Biochemical studies of isolated hamster tracheal epithelium.

The epithelial lining of respiratory air passageways is a primary target tissue for toxicity and carcinogenesis in man and in animal models of human disease. The importance of this target tissue was the basis for development of methods to study its biochemistry, and with this information to distinguish the unique properties of this tissue from properties common to all cell types. Biochemical methods employed labeling of macromolecules in isolated hamster treacheas during brief (less than 4 hr) incubation in vitro. Studies of RNA metabolism in isolated tracheas demonstrated a pattern of maturation of ribosomal RNA like that shown for other cell types. Alterations in RNA metabolism were observed in isolated tracheas obtained from vitamin A-deficient hamsters and hamsters previously treated by intratracheal administration of benzo[a]pyrene (BP) plus ferric oxide (Fe2O3) in vivo. Studies with toyocamycin, actinomycin D, and alpha-amanitin, all inhibitors of RNA metabolism, were performed to characterize the class of RNA molecules with a decreased proportion of labeling in tracheas from vitamin A deficient hamsters. In another series of experiments, BP was shown to bind to DNA in epithelial cells of isolated tracheas. The quantity of BP binding was increased by prior intratracheal treatment of hamsters with BP plus Fe2O3 in vivo, this induced binding was inhibited by addition of 7,8-benzoflavone to the incubation medium. Increased BP binding was also observed in isolated tracheas from hamsters believed to be in states of increased susceptibility to respiratory carcinogenesis in vivo. The results show that biochemical studies are feasible with this tissue. Furthermore, a number of questions of importance with regard to this target epithelium are best studied directly in its constituent cells.


Labelling and metabolism of methionine-methyl-11 C.

Carbon 11 which is a 20.4 minutes half life isotope emitting positrons was used for methionine labelling on the methyl group by action of 11C-methyl-iodide on DL or L homocysteine. With the method described, 20 to 30 mCi of 11C-methyl-methionine (Specific activity 50 mCi/muM) may be obtained within 25 minutes. The 20 Mev proton beam used for 11C production was 10 muA. The metabolism of 11C methionine studied on mice shows a high uptake in pancreas and to a smaller extent in brain. On humans sequential images were obtained at the head level which allowed measurement of the uptake of the radio-labelled compound in the brain so as to study the radioactivity curve in different parts of the organ.


Experience with 201 thallium in detection of myocardial infarction.

Our preliminary experimental and clinical results with 201Tl myocardial scanning are presented. 48 patients with normal coronary vessels, acute trasmural myocardial infarction, localized and diffuse coronary heart diseases and congestive myocardiopathy were investigated. Results of scans and the usual cardiological investigations were in good agreement thus justifying further use of 201Tl myocardial scintigraphy as an adjunctive method in cardiology.


The uptake of gallium 67 in colonic macrophages.

A case is presented in which a patient with a well-differentiated adenocarcinoma showed high gallium concentration in the segment with melanosis coli proximal to the obstruction. Although in this case the Gallium was associated with an increased number of faecal pigment containing macrophages it is unlikely that macrophages are the main factor in tumour uptake of Gallium compounds.


Technetium-99m-sulfur colloid. In vitro studies of various commercial kits.

The quality of five commercial 99mTc-sulfur colloid kits was compared. A number of chemical parameters, which characterize the colloids, was used in order to study the influence of variations in the preparation procedures and storage of the final products. The differences between the kits could mainly be referred to the order of addition of the reagents. The quality was generally unaffected by variations in time-intervals during preparation. However, a certain heating time was necessary for optimal labeling. Variations in quantities of acid and buffer were found to influence the particle size as well as the content of unreacted pertechnetate. No deterioration in quality by storage was observed; on the contrary in some cases the content of free activity decreased.


Specificity of immunoassays. I. Effect of plasma proteins on the specificity of steroid immunoassay.

The theory of the measurement of the specificity of antigen binding by antibodies is reviewed. The specificity of steroid immunoassay has been investigated using a new solid phase radioimmunoassay system. The effects of plasma proteins on the specificity of the immunoassays have been tested. The methods used and the conclusions reached have been tested with homogeneous antibodies in order to simplify the interpretation of the results obtained. A new criterium of antibody homogeneity is proposed. The importance of correcting all results accurately for "non-specific binding" is emphasised. A new method for plotting radioimmunoassay standard curves is presented.


Trace elements analysis in biological samples by radioisotopic x-ray fluorescence.

The X-ray fluorescence technique, induced by radioisotopic sources, provides a very simple method for the simultaneous analysis of trace elements in biological samples. For blood, serum, platelets, etc., samples of about 0.1 ml were deposited on filter paper disks, dried, and analyzed. In such a way the "thin specimen" approximation is realized, resulting in the following advantages: The X-ray intensity of a given element is a liner function of mass per unit area over several orders of magnitude. Interelement effects became negligible. The ratio of fluorescent X-rays to scattered radiation is increased. The sensitivity of the technique for elements with atomic number ranging from about 20-92 varies from some units to some tens of parts per million by weight in 100 s measuring time, by using a gas proportional counter, and from about some tenths to some parts per million by using an X-ray semiconductor detector, in a measuring time of 10(3)-10(4)s. In such a way and with the described features, the Cl, K, Ca, Fe, Cu, Zn, Br content of several speciments of blood and serum was determined. Measurements were further carried out in order to labelling blood components with stable tracers and to detect their concentration by means of the X-ray fluorescence technique. The life span of platelets was, for example, measured after labelling platelets with stable Selenocystine. The sensitivity of the XRF technique can further be enhanced by about three orders of magnitude by using a pre-enrichment step with ion-exchange resins and liquid volumes not lower than 500 ml. Urine analyses have been carried in such a way, and copper in about 20 ml serum after selective extraction.


A rational approach toward determining the candidacy of the prostatic cancer patient for cryoimmunotherapy: an interim report.

While receiving only cursory attention compared to that of other malignant neoplasms, studies of patients with prostatic cancer have suggested that host responses, mediated in part by immunobiologic factors, may play a significant role in the pathogenesis and thus, the therapeutic management of this disease. For nearly a decade cryosurgery has gradually attained some degree of acceptance as one of the efficacious treatment modalities available in the therapeutic armamentarium for prostatic cancer. In addition to the localized destruction of the primary tumour, reports of secondary tumour cell destruction, i.e. of distant metastases, have supported the suggestion that cryosurgery, as documented in various animal species, may also be immunopotentiating in man. Although our understanding of immunopotentiation of the host's response to tumour via cryosurgery is far from complete, information derived from experimental studies demonstrating that the developement of an immunologic response following cryosurgery of the prostate may be attributed to androgenically and ontogenically dependent autoantigens may have clinical relevance. This together with knowledge that in the therapeutic management of the patient with prostatic cancer we are confronted with the treatment of an individual who, in the majority of cases, possesses waning immunocompetence, emphasizes the potential significance of evaluating what may be referred to as the 'cryosensitivity' of the prospective cryosurgical patient. At present this 'cryosensitivity' may be said to be dependent upon: (1) concentration of prostatic tissue [secretory(tumour?)]-specific or tumour-associated auto-(neo?) antigen(s); (2) physiologic state (elaboration of androgen), and (3) immunocompetence. It is hopeful that evaluation of these parameters may provide a rational approach toward determining the acceptability of cryosurgery as the treatment of choice in a given patient.


Inactivation of 5-fluorouracil by the liver during continuous regional and systemic infusion in pigs.

During continuous systemic or portal infusion of 5-fluorouracil (5-FU) to anaesthetized pigs, the cytostatic activity was reduced in blood traversing the liver. The liver eliminated between 15 and 50% of the amount 5-FU given per time unit. During jugular infusion the concentration of cytostatic compounds in portal blood was equal to or less than in systemic blood. The cytostatic activity was much higher in portal blood and lower in systemic blood during portal infusion. The findings speak in favour of portal infusions of 5-FU to patients with disseminated cancer in the liver.


The effects of transections on the basic electrical rhythm in the canine jejunum.

The basic electrical rhythm (BER) was studied in situ in the jejunum in 14 anaesthetized mongrel dogs by the mean six monopolar electrodes. The BER frequency was measured in the intact intestine and after proximal and distal transections of the gut 5 cm apart from the electrodes. No significant differences were found between the BER frequencies recorded by each electrode, demonstrating the existence of a frequency plateau which remained after each transection. In the intact intestine the frequency in the plateau was 13.2 +/- 0.3 cpm2. After the proximal transection, this frequency dropped to 12.0 +/- 0.4 cpm (p less than 0.05) and, after the distal transection, it dropped to 10.9 +/- 0.4 cpm (p less than 0.005). This last frequency change shows the influence of the distal intestine on the electrical behaviour of the jejunum.


Survival in burned mice after treatment with tryglycylvasopressin.

Standardized skin burn injuries were induced in 253 NMRI mice. The burned surface corresponded to 15% of the total surface of a 25-gram mouse. All animals received intraperitoneal injection of an isotonic saline solution in a dose of 20% of body weight/day for 5 days. The material was divided into three groups, i.e. group A (controls) which received no further treatment, groups B and C which, in addition, received triglycylvasopressin (a vasopressin with prolonged effect) 100 and 200 mug/kg body weight, respectively, subcutaneously twice a day. The highest survival rate was registered in group B (61%), while the controls had a survival of 36%.


Pancreatic metabolic rate measured in vivo with heat-accumulation technique.

This study is the first attempt to apply the heat-accumulation technique for metabolic studies to the pancreas. The initial temperature rise during arterial occlusion was measured with thermocouples sutured into the pancreas of seven anaesthetized pigs. Temperature recording were obtained during alterations of the metabolism induced by infusions of 2,4-dinitrophenol (DNP) and sodium cyanide (NaCN) into the pancreatic head. DNP 2.0 mg/min almost doubled, and NaCN 0.6 mg/min reduced the heat accumulation rate to one half of control. In four pigs the metabolism was estimated by measurements of oxygen consumption in an isolated in situ preparation of the pancreatic head. Median metabolic rate in the unstimulated gland was 0.09 cal/cm3-min. Metabolic rate estimated by heat-accumulation technique in a similar situation was 0.11 cal/cm3-min. The method is considered useful for evaluation of relative variations of pancreatic metabolism.


Memory and blood pressure in the aged.

Memory loss, as measured by the Wechsler Memory scale was examined as a function of diastolic blood pressure during a 6.5-year follow-up period among individuals initially tested in their 60's. On the initial testing, memory was not related to blood pressure. At the end of the follow-up period, the hypertensives showed greater impairment in memory for nonverbal material involving time limits and a psychomotor component than did their age peers with normotensive and borderline elevations of blood pressure. The hypertensives' poor performance, however, was found only on specific sub-task items and appeared not to be influenced by item difficulty alone but rather by other performance factors such as difficulty in deciding what to do, understanding test instructions, or state anxiety associated with the testing situation. Memory for highly meaningful verbal material was not related to blood pressure.


Biogenic amines in the Caenorhabditis briggsae.

Dopamine, epinephrine, norepinephrine and serotonin were demonstrated from homogenates of Caenrohabditis briggsae by two-dimensional thin layer chromotography and the identification confirmed by gas liquid chromtography. In Vitro studies with 14C precursors of these biogenic amines demonstrate the ability of C. briggsae to synthesize each compound. The results provide required preliminary data for studying the neurophysiology of aging utilizing the nematode as a model.


Age differences in learning and memory on a digit-symbol substitution task.

Fifteen young (18 to 28 years) and fifteen old (65 to 75 years) persons were given ten 30-second trials on a modified Digit-Symbol task. Both immediate and delayed (24-hour) recall and recognition measures were used to determine how well they remembered the digit-symbol pairs. Both age groups showed similar, significantly improvement over the 10 trials, although the performance level of the young group was higher throughout. The young group showed significantly higher recall and recognition (both immediate and delayed) for the digit-symbol pairs and were more likely to report the use of mnemonic techniques in learning the pairs.


Disparate time spans in sequential studies of aging.

In several published studies of intelligence and adult age, a sequential design was used in which birth cohort and time of measurement were the independent variables in an ANOVA. The time span of these two variables were quite disparate; the cohort variable covered about 50 years whereas the time-of-measurement variable covered 7 or 14 years. It was demonstrated here that when time spans are disparate, even when all differences are attributable entirely to age changes, the F values typically will be larger for the cohort variable and errors in interpretations became likely. When cohort differences are statistically significant and time-of-measurement differences are not, the conclusion that age differences are "generational" and not due to age changes within individuals may be wrong.


Health status as a variable in aging research.

Findings from several studies bearing on the association between disease and age-associated behavior changes were briefly reviewed in order to stress the need for health assessment in gerontological psychology research. Despite the evidence favoring the need for health assessment such procedures have generally not been undertaken. Implications for experimental aging research were discussed.


Partitioning chi-square the analysis of contingency tables with repeated measurements.

Categorical variables are commonly used in gerontological research. Although analysis of such variables presents no problem as long as the observations are independent, problems do arise when they are found in a design with repeated measurements. In this paper, two procedures from the statistics literature are combined to provide an analysis for data from a mixture of between and within categorical variables. First, a response pattern is used to form a contingency table with observations which are completely independent. Next, the Pearson chi-square statistic from the table is partitioned to provide tests analogous to simple effects in analysis of variance.


"Attitudes" toward the elderly: a comparison of measures.

College students were presented five questionnaires traditionally used to assess attitudes toward old people. The intercorrelations among the measures were low, accounting for no more than 24% of the variance between any two measures. The results suggest that the measures are not equivalent; it was argued that the practice of utilizing a single instrument to measure attitudes toward the elderly may contribute to inconsistencies reported in the literature.


Age differences in cognition in healthy educated men: a factor analysis of experimental measures.

Performance measures for a wide variety of cognitive laboratory tasks were factor analyzed, and the factors were identifiable as aspects of cognitive processing. The sample consisted of 96 healthy, educated men whose ages ranged from 20 to 80 yr. The factors were identified as speed of information processing, secondary memory, attention, and primary processing efficiency. Factor scores for each factor were correlated with age; r = -0.35, -0.30, -0.40, and -0.15 respectively, with better performance associated with lower age. The sample was divided into subsamples of 32 young (20-39), 32 middle (40-59), and 32 old (60-80) subjects; and each subsample was factor-analyzed separately to determine whether the factor structure was similar for all age groups. Evidence for factor-structure invariance with adult age was found in that all four factors in the primary analysis were identifiable in each of the age subsamples. The findings are consistent with a model of continual cognitive decline with age in healthy, educated adult males.


Age and tachistoscopic perception.

A perception experiment involving tachistoscopic exposures of 10 alphabetic characters was conducted in order to answer the following questions. Do young and old adult subjects exhibit performance differences in tachistoscopic perception which involves the earliest stages of information processing; and, if so, what is the nature of these differences? The answer to the first part of the question was a clear and definite yes. Old adult subjects were found to perform at a significantly lower level than younger adult subjects in nearly all measures of perceptual performance. With respect to the second part of the question, both strategy and capacity differences were found to be responsible for the poorer performance of the older subjects. The older subjects used a suboptimal performance strategy more frequently, and were apparently slower at processing visual information than younger subjects.


Aging and in vivo norepinephrine-uptake in mammalian brain.

In order to examine the cellular effect of aging in the central nervous system, the regional distribution and the dynamic aspects of catecholamine metabolism in the brain were investigated. Results indicated that the endogenous norepinephrine (NE) content is lower in hypothalamus and brain stem of older rats (25 mo. n = 6) than younger rats (12 mo. n = 6). We have also observed in these animals that the age pigments were apparently absent in the brain tissue of young rats but become a very distinct feature for the old rats and that the catecholamine strong vesicles appear to be less dense in the nerve terminals of old as compared with the young ones. 3H-NE was administered intracerebrally to mice of different age groups (4, 8, 12, 21 and 24 months) and the NE-uptake activity was examined by measuring the radioactive NE inside the isolated synaptosomes 5 min after 3H-NE injection. The result indicated that the young group (4 mo) has highest uptake activity. The uptake activity decrease with the older mice and reached the lowest in the age group of 21-24 mo. The decrease in NE-uptake activity may be related to the deterioration of synaptosomal membranes.


Growth, development and activity in rat offspring following maternal drug exposure.

Seventy-nine Sprague-Dawley derived primimparous rats were injected subcutaneously throughout pregnancy and the nursing period with either (1) 30 mg/kg of pure nicotine, (2) 5.0 mg/kg methamphetamine HCL, (3) saline vehicle, or, (4) non-injected. Vital and developmental measures were taken on the offspring throughout the nursing period and for one additional week. Metamphetamine-injected females had a shorter, and nicotine-injected females a longer gestational period, and both gained less weight over the 21-day period than the control groups. The pups of methamphetamine and nicotine dams were significantly underweight at birth and the 28 day postnatal period and exhibited developmental delay. Male offspring were divided into behavioral, aging, and autopsy on Day 28. Male offspring of methamphetamine-injected dams remained significantly lighter in weight for the first 15 months of life (aging groups). Their counterparts in the behavioral groups and the offspring of non-injected dams exhibited significantly greater activity for eight of the first twelve monthly assessments which began at 90 days of age. Additional vital, performance, and sensory measures will continue throughout the lifespan of the animals.


Age, sex and genotype effects on stimulus exploration and locomotor activity in young mice.

Age and sex effects on stimulus exploration and locomotor activity were investigated in three genetic stocks of mice. Three measures of exploratory behavior and one measure of locomotor activity were recorded in an arena testing situation. The results showed that measures requiring locomotor activity are more affected by differences in age and sex than measures of stimulus exploration. The results are discussed in terms of the previously established genetic models of stimulus exploration and activity.


Matching, the null hypothesis and the aging variable: would the real age effect please stand up.

The concepts of hypothesis testing and maching are discussed in terms of their relationship to the findings of no age differences and sample bias, respectively. Suggestions are also offered concerned statistical substitutes for more rigid experimental controls.


Age-related increase of cuticle permeability in the nematode Caenorhabditis briggsae.

The external cuticular surface of nematodes, which resembles cellular membranes in certain ways, appears to deteriorate with age. For example, when the permeabilities to radioactive water of young and old nematodes were compared, and the data were corrected for the different surface: volume ratios, the older nematodes were significantly more permeable. In both living and dead nematodes, the same rates of water exchange were observed, indicating that the major route of exchange was probably by passive diffusion through the cuticle rather than by active processes such as swallowing or excreting water.


The relationship of scoring treatment and age in perceptual-integrative performance.

The present study was designed to reexamine the hypothesis that timed perceptual-integrative performance tests are negatively biased measures of the abilities of the elderly. Unlike an earlier study by Doppelt and Wallace (1955) which did not support this hypothesis, the current study consisted of a college-age group in addition to the elderly group, and also included an additional scoring treatment. Each subject was tested with the WAIS Block Design and Object Assembly. Tests were scored in three ways: (1) Standard scoring (WAIS Manual); (2) "regular" scoring (timed, omitting bonus points); (3) "Irregular" scoring (untimed, omitting bonus points). For both tests, Age, Scoring, and the Age by Scoring ineraction were significant. Post hoc analyses for significant effects suggest that the elderly are helped most by additional solution time, whereas younger adults derive greater benefits from the bonus points for quick performance. The results also suggest that subjects must be of sufficiently high ability to effectively use increased or unlimited solution time.


The effect of age on the speed of sentence formation and incidental learning.

To test the hypothesis that older persons tend not to use verbal mediators in paired-associate learning because it takes them too long to form an appropriate mediator, the time needed by young and old subjects to generate sentences incorporating given pairs of nouns was measured. Older subjects formed sentences just as rapidly as did the young. Despite their equivalent speed in creating these verbal associations when tested later for the occurrence of incidental learning of the noun pairs, the older subjects showed much poorer recall than did the younger subjects. This age difference in learning did not appear to be a function of any major dissimilarities in the generated sentences themselves, i.e., in the grammatical constructions used, or in the imageability of the relationships expressed by the sentences. The rated imagery value of the stimulus nouns was found to affect both the speed of sentence formation and the accuracy of incidental learning; in both younger and older subjects, formation time was less, and recall was better for the high imagery noun pairs.


Differences in the sequential integration of form as a function of age and interstimulus interval.

The sequential integration of visual stimuli was studied in 12 young (18-28 years) and 12 old (51-62 years) men and women. Stimuli were constructed as corresponding word halves and inter-stimulus intervals (ISI's) of varied duration (0-150 msec.) were introduced between the presentation of the two halves. Correct word identification was found to be an inverse function of ISI for both young and old subjects. The number of stimuli correctly identified was significantly lower for the older subjects at all levels of ISI. None of the interactions of age, sex, and ISI was significant. The data appear to question the "stimulus persistence" model as applied to age differences in the temporal organization of form.


Speed and age: multiple rates of age decline.

There is frequent reference in the literature on aging and performance to the "slowing with age phenomenon". If there truly is one "slowing with age" phenomenon, then all activities requiring speeded performance should decline with age at approximately the same rate. This report compares relative rates of age decline in several speeded physical activities ranging from simple reaction time to long distance running events. The activities differ in the rate of slowing with those requiring a greater muscular involvement or more stamina exhibiting the steepest declines. It is concluded that when one refers to slowing with age it is necessary to be quite specific about the activity to which one is referring because different activities decline at different rates.


Attrition in a longitudinal study of an aged population.

This report focuses upon attrition in longitudinal studies of older persons using a Florida survey as an illustration. In 1959 interviews were completed with a probability sample (N = 2544) of older noninstutionalized residents (age 65+) of a retirement community. Data were collected on health status, health practices, social factors, and activities. Nine years later a follow-up study of the same sample was undertaken. In this report 1959 data for 2497 of these persons are analyzed by results of the 1968 effort (reinterviewed, lost to follow-up, or deceased). About one third of this highly migratory sample could not be located in 1968; death certificates were located for another one third; and the remaining one third was reinterviewed. Social characteristics, housing arrangements, activities, and chronic conditions of the three subpopulations are compared. Persons reinterviewed were found to differ from dropouts in age, sex, type of dwelling unit, activity patterns, and prevalence of chronic conditions. No significant differences were found in educational level, household composition, usual occupation, and retirement status (when controlled for sex).


Thresholds of food odors in the elderly.

Thresholds for nine food odors were found for two groups of subjects, young and elderly. Dravniek's dynamic triangle olfactometer, which employs the forced-choice, triangle principle and controls for guessing was used. Elderly subjects were found to have a considerably reduced sensitivity to these odors compared with young subjects.


Relationship between central and autonomic nervous system activity: correlates of psychomotor performance in elderly men.

The relationship between heart rate deceleration (HRD) and the contingent negative variation (CNV) was evaluated in 12 healthy, elderly men during performance of a signaled reaction time task. While amplitude of the CNV and HRD did parallel RT, CNV alone was found to be predictive of individual differences in speed of response indicating that phasic concordance of these physiological responses is probably not an important factor in age changes in RT. The results indicate the probable importance of central physiological indices such as the CNV over peripheral events such as HRD in the evaluation of RT performance in elderly individuals.


Ethanol preference in C57BL/6 and BALB/c mice at three ages and eight ethanol concentrations.

Eight ethanol concentrations (4%, 6%, 8%, 10%, 12%, 14%, 16%, 18%) were used. A reduction in ethanol preference with increasing age was seen in the C57BL/6 mice, but not in the BALB/c animals. For C57BL/6 mice the largest difference in ethanol preference occurred between the 10% and 18% ethanol solutions. It was found that the ethanol preference of the 14-16 mo. C57BL/6 mice was similar to the 7-9 mo. old C57BL/6 mice at the first 5 concentrations. For the remaining concentrations the 14-16 mo. mice more closely resembled the 22-24 mo. mice in ethanol preference. The results of this study suggested that increased age does not simply result in a reduction in ethanol preference, but is a function of the genotype and concentration of the ethanol solution.


The relationship of task reinforcement to personal loss themes revealed in earliest memories of elderly subjects.

Institutionalization of the aged has been viewed as an environmental stressor, producing covert negative affect which is manifest as personal loss themes in the individual's earliest memories. It was hypothesized that reinforcement given for a cognitive task would produce a positive emotional response in the individual and result in decreased personal loss feelings. Subjects were 64 elderly persons (aged 65-88); half of each sex, half nursing home and half community residents, half receiving reinforcement and half receiving none. Subjects' earliest memories were scored for personal loss themes. Significant findings were that among subjects who were reinforced, those in the community had higher loss scores than those in the nursing home; there was no difference in loss scores between community and nursing residents who had not been reinforced. Among community subjects, those who were reinforced had significantly higher loss scores than those who were not; the opposite tendency was observed in nursing home subjects.


Misuse of analysis of covariance in aging research revisited.

Storandt and Hudson's treatment of the issue of which general linear model technique is preferable to use when age effects are confounded is misleading. Contrary to their position that hierarchical ANOVA or step-wise multiple regression is superior to ANCOVA, it is demonstrated, using hypothetical data, that identical amounts of variance can be explained by ANCOVA relative to hierarchical ANOVA and multiple regression. Multiple regression is recommended as the most appropriate technique for a variety of pragmatic reasons concerning calculation of significance tests, the distinction between gross and net effects, and the choice of the metric used in measurement.


Monetary incentive, age, and cognition.

Results from studies of cohort differences suggest that older and younger volunteers may differ in aspects other than age. In this study subjects, who had or had not been promised $10.00 payment for their participation, were compared on certain personality and intelligence factors. No differences between incentive conditions were observed for 2466 potential subjects on willingness to participate, nor for 591 subjects eventually tested on their scores on the Primary Mental Abilities Test, the Test of Behavioral Rigidity and Cattell's 16 PF. However, differences by incentive condition were observed on the intercorrelation matrices for women on Form B of the 16 PF. Results of these analyses suggest that, with few exceptions, supplying a monetary incentive to induce subjects to participate in a study does not significantly alter the characteristics of a volunteer sample with regard to age or sex.


Aging effects on hypothalamic dopamine and norepinephrine content in the male rat.

Hypothalamic content of dopamine and norepinephrine was measured in young (4 mo) and aged (24-26 mo) male rats by aluminum oxide adsorption and microfluorescence. Hypothalamic content of both dopamine and norepinephrine was significantly less in aged than in the young groups. Average dopamine content of the young and aged groups was 32.5 +/- 9.3 and 15.6 +/- 2.5 ng/hypothalamus, respectively. Norepinephrine content averaged 47.6 +/- 10.7 and 22.8 +/- 1.8 ng/hypothalamus in the young and aged groups. These data suggested that alterations in hypothalamic catecholamine function contribute to changes in endocrine control mechanisms during aging.


O- and N-alkylation with "Meerwein's reagent": the unusual behaviour of two lactams.

Usually tertiary oxonium salts are excellent O-alkylating agents of lactams; in some cases indiscriminate O- and N-alkylations have been described. In this paper the particular behaviour towards Meerwein's reagent of two isomers with a lactamic structure is pointed out: in one case the usual O-alkylation occurs, in the other N-alkylation is the only reaction that takes place.


[Effects of various natural prostaglandins on human gastrointestinal motility in vitro].

The effects of three natural prostaglandins, E1, E2 and F2alpha, on the human gastrointestinal tract were investigated by means of an in vitro technique. Prostaglandin F2alpha showed a stimulatory effect on all the segments examined and its activity was comparable to that of acetylcholine (threshold doses 0.5-2 mug). Prostaglandin E1 relaxed the circular muscles of the stomach (minimum active dose was 1 mug/ml) but contracted the longitudinal ones and taenia coli. Prostaglandin E2 showed an interesting inhibition of the stimulant effect of acetylchooline on circular muscles of the stomach (1 mug/ml) and a weak spasmogenic activity on the other tracts. The mechanism of action of prostaglandins has not been completely elucidated; it seems plausible to suggest a direct effect of the drugs on the smooth muscle, however the release of an unknown mediator cannot be excluded.


[Homoanalogs of aldofuranosylnucleosides. XI. 3,6-Anhydro-1-deoxy-1-(5-halogenouracil-1-yl)-D-mannitol].

3,6-Anhydro-1-deoxy-1-(5-bromouracil-1-yl)-D-mannitol (II) and 3,6-anhydro-1-deoxy-1-(5-iodouracil-1-yl)-D-mannitol (III) were prepared by direct halogenation of the corresponding bis-homonucleosides; the 5-fluoro isomer (V) was prepared by N-alkylation of 5-fluorouracil by 2-o-acetyl-3,6-anhydro-4,5-o-isopropylidene-1-o-p-tolysulfonyl-D-mannitol in dimethylsulfoxide in the presence of potassium carbonate followed by hydrolysis of the protective groups in an acid medium. The ultraviolet spectroscopy, mass spectrometry and nuclear magnetic resonance studies of these compounds are described and the results of pharmacological tests on L 1210 leukemic cells are given.


[Research on heterocyclic compounds. V. Imidazo/2,1-b/thiazole-6-ascetic acids and imidazo/2,1-b/benzothiazole-2-acetic acids].

We have prepared a group of ethyl imidazo [2,1-b]thiazole-6- and imidazo[2,1-b]benzothiazole-2-acetates, starting from some substituted 2-aminothiazoles and 2-aminobenzothiazoles, by reaction with ethyl 4-bromoacetoacetate. From these esters we have obtained the corresponding acetic acids, and we have tested their anti-inflammatory activity.


Structure-activity relationship for antitumor thiosemicarbazones.

The in vitro antitumore activity of a series of thiosemicarbazones was studied by means of the Free-Wilson method. Both lipophilic and electronic effects are shown to play an important role.


Antimycotic activity in vitro and in vivo of a new hydrosoluble polyene antibiotic.

The in vitro and in vivo activity of a new water soluble polyene antibiotic, anmed SPA-S-222, has been studied on numerous Candida and Cryptococcus species. The in vitro tests were carried out in comparison with nystatin and amphotericin B whose antimycotic properties are already well known. The inhibition of "germination" of various strains of Candida albicans was also investigated. The results show that SPA-S-222 has greater antimycotic activity than nystatin or amphotericin B. Tests on the protection afforded by SPA-S-222 in Swiss albino mice infected with C, albicans were satisfactory as regards both the total protective dose and the partial protective dose (P.D. 50%).


Derivatives of 2H,3H-benzimidazo(1,2-b)oxazole.

The Authors report the synthesis and chemical properties of a number of derivatives of 2H,3H-benzimidazo(1,2-b)oxazole. These substances were prepared in order to investigate their pharmacological activity.


[Relationship between chemical structure and sweet taste. XIII. Derivatives of L-acylamidosuccinanilic acids].

Several derivatives of L-acylamidosuccinanilic acids have been prepared inorder to study the relationship between the chemical structure and the sweetening activity by modifying the amino or the acylamido portions of the molecule. Some synthesized compounds possess a pronounced sweet taste, the L-4'-nitro-(2,2,2-trichloroacetamido)succinanilic acid is the most outstanding compound, being approximately 3000-4500 times as sweet as sucrose.


[Retrospective analysis of drug projection using correlative technics].

The problem of choosing substituents to allow correct correlative analysis according to the "Hausch Approach" is discussed. The problem of colinearity among parameters is considered in a case study on 296 anilides which inhibit the Hill reaction. The difficulty in of determining whether, pi or MR is the important variable in changes in activity is shown. "Cluster analysis" is discussed and proposed as a rational method for the selection of substituents to be introduced into biologically active structure in order to explore the scope of each defined physico-chemical parameter. An example of the use of this method conerning auxin activity of 1- and 2-benzotriazole derivatives is given.


Biological activities of a new specific stimulant of histamine H2 receptors.

Compound N-methyl-2-(5-methyl-4-imidazolyl)ethylamine (5-methyl-N-methylhistamine) was submitted to a thorough pharmacological examination and was found to be a potent stimulant of H2 receptors, devoid of any appreciable effect on H1 receptors. Because of its high degree of specificity it therefore seems to represent an interesting drug to be used in clinical gastric secretory tests and an useful tool for the study of histamine H2 receptors.


[Influence of frequency of splanchnic nerve stimulation on development of habituation in the cat cerebral cortex].

Changes of amplitude of evoked potentials in the areas SI and SII of the cortex on repeated stimulation of the splanchnic nerve were studied in anesthetized and immobilized cats. The rate of decrement amplitude responses is increased with increasing of the frequency of stimulation from 0.5 to 5 stimuli per 1 sec. in the focus of maximal activity and in peripheral areas SI and SII. The decrement responses are more obvious in the peripheral sites of these areas. The data obtained seem to indicate a development of habituation in the cortex.


[Role of the medial region of the hypothalamus in regulating the activity of the respiratory neurons of the medulla oblongata].

The influence of high frequency stimulation of postero- and anteromedial hypothalamic regions on the activity of single neurons of the bulbar respiratory center was studied in anesthetized cats with normal respiration. No strictly localized facilitatory or inhibitory points were found in these regions. Excitatory as well as inhibitory descending pathways were activated by the hypothalamic stimulation. The effect was mainly facilitating. The excitatory and inhibitory influences of the medial hypothalamus modulated spike activity of both inspiratory and expiratory neurons of the bulbar respiratory center. Some functional aspects of the mechanism for hypothalamic regulation of the activity of bulbar respiratory neurons are discussed.


[Features of individual sympathetic preganglionic neurons and their axons in the superior thoracic portion of the spinal cord].

The existence of B- and C-preganglionic fibers in T3 spinal cord segment was shown with the aid of recording the antidromic waves in the ventral root filaments elicited by corresponding white ramus stimulation. Conduction velocity, excitability, and refractory period of these fibers were obtained. Antidromic discharges of sympathetic preganglionic neurons with high-speed B-axons were found in ventral horn. Sympathetic preganglionic neurons of the lateral horn have B-axons with slower conduction velocity, and those situated in lateral part of the intermediate zone have C-axons.


[Phasic character of the process of color sensitivity in the visual analyzer].

In subjects with normal three-chromatic vision, during long-term uninterrupted adaptation (6--8 min) to spectral stimuli of different spectral areas (lambda=650+585 nm; lambda=535+585 nm), it was found that the state of color sensitivity undergoes changes in the form of alternating active (correct) and passive (wrong) phases of color discrimination. First, the phase of active color discrimination prevails, then both phases become sort of balanced, and in the end of the adaptation the phase of passive color discrimination increases considerably. The time of duration of these phases depends on the wave--length of the adapting stimulus.


[Interaction of muscle fibers in preserving indefatiguability].

Dynamics of isometric tension, EMG, and character of AP generation were studied in separate muscle fibers in albino rats during prolonged indirect stimulation (40 HZ) of m. gastrocnemius and m. soleus. M. soleus was capable to maintain 50--60% of maximal tension during 2.5 hrs, whereas m. gastrocnemius maintained only 15--20% of the maximal tension for about 15 min after the onset of stimulation. According to character of AP generation, fibers of the muscles were divided into three major types: "silent", sporadically functioning, and constantly functioning. Mechanisms of these features of the muscle function are discussed.


[Effect of intravenous infusions of thrombin and heterogenous blood on lymph coagulability].

In dogs, i.v. administration of thrombin leads to hypocoagulation, consumption of fibrinogen, increasing fibrinolysis, and to a slight raise of antithrombin. This has no connection with appearance of natural anticoagulants and fibrinolytic agents in the lymph stream. After the heterotransfusion shock, apart from hypocoagulation and hyperfibrinolysis in the blood, the incoagulability of lymph developes due to a sharp increase of free heparin in it. The hypocoagulation after the heterotransfusion shock seems to depend on appearance of anticoagulants in the tissue fluid and lymph. Common and different features of thrombin and heterogenic blood effects on the mechanism of hypocoagulation and hyperfibrinolysis, are discussed.


Benin: nutritional considerations on trace elements in the diet.

The increasing use of the atomic absorption technique makes it possible to study man's trace-element requirements with a very accurate methodology. Some of these elements are present in the daily diet in minute quantities of micrograms which are, however, indispensable for the proper functioning of the body. But apart from such trace quantities present in conditions which are not affected by abnormal environmental concentration, there may be situations in which trace-element levels in foods and diets reach very high values. If very high, the levels may expose a population to the risk of toxicity; on the other hand, they may lead to wrong interpretations of trace-element requirements because they may lead the nutritionist to regard some high values as normal levels and therefore appropriate for meeting man's requirements. Inversely, they may also induce the nutritionist to regard lower values as unsatisfactory. Therefore, since these environmental factors, which are not always identifiable, can induce erroneous judgements due to overestimation of the requirements, it would seem appropriate, if figures on the total supplies of the diet are to be used, to refer to the tabled values of the individual foods of the diet, rather than to analyses of the whole diet ready for consumption. In fact, an abnormally high or low value of a trace element of any single food of a food composition table would have little influence on the calculation of the total supply of the diet, whereas the use of values obtained from meals which have been exposed to contamination during technological processes(e.g., through the cooking water of foods or cooking utensils) may result in overestimation. However, the analysis of global diets seems to be the method of choice in toxicological research, because in this type of investigations the basic elements of an evaluation often derive indeed from abnormal conditions identified at consumer level. Regarding the importance of copper and iron in haematopoiesis, the following hypotheses can be put forward: (a) In the haematopoietic phenomena occurring in intrauterine life, copper seems to play a role equal to that of iron, and perhaps even more important. (b) This role does not seem to be an autonomous one, but is mediated by availability of serum globulin to the child. In other words, this hypothesis relates the problem more generally to the protein nutrition of mother and foetus...


Role of keratinases in dermatophytosis. IV. Reactivities of sera from guinea pigs with heat-inactivated keratinase II.

Complement-fixing antibodies to the heat-inactivated keratinase II of Trichophyton mentagrophytes var. granulosum were detectable in sera from approximately 40% of the Hartley strain guinea pigs previously infected with this dermatophyte. However, no precipitating antibodies to the heat-inactivated keratinase II were detectable in these sera. Guinea pigs immunized with the heat-inactivated keratinase II had both complement-fixing and precipitating antibodies to the keratinase II. Circulating antibodies in sera from both the infected and the immunized guinea pigs also reacted with the active keratinase II but did not inhibit its proteolytic activity.


[Corneal lesions in ichthyosis].

Corneal lesions in ichthyosis, here combined with alopecia, are rarely described in the literature. The present observation relates to two sisters, whose grandparents were siblings. The mode of inheritance is autosomal recessive, as is usual in ichthyosis congenita but is also observed in ichthyosis vulgaris. The clinical picture and the histological findings correspond to ichthyosis vulgaris.


Treatment of vitiligo with oral corticosteroids.

17 patients with generalized vitiligo and 5 patients with localized vitiligo were treated with oral corticosteroids. Six patients with generalized vitiligo showed over 75% repigmentation in at least one of the patches. Two patients with generalized vitiligo and 1 patient with localized vitiligo showed a partial repigmentation of 25-75%, while 5 patients with generalized vitiligo and 1 patient with localized vitiligo showed a minimal repigmentation of less than 25%. Four patients with generalized vitiligo and 3 patients with localized vitiligo failed to respond. Repigmentation became evident within 4 weeks in most cases, and in general was more markedly noted in exposed areas.


Lymphangioma circumscriptum of the tongue.

A case is reported of severe transient macroglossia after biopsy from the tongue in a 13-year-old boy who has had intermittent macroglossia since the age of 1 year as a result of extensive lymphangioma circumscriptum of the tongue. The acute lesions appear to result from haemorrhage into the lymphatic spaces following rupture of blood vessels in connective tissue septa and possibly secondary infection.


Generalized granuloma anulare in a 15-month-old infant.

A Japanese girl aged 15 months had an eruption of 3 months' duration on the face, trunk, and extremities except for the palms and soles. The lesions were infiltrated papules varying from 2 to 3 mm in diameter. Blood eosinophilia of 5% was demonstrated. Skin biopsy specimen revealed a necrobiotic palisading granuloma in the corium. All lesions began to subside after 1 weeks' administration of oral corticosteroid and completely involuted in 2 months. A possible etiologic role of insect bites was considered.


Cell-mediated immunity in epidermodysplasia verruciformis.

Investigations were performed in 6 cases of epidermodysplasia verruciformis and 2 healthy family members. Nonspecific cell-mediated immunity (CMI) was studied by measuring response to phytohemagglutinin (PHA) and concanavalin A (Con A), percentrages of E- and EAC-rosette-forming lymphocytes, bacterial skin tests, and allergic reactions to dinitrochloro-benzene (DNCB). Impairment of CMI was manifested by reduction in the percentage of E rosettes, and lowered response to PHA, and- to a lesser degree- to Con A. The immune response to DNCB sensitization was invariably negative. Impairment of CMI was greater in cases of long duration and with extensive lesions. The cases of similar duration and extent of lesions, which never showed tendency to tumor formation, were not different in CMI in comparison with cases with numerous tumors. Only in cases with very advanced tumors CMI was impaired parallel to the gravity of the patient's general condition.


Onset of the vasoconstrictor effect of diflucortolone valerate, betamethasone valerate, and fluocinolone acetonide ointments applied for varying periods under occlusive dressings.

Evaluation of cutaneous vasoconstriction after applications of varying duration of topical corticoids on the flexor surfaces of the forearms of 20 patients with intact skin shows a significantly faster blanching effect with diflucortolone valerate ointment than with fluocinolone acetonide and betamethasone valerate ointments. Furthermore, the test shows that even for a highly active preparation, such as the diflucortolone valerate ointment, an application time of less than 3 h only exceptionally leads to vasoconstriction in the healthy skin.


The epidemiology of hyperlipoproteinemia in a Rumanian general population sample. Study of 7,085 cases.

Using a two stages screening method the prevalence in the general population of hyperlipoproteinemias (HLP), separated in the five types proposed by Fredrickson, Levy and Lees, and adopted by WHO has been studied. The study included 7,085 subjects of both sexes, aged 25-65 years, representing 84,52 % of a population taken at random within a district of Bucarest. HLP was found in 1,013 cases, i.e. 14,29 % of the investigated population. 48.37 % were men and 51.63 % women. The prevalence of HLP was lowest in the first decace of age studied (25-35 years) and highest in the last two decades (45-65 years). Overweight was more frequently encountered in these patients (64.46 %) than in the total population (32.3 %). Of the 1,013 cases with HLP, 42.35 % (6.05 % of the total population) were of type IV, 27.05 % (3.86 % of the total population) of type II-b, 22.80 % (3.26 % of the total population) of type II-a, 4.74 % (0.67 % of the total population) of the type III and 3.06 % (0.43 % of the total population) of the type V. 22.70 % of the HLP patients were considered primary familial HLP, 66.54 % primary non-familial HLP and 10.76 % secondary HLP; IN 109 secondary HLP, the most frequently encountered disease was diabetes mellitus (42.20 %), followed by hypothyroidism (24.77 %), alcoholism (12.84 %), obstructive liver diseases (9.17 %), pancreatitis (5.50 %), nephrotic syndrome (2.75 %) and treatment with estrogens and steroids (2.75 %).


[Diabetes and synovial chondromatosis (author's transl)].

In the series of the fourty cases of synovial chondromatosis observed at the the department of rheumatology of Marseille since 1960, seventeen patients were suffering from diabetes mellitus, all of them not-insulin-dependent. This raises the question of the nature of this association, not previously reported.


Vitamin B 12 and folic acid serum levels in diabetics under various therapeutic regimens.

The aim of the present study was to reconsider the problem of the haematological consequences of biguanide treatment by evaluating serum vitamin B 12 and folic acid levels as well as classical haematological parameters in 30 diabetics treated by metformin. For purpose of comparison, similar evaluations were done in diabetics treated with insulin (27 patients) or sulfonylureas (13 patients). Results indicated that mean serum levels of vitamin B 12 were significantly lower in patients receiving metformin than in both other groups. In the metformin-treated group, five patients had serum levels of vitamin B 12 below 270 pg/ml and five had borderline values. No difference was found in the mean serum folic acid levels between the three groups. Similarly, there were no differences in the red blood cell counts, volumes or haemoglogin concentrations nor in the mean values of serum iron and lacticodeshydrogenase levels between the three groups. Since the haematologic and neurologic complications of vitamin B 12 deficiency may only appear after the deficiency had existed for 10-15 years, the lack of haematological alteration may be explained by the fact that the vitamin B 12 deficiency was not present for a sufficient period of time. We conclude that it may be wise to monitor the haematological values as well as vitamin B 12 levels at regular intervals in diabetic patients treated with metformin so that B 12 hypovitaminosis and its complications can be prevented.


Hypoglycaemia induced by adrenal gland neoplasia (Anderson's syndrome) : report of a case.

A patient with hypoglycaemia associated with an adrenal neoplasia (Anderson's syndrome) is reported. Endocrinological investigation showed increased secretion of cortisol and catecholamines as well as an increased urinary steroid excretion along with profound inhibition of both basal and stimulated insulin secretion. During IVGTT, Conard's coefficient was reduced. The hyperglycemic response to glucagon injection was blunted, suggesting that liver glycogen stores were decreased or unavailable.


[Sex differences in the blood glucose fall induced by short fasts (author's transl)].

Overnight fasting venous plasma glucose concentration was lower in premenopausal women than in men. This difference increased during a low caloric and low carbohydrate diet and above all after a 48 h fasting period. Venous blood glucose variation during this period of fasting was the same in post-menopausal women as in men. These facts and the previous observation by our group of a fall in fasting and post absorptive venous blood glucose after intramuscular injection of oestradiol benzoate (10) indicate that sex variations in the blood glucose fall following a period of fasting are at least partly linked to the oestrogenic status of the premenopausal woman.


Accuracy of diagnosis of cancer among autopsy cases: JNIH--ABCC population for Hiroshima and Nagasaki.

The accuracy of death certificate diagnoses of cancer in the fixed population of about 100,000 samples in Hiroshima and Nagasaki was determined for the period 1961 approximately 1970 by comparison with autopsy findings. In general, when the death certificate listed cancer as a cause of death it was found at autopsy in a high proportion of cases. However, cancer was not always reported on death certificates, indicating that cancer occurs more frequently than recorded by official mortality statistics. Older persons, persons who die at home, and persons with certain cancers are more likely not to have cancer named on their death certificates. It is estimated that in the 10,749 deaths occurring at home or in hospital, there were 32% more deaths due to cancer than certified on death certificates (3,095 vs. 2,345) and for persons aged 70 or more dying at home it is estimated there were 55% more stomach cancer (269 estimated vs. 174 listed) and 244% more lung cancer (141 estimated vs. 41 listed) than were certified on death certificates. The death certificate is not a good source of information for cancer of the cervix because many cases of this disease reported on death certificates as cancer of the uterus. This practice needs to be taken into account in the use of mortality data for cervical cancer in Japan.


Predication of the effect of carcinostatic agents on tumor-bearing host by the sensitivity test using acid phosphatase activity in vitro.

For the purpose of predicting the effect of carcinostatic agents on tumor-bearing host in vitro, a sensitivity test of a drug in tumor bearers was developed. This test is based on the change in the specific activity of acid phosphatase of individual tumor and liver tissue, and the difference in them was used as an indicator of effectiveness. The value was called the "effective value." The present papar is concerned with the relationship between the effective value and effectiveness of the agents in rodents and man. The results showed that the effective value became higher with increasing concentration of Mitomycin-C incubated with tumor and liver tissues. The survival time of Ehrlich carcinoma-bearing mice, which were given Mitomycin-C intraperitoneally, was longer and increase in the dose of Mitomycin-C. In ascitic or subcutaneous form of Ehrlich carcinoma, AH-130, and Yoshida sarcoma, the effective value was parallel with the survival time of or the inhibition of tumor growth in tumor-bearing animals treated with Mitomycin-C. In 25 patients with gastric carcinoma treated with Mitomycin-C, the postoperative survival time was more closely correlated with the effective value calculated by the titers of both tumor and liver than the value of tumor alone.


Interaction of antitumor agents including carboquone in sarcoma-180 system.

Combination effect of antitumor agents including carboquone was evaluated on the concept of pharmacological synergism and not therapeutic synergism in ascites sarcoma-180 system. Combinations of carboquone plus cyclophosphamide, doxorubicin, and Methotrexate in simultaneous administration and carboquone plus doxorubicin in alternate one provided synergism. Combination effect of agents was affected by the schedule of drug administration. Toxicity of carboquone in combination with many antitumor agents, generally, decreased in simultaneous administration. Approved agents in combination with carboquone in simultaneous administration were Mitomycin-C, daunorubicin, Actinomycin-d, vinblastine, vincristine, Ancytabine, and 6-mercaptopurine. Those in alternate administration were Actinomycin-D and vinblastine.


Antibody-dependent macrophage-mediated cytolysis in a murine syngeneic tumor system.

Peritoneal immune macrophages from C3H mice immunized against syngeneic MM46 ascites tumor cells specifically lysed these tumor cells in the presence of immune sera in vitro. An active factor(s) essential for macrophage-mediated cytolysis was purified nonspecifically by gel filtration and then three types of ion-exchange column chromatography. One factor was a specific antibody belonging to the IgG2 a subclass. Neither immune macrophages nor the syngeneic antitumor antibody alone had a cytolytic action on the target cells. Thus, we named the reaction antibody-dependent immune macrophage-mediated cytolysis. The immune macrophages apparently destroyed the sensitized tumor cells in vitro by a nonphagocytic form of cell-contact and this type of cytolysis was independent of a complement. No evidence was obtained for a soluble cytotoxic factor released on interaction of immune macrophages with sensitized tumor cells. Living immune macrophages were essential for the cytolytic action and their activity depended on contractile microfilaments and protein synthesis as revealed by studies with specific inhibitors.


Methylguanidine content in food.

A combination of column chromatography using microcrystalline cellulose and ion-exchange resin, paper chromatography, gas chromatography, and gas chromatogrraphy-mass spectometry was used to determine the content of methylguanidine in various meats of fish and animals, and their processed products. All the samples of fresh fish meat and beef analyzed contained trace amounts (0.2 approximately 0.9 ppm) of methylguanidine. Various types of dried or canned fish also contained trace amounts, while most of the "Bushi-rui," a highly processed dried meat of bonito, mackerel, or sardine contained 21 to 106 ppm of the compound. Two brands of peptone made by digesting meat probably with pepsin and trypsin also contained 12 and 70 ppm of methylguanidine, respectively. Samples of ham, sausage, salami sausage, powdered skim-milk, and a few others did not contain any detectable amount (less than 0.2 ppm).


Differentiation of host-mediated antitumor agents from mitotic posons by the antitumor foot-pad reaction in Ehrlich carcinoma-ddY mouse system.

The effect of antitumor agents (lentinan, PS-K, Mitomycin-C, 6-mercaptopurine, etc.) on the antitumor delayed hypersensitivity reaction (DHR) measured by the foot-pad test was compared with their effect on tumor growth in ddY mice with Ehrlich tumor. These agents all inhibited growth of Ehrlich carcinoma. Lentianan and PS-K enhanced the antitumor DHR, but Mitomycin-C and 6-mercaptopurine did not. By plotting the effect of agents on the anti-tumor DHR against these effects on tumor weight, host-mediated antitumor agents could be differentiated from mitotic poisons. Attempts to distinguish these two types of agents by the same method using a syngeneic tumor system were unsuccessful.


Blastoid transformation of human lymphocytes cultured with protein-bound polysaccharide preparation, PS-K, in vitro.

The protein-bound polysaccharide preparation, PS-K, isolated from a mushroom, Coriolus versicolor, was found to stimulate human lymphocytes and induce them into blastogenesis in vitro. This stimulatory effect seemed to be nonspecific since lymphocytes from cord blood of newborn babies were also stimulated by PS-K. The highest lymphocyte blastogenesis by PS-K was observed after 5 days in culture.


Micrometastasis in resected lungs of lung cancer patients.

In order to find causes for recurrence and/or metastasis after removal of human lung cancer, microscopic metastasis was examined histologically in the seemly unaffected areas of the lung in primary lung cancer patients. In 55 of 116 cases (47%), microscopic metastases were found in the areas of the lung which looked normal. These micrometastases were localized in 22 cases and disseminated in 33 cases. The sites where tumor cells were growing were identified in lung tissue as blood vessels, lymphatics, and aerial spaces, although it was difficult to identify a few cases. The incidence of microscopic metastases was significantly lower in the lungs of the group in which the diameter of a tumor was less than 3 cm, than those in which the diameter was more than 3 cm. In addition there was a significant decrease in the rate of microscopic spreads in the specimens without lymph node involvement as compared to those with lymph node involvement. The rate of postoperative recurrence and/or metastases was significantly high in the cases with micrometastasis compared to those without, suggesting that most of the microscopic spreads would become distinct tumors if unresected.


Antitumor activity of 1-hexylcarbamoyl-5-fluorouracil in a variety of experimental tumors.

Antitumor activity of 1-hexylcarbamoyl-5-fluorouracil against various tumors was examined. Therapeutic ratio (ILSmax/ILS30) in L-1210 system was 4.5 by oral administration, while those of 5-fluorouracil and 1-(2-tetrahydrofuryl)-5-fluorouracil were 1.9 and 1.0, respectively. Therapeutic ratio of the compound in C-1498 system was 11, while those of 5-fluorouracil and 1-(2-tetrahydrofuryl)-5-fluorouracil were 3.3 and 2.5, respectively. 1-Hexylcarbamoyl-5-fluurouracil was also active against solid and ascites tumors by oral administration. It was markedly active against Nakahara-Fukuoka sarcoma, adenocarcinoma=755, and ascites sarcoma-180, and moderately active against Ehrlich ascites carcinoma. This compound had a wider tumor spectrum than 5-fluorouracil and 1-(2-tetrahydrofuryl)-5-fluorouracil by oral administration.


Further studies on the isozyme patterns of branched-chain amino acid transminase in cultured rat hepatocytes.

Among several lines of cultured rat hepatocytes examined, one line, IAR-22, contained enzyme III as well as enzyme I of the isozymes of branched-chain amino acid transaminase (EC 2.6.1.42) and this cell line was tumorigenic. None of the cell lines tested contained enzyme II (EC 2.6.1.6) or tyrosine transaminase (EC 2.6.1.5) and addition of dexamethasone did not induce these transaminases. The PC-1 line, containing only enzyme I and having a high percentage of diploid cells, showed deviation of its chromosomal number and tumorigenicity, but no change in its isozyme pattern when transformed with N-methyl-N'-nitro-N-nitrosoguanidine. Therefore, judging from expression of isozymes of the transaminase, this transformed cell line retained moderate differentiation.


Effect of enterohepatic circulation on bile production in regenerating liver.

In an investigation of the role of portal blood flow in bile production and of changes in the enterohepatic circulation of bile in the regenerating liver, various branches of the portal vein were ligated in dogs, bile was collected from the liver lobes supplied by ligated and by nonligated portal branches, and the composition of the bile was analyzed. 1. Bile flow and bilirubin excretion from the ligated, atrophic liver lobes decreased with a disappearance of glycine-conjugated bile acids, but bilirubin excretion and especially bile flow increased greatly without any changes in bile acids composition in the nonligated, regenerating liver lobes as the portal blood flow to them per liver weight increased. 2. Infusion of gallbladder bile into the terminal ileum stimulated bile secretion in the nonligated lobes in the postoperative period, but not in the ligated lobes except immediately after the ligation of the portal vein branches supplying two-thirds of the liver. These findings indicate that bile secretion by the ligated lobes could be stimulated via the hepatic artery and the nonligated lobes might be via both the portal vein and the hepatic artery after the infusion during early postoperative period.


Studies on the functional disturbances of the papillary region using a pressure sensor.

Investigation of the duodenal papilla and the bile duct by EPCG is essential to diagnose the organic and functional disturbances of the papillary region. We have developed a pressure sensor based on a semi-conductor in order to obtain a more objective observation of pathological conditions in the papillary region. Using a duodenofiberscope, the pressure sensor was placed on the tip of canula, and it was inserted into the papilla and measured the movements of the papillary region. The pressure sensor method was carried out in 18 normal subjects and 69 patients with various diseases. As the result of analysis of wave forms in normal subjects, regular wave form patterns were obtained. In about 71% of cases with biliary diseases irregular wave forms were observed. Irregular wave form patterns were also observed 40% of cases with cholecystolithiasis, while irregular patterns were revealed in 86% cases with choledocholithiasis. The pressure sensor method during for duodenofiberscopy is important diagnostic procedure for the determination of functional disturbances in the papillary region.


Serum glycoproteins in the liver diseases. I. Studies on sialic acid-free glycoproteins-improved competitive binding assay of desialylated glycoprotein by rat liver plasma membrane.

An improved method for quantitation of desialylated glycoproteins was developed. The assay was carried out in non-saturating condition other than saturating condition which has been used by the other authors. In the present method a lower radioactivity in the assay solution can be used. Standard curves obtained by adding an increasing amount of desialylated alpha1-acid glycoprotein to the assay solution made it possible to measure desialylated glycoproteins equivalent to 5-200 ng of desialylated alpha1-acid glycoprotein. Desialylated alpha1-acid glycoprotein used for the assay could be prepared in large scale by hydrolysis with 0.1 N-H2SO4.


Serum glycoproteins in the liver diseases. II. Radioimmunoassay of alpha-1 acid glycoprotein.

A radioimmunoassay for human alpha1-acid glycoprotein has been developed. 97.8% of 125I-alpha1-acid glycoprotein prepared for the assay were immunoprecipitable with specific anti-sera against the protein. alpha1-acid glycoprotein concentration in sera from normal adults was found to range between 70 and 114 mg/100 ml, with a mean of 93. Fulminant hepatitis, liver cirrhosis or chronic active hepatitis with sublobular necrosis caused a significant lowering of alpha1-acid glycoprotein concentration. Sera obtained from patients with acute hepatitis in convalescence, chronic inactive hepatitis or primary biliary cirrhosis gave normal concentration of the glycoprotein.


Gastric carcinoma combined with distant gastric ulcer.

The cases of the gastric carcinoma combined with distant benign gastric ulcer were 90 of 1257, 7.1%, and the carcinomas were frequently found in the lesser curvature of the antrum and the combined gastric ulcers frequently in the lesser curvature and posterior wall of the corpus. Average age in the combined cases was 58.8 which was older about 7 years than that in the cases of the gastric ulcer. The cases, in which the ulceration in the gastric ulcer was same or deeper than that in the gastric carcinoma, occupied about 70% of these combined cases. It should be considered that the malignant transformation does not always occur in the preceding ulcerative lesion. However, the intestinal metaplasia was usually severe, and so the well-differentiated carcinomas were twice frequent to the low-differentiated ones. The repeated regeneration of the epithelial cells associated with the erosive or ulcerative change may be of some relation to the carcinogenesis, because the intestinal metaplasia appears usually associated with the repeated defect and repair of the propria mucosae.


Sibling cases of chronic recurrent hepatocerebral disease with hypercitrullinemia.

Two sibling cases with chronic recurrent hepato-cerebral syndrome which correspond to the nutritional form of hepato-cerebral disease entitled by Shikata et al. and the data of plasma free aminoacids analyses of these cases were reported. The one case is 27 years old male and the other case is 36 years old female. Their parents were cousins. Both cases have had unbalanced diet, especially liked legumes unusually. Their main symptom was recurrent disturbance of conciousness and convulsive seizures. Slight abnormality of liver function test and hyperammonemia were demonstrated. Electroencephalogram showed the pattern of triphasic wave. Coeliac angiography did not revealed a portal-systemic shunt. Hepatic biopsy specimen revealed liver fibrosis with fatty change in the one case and mild fatty change in the other case. Analyses of plasma free aminoacids showed particurally high level of citrulline in both cases. From the results of plasma free aminoacids analyses, it is considered that pathogenesis of these patients is congenital hereditary urea cycle disorders.


The application of caerulein to cholangiography.

Caerulein was applied to oral cholecystography and the opacity of the common bile duct was evaluated at intervals. To 127 subjects whose gallbladder had been visualized by cholecystography was administered caerulein by intramuscular route in a dose of 0.2 mug per kg of body weight. As a result: 1. The visualization of the common bile duct reached its maximum 15 minutes after administration of caerulein (52% of the subjects); in total, 62.2% of the subjects responded to this cholecystography. 2. The visualization by caerulein was superior to that by the yolk both in its rate and intensity. 3. The cholangiogram taken after administration of caerulein was preferably available for diagnosis of bile duct lesions. Caerulein used for a pretreatment of drip infusion cholangiography (DIC) remarkably improved the picture in 3 of the 10 subjects in whom DIC alone had failed to show the bile duct. Thus, the application of caerulein to cholangiography facilitated diagnosis of bile duct lesions.


Basic studies on cholesterol solubilization in bile salt solution.

Previous studies on cholesterol solubilization by bile salts have often shown inconsistencies. To obtain basic informations on this problem, cholesterol solubilization in the aqueous solution of several bile salts have been reexamined. Kinetic studies revealed that not only the rate but also the magnitude of solubilization depended on the amount of excess cholesterol and the concentration of bile salt. An appropriate proportion of added cholesterol to bile salt was evaluated as 1:5-10 (w/w), corresponding to about 200% excess amount to approximate supposed solubility. The solubilization equilibrium was rather difficult to fix and must be checked by the procedure used. A linear relation was obtained between the quantity of solubilized cholesterol and the concentration of bile salt. The slope of the straight line was designated k. As the solubilizing power could be given by the ratio of the solubilizate to the solubilizer, it was expressed numerically by k value as well as graphically by the molar ratio of cholesterol to bile salt as ordinate and the molar concentration of bile salt as abscissa in which the above relation was hyperbolic, k being as asymptote. k values obtained for cholate, chenodeoxycholate, deoxycholate and equimolar cholate-deoxycholate mixture were 3.72 X 10(-2), 6.79 X 10(-2), 8.10 X 10(-2) and 6.55 X 10(-2) respectively.


Studies on intestinal malabsorption in chronic pancreatitis.

Pancreozymin-secretin test (PS test) and intestinal absorption tests were performed in 21 patients with chronic calcific pancreatitis and 32 patients with chronic noncalcific pancreatitis to evaluate exocrine functions of the pancreas. And the following results were confirmed. (1) Fecal fat excretion increased in 33% of chronic pancreatitis (47% of calcific pancreatitis and 25% of noncalcific pancreatitis). Serum carotene leves showed significantly low levels in 44% of chronic pancreatitis (67% of calcific pancreatitis and 27% of noncalcific pancreatitis). (2) D-xylose tolerance test was abnormally low in only 6% of chronic pancreatitis, but Schilling test was evaluated abnormally low in 29% of chronic pancreatitis (50% of calcific pancreatitis and 11% of noncalcific pancreatitis). (3) Fecal fat excretion increased in cases of severe exocrine insufficiency of the pancreas with decreased amylase output and decreased maximum bicarbonate concentration in PS test. (4) Correlation of fecal fat excretion to maximum bicarbonate concentration was statistically significant, but those to amylase output or volume of pancreatic juice were not significant. (5) Antacid drugs combined with pancreatic extracts seems to be indispensable in the treatment of chronic pancreatitis as far as malabsorption in chronic pancreatitis is concerned.


Effect of intraluminal oxygen on experimental ischaemia of the intestine.

The small bowel of 44 rats has been made ischaemic for 120 minutes by occluding the superior mesenteric artery. Gaseous oxygen was introduced into the small bowel lumen of 18 of the rats, and gaseous nitrogen into the bowel lumen of a further eight, 30 minutes after the start of the ischaemia. The mortality rate of the control group of 18 rats was 89%, significantly higher than the 39% mortality of the oxygen-treated rats (p less than 0-005). None of the eight rats treated with intraluminal nitrogen survived. Histological changes caused by ischaemia were much reduced in the intestine of the oxygen treated rats. It is suggested that intraluminal oxygen might be useful additional form of therapy for the treatment of the partially ischaemic bowel that may be retained after the resection of definitely non-viable ischaemic bowel at initial laparotomy.


Evidence for the mixing of residue in the human gut.

Mixing the residue in the gut has been studied in 24 normal subjects using five different types of radio-opaque pellets. By giving single doses of different pellets to the subjects on three successive days and measuring their appearances in the stool by radiographs evidence of mixing was found in 83% of studies. Mean transit time (MTT) of markers through the gut was measured from the single dose studies (MTT-S) and also by giving the pellets to subjects continuously with each meal (MTT-C). By comparing MTT-C with MTT-S evidence was found for a mixing pool with exponential decay. The turnover time of this pool was estimated as about 30% of the total MTT.


Effect of motilin on the lower oesophageal sphincter.

The effect of motilin on lower oesophageal sphincter (LES) pressure has been studied in unanesthetised specially trained dogs using an infusion manometric technique. Motilin produced significant rises in resting pressure and contractions of the LES after doses ranging from 0-009 mug/kg to 0-05 mug/kg. Doses greater than 0-05 mug/kg resulted in repetitive high amplitude contractions. Atropine 30 mug/kg completely abolished the effect of the lower doses of motilin. Higher doses of motilin in atropinised dogs still caused a small rise in baseline pressure and contractile activity still appeared. Hexamethonium 2 mg/kg resulted in both a diminished rise in LES pressure and the disappearance of contractions after motilin. Hexamethonium and atropine together completely abolished the LES response to motilin. We conclude that motilin increases LES pressure by acting on preganglionic cholinergic neurones to release acetylcholine which excites other cholinergic neurones supplying the circular muscle of the LES.


Responses of the competent and incompetent lower oesophageal sphincter to pentagastrin and abdominal compression.

Responses of the lower oesophageal sphincter (LOS) to pentagastrin, given by continuous intravenous infusion in doses ranging between 0 and 9 mug/kg/h, and to external abdominal compression were measured by infused catheters in healthy subjects and in a group of patients with reflux oesophagitis. In separate experiments, pressures were measured both by sensors stationary within the LOS, and by repeated continuous withdrawals of sensors from stomach to distal oesophagus. In normal subjects, doses of pentagastrin within the physiological range (0.9 mug/kg/h) produced modest but statistically significant increases in LOS pressure. By comparison, sphincteric responses in patients with oesophagitis were small and a dose of 4-5 mug/kg/h was the lowest that produced a significant increase in LOS pressure. During abdominal compression increases in LOS pressure did not significantly exceed increases in intragastric pressure in either patients or normal subjects. This was so at all doses of pentagastrin that were tested. Hence, there was no evidence of synergism between the effects of pentagastrin and abdominal compression upon the LOS. We infer from our findings that gastrin does play a modest role in the physiological regulation of human LOS tone. Relative insensitivity of the incompetent LOS to pentagastrin represents, we believe, sphincteric muscle failure. Our results are not consistent with the hypothesis that LOS incompetence is due to loss or impairment of an adaptive response of the LOS to alterations in intra-abdominal pressure.


Pancreatitis--a retrospective study.

A retrospective study has been made of all adult patients admitted to Manchester Royal Infirmary with exocrine pancreatic disease between 1968 and 1974, in order to define the factors which influence the variable mortality and morbidity rates in published accounts of patients with acute pancreatitis. The most plausible explanation is that some series with low mortality rates include a variable number of patients with relapsing acute pancreatitis and acute exacerbations of chronic pancreatitis. Both these pathological entities have a negligible mortality and morbidity rate compared with single attacks of acute pancreatitis. The difficulties encountered by the clinician in determining the prognosis of acute pancreatitis at the time of admission to hospital are discussed. Attention is drawn to the differing role of alcohol as an aetiological factor in relapsing chronic pancreatitis and acute pancreatitis.


Suppression of giardiasis during the intestinal phase of trichinosis in the mouse.

The interaction of the intestinal phases of Giardia muris and Trichinella spiralis was investigated in Swiss albino mice. Intraoesophageal inoculation of G. muris cysts seven days before, or seven days after, similar inoculation of T. spiralis larvae resulted in significant reduction in the numbers of Giardia trophozoites in small bowel and Giardia cysts in stools. This effect was not observed when G. muris cysts were administered after resolution of the intestinal phase of trichinosis. Giardiasis had no effect on trichinosis as assessed by numbers of adult worms in small bowel and larvae in skeletal muscles. Studies of small bowel morphology showed that the intestinal phase of trichinosis was associated with increased numbers of inflammatory cells in the lamina propria, a significant increase in Paneth cells in crypts, and a marked reduction in the villus:crypt ratio of jejunum. These observations suggest that the intestinal phase of trichinosis induced environmental changes in small bowel, perhaps related to inflammation, which resulted in suppression of proliferation of Giardia trophozoites.


Galactose elimination capacity as a prognostic index in patients with fulminant liver failure.

In 25 patients with fulminant hepatic failure the prognostic value of a quantitative liver function test, the galactose elimination capacity, was assessed and comapred with routine liver function tests and clinical features. The galactose elimination capacity was significantly higher (P less than 0-05) in the five patients who survived than in the 20 patients who died. None of the other liver function tests, was significantly different. The values of the galactose elimination capacity overlapped considerably between survivors and non-survivors, but all patients with a galactose elimination capacity below 12-8 mumol galactose/min and kg body weight died. The disease among most patients who died having a galactose elimination capacity greater than 13 mumol ran a subacute course. It is suggested that quantitative liver function tests be included when new treatments of fulminant hepatic failure are investigated.


Idiopathic bile acid catharsis.

In the course of extensive routine screening for bile acid malabsorption a few patients were detected in whom chronic diarrhoea was apparently induced by excess bile acid loss which was neither associated with demonstrable conventional ileopathy nor with any other disorder allied to diarrhoea. In three patients subjected to scrutiny the results obtained were in harmony with a concept of idiopathic bile acid catharsis. Ingestion of cholestyramine was followed by immediate relief, but the diarrhoea recurred whenever this treatment was withdrawn. It it suggested that idiopathic bile acid catharsis should be suspected in patients with unexplained chronic diarrhoea and especially in those with a diagnosis of irritable colon with diarrhoea.


Intravenous administration of diazepam in patients with chronic liver disease.

The EEG response and drug kinetics after intravenous infusion of diazepam at 1-0 mg/min until nystagmus, dysarthria, and moderate sedation developed, has been investigated in five normal subjects and 17 patients with chronic liver disease. Diazepam induced adequate premedication with a similar clinical response in all subjects with no adverse reactions. Maximal response was during or within five minutes of infusion. The dose of diazepam required in liver chronic disease was 17-9 +/- 1-4 mg (M +/- SEM) compared with 27 +/- 5-4 mg in controls (p less than 0-01). Dose correlated significantly with serum albumin (p less than  0-05). Baseline mean dominant frequency (MDF) and slow wave index (SWI) significantly correlated with albumin (p less than 0-01). After diazepam, the MDF decreased and SWI increased. The change was greatest at the time of maximal clinical response. It was greater in liverdisease and was greatest in patients with previous hepaticencephalopathy. In spite of reduced dose requirements in liver disease, there was no significant difference in plasma concentration at the end of drug infusion...


Patchiness and duodenal-jejunal variation of the mucosal abnormality in coeliac disease and dermatitis herpetiformis.

The incidence and degree of patchiness of mucosal abnormality in both coeliac disease (CD) and dermatitis herpetiformis (DH) is documented. As judged by both stereomicroscopy and subjective histology, patchiness occurred frequently in both CDand DH patients. In most cases the difference of abnormality was of only one grade, but in approximately 25% as assessed by stereomicroscopy and 10% as assessed by histology the difference was of two or more grades. In control subjects with normal small bowel mucosa the variation of the mucosal appearance between the duodenum and proximal jejunum was studied. Contrary to popular belief, no significant difference of villous and crypt measurements or of apparent villous "bridging" and "branching" between these two sites was found, if only well-orientated sections were studied. The stereomicroscopic appearances were also similar at these two sites, although villi tended to be broader in the duodenal biopsies. The duodenal-jejunal variation was also studied in CD and DH patients and although by both stereomicroscopy and subjective histology the appearances were similar in most patients, in approximately 33% the duodenal abnormality was the most severe and, surprisingly, the jejunal abnormality was more severe in approximately 15%. It is concluded that multiple, precisely located biopsies of both the duodenum and proximal jejunum are invaluable in the investigation of small bowel disease and in assessing response to treatment.


Potential difference across the normal and the abnormal gastric mucosa in man.

The mucosal potential difference in the body of the stomach was measured in 18 patients with gastric ulcers, five with gastritis, and three with pernicious anaemia. The results were compared with those of 12 normal volunteers. Significantly lower than normal levels were found in the groups of patients with gastric ulcers and gastritis. The patients with pernicious anaemia had even lower potential differences. In an additional 25 subjects, measurements were made in the duodenal bulb and at five sites in the stomach under direct vision at endoscopy. Biopsies were taken from each site for histology. Subjects with gastritis at the high lesser curve had a significantly lower potential difference at that site than those without gastritis. In the latter group, the potential difference at the high lesser curve was as low as in the antrum, and invariably lower than at the high greater curve.


Predictive value of perioperative gastric acid tests.

Preoperative acid studies and early postoperative insulin tests in 275 patients undergoing various forms of vagotomy have been related to recurrent ulceration. Follow-up time has been from two to nine years, mean 4-3 years. Recurrence is directly related to basal acidity in both tests but is not related to stimulated acid levels preoperatively. In the insulin tests higher levels of acidity after insulin are associated with a higher incidence of recurrence. When positive, Hollander's and multiple criteria are both associated with a higher recurrence rate.


Antifactor Xa activity measured with amidolytic methods.

Methods for the assay of antifactor Xa activity in the presence and absence of heparin are described. Diluted plasma is incubated with bovine, activated factor X (Xa) in stage I, and remaining Xa is measured with the chromogene substrate Bz-Ile-Glu-Gly-Arg-pNA in stage II. In the presence of heparin, the inactivation is completed in 30 sec, and this method measures total Xa-inactivating capacity in diluted plasma (Method I). In a clincal material, this capacity showed a strong positive correlation (r=0.85) to the thrombin-inactivating capacity of diluted heparinized plasma (heparin cofactor activity) and apparently reflects antithrombin III (At-III) concentration. In the absence of heparin, the inactivation of factor xa occurs slowly. With an incubation of 5 min, about 25% of Xa is inactivated, and this assay reflects initial inactivation of Xa (Method II). With this method, a positive, but less strong correlation to the thrombin-inactivating capacity was found (r=0.58), indicating that inhibitors different from At-III accounts for a minor part of the initial inactivation. Determinations in plasma, in which At-III was removed by immunoadsorption, indicated that At-III accounts for about 80% of the initial inactivation. The results of the assays are not significantly influenced by varying concentrations of fibrinogen, fibrinogen degradation products or heparin in the test plasma.


Evaluation of hypercoagulability in septic abortion.

Soluble fibrin monomer complexes (SFMC) were determined in patients with septic abortion (body temperatures of more than 39 degree C and/or chills without apparent signs of endotoxic shock), with infected abortion, with non-infected abortion and with normal pregnancies. Quantitative gel filtration (4% agarose) of beta-alanine precipitated plasma samples yielded the relative (percent of total fibrinogen content) and absolute (mg/100 ml plasma) amount of SFMC. The relative (5.5+/-1.4%, mean+/-SD) and absolute (21.5+/-8.6 mg/100 ml) amount of SFMC was significantly increased in patients with septic abortion compared to patients with normal pregnancies or non-infected abortion (p less than 0.001). Patients with infected abortion (p less than 0.001). Patients with infected abortion already revealed increased levels of SFMC (4.3+/-1.2%, 14.2+/-6.8 mg/100 ml) though their platelet count was still unaltered (infected abortion: 221+/-47 X 10(3) platelets/mm3; septic abortion; 99+/-36 X 10(3) platelets/mm3). The use of heparin in patients with septic abortion resulted in a decrease in SFMC. Chain characterization of SFMC frequently revealed a slight degradation of the alpha-chains probably due to fibrinolytic activity in vivo; gamma-gamma dimers representing intermolecular covalent bindings were not observed. The findings are in agreement with our former assumption that patients with septic abortion have a pronounced state of hypercoagulability.


A technique for the evaluation of platelet-collagen adhesiveness in vitro.

A method for the evaluation in vitro of platelet-collagen adhesiveness has been developed. This method is based on counting platelets both before and after their contact with an insoluble collagen (IC) suspension. The results are expressed as adhesiveness index (AI). A number of variables which could influence the test has been evaluated and standardized in a way suitable for the routinary use of the technique described.


Coagulation defect in experimental trypanosomial infection.

Some coagulation parameters have been studied in animals experimentally infected with trypanosomial organisms (T. brucei or T. congolense). The partial thromboplastin time test with kaolin was regularly abnormally prolonged in all animals during infection. Although results of some coagulation factors in the intrinsic pathway cannot be used to explain this finding, it is suggested that the partial thromboplastin time test can be used as a test to monitor infection and recovery from this organism.


Treatment of thrombosis by sequential therapy with ancrod followed by streptokinase. Clinical pharmacology and rheology.

The effects of sequential therapy with ancrod followed by streptokinase are reported in a series of patients with thrombotic disease. Measurements have been made in blood coagulation, fibrinolysis and whole blood and plasma viscosity. Intravenous infusion of ancrod resulted in a significant reduction in plasma fibrinogen which was associated with highly significant reduction in both plasma and whole blood viscosity. Sequential therapy with streptokinase resulted in a gradual rise in fibrinogen and a slight but significant rise in whole blood and plasma viscosity. All patients showed clinical improvement and no haemorrhagic complications resulted.


Distribution and variation of fibrinolytic activity in the walls of human arteries and veins.

A systematic study on the location and intensity of the fibrinolytic activity in more than 500 samples of human arteries and veins from 50 routine necropsies and 35 blood vessel biopsies was performed. Data were obtained for an overall comparison of the fibrinolytic activity along and across the walls of human blood vessels by the use of a standardized fibrin slide technique. Arteries generally showed little or no fibrinolytic activity in the intima and media but strong activity in the adventitia. Veins showed a comparable strong fibrinolytic activity in the external layer of loose connective tissue. Fibrinolytic activity in the venous intima, media and adventitia was generally weaker but varied greatly according to position in the body. Veins situated in the lower parts of the body had less fibrinolytic activity than the veins at the upper levels. Fibrinolytic activity was found to be related to the endothelium of the vasa vasorum and/or of the main lumen of the vascular wall. Increased fibrinolytic activity was observed in arteries and veins in cases of sudden death, vasogenic shock, cerebral hemorrhage and cirrhosis. Decreased fibrinolytic activity was encountered in blood vessels in cases of endotoxin shock, hyaline membrane disease and a case of Waterhouse-Friderichsen syndrome.


First record of bacillary rickettsia-like organisms in European tick Dermacentor marginatus (Sulzer).

Bacillary rickettsia-like organisms (BRLO) were found in the tick Dermacentor marginatus. They are gram-negative and differ from common bacteria and reckettsiae both in the cultivation conditions and morphology. BRLO are non-pathogenic for ticks and guinea pigs. In our studies they were isolated on half-engorged females of D. marginatus, on which they are still maintained.


Observations on the development of Rhabdochona phoxini Moravec, 1968 (Nematoda: Rhabdochonidae).

The life-cycle of the nematode Rhabdochona phoxini, an intestinal parasite of the fish Phoxinus phoxinus, has been studied experimentally. The mayfly nymphs, Habrophlebia lauta Eaton and H. fusca (Curtis) were found to serve as experimental intermediate hosts. After the eggs of R. phoxini have been swallowed by the mayfly nymph, the toothed first-stage larvae of this parasite are released and penetrate through the intestinal wall into t-e body cavity of the mayfly. Before reaching the infective third stage, the larvae moult twice in the body of the invertebrate host (2 to 16 and20 to 36 days after infection at water temperatures of 13--15 degrees C). However, the development of the encysted infective larvae does not cease in the intermediate host and the larvae may undergo one more moult. One of two moults then occur in the intestine of the definitive host (Phoxinus phoxinus) (depending on the fact whether it was infected with third- or fourth-stage larvae) before the larvae attain the maturity. The development of R. phoxini in the definitive host lasts about two months.


Morphological determination of the age of Cysticercus bovis in very young calves with cysticercosis.

Characteristics and measurements are given for early developmental stages of Cysticercus bovis. The data emerging from our study indicate that the age of a one to two month-old larva from a spontaneous infection can reliably be determined in histological sections. On these grounds we have been able to determine that the cysticercus infection in the two calves (aged 21 and 27 days respectively) had been acquired prenatally.


Influence of microclimate on the life cycle of the common tick Ixodes ricinus (L.) in thermophilic oak forest.

Under conditions of the South Moravian thermophilic oak forest (Valtice near Breclav), the life cycle of the common tick Ixodes ricinus was studied by continuous recording of main elements of microclimate (temperature and humidity) in three different biotopes: forest, margin of the forest and meadow. Simultaneously conditions and the process of tick hibernation were studied in four soil layers (surface, depths of 10, 20 and 30 cm). Observations made in the winter and vegetation periods were assessed by mathematical-statistical tests. Results obtained in the forest biotope and at its margin are presented in this paper; results from the meadow biotope will be published separately.