[The effect of sugar phosphates, phosphoenolpyruvate and adenylic acid on muscle, brain and heart creatine kinases].

The effect of adenylic acid, glucose-6-phosphate, fructose-1,6-diphosphate and phosphoenolpyruvate on creatine kinase isoenzymes (brain extract, muscle and heart extracts and purified muscle enzyme) was studied. These effectors, especially phosphoenolpyruvate, are shown to inhibit in different degree the reaction of ATP formation catalysed by creatine kinase from all tissues. The effectors do not inhibit the creatine phosphate synthesis in extracts, but depress purified creatine kinase. The interrelationship of the creatine kinase system and the key glycolytic enzymes (phosphofructokinase, hexokinase, pyruvate kinase) is discussed.


[Isolation of chloroplasts and chloroplast DNA from pea leaves].

A method of isolating DNA from pea chloroplasts (ch-DNA) in CsCl density gradient is described. DNA preparations are free of 5-methylcytosine and have a melting temperature of 86.5 degrees. Denatured DNA molecules completely reassociate for 3 hours at 60 degrees C. It is concluded that the preparations obtained are pure ch-DNA.


Electrodermal responses, subject control and delay of aversive stimulation.

The aim of this study was to investigate the effect of different delays between a shock releasing motor response and shock (UCS) on the anticipatory and unconditioned SCRs within the subject-control paradigm, assuming a smaller degree of control with increasing delay. Four groups of 12 subjects receiving the UCS with no delay, 0.5, 2 and 6 sec delay respectively, between motor response and shock, were run together with a control group not receiving the UCS. The latter group was included to control for the effect of the motor response on the SCR. All groups were given 20 trials with signals when to perform the motor response. The results were that no or very short delay of shock produced larger first-interval anticipatory responses than longer delays. For the UCR, it was found that the effect of shock on the UCR was an increasing function of the duration of the delay, when the effect of press on the UCR magnitude was taken into account.


Test of an orienting-reaction-recovery account of short-interval autonomic conditioning.

The electrodermal and plethysmographic components of the orienting reaction in 24 subjects were examined in a conditioning-analog arrangement (tones and lights patterned analogously to CS and UCS presentations in classical conditioning) in order to test the orienting-reaction-recovery (ORR) account according to which apparent short-interval autonomic conditioning (SIAC) can be completely accounted for by an ORR effect. The form of the test was to see whether ORR following change from a repeatedly presented forward ('CS-UCS') analog would exceed that to change from a backward ('UCS-CS') analog, as is the case in SIAC with CS-alone test trials following repeated CS-UCS versus UCS-CS pairings. The results did not support the ORR account, although they were shown to be consistent with the relevant experimental literature, when critically examined, and to provide internal evidence for the adequacy of the present test of this particular formulation of the ORR account of SIAC.


The impact of two different reinforcers on conditioned operant heart-rate acceleration and deceleration.

The effects of two types of reinforcers on operant heart-rate acceleration and deceleration conditioning were examined over a number of sessions. The initial use of monetary reinforcement facilitated discriminative pre-trial to trial heart-rate acceleration during sessions utilizing both monetary reinforcement and visual feedback. The initial use of visual feedback did not produce such discriminative control, but the subsequent use of monetary reinforcement resulted in increases in pre-trial and trial heart rate over sessions. No effects due to type of reinforcement were noted for heart-rate deceleration. Increases and decreases in cardiovascular functioning were imposed upon a background of increased skin responding. The cardiovascular responses that developed over sessions appeared to be relatively independent of changes in skin response.


EEG correlates of eye contact and interpersonal distance.

The EEG of 18 male subjects was monitored while the subject gazed at the eyes of a male experimenter located 2, 4, 8, 16 or 32 ft from the subject. The experimenter either gazed directly at the subject or averted his eyes. EEG arousal was highest when the experimenter was at 2 ft and gazing into the subject's eyes. EEG arousal diminished as a function of distance, while arousal for direct gaze was always higher than for averted gaze, whatever the distance.


Reaction-time variability, periodicities in reaction-time distributions, and the EEG gating-signal hypothesis.

Variability in a person's reaction time (RT) was investigated in relation to a model which hypothesized that the speed of information processing is a function of two factors, namely, the time characteristics of a cortical gating signal, and the recovery period of the events activated by the gating signals. A total of 280 RTs were obtained from each of six young adult subjects while electroencephalograms (EEGs) were simultaneously recorded. Half of the trials were performed under conditions which yielded short, low variability RTs while the other 140 trials were obtained under conditions which produced longer, highly variable RTs. Distributions of RTs from the two conditions were examined in relation to distributions of EEG half waves - which were assumed to define the period of the cortical gating signal - taken from the interval between stimulus and response. Findings were consistent with the model under investigation, namely: (1) the two different conditions produced periodicities or multiple peaks in the RT distributions; (2) the magnitude of the time intervals between consecutive peaks in the subjects' RT distributions was correlated with the duration of the most frequently occurring half waves in their EEGs; and (3) inter-subject differences in variability of the RT distributions were associated with differences in variability of the EEG distributions.


Effects of warning-signal duration on the early and late components of the contingent negative variation.

Slow EEG potentials were recorded from three sites on the scalp (Fz, Cz and Pz) during a simple reaction time task in which the duration of the warning signal was either 0.5 or 2 sec. The duration of the foreperiod was held constant, and order of conditions was varied according to a latin square design. As predicted, the longer warning signal evoked increased amplitude of the early component of the contingent negative variation (CNV). These results confirm the interpretation of that wave as an orienting response. In contrast, the duration of the warning signal did not affect the second CNV component or reaction time latency. Additional dissociation between the two CNV components was evident in their distribution on the scalp. The early component was smallest at Pz, whereas the late component attained its lowest amplitude at Fz. Concurrently recorded palmar skin potentials exhibited different polarity and latency from the CNV.


Stimulus omission and recovery of the electrodermal and digital vasoconstrictive components of the orienting response.

Three experiments are reported which investigated Sokolov's (1968) hypothesis that, after a number of stimulus presentations, complete omission of a stimulus leads to increased responsiveness of the orienting response (OR). The skin conductance response (SCR) and finger pulse volume (FPV) response components of the OR were studied. In experiment 1 (N=60), the effect of number of pre-omission training trials on response recovery was investigated, while experiment 2 (N=120) investigated the effects of stimulus intensity (70 or 90 dB) and interstimulus interval (12 or 21 sec) on recovery to stimulus omission following a fixed number of training trials. In experiment 3 (N=40), an attempt was made to control for possible below-zero habituation effects by training each subject to a habituation criterion before stimulus omission. All experiments employed a 1000 Hz tone of 3 sec duration which was presented at a constant interstimulus interval. Although recovery of the SCR did occur under some conditions, the results were largely negative. Manipulation of the number of training trials, training stimulus intensity and interstimulus interval had little effect on response recovery. A consistent finding, however, was that subjects who displayed SCR recovery also displayed significantly more spontaneous fluctuations in skin conductance during the pre-stimulus period and required significantly more training trials to reach the criterion of habituation than did subjects displaying no recovery. Moreover, the SCRs displayed by 'labile' subjects on omission trials were significantly larger than those displayed on either the last training trial or during a control interval just prior to stimulus omission.


Within mode quality and intensity changes of habituated stimuli.

Habituation of skin conductance response (SCR) magnitude was established by a number of presentations of a short burst of moderate intensity white noise. The 6th, 11th, or 21st stimulus event was either a pure tone of unchanged loudness or another noise pulse of greatly reduced loudness. Mean SCR magnitude to the reduced intensity noise pulses was consistently smaller than that to the tones, but the difference of each of these response from the habituation curve varied with the number of prior habituation trials. The qualitative changes in the stimulus produced a consistent increase in SCR magnitude; the greater the number of prior habituation trials, the larger the difference from the habituation curve. The reduced intensity noise stimulus reduced SCR magnitude below that of the habituation curve at the 6th trial, equalled the curve at the 11th trial, and yielded a greater response than the habituation curve at the 21st trial test position. The response to the tone was superior to that to the reduced intensity noise by a constant amount over the three habituation curve test points.


Time of day effects on extroversion and salivation.

A circadian rhythm in the biological basis of extroversion-introversion (E-I) was hypothesized. Eighty subjects had their EPI E-I scores and lemon juice test (LJT) scores assessed at a.m. and at p.m. Results showed that : (a) there were high intra-test correlations for EPI E-I and LJT; (b) a significant correlation between EPI E-I and LJT was only found for a.m. and not for p.m.; and (c) there were large individual differences in LJT scores. It was concluded that a circadian rhythm of E-I could not be detected by these measures, and that applicability of the LJT to E-I depends upon the time of day of assessment and the measurement procedure employed.


Binocular convergence in man during total sleep deprivation.

It was proposed that binocular convergence (lateral phoria) for near and far vision would reflect the states of visual functioning and that there would be a progressive reduction in phoria during sleep deprivation. Six young male subjects underwent two conditions of sleep deprivation on separate occasions. One condition incorporated a high visual load and the other a low load. Exercise and sound were balanced. Lateral phoria for near and far vision was carefully measured, regularly, before, during and after sleep deprivation. It was found that a reduction in convergence (exophoria) for both near and far vision became increasingly apparent with progressive sleep deprivation, especially with near vision and under high visual load. The near vision measure, which included accommodation convergence, appeared to be more sensitive to sleep deprivation generally, whereas far vision tended to produce a greater differentiation between the conditions. The implications of these findings for REM sleep and oculomotor innervation are discussed.


Effect of a memory retrieval task on recall of verbal material obtained after awakening from sleep.

After 66 awakenings from sleep without spontaneous recall of verbal material in the report, the subjects were submitted to a memory retrieval task concerning this kind of material. In 39.3% of the awakenings we found either syntactic, semantic or generic material (the latter never appeared in spontaneous recall); differences are found between fast sleep and slow wave sleep concerning semantic and generic material. The results are discussed in relation to the problem of retrieval and of hypothetical coding and verbal material assessments.


Legislation to regulate medical devices.

The history of medical device regulation began with the need to rid the marketplace of bogus inventions which were either harmful in themselves or harmful because they delayed meaningful treatment of illness. Since World War II, sophistication in medical technology and development of electronic and other types of medical devices has created a new need for regulation of safety and performance of devices used to cure and mitigate disease in man. The 1938 amendments to the Food, Drug, and Cosmetic Act gave FDA authority over labeling and advertising of devices, enforceable only after devices were marketed. In 1969 a study by an HEW commission documented the need for further legislation. The commission recommended three categories of medical devices: those requiring premarket clearance or scientific review, those for which standards could be established to protect the public, and those which are generally recognized as safe and for which nor standards would be necessary. In 1974 the Senate unanimously approved Senator Kennedy's "Medical Device Amendments of 1973" legislation which fulfills the recommendations of the HEW commission report. The House of Representatives failed to pass their version of the legislation in the 93rd Congress. Senator Kennedy re-introduced the bill in the 94th Congress and it passed the Senate in April 1975. Representative Rogers re-introduced an amended bill. The bill is expected to become law in 1975.


Chemical composition and biophysical properties of porcine cardiovascular tissues.

Collagen from the cardiovascular system is extremely resistant to proteolytic digestion, in contrast with the proteoglycans of these connective tissues. In particular this is true for the heart valves, which contain the largest proportion of collagen. The tensile strength of aortic tissue incubated at 37 degrees C declines rapidly unless fixed with aldehydes. Stabilized glutaraldehyde gives rise to the most stable form of cross-link and renders the tissue structurally intact after more than 4 years of incubation at 37 degrees C in physiological solution. Formaldehyde, on the other hand, gives rise to transcient cross-links.


Activated carbons for medical applications. In vitro microparticle characterization and solute adsorption.

Activated carbon is a high surface area adsorbent. Its ability to adsorb nitrogenous metabolic wastes and exogenous poisons from blood has been well documented. Polymeric coatings on activated carbon enhance its biotolerability and make it feasible for use in hemoperfusion devices. The only drawback seems to be the presence of microparticles on the carbon surface. These particles may become emboli during hemoperfusion. This paper describes a series of in vitro tests used to evaluate many commercially available granular and pelletized activated carbons. The tests were as follows: 1) creatinine adsorption capacity and kinetics, 2) initial cleanliness, 3) washability, 4) attrition resistance, and 5) carbon particle surface morphologymone grade of activated carbon has been chosen for hemoperfusion studies on the basis of the above evaluations; The nature of the microparticles and the approach used to remove them from this carbon is described.


Reactivity of blood with biomaterials in vitro: evaluation of some in vitro test systems for estimation of the blood compatibility of biomaterials.

Several different in vitro tests designed to estimate the degree of compatibility of blood with biomaterials have been examined to determine possible effects of donor or donor-material interaction. Statistical evaluation of data was performed, and adequate data were collected with each different test system to render such evaluation meaningful. Isolated examples of donor and donor-material interaction were detected, but these proved to be minor or insignificant in each case. Data are presented for each of the in vitro test systems examined to indicate the number of replicate determinations required for observed differences to be significant at the 5% level.


Histologic reactions of the thymus, spleen, liver and lymph nodes to intravenous and subcutaneous BCG injections.

The tissue reactions of non-tumor-bearing F1 (DBA/2 X C57B16) mice to i.v. and s.c. injected BCG were studied in animals sacrificed at planned intervals following the injection. No appreciable changes were observed prior to day 6, when the thymic cortex and medulla began to show hyperplasia of epithelial cells; many of them had PAS positive cytoplasm and some of these cells were contiguous with the walls of small blood vessels and large cystic spaces containing PAS-positive secretions. The thymic cortical lymphocytes showed, on day 6, a pronounced pyroninophilia and increased mitotic activity without increase in thymic weight. These changes were considerably more striking in the i.v. than in the s.c. injected animals. On the same day a pronounced multifocal lymphocytic infiltration involving the red pulp and the parafollicular and periarteriolar zones of the spleen were observed. It was more pronounced in the i.v. than in the s.c. injected animals. The thymic changes were seen only in animals killed on day 6 and day 10, but were no longer observed on day 14. Beginning with day 14 a pronounced histiocytic granulomatous reaction was observed in the liver. On day 18, this granulomatous reaction was also seen in the spleen, lymph nodes, and lungs of i.v. injected animals. It persisted until day 45. In the s.c. injected animals histiocytic granulomas were seen only at the site of injection and in the regional lymph nodes.


Left ventricular ejection time. multiple relation to physiological and biometrical data; prediction of reference standards.

The relationship between left ventricular ejection time, and physiological or biometrical data, is submitted to multivariate statistical analysis. Methodology is intended to attain three objectives: 1) to simulate a controlled-condition experiment in clinical research, by using the statistical method of multiple regression; 2) to get a wide inference of conclusions, by selecting a sample of two hundred subjects whose biological data cover a wide field; 3) to check the really prospective value of results, by applying the formula worked out in a group of a hundred subjects to another independent group of a hundred subjects. The prediction formula of ejection time takes into account: stroke volume, cardiac cycle duration, body height, sex, age, pulse pressure, blood capacity in oxygen, presence or absence of digitalis treatment or atrial fibrillation. The first aim of the formula is to better evaluate the normal relationship between considered variables. Secondarily it leads to a proposal for estimating mechanical performance of the left ventricle.


Studies of granulocyte kinetics in normal and granulocytopenic subjects.

Granulopoiesis was studied simultaneously by three methods in normal subjects and in subjects with neutropenia of various aetiologies: in vitro labelling of autologous and homologous granulocytes for the study of peripheral kinetics, in vivo labelling with DF32P (di-isopropyl-flourophosphate 32P) or 75Se-selenomethionine, and bone marrow autoradiography after in vitro labelling with 3H-thymidine for the study of bone marrow granulopoiesis. Three main mechanisms of neutropenia can be distinguished: a) peripheral hyperdestruction, corpuscular or extra-corpuscular, and false leukopenias (change in the distribution of peripheral granulocytes from the circulating to the marginal granulocyte pool; b) quantitative bone marrow insufficiency without qualitative abnormality; c) qualitative abnormality in bone marrow granulopoiesis with cell death in either the maturation stage or the proliferative stage. There is no exact correlation between clinical and kinetic classifications, but most cases of post-infection chronic neutropenias and idiopathic neutropenias fall into the first two categories, and most cases of benzol intoxication and bone marrow insufficiency due to X-irradiation fall into the last category. Some of these last patients developed an acute myeloblastic leukaemia in the two following years and can be considered as preleukaemic states.


Kinetics of HBs antigen in man.

The metabolism of HBs Antigen had been studied in three human volunteers. One had chronic hepatitis and two were "silent carriers". The HBs Antigen had been isolated and purified from the plasma of each of the three subjects and, after iodination, reinjected to the same donor. The parameters of plasma kinetics of 131I HBsAg have been analyzed according to a two compartmental model on the basis of the radioactivity of TCA precipitate (TP) and immunoprecipitate (IP). The fast initial volume of distribution was approximately equal in the three subjects (46.6 ml/kg). The metabolic clearance rate (MCR) of IP was the very same in two subjects but is four times higher in one of the silent carrier. The total renewal time (TRT) was about 3.3 days. Assuming that the HBs Antigen extraction was of the order of 65% the plasma HBs Antigen concentration per liter of plasma would be 12 and 53 mg/liter fot two silent carriers and 61 mg/liter for the patient with chronic hepatitis. The radioactive efflux from the model (calculated as IP.MCR multiplied by HBs Antigen concentration) was identical for the two silent carriers adn 50% higher in the patient with chronic hepatitis. This increase possibly reflects an increased synthesis of HBs Antigen in the patient with chronic hepatitis. The cumulative urinary radioactivity when added to the whole body counting demonstrated that radioactivity was excreted solely in the urine. The ratio of organ counting to precordium counting did not vary significantly with time in all subjects.


[Multidimensional analysis in clinical investigation. Application to the pathogenic classification of idiopathic hypercalciuria].

Multidimensional analytical techniques enable any number of variables to be studied simultaneously. These techniques have been described and a few examples of their application to biomedical research given. A classification of so called "idiopathic hypercalciuria" was made using this approach which demonstrated the existence of three possible mechanisms of pathogenesis.


[The effects of arginine and growth hormone on the nitrogen balance of rats].

Intramuscular administration effects of arginine aspartate (AA : 0,50 g a day for 4 days), arginine chlorhydrate (CA : 0.34 g a day for 4 days), potassium aspartate (AK : 0.22 g a day for 4 days) with equal arginine base and aspartate ion supply for all products, bovine growth hormone (STH : 2 U.I. a day for 4 days), and the association of these substances, are studied on 6 rats, during a 74 days nitrogen balance period. Arginine (endogenous STH secretion stimulation) produces a greater nitrogen retention with AA (+ 184%, p less than 0.01) than CA (+ 71% p less than 0.10). A.K. had no effect. With exogenous STH, effect is important (+ 248%, p less than 0.01) but does not significantly differ from AA. STH + A.A. and STH + C.A. associations (exogenous and endogenous STH) produce a very marked nitrogen retention (+ 282% and + 252%, p less than 0.01) which, however, does not significantly differ from STH when given alone.


New studies of cranial growth.

Additional experimental data indicate that cranial base elongation is secondarily responsive to prior alterations of the neural mass, further supporting the functional matrix concept. Additional studies of epithelial growth and of muscle regeneration suggest that neurotrophic processes, regulating functional matrices, may play a significant role in both normal and abnormal cephalogenesis.


Difficulties and problems to be solved in the approach to craniofacial malformations.

Orbitocraniofacial surgery offers great possibilities to some grossly deformed patients. It is unlike any other aspect of plastic surgery, meriting the creation of a new full-time specialty. The development of a few regional clinical basic science teams located strategically throughout North America is suggested. The primary aim of the teams should be a broad interdisciplinary approach involving basic and clinical research focused on craniofacial anomalies. However, to bring all the necessary multidisciplinary groups into an interdisciplinary team requires central funding to make available the necessary commitment of time to organize a unified thrust of research effort.


[Growth rate and natural history of breast cancer].

Available data on growth rate of human breast cancers and their kinetic of cell proliferation were reviewed. Breast cancers are among those human cancers with the longest doubling time and the lowest labelling index, however the spread of the individual values is especially large. Analysis of the data indicate that half of the metastases began to grow more than about two years before the time when the primary tumor reached a clinically detectable size. The prognostic influence of the delay between the time when the tumor reached a clinically detectable size and the treatment is discussed. A correlation is observed between the growth rate of the primary tumors and the mean survival of the deceased patients. This is probably due to correlation between the growth rates of the primary and of the metastases. The growth rate of the primary seems to have little influence, if any, on the probability of metastatic dissemination per tumor cell. This probability varies widely among various clinical types of breast tumors and is probably correlated with other parameters such as the presence of an inflammatory reaction.


[Local and regional lymph node invasion in breast cancer].

The significance and the pronostic value of nodal involvement were studied in patients suffering from mammary carcinoma over the past fifteen years at the Institute Gustave-Roussy. An average of eighteen lymph nodes per patient were examined by routine methods. In 70% of the cases there was axillary involvement as well as in 42% of the cases classified as NO. Such involvement seems to proceed step by step from the lower lymph nodes to the upper ones and is significantly more frequent when the tumor is located externally or centraly (70%) than when the tumor is located in an internal quadrant (55%). Involvement of the interpectoral chain of Rotter was found in only 12% of these cases and practically never in an isolated manner. Internal mammary chain involvement, present 25% of the cases, did not seem to be connected to a median or lateral location of the tumor. The number of involved nodes has great prognostic significance, much more so than the presence of capsular rupture or sinus histiocytosis. The prognosis is much poorer if three or more nodes are involved: the seven year survival is about 85% when 0, 1 or 2 nodes are involved, and falls to 44% when three or more are involved.


[Current data on radiotherapy of breast cancer].

At the Symposium in Teheran two aspects of radiotherapy in mammary cancer came up for discussion: post-operative radiotherapy and the possibilities of conservative treatment, combining tumorectomy ("lumpectomy", "tylectomy ") for stage 1 cases. The place of post-operative irradiation was discussed in relationship to the appearance of local recurrences, metastases and the survival rates available from published data (therapeutic trials and retrospective studies) and in relationship with a population of 206 cases treated at the Gustave Roussy Institute between 1963 and 1966. The possible relationship between post-operative irradiation and immunity were mentioned. With identical wide surgical excision the essential role of post-operative irradiation consists of diminishing in a significant fashion the level of local recurrences. With more restricted surgery of the simple mastectomy type one asks whether irradiation could not replace radical node dissections. It should be reserved for the bad N+ cases. A retrospective study of 44 cases coded T1 NO/N1 MO/PevO treated by tumorectomy and cobalt 60 was compared with 44 matching cases which differed only in their local treatment which consisted of wide surgical excision. The survival actuarial rate at 8 years is 88.6% for the more conservatively treated group compared with 73% for the radical group. In order to provide a quite impartial result a WHO therapeutic trial was begun in 1972.


[Epidemiology of colorectal cancer].

Some of the more recent contributions of epidemiology to knowledge of the causation of colo-rectal are reviewed. Geographical differences and changes in migrants suggest the importance of enviornmental (especially dietary) factors. High dietary fat is believed to stimulate increased bile secretion and thus provide a substrate for bacterial conversion to carcinogens or co-carcinogens. The association of beef consumption to colorectal cancer may relate to the fat content of beef. There is so far little direct evidence to support the alternative dietary fibre deficiency hypothesis.


Kinetics and possible regulation of crypt cell populations under normal and stress conditions.

The proliferative organisation of the crypts of the small intestine is considered with special reference to the existence, location and numbers of stem cells. It is concluded that the crypt contains a minority population of cells at its base that are the true stem cells. These cells provide an input of cells for the larger proliferative compartment higher up the crypt. The presumptive stem cells may be pluripotent and produce Paneth, goblet and columnar cells. They are probably also the cells which are capable of regenerating the crypt after X-ray depopulation. Radiobiological experiments indicate that the number of cryptogenic cells is less than 80, while the results of several experiments on the kinetics of the cell populations indicate that the number of stem cells is about 20. The stem cells are located in the Paneth cell zone of the crypt, and are apparently passing through the cell cycle at about half the speed of the proliferative cells. It is these vital stem cells that will determine the response of the mucosa to therapeutic agents, probably play a role in carcinogenesis and play a dominant role in mechanisms controlling cell proliferation.


[Immunologic research on human colonic cancer].

Immunological studies on human colonic tumors were oriented in two ways according to their methodology: immunochemistry or cellular immunology methods. Immunochemical studies allowed to characterized several tumor associated antigens although no one was proved as cancer specific. The most famous of these antigens is no doubt the carcinoembryonic antigen of the digestive system or shortly CEA. This is a perchlorosoluble glycoprotein which is associated to the apical pole of glandular cells. It is found in relatively large amounts in colonic carcinomas, mainly the well differentiated ones, and in traces in non cancerous colonic mucosa. By radioimmunoassay CEA level was found elevated above 2,5 ng/ml in most of the sera of patients bearing a digestive cancer but also in a fair number of patients having non-digestive cancer or an inflammatory disease involving or not the digestive system. Morever CEA increase is noted in only one third of incipient colonic carcinomas. CEA assay is thus not reliable for diagnostic of colon cancers, specially the localized ones. On the contrary, this assay seems to be of great value in the follow-up of patients operated for colonic carcinoma. Cellular immunology methods aim to characterize the reactivity of patients lymphocytes to antigens carried by their own tumor. Results obtained by microcytotoxicity are now questioned. Migration inhibition of peripheral blood leukocytes and lymphoblastic transformation give perhaps more reliable informations. The same is likely true for skin tests made in cancerous patients with extracts of their own tumor.


[Clinical use of carcinoembryonic antigen (CEA) determination].

The carcinoembryonic antigen (CEA) is a tumor marker defined by specific heterologous antisera. Elevated levels of circulating CEA have been detected by radioimmunoassay in 20-90 per cent of cases of colorectal carcinomas depending on the degree of tumor spread. The fact that elevation of CEA level can also be observed in other types of carcinomas and in several non malignant conditions greatly limit the value of the CEA test for the early diagnosis of colorectal carcinoma. Thus, the CEA assay should not be used as a screening test for cancer. Repeated CEA measurements, however, appear to be of importance for the evaluation of tumor resection and the detection of tumor recurrence. The only localized tumors known to produce elevation of CEA above the levels observed in non malignant diseases are carcinomas of the large bowel and the pancreas. In carcinomas derived from other organs a marked increase of CEA level is always associated with the presence of distant metastasis. Therefore at the present time the clinical applications of the CEA radioimmunoassay should be limited to the differential diagnosis of patients with suspicion of primary colorectal or pancreatic carcinoma, to the detection of distant metastasis in other types of carcinomas and to the post operative follow up of patients who had elevated levels of CEA before surgery. Well-controlled studies are still needed to determine if therapeutic decisions based on CEA results can lead to improved survival.


Observations on the epizootiology of vampire bat rabies.

Vampire bat populations were opportunely sampled before, during, and at varying intervals after outbreaks of bovine rabies. The captured bats were examined for rabies neutralizing antibody and virus. In all, sera from 1,024 vampire bats were tested for antibody, and tissues from these bats plus 83 others were tested for virus. Neutralizing antibody only rarely appeared in vampire serum samples taken before bovine rabies outbreaks, and only low percentages of samples positive for rabies antibody were obtained from bats captured during bovine outbreaks. In contrast, varying percentages of positive samples (including some high percentages) were taken from bats captured at various intervals after bovine outbreaks. Only eleven rabies virus isolations were obtained in the course of this study. In each case the virus came from a bat captured just before or during a bovine outbreak. The authors suggest that rabies virus behaves in vampire populations the way diverse infectious agents typically behave in other hosts. That is, the virus infects many individuals; some die and others survive to demonstrate their exposure through the appearance of anitbody. The disease disappears from the bat population in time and does not return until a sufficient number of susceptible bats have re-entered the population.


Attitudes toward population control in Santiago, Chile.

This article explores Chilean attitudes toward the national population's size and rate of growth, as indicated by a special survey conducted for this purpose. The survey sample consisted of 1,410 men 20 to 54 years of age in urban Santiago, who were separated into six categories on the basis of their education and socioeconomic status. The subjects were interviewed by 36 students from the University of Chile who utilized a prepared questionnaire including both open-ended and multiple-choice questions. The results clearly indicate that men in the lower socioeconomic categories tended to know less about the population's size and growth than their better-off counterparts. Nevertheless, they more often felt that Chile had "too many" inhabitants, that recent population growth had been rapid, and that this rate of growth should be reduced.


Leptospira fort-bragg isolated from a rat in Barbados.

Leptospira fort-bragg was isolated from the kidney tissue of a rat (Rattus rattus) trapped on a plantation in St. Philip Parish, Barbados. This constitutes the first reported isolation of this Autumnalis group serotype outside of the United States and its first known isolation from an animal species. Serologic evidence is presented which indicates that this serotype may be the cause of leptospiral infections in Barbadian cattle.


Investigation of the prevalence and inheritance of bronchial asthma in San Antonio de los Baños, Cuba.

A survey of bronchial asthma prevalence and inheritance patterns was carried out in the municipality of San Antonio de los Banõs, La Habana, Cuba, employing as a sample 3,295 of the area's inhabitants. These persons, selected by stratified, non-restricted sampling techniques, represented 11.02 per cent of the total population. The asthma prevalence found in this sample, which was considered representative of the local population, was 9.74 percent. No significant variations were noted in male and female prevalence rates. The occurrence of bronchial asthma is strongly influenced by inheritance. Our survey supported this view, and also showed that the age of asthma onset is influenced by whether or not the subject's family has a positive history of allergy or not. However, patients with a positive history on one side of their family had an age of onset that was not significantly different from patients with a positive history on both sides (p less than 0.35). Overall, the results tend to confirm that the inheritance of bronchial asthma is autosomal and does not conform to simple dominant or recessive inheritance patterns. Rather, asthma inheritance appears multifactorial, perhaps involving varying degrees of expression, indicating that more is involved than absence or deficiency of a single enzyme.


Results of spraying with ultra-low-volume malathion at ground level in Panama City.

Several ultra-low-volume (ULV) sprayings of technical malathion (95 per cent) were carried out in Panama City. Their purpose was to find out how useful this ULV technique could be in helping to combat mosquitoes, especially Aedes aegypti. Two residential areas were selected as sites for the trials. One of these was San Francisco, a district near the shoreline of the Bay of Panama with many individual houses and a few tall buildings. The other was El Cangrejo, a district further inland containing numerous multi-story apartment buildings and several luxury hotels. Two trials were conducted in San Francisco, both involving a single application of insecticide. One of these tested the effect of street spraying on mosquitoes and larvae left inside and outside of one and two story dwellings, while the other involved similar testing of the effects on ten floors of a high-rise apartment building. There was only one trial in El Cangrejo, but this employed three applications of insecticide at two-day intervals. Like the second San Francisco trial, it tested the effect of the spray on mosquitoes and larvae left in a high-rise apartment building. All the mosquitoes used were obtained from the insectarium of the National Malaria Eradication Service. A. aegypti adults and larvae and Anopheles albimanus larvae were used in the first San Francisco trial. Thereafter, because available supplies of A. aegypti were exhausted, An. albimanus adults and larvae were used alone. The results of these trials were very satisfactory. All adult mosquitoes were killed in most cases, the only exceptions being mosquitoes exposed to a single application that was made under adverse conditions. Fairly high rates of larval mortality were also obtained. Overall, the results strongly indicate that thrice-weekly ground-level ULV spraying with malathion can serve as a highly effective mosquito control measure.


Cancer of the reproductive organs in Costa Rica.

This article analyzes deaths and hospital discharges involving cancer of the reproductive organs in Costa Rica during the period 1956-1969. The focus in on breast, prostate, and uterine cancer, since these three types account for virtually all of the known cases. It is noted that while rates of breast and prostate cancer are very low in Costa Rica, very high rates of uterine cancer have been reported. There appears to be an opportunity for reducing these excessive rates, which have a particularly strong impact on those 45 and over, through special health programs. The analysis also shows a six-year decline in mortality and hospital discharge rates for cancer of the cervix uteri. This progressive decline in cervical cancer, together with a rise in breast cancer, runs parallel to a decline in fertility rates during the same period. The observed rates of prostate cancer was very low, but a progressive rise was noted among those 65 and over. Both this time trend and the observed geographic distribution of prostate cancer in Costa Rica are in conformity with general epidemiologic features of prostate cancer described by studies made in the United States.


St. Louis encephalomyelitis in Hermosillo, Sonora, Mexico.

This report, which describes an epidemic of St. Louis encephalitis in northwestern Mexico, was prompted by the apparent infrequency of previous Mexican outbreaks of this disease. The site of the epidemic was the Municipality of Hermosillo in the State of Sonora. This municipality, with a population of about 273,000, is situated in a hot flat area which is naturally dry but which is also well-irrigated. Here, over an eithy-week period, 51 persons became ill and were hospitalized with symptoms including fever, vomiting, stiff neck, lethargy, and increased cell/protein levels in their cerebrospinal fluid. Sera from 12 of these patients were tested for SLE antibodies by hemagglutination inhibition, complement fixation, and neutralization. The results of these tests were positive and showed a fairly high degree of correlation. In addition, paired serum samples showed a significant rise in SLE antibody titers. Over half of the cases occurred in the City of Hermosillo, the municipal seat; the remainder occurred in 13 outlying areas, most of them quite nearby. Virtually all of the city dwellers affected were residents of low-income districts. The rate of hospital cases was roughly 19 per 100,000 inhabitants, and the case-fatality rate among these cases was approximately 20 per cent. The ratio of male to female patients was 1.3 to 1; sixty-nine per cent of the patients were under 16 years of age.


Diabetes mellitus: a challenge for the countries of the region.

PAHO recently convened a meeting of experts on diabetes mellitus for purposes of underlining the importance of the disease as a health problem and developing recommendations to assist the countries of the Region in establishing control programs. Existing data on the prevalence of diabetes mellitus in different countries are not comparable, since population samples are not always representative and diagnostic criteria vary. Ten different countries set the prevalence figure at anywhere from 1.2 to 6.9 per cent. Mortality from diabetes reveals only part of the problem, largely because of registration difficulties. The figures that are available, however, show that the situation is very serious in several Carribbean countries; that is, Barbados, Trinidad and Tobago, and Jamaica rank first, second, and third, respectively, among 22 countries in the Americas. The data now available on morbidity and mortality, expected population growth, and probably increases in the relative size of older population groups lead to the assumption that diabetes mellitus, together with its complications, will become an increasingly serious problem in the Region over the next 10 to 15 years. Programs for the control of diabetes mellitus should include educational campaigns for patients, the public, and health professionals; early detection of the disease in high-risk groups; registration and followup of cases and the organization of systems for providing comprehensive care. Promotion of basic, clinical, and epidemiologic research directed at local problems and seeking to acquire a better understanding of the nature of the disease and its complications is also highly recommended. Naturally, each country should adapt current methods of treatment to local socioeconomic and cultural circumstances, especially with regard to dietary therapy, prescribed insulin dosage, and use of the controversial oral hypoglycemic drugs. Despite the important contribution that research can make to a better understanding of diabetes mellitus, it is the health authorities, the patients, and the public who still have the major task of coping with this increasingly prevalent disease, which more and more is revealing the consequences of its chronic  nature and complications in our Region.


Cigarette smoking in Latin America--A survey of eight cities.

During the period 1962-1964, diseases related to cigarette smoking were responsible for 20 per cent of all deaths in men between the ages of 35 and 64 in 10 large Latin American cities, and in the years that followed various indicators pointed to the fact that cigarette smoking was reaching very high levels in several countries of the Region. In the light of these trends, an investigation was undertaken in eight cities selected for their geographic, ethnic, and demographic diversity--Bogotá, Caracas, Guatemala City, La Plata (Argentina), Lima, Mexico City, Santiago, and São PAulo. The aims of the study were: to obtain a reliable estimate of the prevalence of cigarette smoking in urban communities in Latin America, to establish a correlation between the habit and certain symptoms of cardiorespiratory and other disability, and to obtain an accurate assessment of public beliefs and attitudes with respect to cigarette smoking and its relation to health. One of the questionnaires used was similar to one employed in comparable investigations made in the United States in 1964, 1966, and 1970. Additional information on cardiorespiratory symptoms, non-specific mortality, absenteeism, and other subjects was collected on two other forms, one recommended by AHO and the other by the United States National Health Statistics Center.


Formulation of goals for life expectancy at birth in Costa Rica (report of one experience).

Costa Rican authorities have finished a national adaptation of the goals of the Hemisphere's Ten-Year Health Plan for the Americas and have formulated a National Health Plan for 1974-1980. This work was coordinated by the Health Sector Planning Unit and was assisted by various multidisciplinary and multi-institutional working groups. The methodology set forth in this article was developed by a group responsible for formulating goals with regard to life expectancy--the last of five health-related subjects analyzed, and one regarded as dependent on the rest. In brief, this methodology was as follows: Birth rates, death rates, and life expectancy at birth in the other countries of the Region and in a developed country (Sweden) were compared with those prevailing now and in the past in Costa Rica. This served as a basis for projecting Costa Rica's future prospects if no changes were made, or if certain changes were made through implementation of new programs. This was followed by analysis of leading caused of death in the country--by age group and vulnerability of those dying, and by probably reductions in mortality that would result from achieving the goals established for other programs. On this basis, various alternative reductions in mortality for each age groups were considered. Using these alternative, abridged life tables were devised, and these in turn were used to draw up a table showing the life expectancy at birth that would result from realization of each alternative. This made it possible to derive life expectancy goals that were consistent with the goals for reducing mortality in each age group that were formulated during the sectoral planning process. It is hoped that this general procedure, illustrated here with data from the Costa Rican case, may prove useful to others engaged in health planning work.


Pulmonary function in miners working in British collieries: epidemiological investigations by the National Coal Board.

Epidemiological investigations of ventilatory capacity in men working in British coal mines are reviewed. The results are related to radiological category of pneumoconiosis, respiratory symptoms, cigarette smoking and dust exposure. In summary it was found that dust exposure was associated with a fall in FEV1.0 but that there was no further fall assoicated with the presence of simple pneumoconiosis. Simple pneumoconiosis appeared to be evidence of the amount of previous dust exposure and suggested that this had been sufficient to cause a measurable fall in FEV1.0. The extent of the ventilatory impairment associated with simple pneumoconiosis was less than that due to age alone in most men. Cigarette smoking was found to be an important cause of ventilatory impairment.


Pulmonary function profiles in Quebec asbestos workers.

Lung function profiles were defined in over 1,000 Quebec chrysotile asbestos workers using five standard tests of lung function, and were related to dust exposure and smoking. Close to half the men (44.3%) had a normal lung function profile and a further 26.5% some function changes but no definite profile. Amongst the remainder restrictive and obstructive function profiles occurred with equal frequency (12.8 and 12.2% respectively). Both were associated with radiologic asbestosis; both occurred infrequently in the absence of the smoking habit. These findings suggest an association between the smoking habit and the harmful effects of asbestos exposure on lung function, and by implication on the development of lung fibrosis. A similar association has been recognized in respect of bronchogenic carcinoma. This experience, in the primary mining and milling of pure chrysotile asbestos, may not be directly applicable to secondary industries concerned with the further processing of this fibre.


Impairment of pulmonary mixing in simple and complicated silicosis.

Two simple indices of pulmonary mixing (helium mixing time in a closed circuit, and mixing ventilation) were measured in 274 patients (mostly miners) with silicosis, aged 50 years or less (mean 42.4 years); the results were analysed in respect to silicosis category and type, presence of co-existent chronic bronchitis and ventilatory performance, and were compared to those of a group of normal subjects to assess statistical significance. The average results for the whole group were 5.81 min for mixing time (tmix) and 62.3 1 for mixing ventilation (Vmix), representing 1.8 times and 2.4 times the normal, respectively; the results were higher for patients with co-existent chronic bronchitis within each radiological category, except the last ("C" opacities), but the differences were significant only for patients with small opacities and with "suspect pneumoconiosis". Among patients with small rounded opacities the co-existence of healed tuberculosis (apical fibrous nodules) or of other X-ray changes did not influence the pulmonary mixing; no difference was found between the three types of small opacities. A slight tendency towards lower values in patients with early conglomeration ("A" opacities) allows the suggestion of conglomeration starting in "slow" lung spaces. The best results were those of patients with normal ventilatory function followed by those with a restrictive and then by those with an obstructive ventilatory impairment. The most severe mixing disturbance was found among patients with chronic bronchitis and obstructive defect with "suspect pneumoconiosis", who are not covered by occupational disablement compensation.


Physiological/pathological correlations in coal workers' pneumoconiosis.

There is remarkably little information about the direct relationship of physiological abnormality in coal workers' pneumoconiosis with structural changes in the lung and there are major difficulties in attempting such a correlation. The general population, including coal workers, has a regrettably high prevalence of pulmonary functional abnormalities attributable to chronic bronchitis or to emphysema occurring either separately or together. The pathological basis for the functional impairment in chronic bronchitis and possible functional sequelae to the anatomical changes of emphysema are not clearly understood, making it extremely difficult to identify separately the functional effects associated with coal workers' pneumoconiosis. Any study of coal workers' pneumoconiosis must take into account the background population. The published investigations relating the functional abnormalities and pathological changes in the lung in coal workers' pneumoconiosis are reviewed. The relationship of functional change to emphysema, chronic bronchitis, cor pulmonale and the specific lesions of coal workers' pneumoconiosis are dealt with. There is great need for further work in this field, both in the form of simple studies of pathological changes in miners' lungs as well as more complex attempts to correlate such pathological surveys with physiological abnormalities in life.


Chronic obstructive airway disease in pneumoconiosis in comparison to chronic obstructive airway disease in non-dust exposed workers.

Many types of dust, including cigarette smoke, cause an impairment of lung function. This lung function impairment does not affect working capacity provided the dust is not fibrogenetic. Quartz, normally present in coal mine dust in concentrations between 2 and 10% is claimed to be responsible for coal workers' pneumoconiosis (CWP) by some writers. However the evidence is conflicting and firm conclusions cannot be drawn at present. From the clinical point of view CWP is characterized by an increased airway resistance. All correlations between airway resistance, arterial oxygen and carbon dioxide pressure and intrathoracic gas volumes (IGV) in patients having CWP and obstructive airway disease are similar to those in non-dust exposed patients with obstructive ariway disease. Patients with CWP, at equivalent values of airway resistance have smaller mean values of IGV. The relationship between arterial oxygen pressure and pulmonary arterial pressure is the same in patients with CWP and obstructive airway disease as in patients with chronic obstructive airway disease but without CWP. The effect of therapy in CWP with obstructive airway disease corresponds very well to that seen in patients without CWP.


Pulmonary diffusing capacity for carbon monoxide in simple coal workers' pneumoconiosis.

The lung diffusing capacity for carbon monoxide (DLCO single-breath) and its two components, the capillary blood volume (Vc) and the diffusing capacity of the membrane (DMCO) were measured at rest in 43 miners and 141 control subjects, the values in whom enabled reference formulae to be established; in 30 control subjects and in the majority of the miners these indices were measured during exercise. The main results are as follows: the diffusion indices are on average slightly decreased in simple coal workers' pneumoconiosis; both DMCO and Vc contribute to the lowering of DLCO, at rest and during exercise; individually Vc is more often significantly altered than DMCO; on effort the percentage increase of DLCO is normal in coal miners; the data during exercise suggest that smoking habit contributes more to lowering DLCO than does pneumoconiosis itself; lastly the diffusion indices are lower in miners with "pin-head" than those with micronodular opacities: this tendency is more pronounced during exercise. These findings are discussed.


Central effects of clonidine 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride in fowls.

1 The effects of clonidine infused into the IIIrd cerebral ventricle, the hypothalamus or intravenously were studied on behaviour, electrocortical activity, body, comb and leg temperatures, respiration and carbon dioxide elimination in adult and young fowls (Gallus domesticus). 2 Behavioural and electrocortical slow wave sleep were induced by clonidine infused into IIIrd cerebral ventricle, the hypothalamus or intravenously. Suprisingly, sleep elicited by intravenous clonidine was much longer-lasting than that induced by an identical dose given intraventricularly. 3 Body temperature was lowered by clonidine given intraventricularly or infused into the hypothalamus. Depending on initial comb temperature and ambient temperature, comb temperature was elevated, unaffected or lowered as body temperature fell; temperature of the unfeathered legs also rose as body temperature declined after clonidine. 4 Following clonidine, but before any considerable decline of body temperature, tachypnoea and wing abduction developed; during recovery of body temperature, the wings were lowered and applied closely to the trunk and the feathers partly erected. 5 CO2 elimination fell more swiftly than body temperature following intrahypothalamic clonidine in young chicks; initial recovery developed sooner than that of body temperature, but eventual recovery was delayed compared to that for body temperature. The effects of clonidine were much more marked in young chicks studied at an ambient temperature below thermoneutrality as compared to thermoneutrality. 6 The soporific effects of clonidine were attenuated by intraventricular phentolamine; its hypothermic effects were prevented by phenoxybenzamine and prevented or attenuated by phentolamine. Intraventricular atropine, haloperidol, methysergide and propranolol were ineffective. 7 Larger doses of intraventricular phentolamine elicited shivering, tachypnoea and wing abduction; body temperature was elevated, to the extent even of lethal hyperthermia. Intraventricular atropine also elevated body temperature. 8 Clonidine infused intravenously, intraventricularly or into the hypothalamus, replaced the behavioural and electrocortical arousal evoked with dexamphetamine, by sleep associated with slow wave electrocortical activity.


Cardio-respiratory function in United States coal workers.

Over the past five years the cardio-respiratory function of selected groups of U.S. coal workers has been intensively studied. The subjects studied included approximately 10,000 working miners at mines selected as part of an epidemiological study of the prevalence and progression of coal workers' pneumoconiosis (CWP) as well as selected groups of non-working symptomatic miners. The occupation of coal mining per se is sometimes associated with a mild reduction in ventilatory capacity which is not closely related to radiographic category of simple CWP. Slight abnormalities in gas exchange and lung mechanics appear to be associated with the higher categories of simple CWP which do not appear to affect longevity. Subjects with complicated CWP (massive fibrosis) demonstrate moderate to severe degrees of obstruction, abnormalities of gas exchange and lung mechanics that generally relate to the extent of the massive fibrosis and result in premature disability and death.


Effects of dopamine on sinus rate and ventricular contractile force of the dog heart in vitro and in vivo.

1 Experiments were carried out on dog isolated papillary muscle and sinus node preparations perfused with arterial blood from a donor dog. The chronotropic and inotropic effects of dopamine were analysed by using reserpine, desmethylimipramine (DMI), cocaine and phenoxybenzamine, and the relative chronotropic and inotropic effects defined, the results being compared with those for noradrenaline (NA). 2 The effects of dopamine administered intra-arterially into the isolated preparations were reduced by pretreatment of animals with reserpine both in the papillary muscle and sinus node. The chronotropic effects, however, were affected less by pretreatment with reserpine than were the inotropic effects. 3 Desmethylimipramine (DMI) reduced the inotropic and chronotropic effects of dopamine, and enhanced the effects of NA and nerve stimulation; the chronotropic effects of the amines were less affected than the inotropic effects. 4 Cocaine enhanced considerably the inotropic and chronotropic effects of NA, and decreased the inotropic but not the chronotropic effect of dopamine. 5 Phenoxybenzamine enhanced the inotropic effects of dopamine, NA and nerve stimulation, but did not affect the chronotropic effects of the amines. 6 When dopamine (1 to 300 mug/kg) was administered intravenously to the donor dog, it increased preferentially the contractile force of the ventricular myocardium with a comparatively small change of the sinus rate in the isolated preparations as well as in the heart in vivo. NA (0.1 to 10 mug/kg) caused effects similar to those of dopamine. The maximal inotropic responses to these catecholamines were reached with lower doses than the chronotropic ones. 7 It is concluded that both the positive inotropic and the positive chronotropic responses to dopamine are mediated partially by a direct and partially by an indirect stimulant effect on beta-adrenoceptors in the dog heart. The present results suggest that the difference in activity of dopamine and NA between the ventricular myocardium and the sinus node may be ascribed to the unequal innervation with adrenergic nerve fibres of the atrium and the ventricle (Furnival, Linden & Snow, 1971). The sinus node which is densely innervated by adrenergic nerve fibres may inactivate noradrenaline and dopamine more effectively than the ventricular myocardium through the uptake into the nerve and thereby be less sensitive to the exogenous catecholamines.


Respiratory and cardiac function tests in relation to occupational lung diseases.

Tests of lung function have a number of important roles in occupational medicine but the results need to be of high technical quality if they are to be useful. On this account, as well as careful supervision and scrutany of results, only appropriate tests should be applied. The choice will vary with circumstances; it is likely to be made from a limited number of procedures including those recommended in Respiratory function tests in pneumoconioses (I.L.O., 1966). Tests of maximal and near maximal exercise are seldom indicated. Care should be taken over the selection of reference values and of mathematical treatments for the results.


Some pharmacological properties of the cremaster muscle of the guinea-pig.

1 The tension developed in the guinea-pig cremaster was recorded during spontaneous activity and electrical stimulation. Spontaneous rhythmic contraction was observed in many preparations, particularly in the tip of the cremaster. These contractions were very slow, lasting about 20 s and occuring at about 2 min intervals, but different preparations varied greatly. Twitches produced by electrical stimulation were similar to those in other skeletal muscles, being reduced by (+)-tubocurarine and abolished by tetrodotoxin. 2 A slow contraction could be initiated by electrical stimulation using a pulse longer than 10 ms in spontaneously active preparations and in some quiescent preparations. Spontaneous and evoked slow contractions were not suppressed by tetrodotoxin, but were selectively abolished by verapamil. Histamine increased the basal tension and generated spontaneous contractions in quiescent preparations. Hypertonic solutions also had excitatory effects. 3 Contractions produced by acetylcholine and carbachol were blocked by atropine. Those produced by adrenaline and noradrenaline were stronger than those due to histamine, acetylcholine and carbachol and were abolished by an alpha-adrenoceptor blocking agent, phentolamine. In the preparations in which the slow contraction was not observed, histamine, acetylcholine or adrenaline had very little effect. 4 It is suggested that the cremaster muscle consists of striated muscle together with some smooth muscle having properties similar to that in the vas deferens.


[Respiratory parameters in pneumoconiotic miners in the north French coal district (author's transl)].

The authors examine the respiratory tests performed during a two years-period in 676 pneumoconiotic miners. Spirography was normal in 8% of the cases; a mixed ventilatory impairment, with an obstructive prevalence of variable extent, was present in 2/3 of the cases. Pharmacodynamic tests in 353 subjects showed a frequent non-specific bronchial sensitivity (34.2% of the whole group). Hypoxaemia (PaO2 below 75 mmHg) with normo- or hypocapnia was observed in 379 patients; hypercapnia was relatively uncommon (9.9%) and occurred mainly in bronchitic patients. The breath holding CO lung transfer test was very often disturbed, as the diffusing capacity (DLCO) was below the predicted value in about 80% of the population. Radiofunctional comparisons were carried out in an homogeneous group of 212 subjects. The data clearly demonstrate that functional abnormalities were not exclusively seen in extensive radiological forms. As far as it goes beyond a simple ventilatory study, the measurement of the breath holding lung transfer factor for CO has proved to be a valuable element in the functional statement of anthracosilicosis. The polymorphism of the pulmonary repercussions of dust exposure explains individual differences between the results of the main investigations, and this emphasizes the need for a series of diversified tests.


The development of antisera to prostaglandins B2 and F2alpha and their analysis using solid-phase and double antibody radioimmunoassay methods.

1 A method for the production of highly substituted prostaglandin-bovine serum albumin conjugates has been developed. 2 Antisera to prostaglandins B2 and F2alpha were raised in rabbits immunized with prostaglandin-bovine serum albumin conjugates. 3 The antisera were assessed for specificity and sensitivity by the double antibody radioimmunoassay method and after they were covalently linked to powdered cellulose to form a 'solid-phase' system. 4 Solid phase radioimmunoassays were developed using conventional shaking and in the presence of sucrose which obviates the need for continuous mixing of the incubates.


Blood gases in simple coal workers' pneumoconiosis.

Pulmonary gas exchange was measured at rest and during exercise in 30 normal males (14 smokers) and 43 coal workers free of obstructive syndrome, at three levels of oxygenation: hypoxia, normoxia and hyperoxia. The main results are the following: a) in normoxia PaO2 and (A--a)DO2 are slightly abnormal in coal workers at rest and during exercise; b) in hyperoxia (A--a)DO2 and venous admixture are higher in the miners at rest but not during exercise; c) in hypoxia (A--a)DO2 and DLO2 are abnormal in miners as compared with the control subjects; during exercise there is however no difference between the miners and the smokers of the control subjects; d) there is a correlation between PaO2 and (A--a)DO2 during exercise in normoxia and the various diffusion indices; e) (a--A)DCO2 and VD/VT show relatively slight increases in the miners; f) there are several differences between the miners with pin-head images and those with micronodular ones; g) at rest, (a--A)DCO2 and VD/VT are influenced by the degree of oxygenation. These various findings are discussed.


Pulmonary function in sandblasters' silicosis.

Lung function was examined in 55 patients with sandblasters' silicosis. In this type of silicosis, patients with simple nodular disease had normal function. Restrictive and obstructive impairment was present in patients with large opacities, and was more marked in patients with radiographic evidence of contraction or cavitation. In the last group, striking average annual declines in ventilatory function occurred. Compared to patients with classical silicosis, these patients were younger and had intense, short exposures to free crystalline silica. The pattern of functional abnormalities suggested that restriction of lung volumes is a fundamental abnormality in this form of silicosis.


Tolerance to sympathomimetic bronchodilators in guinea-pig isolated lungs following chronic administration in vivo.

1 Pretreatment of the guinea-pig subcataneously three times daily with either 5 mug/kg isoprenaline or adrenaline reduced the response of the isolated perfused histamine-constricted lung when challenged with either the same or a different sympathomimetic bronchodilator. The longer the animals were pretreated and the higher the dose of bronchodilator the greater was the degree of tolerance developed. 2 Tolerance was developed to aminophline in the same preparation when the guinea-pig had been pretreated with aminophyline or isoprenaline. Cross-tolerance also developed adrenaline when the guinea-pig had been pretreated with aminophyline. 3 Tolerance was still persistent in guinea-pigs one and two weeks after pretreatment three times daily with either isoprenaline of adrenaline (5 mu/kg s.c.) for seven days in the same preparation. Only after three weeks was the tolerance diminished. 4 These results suggest that asthmatic patients who use bronchodilators excessively may become refractory to the bronchodilator effect of these drugs. They also support the hypothesis that induced cross-resistance to endogenous sympathetic stimulation could lead to a deterioration of the asthmatic state in patients using the sympathomimetic bronchodilators and that this may explain the increase in asthma mortality rate. 5 A mechanism of tolerance to sympathomimetic bronchodilators is postulated.


Postnatal development of dopamine deamination in the striatum of the rat.

In the striata of litter-mate rats the development of the monoamine oxidase (MAO) activity towards dopamine in vitro followed a similar time course with age as the tissue concentrations of homovanillic acid and dihydroxphenylacetic acid, the two acid metabolites of dopamine formed by the action of MAO.


Gamma-aminobutyric acid receptor on vascular smooth muscle of dog cerebral arteries.

Gamma-aminobutyric acid (GABA) had a relaxant effect on dog cerebral arteries which was blocked only by picrotoxin, a known antagonist of GABA receptors. Other agents, adrenoceptor and ganglion blocking agents, atropine, reserpine, tetrodotoxin and ouabain, had no effect on the inhibitory action suggesting the existence of GABA receptors in the vascular smooth muscle of dog cerebral arteries.


Alteration in escape responding in the cat. A lesion and degeneration and comparison following stimulation studies.

15 cats were trained to cross a hurdle in a shuttle box when stimulated through a single bipolar electrode chronically implanted in the subthalamic, mesencephalic and most rostral pontine tegmentum. A lesion was then made through one or both electrode poles. Upon recovery, three patterns of response emerged: (1) crossing with higher threshold or longer latencies; (2) no crossing, or (3) no change in crossing. The response pattern correlated with the anatomic findings. The nine animals that crossed before but not after the lesion, showed either lesions or heavy axonal and terminal degeneration in the H2 field.


Variation in form of the pyramidal tract and its relationship to digital dexterity.

A morphometric analysis of the pyramidal tract's relation to digital dexterity was performed on data from 69 mammals. The results show that the variation in digital dexterity among mammals corresponds most closely to the variation in place of termination of pyramidal tract fibers within the spinal cord, corresponds less closely to the variation in the size of the tract itself and its constituent fibers, and does not correspond reliably with any other feature yet reported. Since the termination of pyramidal tract fibers on or very near spinal motor neurons is a prerequisite even for the peculiar kind of dexterity seen in some non-primates (e.g., raccoon, kinkajou), this one feature alone seems to be a critical factor.


The metabolism of labeled parathyroid hormone. VII Attempts to modify hormone deposition.

Using a 125I-labeled parathyroid hormone with apparently full biological activity, a series of experiments was performed on rats to determine the effects of several physiological parameters on the deposition and metabolism of the hormone in the target tissues, liver, kidney and bone. Among the variables studied were: systemic phosphate levels, systemic calcium levels, calcitonin administration, pregnancy, and dosage (at low levels). Some small variations in deposition and tissue metabolism of the hormone were observed but the invariance of the pattern of deposition and the rapid automatic destruction by target tissues was most impressive.


Osteogenesis by chondrocytes from growth cartilage of rat rib.

Chondrocytes were isolated from growth and resting cartilage of rat rib and cultivated in vitro. The cultivated chondrocytes were placed in Millipore diffusion chambers, which were then implanted into the abdominal cavities of rats for several weeks and prepared for histological analysis. The results indicate that growth cartilage cells have a remarkable osteogenic potential, even after cultivation in vitro, whereas resting cartilage cells show no osteogenic activity. However, growth cartilage cells alone do not form new bone but require the participation of certain host cells to initiate osteogenic differentiation.


Effect of phospholipids on the transformation of amorphous calcium phosphate to hydroxapatite in vitro.

The conversion of amorphous calcium phosphate (ACP) to crystalline hydroxyapatite (HA) was studied in vitro in the presence or absence of phosphatidyl serine (PS) and other phospholipids. ACP transformation and HA crystal growth were monitored by electron microscopy, selected-area electron diffraction and X-ray diffraction, and by measuring supernatant calcium and phosphate. PS, and other acidic phospholipids, had a significant stablizing effect on ACP. With performed ACP at ratios of only 1 lipid molecule per 30-50 Ca atoms, PS markedly delayed HA crystal formation. When PS was present during ACP precipitation, inhibition of conversion to HA was less pronounced, but crystal habit and aggregation were greatly altered resulting in stacks of thin, membrane-like sheets approximately 38-42 A thick. PS appeared to be most effective in blocking ACP to HA conversion when oriented primarily on the surface; it most affected subsequent crystal formation when distributed throughout the amorphous precursor. Phospholipids possessing anionic, and hence Ca-binding properties, were effective in stabilizing ACP; neutral zwitterion lipids, which have amphipathic properties but do not bind Ca, were not. In view of the presence of anionic lipids in matrix vesicles and their association with early mineral deposits, the current findings add further evidence that lipids may play a role in the control of normal mineralization in vivo.


[Transfer of 45Ca during amelogenesis studied by autoradiography and electron microscopy].

45Ca transfer through the stratum intermedium and the secreting ameloblasts towards enamel has been studied by quantitative electron microscopical autoradiography in tooth-germs of newborn cats following intravenous injection of the isotope. Two transfer pathways were demonstrated. The relatively more important direct path passed through the stratum intermedium and ameloblast intercellular spaces and reached the enamel directly. The second pathway consisted in an intracellular transfer through the ameloblasts. 45Ca penetrated the cell through its basal pole. The mitochondria were the most highly labeled organelles at the different experimental time intervals studied. A maximum of radioactivity was respectively noticed at 30 min and 1 h in the endoplasmic reticulum and the Golgi apparatus. A total absence of silver grains was noted over the secretory ameloblastic bodies. At 6 h, the highest labeling was observed over enamel and especailly over the inner enamel along the enameldentin junction.


The effect of ultraviolet radiation on the electrical conductivity of human bone.

The electrical conductivity of intact bone, collagen and apatite mineral was determined in the region of moderately high fields. After exposure to ultraviolet (UV) radiation the conductivity of the specimens was redetermined. Following exposure marked decreases in electrical conductivity occurred in all specimens. The possible modes of interaction of UV radiation with bone are discussed. It is suggested that protonic conduction may be an important mode of charge transport in bone.


The National Large Bowel Cancer Project. Its goals and objectives.

The National Large Bowel Cancer Project, therefore, through the combined efforts of the Directorate, Working Cadre, and Subcommittees, has planned and activated a multidisciplinary approach to large bowel cancer aimed at reducing the incidence, mortality, and morbidity of this disease. Every effort is being made to improve interdisciplinary communications among biomedical scientists and clinical investigators involved in studies related to large bowel cancer. Early application of well-established biologic concepts of large bowel cancer to the study and management of patients with this disease, or to individuals at risk for the development of this form of cancer, hopefully will result in improved methods of controlling large bowel cancer.


The control of large bowel cancers. Present status and it challenges.

The incidence of carcinoma of the large bowel in the United States is higher than for any other site. In Japan it is about one quarter as frequent, and the cause of this discrepancy appears to be more environmental than genetic on the basis of migrant studies. The incidence of carcinoma in familial polyposis approaches 100% and in villous adenoma the incidence of carcinoma is 40-50%. The relation of adenomatous polyps to carcinoma is not so strong, yet there is a notable association between the occurrence of polyps and carcinoma in the same bowel. With modern surgical techniques, the risk of removing polypoid lesions of the colon transabdominally appears much lower than the average risk of leaving such lesions alone unless and until they give signs and symptoms of carcinoma. The greater use of the colonoscope should, however, greatly reduce the need for laparotomy.


The gardner syndrome. A study in cell culture.

Tetraploidy was increased in skin fibroblast cultures derived from three probands with the Gardner syndrome and nine affected members of one family as compared to that occurring in cultures from five unaffected family members as well as from six relatives by marriage and 15 normals grown in the laboratory at the same time under the same conditions. Tetraploidy was present at the first subculture (2 weeks after the initial biopsy was cultured) and for each line studied the percentage of dividing cells showing tetraploidy remained constant. Increased occurrence of tetraploidy was not observed in skin fibroblast cultures from patients with the genetic disorders familial polyposis coli, familial osteomas, and familial fibromatosis (neurofibromatosis), each of which show one of the four abnormal tissue growths observed in the Gardner syndrome. The relationship of the observed tetraploidy to the increased risk of such patients to develop abnormal growths and cancer has not been established. The increased tetraploidy should be of value in identifying the presence of the gene for the Gardner syndrome in high risk families.


Arylsulfatse B in colorectal cancer.

Arylsulfatase B activity has been determined in 24-hour urine samples from 243 patients with colorectal cancer. Elevated activity of the enzyme was obsereved in 172 out of 243 (71%) patients. Employing Dukes' modified classification of colorectal cancer, urine arylsulfatase B activity was elevated in Dukes' A lesions-1/8 (12%), Dukes' B lesions-24/43 (55%). Dukes' C lesions-89/111 (80%), and Dukes' D lesions-66/81 (82%). Arylsulfatase B activity in urine, when elevated, may be used to follow response to therapy since in those patients with elevated urine arylsulfatase B values who subsequently responded to therapy, the enzyme values became or approached normal. Urine arylsulfatase B activity also correlated with plasma carcinoembryonal antigen (CEA) as a diagnostic indicator of colorectal cancer in 33/46 (71%) patients. In contrast to the urinary findings, arylsulfatase B activity in tumor tissue was elevated in only 24% (27/110) of the specimens of colorectal cancer. It was also found that in a group of 55 patients treated with 5-fluorouracil, all of the 13 patients that showed objective response to therapy had activities of arylsulfatase B in the tumor tissue within the normal range for large bowel mucosa. Nevertheless, 22 to 26 of the 43 patients that did not respond also presented values in the normal range. The roles of lysosomal enzymes in colorectal cancer are discussed.


Quantification of carcinoembryonic antigen-like activities in normal, human gastrointestinal secretions.

The secretion of carcinoembryonic antigen-like (CEA-like) material into the gastrointestinal tract of 28 fasting normal men was quantified by using intestinal perfusion techniques. CEA-like material was recovered from all levels of the gastrointestinal tract. The highest secretory rate was in the colon (mean +/- SE, 2.41 +/- 2.0 mug/minute per colon), followed by pancreatobiliary secretion and pancreatic secretion. The secretory rate from the stomach, duodenum, jejunum, and ileum was less than 20 ng/minute. After perchloric acid extraction, the CEA-like material from the colon had the same chromatographic and radioimmunologic properties as [125I] CEA. These data suggest that the CEA-like material is normally secreted into the gastrointestinal tract and particularly into the colon.


Urinary polyamine levels in patients with gastrointestinal malignancy.

Polyamine levels (putrescine, spermidine, and spermine) were determined in 24-hour urine samples by a high voltage electrophoresis technique. Eleven of 14 patients with widespread metastatic gastrointestinal cancer had two or more elevated polyamine values. Two patients with cancer confined to the colon and two with cancer spread within the pelvis had two or more elevated polyamine values. Three patients who had all known disease removed by surgery, two patients with gastric lymphoma, and one patient with a vilous adenoma of the colon had normal values. Individual values of spermidine and spermine appeared to be elevated more frequently than putrescine values in these patients.


Selective synthesis and accumulation of nuclear non-histone proteins during carcinogenesis of the colon induced by 1, 2-dimethylhydrazine.

The complement of nuclear non-histone proteins in epithelial cells of the colon is progressively altered during the course of carcinogenesis induced by 1, 2-dimethylhydrazine, until finally the nuclear proteins of tumor cells are easily distinguishable from those of the surrounding normal tissue. These changes in nuclear protein compostion reflect earlier differences in the rates of synthesis of individual protein species. Radioisotopic double-labeling experiments show that the synthesis of nuclear proteins of molecular weights 44,000 and 62,000 is selectively accelerated within 4 weeks after administration of the carcinogen, long before any morphological indications of malignancy appear.


In vivo repair of rat intestinal DNA damage by alkylating agents.

In an effort to evaluate the possible correlation of the transforming ability of the known colon carcinogens dimethylhydrazine, 3-2'-dimethyl-4-aminobiphenyl, and methylazoxymethanolacetate to damage and repair of DNA, a series of compounds known to react with DNA-nitrogen mustard, methylmethanesulfonate, and mitomycin C--were administered to rats that had been prelabeled with 3H-thymidine. The DNA of crypt and villus of the jejunum and crypt and surface cells of the large bowel were analyzed by ultracentrifugation on an alkaline sucrose gradient. All fractions suffered degradation to such an extent that essentially no undamaged DNA was detectable. This was followed by repair and an increase in size. However, in the surface cells of the colon of animals that had received a carcinogenic insult there was far less rapid repair. Since this is the site where tumors would ultimately arise these data are supportive of the hypothesis that there is a relationship between decreased repair and carcinogenicity. In view of the age related incidence of colon cancer, repair in older animals was evaluated and was found to be less than that seen in the young. Since multiple treatment with the carcinogen dimethylhydrazine is required and there is a long latent period, the effect of this treatment on repair potential was evaluated. Similar to what was seen in the older animals, these treated rats had greatly reduced capacity to repair DNA. All these observations are consistent with the hypothesis that decreased repair of DNA alterations is a concomitant of carcinogenesis.


Gastrointestinal cancer. Its geographic distribution and correlation to breast cancer.

Maps of mortality rates in all U.S. counties for cancer of the stomach, colon, and rectum are presented. The maps show a strong geographic dependency indicating that environmental factors are important in the etiology of these cancers. Furthermore, the urban-rural differences which have been noted in the past are not as readily apparent in this study. Evaluation of all cancer sites demonstrates in general that the geographic dependency is highest for organs most exposed to the environment such as the organs along the alimentary canal and lowest for unexposed organs such as prostate, pancreas, and brain. By studying the correlation coefficients between mortality rates for cancer of different organ sites, they were grouped in subsets with high correlations for each pair in the same subset. Cancers of colon, rectum, and breast are shown to be very highly correlated in U.S. data as well as in international data.


Investigations into the metabolism and mode of action of the colon carcinogen 1, 2-dimethylhydrazine.

Chromatographic methods have been developed which allow the separation and identification of azomethane (AM), azoxymethane (AOM), and methylazoxymethanol (MAM). These methods have been applied to the analysis of bile, urine, and the exhaled air of rats treated with the 14C--labeled colon carcinogen 1,2-dimethylhydrazine (DMH) to provide evidence that AM, AOM, and MAM are indeed metabolites of DMH. Investigations into the metabolism and mode of action of DMH and its derivatives by other workers are briefly summarized and reviewed.


Further clinical studies with intrahepatic arterial infusion with 5-fluorouracil.

A total of 419 patients with progressive liver disease, in nearly all cases metastatic from gastrointestinal primaries, were treated by intrahepatic arterial infusion with 5-FU. Three-fourths of these patients had had prior trials with intravenous 5-FU for 1 or 2 months to several years and had been switched to the infusion upon the development of progression. Catheters were placed percutaneously and the patients infused with 5-FU at a dose of 20 to 30 mg/kg/day X 4, then 15 mg/kg/day X 17, at which point the catheter was removed and the patient sent home on weekly i.v. doses at 15 mg/kg. Toxicity, morbidity, and mortality were minimal with the intrahepatic arterial infusion treatment and the rigid criteria of improvement were met by 55% of the study cases. The survival rate of those patients who responded to the treatment was greater than the survival rate of those who failed to respond.


Adjuvant immunotherapy and chemoimmunotherapy in colorectal cancer of the Dukes' C classification. Preliminary clinical results.

Fifty-eight patients with Dukes' C classification of carcinoma of the large bowel were placed on adjuvant immuno- or chemoimmunotherapy with Bacillus calmette guerin (BCG) or combination of 5-fluorouracil (5-FU) plus BCG following primary and definitive surgery, and were followed for up to 21 months. Of twenty-six patients receiving BCG alone by scarification, five have relapsed with 75% of freedom from disease estimated at 15.1 months compared with 10.1 months in a group of carefully selected historical controls who had surgery alone (p = 0.12). The survival of all patients receiving BCG alone has not reached the 75 percentile yet, and the difference from controls is currently estimated at the 18% level. The combination of 5-FU plus BCG (studied in 32 patients) may be superior to BCG alone at this time, in that it appears to more effectively protect against tumor recurrence (75 percentile not yet reached compared to control, (p = 0.08). The survival of patients on 5-FU plus BCG also appears to be improved (p = 0.09). No patients have expired compared to a 75 percentile survival of 16.6 months in the control. Serial determination of plasma CEA was crucial in the clinical follow-up of these patients. Frequent CEA detetminations have led to early detection of clinical relapse. In the elevation of CEA suggests tumor recurrence with a high degree of probability in patients with past history of cancer of the large bowel.


Growth kinetics of human large bowel cancer growing in immune-deprived mice and some chemotherapeutic observations.

Xenografts of human large bowel cancer have been grown in immune-deprived mice. Studies have been made of their intermitotic time and other proliferative characteristics, and their response to single doses of a number of chemotherapeutic agents has been measured. The indications from this study are that, although the growth rate of xenografts is much faster than that for tumors in man, this is likely to be due largely to a difference in rate of cell loss, and the intermitotic time and growth fraction may not have changed substantially. The spectrum of response to chemotherapeutic agents is in line with clinical experience and, although there are many uncertainties and problems still to be resolved, it is indicated that xenografts could provide a useful experimental system for the laboratory study of the chemotherapy of large bowel cancer.


A colon tumor model for anticancer agent evaluation.

Colon tumors of mice were induced with 1, 2-dimethylhydrazine, N-nitroso-N-methylurethane, methylnitrosourea, and 4-methyl-N'-nitro-N-nitrosoguanidine. Of 82 transplantation attempts, four were successful, and the four tumors have been maintained as distinct tumor lines by subcutaneous transplantation. The tumors graded from II, adenocarcinoma, to IV, undifferentiated carcinoma. Volume-doubling times varied over a three-fold range, and metastatic potential ranged from 5 to about 100%. The tumors responded to treatment with some of the same agents found to be active in man. These included cyclophosphamide, 5-fluorouracil, and certain nitrosoureas. Preliminary evidence suggests that these tumor lines may be useful as experimental models.


Purification of tumor-specific antigens. An overview of the relevance to human colon carcinoma.

Methods which dissociate intramolecular noncovalent bonds have been used to prepare soluble derivatives of cell-surface antigens. Applications of these techniques to human colon carcinoma are underway. Continuous tissue-culture strains derived from primary lesions were developed and shown to be composed of malignant epithelial elements. Parallel data on the preparation and activity of soluble materials in a murine model methylcholanthrene system reveal that although cultured cells are a satisfactory source for antigen extraction, they are poor targets of the immune response. The development of methods to quantitate the biologic activity of colon-specific, soluble materials may provide indicator systems to define the antigenic determinants, to permit purification, and to serve as assays of the efficacy of immunotherapy.


The immunology of large bowel carcinoma in a rat model.

A rat large bowel carcinoma model has been established with close similarities to the immunological features of the corresponding human neoplasms as far as those are presently known: (1) common antigens with tissue-type specificity, (2) expression of immunogenic gut-specific embryonal antigens, (3) cell-mediated immunity present in tumor bearers, whose sera are capable of blocking the lymphocyte effect specifically, and (4) rapid disappearance of the serum blocking activity after tumor excision. It is suggested that this model is therefore particularly suitable for further detailed analysis of the potential function in vivo of tissue-type specific antigens. In addition, this model appears to be applicable to correlating alterations in immune status with tumor course after various modes of intervention such as chemotherapy and immunotherapy alone, or in combination with surgery.


The synthesis of 2-acetamido-2-deoxy-6-O-beta-D-mannopyranosyl-D-glucose.

4,6-Di-O-acetyl-2,3-O-carbonyl-alpha-D-mannopyranosyl bromide was condensed with benzyl 2-acetamido-3,4-di-O-acetyl-2-deoxy-alpha-D-glucopyranoside in the presence of silver carbonate to give crystalline benzyl 2-acetamido-3,4-di-O-acetyl-2-deoxy-6-O-(4,6-di-O-acetyl-2,3-O-carbonyl-beta-D-mannopyranosyl)-alpha-D-glucopyranoside in 32% yield. Removal of the protective O-acetyl and cyclic carbonate groups gave the crystalline benzyl alpha-glycoside of the disaccharide, which was catalytically hydrogenolyzed to yield the crystalline, title compound. Proof of the anomeric configuration of the interglycosidic linkage was obtained by comparison of the physical, spectral, and chromatographic properties of the disaccharide and its derivatives with those of the previously prepared alpha-D-linked analog.


Multiple Smith-degradations of carcinoembryonic antigen (CEA) and of asialo CEA.

Carcinoembryonic antigen (CEA) and asialo CEA were subjected to multiple Smith-degradation (i.e., for each degradation, application in sequence of periodate oxidation, borohydride reduction, and mild hydrolysis with acid; borohydride-t was substituted for unlabelled borohydride). High yields of modified glycoproteins were obtained at each stage. After three complete degradations and a further periodate-borohydride-t treatment, the carbohydrate content of CEA and of asialo CEA had decreased from 45-50% to 11-12% (i.e., 90% removal of carbohydrate). Glycerol was always one of the products obtained after each degradation, but threitol and erythritol were not detected. The second degradation caused a substantial loss of 2-acetamide-2-deoxyglucose, which is consistent with the location of some of this monosaccharide towards the terminal (non-reducing) end of the oligosaccharides. The "core" region of the oligosaccharides is composed of galactose, mannose, and 2-acetamido-2-deoxyglucose. After the fourth oxidation, 2-acetamido-2-deoxyglucose was 50-60% of the total content of residual carbohydrate. After the first degradation, there was a progressive loss in antigenic activity, but this was associated with a small amount of hydrolysis of the protein moiety of CEA.


Synthesis of O-beta-D-mannopyranosyl-1 leads to 4)-O-alpha-L-rhamnopyranosyl-(1 leads to 3)-D-galactopyranose, the trisaccharide repeating-unit of the o-specific polysaccharide from Salmonella anatum.

Glycosylation of 1,2:5,6-di-O-idopropylidene-alpha-D-galactofuranose with 2,3-di-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-beta-D-mannopyranosyl)-alpha-L-rhamnopyranosyl bromide, followed by removal of the protecting groups, gave O-beta-D-mannopyranosyl-(1 leads to 4)-O-alpha-L-rhamnopyranosyl-(1 leads to 3)-D-galactose, which is the trisaccharide repeating-unit of the O-specific polysaccharide chain of the lipopolysaccharide from Salmonella anatum. The formation of the beta-D-mannopyranosyl linkage was achieved by a glucose-mannose conversion via stereoselective reduction of the corresponding oxo-disaccharide.


Some benzylidene acetal derivatives of theophylline nucleosides.

The reaction of some hexopyranosyltheophylline nucleosides with benzaldehyde in the presence of zinc chloride gave the expected benzylidene acetals. Thus, 7-alpha-D-mannopyranosyltheophylline gave the 2',3':4',6'-diacetal as a mixture of diastereoisomers, one of which was isolated. The beta-D-galacto- and beta-D-gluco-pyranosyltheophyllines gave the 4',6'-acetals, which were characterised as 2',3'-diesters. Mild, acidic hydrolysis of 7-(4,6-O-benzylidene-2,3-di-O-mesyl-beta-D-glucopyranosyl)theophylline gave 7-(2,3-di-O-mesyl-beta-D-glucopyranosyl)theophylline, and strongly basic hydrolysis gave 7-(2,3-anhydro-4,6-O-benzylidene-beta-D-allopyranosyl)theophylline. Ring-opening of this 2',3'-epoxide with iodide anion afforded mainly 7-(4,6-O-benzylidene-2-deozy-2-iodo-beta-D-altropyranosyl)theophylline, which was characterised as the 6'-acetate.


Effect of ketamine on ventricular dynamics of unanesthetized baboons.

Ketamine hydrochloride is commonly employed to sedate or anesthetize laboratory primates but its cardiac actions have not been previously described in these animals. Four baboons, Papio cynocephalus, were chronically instrumented with electromagnetic flow detectors on the ascending aorta and common carotid artery. Cardiac output, peak aortic flow velocity and peak aortic flow acceleration are all depressed by Ketamine, 5 mg/kg i.m. Peak aortic flow acceleration and peak carotid flow acceleration were equally depressed. Thus, peak carotid flow acceleration is a useful indirect index of the left ventricular response to Ketamine in the baboon.


[Lipids in the renal veins and disseminated intravascular coagulation].

Marked steatosis of glomeruli and of cortical arterioles is a peculiar and hitherto neglected change occuring in generalized Shwartzman's reaction as well as in the haemolytic-uremic syndrome. The fatty deposits originate during the transient hyperlipemia occurring in both the above entities. No comparable steatosis takes place in disseminated intravascular coagulation. In disseminated intravascular coagulation occurring in hyperlipemic rats, however, steatosis of glomeruli as well as of cortical  arterioles is present so that the picture resembles generalized Shwartzman's reaction. Such a comparison poses a lot of further pathogenetic problems.