trisomy 13q resulting from familial reciprocal 5/13 translocation. A female infant with partial trisomy 13, 46,XX,der(5),t(5;13) (p15;q22)mat, for the distal part of the long arm is reported. The clinical and autopsy findings were similar to those of complete trisomy 13, except for harelip and cleft palate, and sloping forehead. Fetal hemoglobin and nuclear appendages in polymorphonuclear leukocytes were normal. Loci for these traits are discussed.


Partial deletion of the X chromosome in gonadal dysgenesis 46,X,del(X)(p22) identified by BudR treatment. In this report we describe a deletion of the short arm of the X chromosome in a 16-year-old female with gonadal dysgenesis. The breakpoint was localized by BUdR treatment and acridine orange staining in region 2, band 2. Of the examined cells, 3% showed an early replication of the deleted X chromosome.


The effect of amphotericin B-deoxycholate on proliferation and protein synthesis in human skin fibroblast cultures. Cultures of adult human skin fibroblasts were grown in the presence of the recommended antifungal dose (3 microgram per ml) of amphotericin B-deoxycholate. A reduction in cell culture growth, measured as DNA content and protein content per culture, was observed. However, radioisotope incorporation into noncollagen protein and, to a lesser extent, collagen protein was enhanced. These effects were due to amphotericin B, not to deoxycholate. These observations were made under several growth conditions and indicate that cell proliferation or isotope-labeling studies in fibroblasts in the presence of amphotericin B-deoxycholate are susceptible to errors in interpretation.


Evidence for clonal attenuation of growth potential in HeLa cells. The growth of primary clones and serial subclones of HeLa cells and of diploid human fibroblast-like cells were compared both in the presence and absence of feeder layers; the latter had no significant effects upon the results. Clones and subclones of both cell types displayed great heterogeneity in growth rates, typically with a bimodality of growth distributions. Serial passages of clones selected on the basis of superior rates of proliferation showed attentuation of growth potentials; the extent of such attentuations was much less in the case of HeLa cells, suggesting at least one possible basis for the differences in long-term growth potential between these two classes of cell lines.


Cellular requirements for the formation of EA rosettes by human monocytes. The binding of sensitized red cells to Fc receptors in human monocytes was studied by evaluating the effects of various pharmacological reagents and other treatments on EA rosette formation. Cytochalasin B and 2-deoxyglucose inhibited rosette formation in a dose-dependent manner. Sodium azide and incubation at 4 degrees also inhibited rosette formation, while at 37 degrees increased numbers of RBCs bound to the monocytes. The microtubular poisons, vinblastine and colchicine at high concentrations resulted in decreased adherence of monocytes and inhibition of rosette formation, while at low concentrations of colchicine, enhanced rosette formation was sometimes observed. Contrary to the effects on rosette formation, binding of [125I] IgG to monocyte monolayers was not altered by treatment of the monocytes with drugs. Magnesium ions were required to promote monocyte adherence, but both magnesium and calcium were needed for the best rosette formation. We conclude that the formation of EA rosettes is dependent not merely on binding of IgG to the Fc receptor but requires metabolically active monocytes, an intact cytostructure and suitable environmental conditions (temperature and cation concentration).


Growth characteristics of PHA-induced colonies in primary and secondary agar culture. PHA-induced colonies were obtained from peripheral blood mononuclear cells (MC) grown in agar-medium. When the colonies were harvested from mass cultures, pooled as single cell suspensions and plated again in presence of PHA, they failed to generate new colonies unless they were seeded on an underlayer containing uncultured blood MC. Cytogenetic studies indicate that most secondary colonies were derived from primary colonies. Autologous as well as heterologous feeder cells were able to promote the growth of secondary colonies. No granulocyte (G) or macrophage (M) colony formation was observed in secondary cultures. These experiments show that the progenitors of PHA-induced colonies differ from G or M CFCs and that they are still detected in these colonies which contain 82 +/- 12% T-cells. In contrast, colony formation requires the presence of factor(s) provided by cooperating cells (CC) which are no longer detected in primary colonies and this is associated with a depletion in non-T elements from the initial MC population.


Migration of human lymphocytes. II. Variation of lymphocyte distribution. Variations in the distribution of 51Cr-labelled human lymphocytes from several donors and from one donor on several occasions have been determined after their injection into carbon-treated mice and reasons for the variation discussed. Natural alteration of the lymphocyte surface (leukaemic lymphocytes) or induced change (trypsin-treatment) reduced lymph node localisation as did treatment with formalin, sodium azide and antilymphocyte globulin. We have concluded that the presence of radioactivity in the lymph nodes is due to the presence of viable, metabolically active lymphocytes with normal surfaces capable of interacting with the endothelium of the post-capillary venules.


Activation of human platelets by platelet activating factor (PAF) derived from sensitized rabbit basophils. Rabbit basophil-derived platelet activating factor (PAF), a mediator of anaphylaxis, induces the aggregation and release of serotonin from rabbit platelets. In the present study, we report that PAF obtained by challenge of specifically sensitized rabbit basophils induced the noncytotoxic release of serotonin from human platelets; maximal extent of release ranged between 34-46%. This release was unaltered in the presence of indomethacin, indicating that such secretion was not a consequence of contaminating arachidonic acid; further, as previously demonstrated with platelets of rabbit origin, it was markedly independent of a requirement for an intact prostaglandin biosynthetic pathway. In contrast to its effect upon rabbit platelets, rabbit PAF did not induce aggregation of human platelets, suggesting that the aggregation and secretion reactions induced by this agent are separable and that this cross-species activation may be incomplete. Whether this is a result of the differential ability of rabbit PAF to bind to and activate rabbit as compared to human platelets or to the existence of a family of PAF molecules is not yet known. The capacity of PAF to participate in a secretory event involving human platelets lends support to the belief that PAF may play an important ubiquitous role in the cooperative, leucocyte-dependent, release of vasoactive amines which results in increased vascular permeability.


Influence of a synthetic adjuvant (MDP) on qualitative and quantitative changes of serum globulins. Administered to guinea-pig, a synthetic compound, N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP), has been previously shown to substitute for Mycobacteria in Freund's complete adjuvant. Moreover, MDP increases the humoral immune response even when administered in an aqueous solution to mice. In the present report, it was demonstrated that administered to guinea-pig in a water-in-oil emulsion, MDP or active analogues favoured the production of IgG2 antibodies against ovalbumin. In contrast, derivatives of MDP which had no adjuvant activity failed to induce this particular class of immunoglobulins. MDP without antigen, in contrast with LPS or FCA, did not induce changes in immunoglobulin levels in mice. Administered in mice with an antigen, MDP induces an increase of IgG1 although the immunoglobulin levels are lower than those observed after immunization with adjuvants injected in a water-in-oil emulsion.


Hyaluronic acid in the pulmonary secretions of patients with alveolar proteinosis. Hyaluronic acid was the only glycosaminoglycan found in the pulmonary secretions of patients with alveolar proteinosis. The compound gave a hexouronate/hexosamine molar ratio of about 1:1. Glucosamine constituted over 98% of the hexosamines, the remaining being galactosamine. It moved as a single spot with the mobility of standard hyaluronic acid on cellulose acetate electrophoresis, and this spot disappeared after digestion with hyaluronidase. It was associated with small amounts of proteins, the major amino acids of which are aspartic acid, glutamic acid, glycine, alanine, and leucine.