Liver tumors and oral contraceptives.

A possible causal relationship between oral contraceptives and liver cell adenomas has been postulated in the recent literature. In this presentation three additional cases are reported to support the existence of such an association. The possible etiologic causes for this newly described condition and specific diagnostic procedures for its accurate diagnosis are presented.


Conservative treatment of endometriosis externa: the effects of methyltestosterone therapy.

Twenty-four women with documented endometriosis externa were treated with methyltestosterone. Twenty-one of these patients desired fertility and three conceived (one after methyltestosterone therapy alone, two after conservative operation followed by methyltestosterone treatment). Ten patients later required surgical therapy for recurrence of pain, although all but one patient had initial relief of pain (3 to 6 months after therapy). These results of therapy are contrasted to those of similar studies in the literature in which methyltestosterone and other agents were used.


Testicular function in patients with familial Mediterranean fever on long-term colchicine treatment.

Sperm counts and hormonal studies were carried out in six patients with familial Mediterranean fever who were receiving long-term colchicine therapy. The duration of therapy ranged between 7 and 31 months. In all subjects, spermograms, testosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin levels were within normal limits.


Intraoperative internal spermatic vein phlebography in the subfertile male with varicocele.

Intraoperative internal spermatic vein phlebography was performed in 20 subfertile patients with a varicocele; 10 patients with varicoceles and left-sided indirect inguinal hernias without fertility problems served as controls. Phlebography was carried out during surgery with the patient supine and in a 45 degree anti-Trendelenburg position to stimulate an "erect" posture. In all 25 patients with a varicocele, valvular insufficiency was demonstrated at the renal-spermatic vein junction. When visualized, the position of the left adrenal vein in all instances was medial to or opposite the renal-internal spermatic vein confluence. This observation, reinforced by simultaneous determinations of cortisol levels in the internal spermatic and antecubital veins, practically excluded the validity of the theory of adrenal hormonal suppression of testicular tissues. In 40% of subfertile patients with a varicocele, double internal spermatic veins and reflux to the distended external spermatic (cremasteric) venous plexus were demonstrated. In no instance were such phenomena observed in the control groups. The not-infrequent failure of operative correction of varicocele seems to relate directly to such overlooked pathology. Broad clinical application of operative phlebography, especially in recurrent, persistent, or clinically advanced cases, will detect such anomalies and should reduce significantly the operative failures in the surgical correction of varicocele.


The bipolar needle for vasectomy. I. Experience with the first 1000 cases.

A battery-powered, bipolar electrocoagulator has been specifically developed for sealing the cut ends of the divided vas at vasectomy. With a minimum of electric power, the electrocoagulator destroys only the mucosa and one or two muscle cell layers of the vas, which leads to optimal fibrosis of the cut ends. This instrument has been used in more than 1000 vasectomies without a known failure and with a minimum of complications. An analysis of these cases is reported with emphasis upon the method's success in sealing the vas.


Hormone studies in a gynandroblastoma.

Plasma gonadotropin, testosterone, androstenedione, and estradiol levels were determined before and after removal of a 37-pound gynandroblastoma from an 18-year-old virilized, mentally retarded female. Testosterone and androstenedione levels preoperatively were in the normal female range and fell dramatically after castration. Histologic examination showed active atypical granulosa and Sertoli elements. The hormonal data obtained do not account for the marked virilization observed.


Investigation of the occurrence of a contraceptive tetrapeptide in hamster embryos.

The synthetic tetrapeptide H-Thr-Pro-Lys-OH, the extract of two-cell hamster embryos, and the oviductal contents devoid of embryos failed to show any in vivo antifertility activity. In addition, the tetrapeptide was not found in the biologic preparations of embryo extract and remaining oviductal contents. These findings are not in agreement with those of previous reports.


Sperm motility within the mammalian epididymis: species variation and correlation with free calcium levels in epididymal plasma.

The region within the epididymis where spontaneous sperm motility first appeared and the extent of later motility within that organ, as shown by microscopic observation of undiluted samples, varied with the species. In the rat, mouse, and hamster, little sperm motility was present. In other species, spontaneously motile sperm were obtained from the caput (rabbit) and corpus (bull and man) regions of the epididymis. Samples from the cauda region of the epididymis were found to contain many motile sperm in the rabbit, bull, and especially man, where most of the sperm were intensely motile. There was a correlation between the amount of free calcium surrounding the sperm within the cauda epididymidis of a given species and the level of sperm motility therein. An inverse relationship was also found between the free calcium concentration in the cauda epididymal plasma of a species and the later inducibility of motility in diluted sperm from that species by calcium ion.


Potentially deleterious effect of cornstarch glove powder in tubal reconstructive surgery.

Even with the most painstaking techniques, cornstarch granules used as surgical glove powder are deposited in the abdominal cavity during laparotomy. In tubal reconstructive surgery, aimed at the elimination of fibrous adhesions, this deposition may have undesirable consequences. After a successful operation, starch particles introduced in the abdominal cavity may result in the formation of new adhesions. It is therefore desirable to develop an alternative, completely nonreactive, glove powder.


[Analysis of the interstructural relationships in the brain by the method of bioregulated micropolarization].

In chronic experiments on cats, automatic regulation of polarizing current, monitored with the EEG changes, aided to study elements of the cerebral selfregulating system. The method proved effective for influencing the functional state of the structures to be regulated which revealed itself in long-lasting shifts of theta-rhythm, in changes of excitability and readjustment of EPs. Three types of connections between the temporal cortex and a number of cerebral modulating structures: rigid (positive and negative) and flexible those, were revealed. The active inhibition was accelerated with the bioregulated micropolarization of temporal cortex and hypothalamus on extinction of alerting response.


[Functional organization of the reticulo- and vestibulospinal synaptic projections of the lumbar motor neurons in rats].

Synaptic events evoked by in lumbar motoneurons ally antidromic by stimulation of identified reticulo- and vestibulo-spinal neurons were studied in the rat. Monosynaptic actions produced by fast-conducting reticulo-spinal fibers were found in different hind-limb motoneurons innervating proximal and distal flexor and extensor muscles. Vestibulo-spinal projections contained relatively few fast-conducting fibers and produced mainly polysynaptic actions in hind-limb motoneurons. The convergence of reticulo- and vestibulo-spinal synaptic influences in different motoneurons was demonstrated.


[Composition and excitability of afferent fibers of the pelvic nerve in cats].

The afferent fibers excitable by pelvic nerve stimulation were as follows: A (81 m/sec), A (59.6 m/sec), A (45.3 m/sec), A (17.9 m/sec), A (31.6 m/sec), B (11.3 m/sec). We failed to find C fibers. Analysis of the distribution of fibers showed that the majority of them entered the S2 dorsal root (DRS2). The fast-conducting fibers (Abeta1 and Abeta2) were found at DRL7--DRS2. The number of slow-conducting fibers increased in caudal direction. The most abundant in the pelvic nerve are Abeta3 fibers, and somewhat fewer in number are Abeta and Agamma fibers.


[Neuro-hormonal mechanisms of hypothalamic influences on the tonus of cerebral vessels].

In anesthetized cats, stimulation of supraoptic nuclei (SON) and dorso-lateral hypothalamus (DLH) led to cerebral vasoconstriction if not prevented by alpha-adrenoblocking drugs. The SON stimulation entailed activation of both the synthesis and the transport of neurosecretory substances and increased the neurohormone release into the blood flow. Delayed ("hormonal") vasoconstrictory responses occurred in these experiments. Stimulation of the preoptic area evoked moderate cerebral vasodilatation, later decreased or blocked by atropine. Neurohormone (vasopressin) seems to participate in the vasoconstriction evoked by the SON stimulation.


[Adaptation and disadaptation of the myocardium of rats trained to hypoxia].

Adaptation to oxygen deficit resulted from training of rats to hypoxia (8--9% O2) at the normal atmospheric pressure, during 3 weeks. Subsequent 2-week training decreased the resistance to hypoxia (disadaptation). Perfusion of the isolated hearts of adapted and disadapted animals at anoxic regimen together with the recording of the systolic pressure in the left ventricle, the rhythm, glucose uptake, lactate excretion, coronary blood flow, and the histochemical data on SDH, MDH, LDH, and hydroxibutyric DH, as well as the electron microscopy of the left ventricle mitochondria, indicate that the range of compensation reactions increases in adapted rats and decreases in disadapted ones.


[Hemodynamic reactions in cats exposed to physical loading].

Cats were trained to pull with a force equal to 50--200% of their body weight. The mean arterial pressure and heart rate increased during the exercise. Pressor response was due to the increase of peripheral vascular resistance, as the cardiac output was constant or even decreased. Blockade of vegetative nervous system led to a 2--3 fold decrease of the pressor response. The conditioned stimulus for "work" had no effects in intact cats, but evoked obvious pressor response in curarized cats. Mechanisms of the vegetative changes during static work are discussed.


[Blood supply in the arterial and venous bed of submaxillary muscle of frogs].

The velocity and morphometric parameters of blood flow in arterial and venous bifurcations of the trunks with diameter less than 85 microns in the frog m. submaxillaris were somewhat different as the angles of the braches II, the length of the vessels, and the bifurcation coefficient were greater in arterial part than in the venous bed. Due to this, the velocity in the arterioles was higher than in veins. According to the Pouiseulus equation, the pressure difference between arterioles and veins was 8.5 torr. About 44% of this difference was due to arterial vessels, about 36%--to the capillaries, pre- and post-capillaries, and about 20%--to the veins.


[Functional stability of the cerebral circulatory system].

Functional stability of the cerebral circulation system seems to be based on the active mechanisms and on those stemming from specifics of the biophysical structure of the system under study. This latter parameter has some relevant criteria for its quantitative estimation. Analysis of common data on various effects upon cerebral vessels shows an essential difference between the functional stability and the idea of "autoregulation of the cerebral circulation". The data obtained suggest that the essential part of the mechanism for active responses of cerebral vessels which maintains the functional stability of this portion of the vascular system, consists of a neurogenic component involving central nervous structures localized, for instance, in the medulla oblongata.


[Relationships between central and local mechanisms regulating hemodynamics].

The quantitative analysis of hemodynamic shifts during cardiovascular responses to stimulation of central neural structures, and recording of electric activity from the sympathetic fibers elucidate different links in the complex mechanism of the hemodynamic control. Monosynaptic connections of the sino-aortic zone with some structures of the bulbar level seem to contain relevant information on the blood pressure and the gas content. Differentiated modulated influences project from the cerebellum to the bulbar level, and complex interrelationships of local metabolic and central reflex mechanisms occur during acute hypoxic hypoxia.


[Relationship between central and peripheral mechanisms in regulating capacitance vessels].

In acute experiments on cats, responses of the resistance and capacitance vessels of the spleen and hindlimbs to local electric stimulation of the medulla oblongata, of the sympathetic nerves, and pressor reflexes during different pressure of the venous outflow, were studied. No structures were revealed which could selectively affect the capacitance vessels. The bulbar structures affected both the resistance and the capacitance vessels. The reflex responses aof the pre- and post-capillary portions of the vascular bed could be different, the transmural pressure being one of the factors for dilatory responses of the capacitance vessels. The different responses of the capacitance vessels could occur on account of both local and central mechanisms, their participation, however, being unequal.


[Shifts in systemic hemodynamics, local blood flow and brain temperature during stimulation of its structures in a chronic experiment].

Electric stimulation of the midbrain reticular formation, of the anterior and posterior hypothalamus of unrestrained cats entailed local raise of cerebral temperature, increase in the local blood flow, and various changes of the central arterial and venous pressure. The stimulation parameters were lower than thresholds for motor responses. The threshold and suprathreshold stimulation of the stem structures led in 60% of cases to diminishing of the local cerebral blood flow together with the pressor shifts in arterial pressure and the raise of local cerebral temperature. The diminishing of the cerebral blood flow contrdictory to increasing demands of the brain tissue for energy supply, could be accounted for by the generalized excitation of the sympatho-adrenal system and indicated inadequacy of the electric brain stimulation when studying hemodynamic components of the emotional-behavioral responses.


[Hemodynamic features of the response to stimulation of the subcortical nuclei of the striopallidal system].

In cats, stimulation of caudate nuclei, putamen, and globus pallidus revealed a weak reactivity and excitability, low lability, inconstancy, and small alterations of the arterial pressure and heart rate as compared with the hypothalamic effects under similar conditions. These data and juxtaposition of hemodynamics and complex behavior singled out the striopallidar nuclei as a separate and relatively independent level of the centra regulation of circulation.


[Functional state of the vasomotor center in the presence of afferent influences from reflexogenic zones].

Redundant afferentation from reflexogenic zones of the lung and skeletal muscles alters effects of electric stimulation of the midbrain reticular formation and posterior hypothalamic nucleus in the cat due to readjustment of the cortico--subcortical interrelationships and to an increase in the excitability of the brain structures. The data suggest that the functional activity of the vasomotor center depends on the character of afferentation from different reflexogenic zones.


[Identification and study of sympathoactivating neurons of the medulla oblongata].

The neurons with descending axons which activate the lateral horn sympathetic preganglionic (vasomotor) neurons were searched in the lower brain stem of the cat. Localization of these sympathoactivatory neurons in the limit zone of medulla was outlined by means of scanning stimulation. The identification of single bulbar sympathoactivatory neurons was based on the recording of their antidromic discharges elicited by stimulation of descending sympathoactivatory pathways with conduction velocity about 4--8.9 m/s in the dorsolateral funiculi of the cervical spinal cord. The neurons studied have a very low frequency spontaneous discharges (0.1--1.0 imp/s) unrelated with cardiac and respiratory cycles. The alterations of spontaneous discharge frequency were in strict correlation with pressor phases of Maer waves and pressor reflex reactions. The inhibitory effects of the baroreceptor nerve stimulation on spontaneous and elicited discharges of these neurons were never seen. A possible role of the sympathoactivatory neurons identified as an output elements of the bulbar "vasomotor" centre is discussed.


[Further study of the descending sympathoactivating pathways of the dorsolateral funiculus of the spinal cord].

The localization and conduction velocities of descending pathways which activate the different groups of sympathetic preganglionic nerons were studied in the cat cervical spinal cord. Certain evidences have been obtained that the fibres located near the dorsal surface of the dorsolateral funiculi with conduction velocities about 24--29 m/sec. can activate the ventral horn preganglionic neurons monosynaptically. In contrast to previous ideas, the sympathetic preganglionic neurons of the lateral horns seem to be activated not by different but by a single group of descending fibers with the conduction velocity 4--8.9 m/sec and localization in more ventral portions of the dorsolateral funiculus. The transmission from these fibers to the sympathetic preganglionic neurons of the lateral horns occurs in two ways: oligosynaptically (probably, disynaptically) and polysynaptically through a more complicated interneuronal chain. The sympathetic preganglionic neurons with unmyelinated axons, localized in the intermediate zone, for the first time were shown to be activated polysynaptically, probably via the same ways as the lateral horn neurons.


[Effect of neuroactive aminoacids on central mechanisms of vascular regulation].

In cats and rats, GABA and glycine depressed pressor vasomotor reactions and responses of sympathetic nerves to stimulation of the medial and vestibular nuclei of the bulbar reticular formation. These drugs depressed vasomotor responses to direct stimulation of the spinal lateral horns. GABA reduced the activated bulbo-spinal influences and inhibition of responses of the "spinal" vessels to stimulation of the solitary tract nucleus and paramedian reticular nuclei. GABA (100--200 mg/kg) depressed vasomotor responses to mechanoreceptor stimulation and increased the responses to chemoreceptor stimulation while glycine did not change them. GABA and glycine exerted no adrenolytic or myotropic effects. GABA did not affect identically the transmission in different sympathetic ganglions. Glycine did not alter the ganglionic transmission. The site and mode of the neuroactive aminoacids effect on the central mechanisms for vasomotor regulation are discussed.


[Effect of neuroactivating amino acids on the system activating sympathetic preganglionic neurons].

In anesthetized cats, the bioelectrical responses were recorded in T3 white ramus during stimulation of intercostal nerve of the T3 segment and of descending pathways (dorsolateral funiculus) of the C5 segment. The effects of GABA, glycine (and its synaptic antagonists picrotoxin and strychnine), and of glutamic acid on different components of the responses were not identical which suggested different sites of the activity effects of glutamic acid and of the inhibitory effects of GABA and glycine in the central pathways for activation of the sympathetic preganglionic neurons.


[Changes in coronary circulation following reflex excitation of the sympathetic nervous system].

The patterns and efferent mechanisms of coronary blood flow reactions in cats following sympathetic activation after hemorrhage and carotid occlusion, were studied. Like in other vascular regions, the sympathetic activation led to alpha-adrenergic coronary constriction which was particularly clear after blocking of neurogenic and metabolic vasodilatory factors (beta-blockers, atropine). The significance of myogenic constrictory component was elucidated as well.


In vitro immunization against tumour-associated antigen of methylcholanthrene-induced sarcoma.

Lymph node cells obtained from B10 mice were sensitized in vitro on monolayers of syngeneic methylcholanthrene-induced sarcoma cells. The in vitro sensitized LNC displayed specific cytotoxic and inhibitory effects on sarcoma cells used for sensitization. The effects were detectable by visual counting and inhibition of 3H-thymidine incorporation. The inhibition observed after admixture of in vitro sensitized LNC was more effective than inhibition produced by LNC from mice immunized with the same syngeneic sarcoma in vivo. Solubilization of sarcoma cells with 3M KCl gave rise to antigenic preparation which was unable to sensitize syngeneic LNC under experimental conditions used.


Isozymic forms of some energy metabolism enzymes during oncovirus-induced cell transformation.

Kinetic studies of changes in isozymic forms of hexokinase, lactate and malate dehydrogenase and in total hexokinase activity during viral carcinogenesis were carried out. The test systems were rat embryo fibroblasts infected with an oncogenic variant of human adenovirus type 12 and an infectious adenovirus type 6, intact REF cultures in different stages of growth (log and stationary phase), and hamster sarcoma A12 and rat reticulosarcoma 321-RRS cell cultures. Molecular isozymic forms of the stated enzymes and total hexokinase activity in the nuclear fraction and cytoplasm of cells in culture were investigated. It was shown that infectious and oncogenic viruses evoked a rearrangement in the spectrum of the energy metabolism enzymes in the nucleus and cytoplasm. The changes appeared in the first days of the contact of REF culture with the virus, and were more pronounced after the oncogenic rather than the infectious virus. The analysis of changes in isozymic forms of the enzymes under study in virus A12-infected REF cultures and in hamster sarcoma A12 and reticulosarcoma 321-RRS cells growing in vitro revealed that they had some features in common. The most pronounced changes were found with hexokinases. The changes described can serve as objective signs of cell transformation.


Electrophoresis of cells at the interface liquid/liquid.

A new method for measuring the mobility of cells in an electric field is described. The movement of cell samples is carried out at the interface: isotonic phosphate buffer (pH 7.37, mu = 2.214) with Ficoll--the same phosphate buffer without Ficoll. After the voltage is switched on, cells are moving in parallel along the interface. The movement is accomplished by sliding on the denser of these two layers in a flat cuvete. Several samples of cells may be applied and their relative displacement compared. The method was established for human erythrocytes and tannined human erythrocytes.


The determinants of marital fertility in the United States, 1968-1970: inferences from a dynamic model.

Criticizing the static assumptions of previous socioeconomic and microeconomic models of marital fertility, particularly regarding the sequential and stochastic facets of family building, this paper advocates a dynamic perspective. Of particular concern is the assumption of equilibrium family size made by those who employ the static perspective. The equilibrium family size assumption implies that the parameters relating social and economic variables to fertility will be similar for all births, regardless of order. To test this assumption of constancy, a two-equation model of fertility and female employment is introduced. Contrary to the static perspective's implication of constant effects, substantial parity differences in the estimates of parameters for both equations are reported, as are several differences between blacks and whites. On the basis of this evidence, I conclude that the static decision-making framework should be replaced by a dynamic approach to marital fertility.


The effects of demographic factors, family background, and early job achievement on age at marriage.

National data for ever-married men age 20 to 65 in March 1973 are utilized to estimate least squares and log-linear structural equation models of age at marriage. We demonstrate that most characteristics of family background (including both the family structure and its socioeconomic standing) are irrelevant in their effect on age at marriage. Intercohort trends are not explicable with reference to the changing socioeconomic, ethnic, or nativity compositions of the cohorts. Regional differences in age at marriage have persisted over the years in only slightly diminished form and cannot be explained by reference to the nativity, ethnic, or socioeconomic compositions of the regions. Early job status relates only weakly to age at marriage. Only those activities that are time-consuming or otherwise disruptive of the smooth operation of normal life-cycle processes during the transition from adolescence to adulthood (such as college attendance and service in the military) seriously affect the age at which a man marries.


The rise in divorce rates, 1960-1974: age-specific omponents.

This paper uses vital statistics data from 15 states in the Divorce Registration Area to decompose into age-specific components the rise in the aggregate divorce rate between 1960 and 1974. While women in their twenties comprise only about 20 percent of the married population, they appear to have contributed over 60 percent of the growth in the divorce rate during the decade of the sixties,


Occupational status scores: changes introduced by the inclusion of women.

This paper examines the impact of women's labor force participation on occupational scores by comparing occupational status scores based on the characteristics of the 1970 male labor force with a set of occupational status scores based on the characteristics of the total 1970 labor force. Although the two sets of scores are highly correlated, important differences are found in the scores for specific occupations as well as for major occupational groups. Using the tradional list of 12 major occupational categories, we find that the positions of clerical workers and craftsmen are reversed when status scores are derived from data on all incumbents in the labor force rather than on male incubents alone. The paper suggests that, with the increased participation of women in the labor force and the concomitant change in the sex composition of the work force, the traditional approaches to the measurement of occupational status based solely on male incumbents may no longer be valid for examining the occupational hierarchy of contemporary American society.


The simultaneous examination of economic and social factors in destination selection: employing objective and subjective measures.

This research examines the role of social and economic factors in the past selection of destinations made by migrants living in Rhode Island. Results indicate that social ties play a more important role in the selection of destinations with low levels of opportunity than they do in the movement to high opportunity areas. An important aspect of the study was the simultaneous investigation of both objective and subjective measures of social and economic factors in the selection of low and high growth destinations. The analysis suggests that the simultaneous consideration of objective and subjective factors provides a more refined accounting of the potential influence of social and economic factors in the selection of destinations. The findings hold when age is introduced as a control.


The urban distribution of headquarters and branch plants in manufacturing: mechanisms of metropolitan dominance.

The proposition that ties between home offices and branch plants constitute a form of metropolitan dominance is evaluated by examining the dependence of these two forms of manufacturing organization on selected characteristics of the 110 largest SMSAs. The predictor variables in the analysis are measures of industry composition, population size, and regional location, factors which past research has shown to be indicators of rank in an urban hierarchy of dominance. The data generally support the hypothesis in revealing that headquarters locate in large, diversified urban areas, whereas branch plant employment is highest in small, economically specialized places. Both headquarters and branch plant activity proved to be associated with the percent of the SMSA labor force employed in manufacturing, however. The suggestion drawn from earlier studies, that specialization in metropolitan financial-commercial functions should be related to the headquarters' presence, receives only mixed and ambiguous support in this investigation.


Estimating demographic characteristics using the ratio-correlation method.

Studies of the relative accuracy of methods of estimating the population at the substate level have generally found that the greatest degree of accuracy is provided by the ratio-correlation, or regression, method. This paper reports on research aimed at evaluating the effectiveness of this method in estimating the age and race composition of populations at the substate level. In addition to the basic multiple regression equation variants such as stratification and the averaging of estimates from simple regression equations are also tested. Surprisingly, for Virginia localities the most satisfactory results are generated by the nonstratified multiple regression equation.


An investigation of the age of an alleged centenarian.

At times, persons have been reported as living to extremely advanced ages such as 130, or even higher (McWhirter and McWhirter, 1977, p. 26; Medvedev, 1974; Merrill, 1976). However, controlled studies of closed groups like Civil War veterans (Myers and Shudde, 1955) have not shown any persons surviving beyond age 110, when age has been reasonably verified. It seems, therefore, highly plausible that reports of extremely advanced ages at death reflect exaggerations of age rather than reality. This note reports a case history which supports this view and illustrates how ages can be verified using available census data.


Dapsone-induced distal axonal degeneration of the motor neurons.

Dapsone proved to be effective treatment in a patient who suffered from erthema elevatum diutinum. Serious neurological side effects, however, appeared. The basic mechanism appeared to be a distal axonal degeneration of the motor neurons. Sensory conduction studies  were normal in five consecutive EMG examinations. A diagnosis of anemia pernicosa was also made bu the blood values returned to normal after starting B12-vitamin therapy. Penicous anemia seemed not be an etiological factor in the polyneuropathy of our patient because we were not able toshow any damage to the sensory axons.


Scintigraphic evaluation of Kaposi's sarcoma.

10 patients with clinical and histopathological evidence of Kaposi's sarcoma were evaluated with 99Tcm-pertechnetate and 67Ga-citrate scintigraphs. Combined studies using these radionuclides are useful aids in investigating, detecting and following-up Kaposi's sarcoma and any associated lymphoma or other malignancies.


Keratosis circumscripta. A distinct dermatological entity or a variant of psoriasis?

45 cases of a dermatosis believed to be the same as those originally described by Schrank in 1963 among Nigerian children of Yoruba ethnic origin and named keratosis circumscripta by him are reviewed. All evidences point towards the fact that the dermatosis observed by us as well as those originally described by Schrank are a variant of psoriasis possibly modified by environmental factors. It has therefore been suggested that this dermatosis should not be regarded as a new dermatological entity, and that the original names should be modified. To reflect the original work done by Schrank as as well as the true clinical picture of this dermatosis, the nomenclature psoriasis circumscripta with palmo plantar keratosis is suggested.


[Association of verruciform acrokeratosis with congenital poikiloderma as a dermatologic entity].

An 18-year-old young man, presents multiple areas of poikilodermia since 1 year of age, and papules like flat warts essentially on the back of his hands and feet, since 10 years of age. The examination of 16 of his closest relatives led us to discover 1 case of poikilodermia and acrokeratosis verruciformis, 1 case of poikilodermia and 3 cases of acrokeratosis veruciformis. Observations on the association of poikilodermia and acrokeratosis verruciformis have already been reported in the literature as well as comparable morphological fact, but without family lesions and without histological examinations. Thus, rare patients are presenting both congenital pikilodermia and acrokeratosis verruciformis. In the families of 3 of these patients, some members are similarly afficted, whereas others present independently either poikilodermia or acrokeratosis. In several reports in the literature and in our cases, the histological picture of verruciform papules was the same as Hopf's acrokeratosis verruciformis. These particularities led us to consider the association of Hof's and Thomson's diseases as an entity.


Dystrophia unguium mediana canaliformis.

An attempt is made to give a sort of classification of the median nail dystrophies. 6 own cases are reported. As there are many morphological transitional forms, it is for the present recommended to call all those forms dystrophia unguium mediana canaliformis.


Schizophrenia and albinism.

A female albino with squamous cell carcinoma and schizophrenia is reported. The association of schizophrenia and albinism is exceptionally rare; the observation that schizophrenia is characterised by hypermelanosis is questioned.


Effect of pimozide and sulpiride on the release of LH and FSH by pituitary cells in culture.

A culture of dispersed rat anterior pituitary cells was used to test the ability of pimozide and sulpiride to affect the basal gonadotropin release and their effects on the response to Gn-RH. Sulpiride did not alter either the basal or the Gn-RH-induced release of LH, and the lowest dose (500 ng/ml) seemed to potentiate the Gn-RH-induced FSH release. On the other hand, both doses of pimozide (100 ng/ml and 10 microgram/ml) significantly inhibited the release of FSH and LH induced by Gn-RH but did not affect the basal release of the two gonadotropins. From these results it is evident that pimozide, at the doses used, is a powerful inhibitor of the pituitary response to Gn-RH in vitro. Sulpiride on the other hand had no effect on the pituitary response to Gn-RH in vitro, except on FSH release, using the lower dose.


Thyroid hormone effects on protein and RNA metabolism in the rat anterior pituitary.

Thyroidectomy reduced the incorporation of [3H]amino acids into total rat pituitary proteins as well as into electrophoretic fractions corresponding to growth hormone (GH) and prolactin. A single injection of thyroxine (200 microgram/kg) reversed the effects of thyroidectomy on the GH (12 h) and prolactin (36 h) fractions. Evidence for a general increase in the rate of pituitary protein synthesis following this treatment was less conclusive, but two injections of the hormone had a definite stimulatory effect. [3H]Uridine uptake by the pituitary and its incorporation into RNA were elevated for 2 weeks after thyroidectomy. Thyroxine failed to suppress these changes for at least 36 h after injection. Actinomycin C (400 microgram/kg) inhibited pituitary RNA synthesis and blocked the stimulatory effect of thyroxine on amino acid incorporation into the GH fraction. These results indicate that thyroid hormones: (1) promote pituitary protein synthesis, probably as a consequence of their effects on somatotrophs and lactotrophs; (2) exert a stimulatory effect on GH synthesis by affecting transcription.


Neonatal ultrasounds elicited by odor cues.

Ultrasounds were monitored from neonatal rats following placement on 1 of 5 types of bedding material. Odors associated with the home cage or an adult male inhibited neonatal ultrasonic signaling. Odors associated with a novel lactating female elicited initially high rates of signaling, the rate lowering across the age range of pups tested. Odors associated with a novel virgin female or with an absence of animal odors elicited increasing rates of signaling across the age range tested.


Effects of differential early experience upon parental behavior in Mus musculus.

Infant mice, reared with both parents were subjected to 1 of 4 different early experience contingencies at 3, 6, 9, and 12 days of age. Observation of parental behaviors following return of the pups to the nest revealed that mothers attended more to pups subjected to intermediate levels of stress, with the differences in maternal behavior persisting across the age span without change. Fathers exhibited marked changes in responsiveness to young across the ages observed, with their attention to young correlating directly with rate of ultrasonic calling by the young.


Locomotor activity and social behavior of old rats after preweaning undernutrition.

Rat pups were undernourished from birth to 25 days of age by giving them a nipple-ligated mother and a normal lactating mother for alternate periods of 12 hr/day, thus providing adequate full-time maternal care. Male and female rats undernourished neonatally had greater locomotor activity than controls in old age (16-20 months)mfemales were more activive than males, irrespective of neonatal undernutrition. At the age of 24 months, social behavior was recorded at various times of the day for pairs of male rats (1 previously undernourished and 1 control). With one minor exception, undernourished animals did not differ significantly from controls in the incidence of the various behavioral items that were scored. Neonatal social factors may compensate for possible negative effects of neonatal undernutrition on later social behavior.


Individual differences during the development of the domestic chick's attraction toward intermittent light.

Stable and persisting differences occur in the domestic chick's attraction toward normally preferred rates of intermittent white light in the vicinity of 4 flashes per second during the period around hatching when this preference develops. These differences are not linked to fluctuations in the test environment, high levels of indiscriminate responding toward flicker in those most attracted, the presence of an alternate rate preference in those least attracted, or to differences among chicks in arousal level or locomotor ability.


Ontogeny of brain catecholamine turnover and susceptibility to audiogenic seizures in DBA/2J mice.

We have investigated the relationship between catecholamine turnover and susceptibility to audiogenic seizures (AGS) in the developing DBA/2J mouse. Turnover of dopamine and norepinephrine was determined after administration of alphamethylparatyrosine at 3 weeks of age when nearly all mice (94%) exhibited AGS, at 6 weeks when only 30% were susceptible, and at 12 weeks when none developed seizures. Turnover of brain dopamine increased progressively from 236 ng/g/hr at 3 weeks to 389 ng/g/hr by 12 weeks of age. Norepinephrine turnover increased significantly between 3 and 6 weeks of age, then remained stable thereafter. Turnover times for each catecholamine did not change appreciably with maturation. Our results support the notion that susceptibility to AGS may be mediated in part by brain catecholaminergic mechanisms.


Relative aversion thresholds for shock in infant mice.

Using a spatial-preference technique, we tested separate groups of mice, 5, 7, 9, 11, 13, and 15 days of age, for escape and avoidance of a range of shock intensities administered from AC contant current and fixed impedance shock sources. With intensities ranging from 0 to .2 mA and 0 to 70 V for the respective sources, near asymptotic escape and avoidance were obtained at .1 mA and at 50 V for ages tested. Although few differences in the relative aversiveness of particular shock intensities were noted across ages with each source, the fixed impedance source produced more consistent avoidance than did the constant source. The findings suggest that the motivational properties of shock remain relatively constant throughout the early development of the mouse and that the technique employed in this study should prove useful in assessing possible age-related alterations in sensitivity to shock as a result of physiological or pharmacological manipulations.


Differential effects of handling on exploration in male and female rats.

In this study, sex differences in the exploratory behavior of handled and nonhandled animals were measured under conditions of both high and low stimulus variation. The apparatus used was a hole-board, which provided an exploratory response independent of ambulation. Significant effects of handling were found: nonhandled animals decreased head-dipping over days whereas handled animals maintained a high rate. Sex differences were also observed: patterns of head-dipping for males and females differed over days depending on whether objects was present (high stimulus variation) or absent (low stimulus variation) under the hole-board; females also head-dipped for  longer durations than males when objects were present; further, males and females showed completely opposite patterns of exploration depending on handling treatment and on level of stimulus variation. We conclude that handling differentially affects males and females, particularly as level of stimulus variability changes.


The role of diet in mother-infant reciprocity in the spiny mouse.

One-day-old spiny mouse pups responded preferentially to bedding soiled by lactating conspecifics fed the same diet as their mothers. Following this test, pups were fostered onto different-diet females. When retested at 84-96 hr of age, no preferences were shown for bedding soiled by a female fed the biological mother's diet vs bedding of a female fed the different diet. When tested again at 120-132 hr of age, however, the pups preferred the bedding associated with their foster mothers' diet. In a 2nd experiment, recently parturient females retrieved 1-day-old pups born of same-diet females faster than pups born to novel-diet females. These results indicate that pup preferences for chemical cues produced by lactating conspecifics can be altered by sufficient exposure to a 2nd female maintained on a different diet and that neonatal chemical cues, like maternal chemical stimuli, are diet-dependent.


The immunohistopathology of glomerular antigens. III. Increased mesangial actomyosin in experimental diabetes in the rat.

Antisera to rat smooth muscle actomyosin (AMY) and myosin localize in the rat glomercular mesangium. The width of mesangial staining for AMY is increased in rats diabetic for four months (p less than 0.01) and seven months (p less than 0.0005) compared with age-matched controls. Mesangial AMY staining of unilaterally nephrectomized control animals was moderately increased after seven months, whereas unilaterally nephrectomized diabetic rats had prominently increased AMY mesangial width at four months, when they were compared with intact diabetic animals (p less than 0.05). Thus, a distinctive alteration that is found in human diabetic nephropathy also occurs in experimental (streptozotocin) diabetes in the rat. Further, this alteration appears to be accelerated by the changes in nephron hemodynamics resulting from unilateral nephrectomy. While the function of mesangial AMY is unknown, it may be related to intrarenal regulation of glomerular ultrafiltration, which appears to be altered in diabetic nephropathy in man.


The effect of hyperglucagonemia on blood glucose concentrations and on insulin requirements in insulin-requiring diabetes mellitus.

The effect of elevated glucagon concentrations on insulin requirements and on blood glucose concentrations was studied in five insulin-requiring diabetic subjects during feedback control of hyperglycemia with an automated glucose-controlled insulin infusion system (artificial endocrine pancreas) for six to eight hours. Two levels of hyperglucagonemia were induced by means of constant intravenous infusion. Raising plasma glucagon concentrations to levels reported in poorly controlled diabetics (450 to 665 pg. per milliliter) did not alter total insulin requirements or blood glucose concentrations. Higher glucagon concentrations (850 to 1,050 pg. per milliliter) caused a modest (26 per cent) increase in insulin requirements and only a slight increase in mean blood glucose concentrations. These studies demonstrate that the degree of hyperglucagonemia found most frequently in insulin-requiring diabetics does not increase insulin requirements or decrease insulin effectiveness in patients given insulin in amounts appropriate to maintain euglycemia.


Impaired granulocyte adherence. A reversible defect in host defense in patients with poorly controlled diabetes.

When the ability of granulocytes from 10 poorly controlled diabetic patients with fasting hyperglycemia and no evidence of ketoacidosis (mean fasting glucose 293 +/- 20 mg. per 100 ml.; mean +/- S.E.M.) to adhere to a nylon fiber column was assessed, the number of adherent granulocytes from whole blood was only 53 +/- 6 per cent of the values observed in controls. After antidiabetic treatment for one to two weeks and lowering of fasting glucose levels (mean 198 +/- 29 mg. per 100 ml.), adherence improved significantly (p less than 0.01) in the diabetics; however, their values were still subnormal (diabetic 74 per cent +/- 8 of control; p less than 0.02). Adherence values before and after treatment correlated with the fasting glucose level (r = 0.88, p less than 0.001). These findings suggest that, in addition to previously reported abnormalities in migration and the ingestion and killing of bacteria, granulocyte adherence may also be impaired in poorly controlled diabetic patients. This functional abnormality correlates directly with the fasting glucose and is reversed by insulin treatment. A defect of this type may compromise the normal inflammatory response in some diabetics and impair their capacity to resist infection.


Interactions of obesity and glucose-stimulated insulin secretion in familial hypertriglyceridemia.

Plasma lipids and lipoproteins, glucose tolerance, plasma insulin response to glucose load, and liver function were examined in 81 relatives of 12 index cases with primary endogenous hypertriglyceridemia, hyperinsulinemia, and hepatic steatosis, as well as in 90 nonrelatives, including the spouses, as controls. Insulin hypersecretion (with or without glucose intolerance), endogenous hypertriglyceridemia, and abnormal liver function suggesting hepatic steatosis were shown to exist in the relatives mostly in combined fashion. Correlation analysis and stepwise multiple regression analysis revealed that the combined disorder developed on the basis of obesity. The incidence of diabetes mellitus was significantly high in the relatives (14.8 per cent) as compared with the normal Japanese population (3.5 per cent). Although the vertical transmission of the combined disorder was noted in almost all pedigrees, the frequency distribution analysis of insulin response, glucose tolerance, and plasma triglyceride showed the histograms of these variables similarly skewed to the right as compared with those of the controls, with no apparent bimodality. In view of the hitherto suggested role of insulin in triglyceride metabolism, it is concluded that hyperinsulinemia coupled with obesity seems to be the basic trait of this form of familial hypertriglyceridemia and hepatic steatosis, though the mode of transmission remains to be elucidated.


Characteristics of human erythrocyte insulin receptors.

Highly specific insulin receptors have been identified on human erythrocytes. A modification of the monocyte insulin radioreceptor technique permitted distinct separation of human erythrocytes with their bound insulin from the free insulin. When incubated with 80 pg. per milliliter of 125I-insulin (pH 8.0, 3.5 hours, 15 degrees C.), erythrocytes from 17 normal volunteers specifically bound 10 per cent (+/- 1.450 S.D.) of the total 125I-insulin. Less than 15 per cent of the total 125I-insulin bound was nonspecific. Binding of 125I-insulin to human erythrocytes was dependent on pH and temperature. Less than 5 per cent of the insulin available to the plasma membrane was degraded. Both calcium and magnesium enhanced 125I-insulin binding by 100 per cent but had no synergistic effect when mixed in a 1:1 molar ratio. Scatchard analysis of the binding data resulted in a curvilinear plot with characteristics typical of negative cooperative interactions between receptor sites and with an unoccupied site affinity constant of 0.1 X 10(8) M-1. Human erythrocytes have 2,000 insulin binding sites per erythrocyte with 14 sites per square micrometer of surface area. The readily available human erythrocyte, thus, has both specific insulin binding sites and binding characteristics similar to other human cell types. These studies have provided the basis for further clinical investigation of polypeptide hormone receptors on human erythrocytes.


Antiketogenic action of fructose in man.

The effect of fructose infusion (10 gm. every five minutes as a bolus followed by 0.5 gm. per kilogram X hours) on arterial concentrations and hepatic balances of ketones was studied in four juvenile diabetics 24 hours after the withdrawal of insulin. Arterial and hepatic venous concentrations of beta-hydroxybutyrate, acetoacetate, free fatty acids, fructose, and oxygen were measured. Hepatic blood flow was also determined. At constant rates of splanchnic fructose extraction, an 82 per cent diminution of the arterial hepatic venous concentration difference of the ketones was observed but the arteriovenous difference of free fatty acis rose moderately. Since hepatic blood flow was only slightly increased (17 per cent) there was no doubt that total hepatic ketone body formation was reduced. The magnitude of this antiketogenic action became apparent from the continuous fall of the arterial ketone concentrations. Since splanchnic oxygen uptake rose 40 per cent, it is suggested that the antiketogenic effect of fructose was due not only to enhanced re-esterification but also to accelerated oxidation of free fatty acids.


Reproducibility and comparative analysis of repeated intravenous and oral glucose tolerance tests.

We have developed a methodology for measuring the reproducibility of the oral glucose tolerance test (OGTT) and the intravenous glucose tolerance test (IVGTT) in normal subjects and in offspring of conjugal diabetic parents. Both groups of subjects revealed more striking correlations of several parameters of blood glucose and insulin secretion between two IVGTTs than between two OGTTs. Employing arbitrary criteria, we calculated a "reproducibility index" as a quantitative measure of blood glucose variability in each subject. No significant difference was found in the reproducibility of OGTT versus IVGTT, nor in normals versus the offspring. Only about 50 per cent of the tests in normals and in the offspring could be considered to be "reproducible." The offspring revealed greater correlations of several parameters, particularly insulin secretion, between the two IVGTTs and between the two OGTTs as compared with the normal group. However, the blood glucose variations tended to be considerably greater in the offspring from one to the other test.


Forearm hemodynamics and responses to exercise in middle-aged adult-onset diabetic patients.

Much of the difficulty in assessing the progress of diabetic angiopathy and effects of experimental modes of therapy arises from the lack of quick, simple, inexpensive, and noninvasive tests to perform on the circulatory system of human subjects. We report here on values obtained by the use of mercury-in-rubber strain gauge plethysmography on 15 middle-aged, adult-onset diabetics who had minimal clinical evidence of microangiopathy. Standard tests are described for assessing forearm vascular function at rest, during tonic exercise of the fingers, and after interrupted repetitive exercise of the fingers. When matched against a similar aged nondiabetic group, the diabetics had slightly higher forearm vascular resistance at each level of exercise, a marked reduction (approximately 50 per cent) in capillary filtration coefficient, which is believed to be related to vascular filtering surface area, and a slight reduction in venous capacitance at all levels of exercise. The method of mercury-in-rubber strain gauge venous occlusion plethysmography provides the clinician with a sensitive and inexpensive tool with which to follow the evolution of angiopathy in diabetic patients.


Aldosterone responsiveness in patients with diabetes mellitus.

Plasma aldosterone (PA) and plasma renin activity (PRA) were determined in 44 diabetics, of whom nine were normotensive but not nephropathic (group 1), 10 were hypertensive but not nephropathic (group 2), and 25 were hypertensive and nephropathic (group 3); they were kept in balance on a diet composed of 10 to 20 mEq. of sodium (Na) and 100 mEq. of potassium (K). Supine PA in group 1 was 38 +/- 7 ng. per deciliter, whereas in normals it was 24 +/- 2 ng. per deciliter (P less than 0.05); beyond that, neither supine nor upright PA or PRA differed significantly from normal in groups 1 and 2. By contrast, in group 3, supine PA was 13 +/- 1 ng. per deciliter and PRA 2.0 +/- 0.2 ng./ml. and upright PA was 39 +/- 7 ng. per deciliter and PRA 3.8 +/- 0.5 ng./ml., all significantly lower than those in the other groups (P less than 0.01). Nine patients, one in group 1 and eight in group 3, had low supine and upright PA and PRA; four had hyperkalemia. An additional nine patients in group 3 had low upright PA, with normal or low PRA; two had hyperkalemia. Of the 18 patients with low upright PA, K correlated with glucose (R = 0.46, P less than 0.05). These results suggest (1) the renin-aldosterone system generally responds normally in diabetics without nephropathy but responds subnormally when nephropathy is present, (2) hyporeninemic hypoaldosteronism is frequent in diabetics with nephropathy but may occur in the absence of clinical nephropathy, and (3) hyperkalemia in some diabetic patients may be secondary to hypoaldosteronemia and hyperglycemia.


The effects of Goldblatt hypertension on development of the glomerular lesions of diabetes mellitus in the rat.

Rats with classic Goldblatt (two-kidney) hypertension had diabetes induced by streptozotocin. After four months of diabetes, glomeruli of the unclipped kidney of hypertensive diabetic rats had markedly increased diabetic changes, including mesangial matrix thickening and mesangial immunoglobulin (IgG and IgM) and complement (C3) localization, when compared with glomeruli of the contralateral-clipped kidneys. Further, glomeruli of the unclipped kidneys of hypertensive diabetic animals had more mesangial thickening and IgG and IgM staining than glomeruli of normotensive diabetic rats. Although glomeruli of clipped kidneys in hypertensive diabetic rats had less mesangial thickening than glomeruli of normotensive diabetic rats, this did not reach statistical significance. However, these glomeruli did have significantly less IgG, IgM, and C3 staining compared with glomeruli of normotensive diabetic animals. Mesangial thickness in glomeruli of clipped and unclipped nondiabetic hypertensive rats did not differ from that in normal animals. However, there was less mesangial IgG staining in clipped than in unclipped kidneys of nondiabetic hypertensive rats or in kidneys of normal animals. We have interpreted these results to imply that alterations in nephron hemodynamics combine with the diabetic state to influence the rate of development of diabetic glomerulopathy in rats.


Restoration of the acute insulin response by sodium salicylate. A glucose dose-related phenomenon.

Adult-onset diabetics have markedly diminished or absent acute insulin responses to glucose that can be partially restored by sodium salicylate infusion. To determine whether this restoration of the acute insulin response is glucose dose dependent and whether complete restoration can be achieved, adult-onset diabetics with a mean fasting plasma glucose value of 216 +/- 20 mg. per deciliter (x +/- S.E.) were stimulated with various doses of intravenous glucose. Restoration occurred in a glucose dose-dependent manner. Complete restoration could not be achieved with the maximal tolerable glucose dose (80 gm.). Second phase insulin secretion also improved in a glucose dose-dependent manner. These findings are compatible with the hypothesis that defective insulin secretion in adult-onset, hyperglycemic diabetics is not due to absolute deficiency of insulin but may be a result of defective recognition of glucose signals by pancreatic B-cells--a defect that can be partially reversed by sodium salicylate.


Enhancement of the mitochondrial Ca2+ uptake rate by phenethylbiguanide and other organic cations with hypoglycemic activity.

At concentrations below 50 micronM, phenethylbiguanide enhanced the initial rate of enertized Ca2+ uptake into energized guinea pig liver mitochondria by as much as 45 per cent; Ca2+-stimulated O2 uptake increased in parallel. The biguanide concentration that enhanced Ca2+ uptake maximally was at least 15 times lower than that required for 50 per cent inhibition of respiration. Kinetic studies indicated that the enhanced rate of Ca2+ transport resulted from an increase in Vmax, while Km for Ca2+ was unaffected by the biguanide. Several other organic cations known to lower blood sugar in intact animals or to block the hepatic gluconeogenic response to glucagon also enhanced the mitochondrial Ca2+ uptake rate; three of these compounds did not inhibit respiration even at high concentrations. One organic cation, triethyltin, which is a potent respiratory inhibitor that does not affect blood sugar, had no effect on Ca2+ uptake. We concluded that enhancement of the mitochondrial Ca2+ uptake rate is related to the mechanism of therapeutic blood sugar lowering by these drugs, probably by impairing the gluconeogenic response of the liver to glucagon.


The response of gastric inhibitory polypeptide (GIP) and insulin to glucose in duodenal ulcer patients.

The response of Gastric Inhibitory Polypeptide (GIP) and insulin to a 50 g oral glucose tolerance test (OGTT) and an intravenous glucose infusion (IVGI), which copied the changes in plasma glucose concentrations during the OGTT, were measured in 10 patients with duodenal ulcer and in 10 healthy control subjects. The mean responses of GIP and insulin to OGTT were significantly increased in the ulcer patients. During IVGI the responses were normal. The degree of increased GIP response in the patients was positively correlated with the plasma glucose increase during the OGTT. It is postulated that the increased GIP secretion is related to a faster glucose absorption due to rapid gastric emptying in duodenal ulcer patients. No correlation was found between basal and peak gastric acid output and the GIP response in the patients. The data demonstrate that GIP secretion is not defective in duodenal ulcer patients.


HLA phenotypes and diabetic retinopathy.

The incidence of HLA antigens B8, BW15, DW3 and DW4 was found to be significantly increased in 99 patients with growth onset, insulin-dependent diabetes of more than 15 years duration. Different degrees of retinopathy were seen in 75% of the patients. No significant correlation between the presence of specific HLA alleles and the stage of retinopathy was found. We have discussed the possibility that all patients who develop diabetes have identical disease-predisposing genes, irrespective of their HLA alleles. If this was the case, the HLA phenotype would not determine the risk of developing diabetic retinopathy.


Insulin receptors on monocytes of young healthy persons correlated with glucose tolerance and insulin sensitivity.

We have studied in normal man the interrelationships between insulin binding to monocytes, glucose tolerance and insulin sensitivity. In 25 young healthy persons we found a significant positive correlation between insulin binding and glucose disappearance rate both after glucose (R = 0.68, p less than 0.001) and insulin (R = 0.49, p less than 0.02) given intravenously.


Branched chain amino acid metabolism in the retina of diabetic rats.

Diabetes is known to produce increased levels of the branched chain amino acids in plasma, heart and muscle as well as increased oxidation of [14C]-leucine by nerves and muscles from rats. Plasma and retinas from streptozotocin diabetic rats had significant elevations in branched chain amino acid levels compared to control. Retinas from diabetic rats have been found to oxidize significantly more of the branched chain amino acids, leucine, isoleucine and valine than did control retinas when incubated in media containing 16.5 mmol/l glucose. Neither the extracellular space nor the tissue pool of leucine was significantly different in the two groups. The addition of 19 amino acids, at normal plasma concentrations, to the incubation media resulted in 80 percent suppression of leucine oxidation without significant change in incorporation of [14C] into protein. These results suggest that the major role for the branched chain amino acids in the rat retina is in protein synthesis which is not affected by short-term diabetes.


Roles of insulin and glucose in the regulation of plasma FFA in the duck. I. In the absence of pancreatic glucagon.

The present study was undertaken to determine how free fatty acid (FFA) release by adipose tissue can occur in the absence of pancreatic glucagon, the most potent lipolytic hormone in the duck. Two possible explanations have successively been investigated. Replacement therapy experiments showed that glucose uptake was implicated in the phenomenon; indeed, when pre-operative insulin and glucose levels were restored after total pancreatectomy, plasma FFA progressively fell to a level significantly lower than the pre-operative value. The same effect was observed when the ducks were kept in a continuous state of hyperglycaemia, whereas "normal" levels of insulin or glucose alone were shown to be ineffective. On the other hand a compensatory mechanism for the lack of glucagon, by other lipolytic agents [with the intestine or the anterior pituitary as possible sources] has been excluded by associating the removal of these two organs with pancreatectomy. These experiments suggest that the lack of pancreatic glucagon induced by total pancreatectomy is essentially masked by a failure in glucose uptake due to the operation.


A rapid micro-scale method for the measurement of Haemoglobin A1(a+b+c).

A rapid method is described for the measurement of total glycosylated haemoglobins (HbA1(a+b+c). The procedure utilizes 0.05 ml of blood and takes forty minutes to complete manually. Eighty blood samples can be analysed without automation by one person in a day. Each analysis uses less than 2 mg of potassium cyanide, resulting in a method that is both safe and rapid for routine hospital laboratories. The inter-assay coefficient of variation was 4% and that for intra-assay measurements 3%, over the range 5-20%, HbA1(a+b+c). The method confirmed that the level of HbA1(a+b+c) is elevated in imperfectly controlled diabetics. Amongst patients with blood glucose levels of less than 10 mmol/l the mean level of HbA1(a+b+c) was found to be 8.5%; samples from 14 known diabetics gave a mean value of 10.9%, whereas 17 known non-diabetic samples gave a mean value of 8.3%. In the group of samples from 27 diabetic individuals with blood glucose levels above 10 mmol/l the mean level of HbA1(a+b+c) was found to be 13.5%.


Acetylcholinesterase differentiation during myogenesis in early chick embryonic cells caused by an inducer RNA.

In the stage 4 chick blastoderm, an area located 0.6 mm posterior to Hensen's node, the post-nodal piece (PNP), consists of an undifferentiated population of cells, since the explants when cultivated in vitro in a variety of media do not develop into any histologically identifiable structures. However, addition of a specific low molecular weight RNA isolated from the 16-day-old chick embryonic heart promotes the appearance of a distinct mode of morphological and biochemical changes that is similar to that of embryonic cardiogenic process. The RNA-induced changes in the PNP also include a marked increase in acetylcholinesterase activity. The increase in enzymatic activity can be measured biochemically, as well as visualized histochemically.


A stage-restricted secretory system in the submandibular gland of the neonatal rat.

Ribonuclease and amylase have been shown to undergo a transient increase in activity in the submandibular gland of the perinatal rat [5]. We report here that brief stimulation with isoproterenol in vitro selectively releases these enzymes. In addition, analysis by polyacrylamide gel electrophoresis showed that the 4-day old submandibular gland contains three other major protein species that are not present in the sublingual gland and two of which are not evident in the adult submandibular gland. These are also selectively released by the drug. Examination of the glands by light and electron microscopy showed that concurrent with release of these protein products, extensive degranulation occurs in the immature acini (terminal tubules). Our experiments suggest that the 4-day glands show a marked incorporation of 3H-leucine into the submandibular-specific, secreted protein species. This indicates that these proteins will provide convenient molecualr markers of early submandibular differentiation.


Studies on Crocker sarcoma 180 under the effect of alkylating agents. IV. Morphological studies of sarcoma 180 during treatment with the antitumour drug cytoxan.

The effect of one massive dose of cytoxan (150 mg/kg), as an alkylating agent, on the morphology of sarcoma 180 cells was followed after 1, 3, 6, 12, 24, 48, 96, 120, and 168 h. After 1 h the cells of treated tumour showed clumping and a decrease in their size. In addition, statistical analysis manifested significant decrease in all phases of mitotic figures. All mitotic figures were completely stopped after 3 h from cytoxan treatment. After 6 and 12 h from cytoxan treatment the hyaline degenerations became more marked in the treated tumour tissue. Chromosomal bridge formation, nuclei aberrations and polynuclear cells were more prominent in 24, 48, and 96 h from cytoxan treatment. Increase in the nuclear size and hyaline degeneration were observed in treated section of 120 and 168 h.


[The organogenic development of the human peroneal muscle of the IVth digit from the peroneal muscle of the Vth digit and the short peroneal muscle from the viewpoint of evolutive myology].

The preliminary author's investigations revealed, that the mm. peronei digitorum group in Mammalia (including Man) underwent its own morphological evolution. The author failed to establish the facts that indicated the homology between the above mentioned muscles and m. extensor digitorum brevis. But, at present due to the lack of detailed determinations of organogenesis of mm. peronei digitorum and of m. peroneus brevis, it was not possible to prove the above mentioned indications. The observations on organogenesis of the respective muscles, carried out at present upon 13 human embryos with 12 to 32 mm crown-rump length and 5 fetuses with 35 to 65 mm crown-rump length, revealed that, mm. peronei digitorum primordium initiated its development as a muscle of two fingers (m. peroneus digiti IV. et m. peroneus digiti V), passed through its one-finger form (m. peroneus digiti V) and usually terminated with its complete reduction.


[Diploid radiation gynogenesis in carp. III. Analysis of gynogenetic progeny by biochemical markers].

Studies have been carried out on carp gynogenetic offspring by four autosome genes: Tf (transferrin), Est(s) (muscle esterases, slow), Est(f) (muscle esterases, fast), My (myogenes). Homozygosity and phenotypical homogeneity by all the loci studied are established for carps of the second generation of the induced gynogenesis. In the first generation obtained from heterozygous females, the correlation of homozygous offspring of two classes corresponding to the theoretically expected one (1:1). Heterozygous offspring makes (%): 5.0 (Tf), 9.1 (Est (s)), 28.4 (Est (f)). Three loci are mapped in relation to the centromere by heterozygote frequency. Genetic inactivation of the radiated sperm has been confirmed using biochemical markers. Due to the codominant nature of inheritance and high polymorphism, protein loci are considered to be convenuent genetic markers.


[Genetic regulation of the lactate dehydrogenase isoenzyme spectrum in mouse erythrocytes].

The pattern of lactate dehydrogenase isozymes was investigated by means of electrophoresis in erythrocytes of CBA/Lac and DBA/2J mice homozygous for b and a alleles of the Ldr-1 locus. It is found that differences in the pattern of LDH isozymes, homozygous for the genes Ldr-1a and Ldr-1b, consist in increased activity of the isozyme LDH-4 in mice homozygous for the gene Ldr-1a (DBA/2J) within 12-14 days of postnatal development. Inhibition of the reaction between 125I-LDH-1 and the respective antibodies has demonstrated that increased LDH-4 activity during development is related to the higher content of B-subunits of LDH. It is suggested that the mechanism of the action of the gene Ldr-1 involves changes in the rate of the synthesis and degradation of B-subunit of LDH.


[Genetic effects of induced in populations by the radioactive nuclear fission products of 235U. II. Prognostication of the genetic effectiveness of irradiation at low dose rates].

Experiments have been carried out on Chlorella, beans, wheat and developing loach eggs to study the dose-response relationship (dose-function of dose rate) with 90Sr, 90Y and 147Pm as the sources of beta-radiation. The yield of point mutations in Chlorella under 147Pm and that of chromosome aberrations in cells of bean roof and apical meristem tissue as well as in meiosis of wheat and bean cells irradiated by 90Sr- 90Y is proved to show degree dependence at a dose less than 1. It means that the dose which doubles the number of induced mutations is not constant and depends on the dose rate. Reverse relationship is shown between dose intensity and genetic effect per dose unit. The decrease in the yield of genetic damages in the range of dose rates analysed is supposed to be due to repair activation induced by ionizing radiations. In view of these results, consideration is given to the role of the level of spontaneous mutagenesis in estimation of the resolution of test systems. An increase in the level of the spontaneous mutational process is shown to increase the size of population samples which are ment, when analysed, to reveal statistically significant differences between the effect observed and the level of spontaneous mutagenesis. The possibility of application of the experimental results to the prediction of effects of ionizing radiations on natural animal and plant populations is considered.


A vector for recombinant DNA in Staphylococcus aureus.

Staphylococcal plasmids pS194 and pSC194 which confer streptomycin and streptomycin-chloramphenicol resistance respectively have been used as vectors for construction of recombinant DNA, since they each carry one single recipient site for endonuclease EcoRI. Hybrid DNA does not express streptomycin resistance, a marker which is present in both vectors, presumably because the marker gene is cleaved by EcoRI. A chloramphenicol marker present in pSC194 was used for positive hybrid selection. Hybrid plasmids generated by joining pSC194 with one or more of the four EcoRI fragments of the large (18.1-10(6) daltons) staphylococcal plasmid pI258 were constructed and permitted us to develop a physical map for pI258.


Effect of carotid ligation on cerebral tissue oxygenation in aging rat.

In order to test the ability of aged animals to compensate a cerebrovascular insufficiency, common carotid ligation was performed on young (12 months) and aged (30 months) rats. By using gold microelectrodes, the pO2 distribution in the cerebral cortex was registered for 1 h following the occlusion of the carotid arteries. It could be shown that, while the young group was able to compensate the reduction in arterial blood supply, the cortical pO2 distribution in the group of aged rats shifted towards a hypoxic profile. These results provide further evidence of the limited adaptability to functional demands with increasing age.


Studies on the degradation of ageing chromatin DNA by nuclear and cytoplasmic factors and deoxyribonucleases.

There are 'factors' in both the cytoplasm and the nucleus which are capable of a limited digestion of the DNA in chromatin. These factors show a pH optimum closer to that of DNase I than DNase II and do not promote the activities of either of these purified enzymes. These factors show considerable tissue specificity, for example, liver extracts are less able to degrade kidney chromatin than the homologous chromatin (40% difference) and slight age specificity since 'age-matched' samples gave consistently higher (10%) extents of degradation. There is no evidence, however, with increasing age in mice, that the accessibility of DNA in chromatin to digestion by deoxyribonucleases is altered.


Cross-linking of collagen depending on age.

The spectrum of aldimine cross-link bonds of skin collagen is dependent on the localization of the examined material. In correlation to this, there is no synchronous behaviour of cross-linkage in the aging process. The age-dependent decrease of HLNL and the increase of DHLNL in the collagen of tail tendon is only unsubstantially found in the skin of neck. It is supposed that environmental conditions or bodily activity in an area might effect the cross-link bonds of collagen.


Age-related changes in collagenous and noncollagenous proteins of skeletal muscle of a short-lived species of reptile.

The collagenous/noncollagenous protein ratio in the skeletal muscle of the male garden lizard increased with advancing age, suggesting increased tensile strength of aged muscle. The solubility of collagen and the soluble/insoluble collagen ratio showed a decline during ageing confirming the development of cross-linkages in the muscle collagen of ageing lizards. It is suggested that these changes are likely to disturb the efficiency of ageing muscle.


Involvement of disulfide bonds in the condensed structure of facultative heterochromatin and implications on cellular differentiation and aging.

In the previous contribution to this debate, the age-associated disulfide bonding between chromatin proteins was suggested as the primary event leading to cellular aging. Evidence is now presented that S-S bond formation in chromatin may be a programmed event. The possible role of SH oxidating random events in the accumulation of S-S bonds in chromatin with age are also pointed out. Finally, the possible slowing down of the aging process with the sulfhydryl protecting-disulfide reducing agents is discussed together with some supporting experimental results.


Accelerated aging due to enzymatic racemization.

Thermodynamic racemization may be a cause of aging. Racemases might accelerate the aging process. If enzymatic racemization does accelerate aging, then the use of chemical or immunological inhibitors of racemases might retard aging.


Normal chromosome banding pattern in Alzheimer's disease.

Lymphocyte chromosomes were studied in 10 female patients with Alzheimer's disease, including 5 cases with positive heredity for organic dementia. The chromosomes were analyzed by means of the Giesma banding technique. All patients had a normal karyotype with a completely normal banding pattern in all metaphases analyzed. It may be concluded that chromosomal changes demonstrable with methods available today are not involved in the causation of Alzheimer's disease, whether sporadic or with positive heredity for organic dementia starting in the presenile or senile periods.


Drug metabolism in a case of progeria.

A case of premature ageing (progeria) in a 3-year-old Indian child is described. The conjugations of paracetamol with glucuronic acid and sulphate, of benzoic acid with glycine and of phenylacetic acid with glutamine have been investigated in this child, in view of suggestions that these reactions are impaired in old age. The results suggest that the glucuronic acid conjugation pathway may be quantitatively less important in the progeric child than in normal children and adults.


Ageing does not change blood granulocyte bactericidal capacity and levels of complement factors 3 and 4.

The bactericidal capacity of blood polymorphonuclear granulocytes and the plasma levels of complement factors 3 and 4 did not differ between 15 aged patients and 15 young control subjects, nor did these important antimicrobial functions predict morbidity and mortality in the next 6 months.


Mitochondrial enzyme activities in liver biopsies from patients with alcoholic liver disease.

The hypothesis that mictochondrial damage is a significant factor in the pathogenesis of alcoholic liver disease (ALD) was investigated by enzymic analysis of mitochondrial fractions isolated from needle biopsy specimens from control patients, patients with fatty liver due to chronic alcoholism, and from patients with other forms of liver disease. Enzymes associated with the inner and outer mitochondrial membranes showed normal levels in ALD. Enzymes associated with the mitochondrial matrix, glutamate dehydrogenase, malate dehydrogenase and aspartate aminotransferase showed significantly raised levels in ALD, but the levels in patients with non-alcoholic liver disease was normal. In addition, analysis of the mitochondria by sucrose density gradient centrifugation revealed no differences between control tissue and liver from patients with alcoholic liver disease. These results do not indicate that there is significant mitochondrial damage in ALD. The raised mitochondrial matrix enzymes may represent an adaptive response to the ethanol load.


Familial and nonfamilial benign recurrent cholestiasis distinguished by plasma disappearance of indocyanine green but not cholylglycine.

To determine whether a defect in uptake of organic anions is present in patients with benign recurrent cholestasis, the plasma disappearance of simultaneously injected indocyanine green and cholyglycine-1-14C was measured in eight patients with asymptomatic benign recurrent cholestasis, four with the familial type, as well as 22 healthy control subjects. Evans blue was also simultaneously injected to permit correction for variation in blood volume and speed of mixing. Uptake of indocyanine green was decreased in all three patients with nonfamilial benign recurrent cholestatsis, but normal or increased in the four patients uith the familial form of the disorder. By contrast, cholyglycine-1-14C uptake was abnormal in one patient with each type of the disorder. Thus, patients with nonfamilial benign recurrent cholestasis have a defect in indocyanine green uptake, and patients with benign recurrent cholestasis are heterogeneous with respect to organic anion uptake.


Comparison of the biological potency of a new synthetic preparation of secretin with that of natural porcine secretin in the dog.

The biological activity of the new synthetic secretin, Roche, on exocrine pancreatic secretion was determined in conscious dogs with chronic gastric and duodenal fistulae and compared with that of pure porcine secretin (GIH, Karolinska Institutet, Stockholm). The two secretin preparations were found to be equipotent as to pancreatic volume and bicarbonate response on a molar basis. It was concluded that the new synthetic secretin is useful for clinical and research purposes.


Acute pancreatitis and serological evidence of infection with Mycoplasma pneumoniae.

Paired acute and convalescent serum samples from 27 consecutive patients with acute pancreatitis were examined for evidence of infection with several viral agents. Evidence of infection with Coxsackie viruses group B was found in three patients, and of infection with Mycoplasma pneumoniae in nine patients (33%). This latter finding confirms recent reports from Scandinavia linking pancreatitis and serological evidence of infection with Mycoplasma pneumoniae. The possibility that a true association exists between the two conditions is considered, together with alternative explanations, and further work is envisaged to elucidate these findings.


Pancreatic enzymes in human duodenal juice--a comparison of responses in secretin pancreozymin and Lundh Borgström tests.

We have compared the concentrations and total outputs of trypsin, amylase, and lipase secreted into the duodenum during secretin pancreozymin and Lundh Borgström tests in order to assess the relative intensity of pancreatic stimulation provided by these means. The mean concentration of trypsin, and the mean 10 minute total output of trypsin, amylase, and lipase after the meal (though less than the peak post-prandial responses) were equal to the respective peak enzyme responses after intravenous injection of 2 Crick Harper Raper units per kg of secretin Boots; and after intravenous injection of 2 Crick Harper Raper units per kg of pancreozymin Boots.


Comparison of radio-opaque pellets and chromium sesquioxide as inert markers in studies requiring accurate faecal collections.

Radio-opaque pellets (ROP) similar to those currently used to measure gastrointestinal transit time have been compared with chromium sesquioxide to assess their suitability for use as inert markers in the gut. Five healthy subjects took both markers with every meal for two separate three week periods while taking metabolically controlled diets. Overall recovery of both markers was satisfactory; ROP 99.7 +/- 0.3% (SD) and chromium 97.8 +/- 1.6% (SD). A comparison of the amount for each marker recovered in 69 separate faecal collection periods of various lengths showed close agreement (R = 0.99) and the tail-off in marker excretion after cessation of ROP and chromium intake was similar, although slightly more prolonged for chromium. The amount of marker retained in the gut was 13.5% greater for chromium at the end of the three week study periods. Both markers proved satisfactory for correcting variations in faecal calcium output. The ROP, however, offer clear advantages over chromium in that they are considerably easier and quicker to measure, the method of measurement using x-rays does not alter the stools and faecal handling is minimised. The precision of ROP measurement is greater and, because of the variety of ROP available, they offer more flexibility for metabolic studies. In addition, stool by stool analysis is possible enabling simultaneous measurement of mean transit time to be made in experimental subjects.


Effect of codeine phosphate, Lomotil, and Isogel on iileostomy function.

The effect on ileostomy function of codeine phosphate, Lomotil, or Isogel was tested in 20 subjects at home living a normal life, studied over two three-day periods on and off treatment. Codeine phosphate 60 mg three times daily was associated with a reduction in the mean total weight of ileostomy output and the ileostomy outputs of water, sodium, and potassium (p < 0.05). The proportion of faecal solids increased on codeine and the effluent appeared thicker but the output of faecal solids remained unchanged. Mean faecal fat increased on codeine. The transit rate from mouth to stoma was slower in four of the five subjects on codeine and a further two subjects withdrew from the trial with temporary intestinal obstruction while on the drug. Lomotil two tablets three times daily was associated with a small and statistically not quite significant fall in the mean total weight of ileostomy output and the ileostomy output of water. Sodium and potassium outputs in the effluent fell on Lomotil (p < 0.05) but the other parameters remained unchanged. Isogel 15 ml three times daily was associated with an increase in the mean total weight of ileostomy output and the ileostomy outputs of water, sodium, potassium, and faecal solids (p < 0.01). Although the effluent looked more viscid on Isogel, the proportion of faecal solids was unchanged. These results suggest that codeine phosphate has a beneficial effect on ileostomy function, reducing the loss of water and electrolytes, while Lomotil has a similar but less effective action in the dosage tested. By contrast, Isogel increases the ileostomy loss of water and electrolytes and will aggravate their depletion in patients with excessive fluid effluents. The increase in faecal fat associated with taking codeine phosphate suggests that it should be stopped before collecting specimens for faecal fat estimations.


Age-related changes in the colonic blood supply: their relevance to ischaemic colitis.

Ischaemic colitis due to non-occlusive mesenteric ischaemia is a disease of the elderly which commonly involves the left side of the colon; selective splenic flexure involvement is said to be especially common. In an attempt to explain these features postmortem angiograms were performed on the superior and inferior mesenteric arteries of 37 postmortem subjects. A distinct age-related tortuosity of the long colic arteries was noted which could account for the increasing incidence of ischaemic colitis with age. No anatomical basis for the higher incidence of left-sided involvement was found and, specifically, no critical point in the arterial circulation at the splenic flexure was demonstrated.


Is there a myoelectrical abnormality in the irritable colon syndrome?

Although recent work has suggested that an abnormality of the 0.05 Hz (3 c/m) slow wave electrical activity exists in the distal colon of patients with the irritable colon syndrome, it is not established whether this is related to altered bowel habit alone, or whether it is specific to the irritable colon syndrome. We have therefore studied 10 patients referred with this disorder and compared their colonic myoelectrical pattern with 10 patients suffering from assorted disorders with similar symptoms--for example, chronic pancreatitis, diverticular disease, ulcerative colitis, etc. Transit time, stool weights, percentage motility, and slow wave electrical activity were measured in each patient. The two groups were well matched for age and patients with similar symptoms in the two groups had similar values for transit time and percentage motility. There was a statistically significant increase in the 3 c/m electrical activity in patients with the irritable colon syndrome unrelated to the degree of diarrhoea or constipation. It would appear, therefore, that the abnormally high incidence of 3 c/m electrical activity in the colon is specific to the irritable colon syndrome and not merely a feature of altered bowel habit.


Transmucosal potential difference; diagnostic value in gastro-oseophageal reflux.

Nineteen patients with symptoms of upper gastrointestinal disease were assessed by endoscopy. Transmucosal potential difference (PD) in the lower oesophagus was recorded and suction biopsy specimens were obtained from the site of measurement and examined by light microscopy after haematoxylin and eosin staining. In 10 patients with normal histology, mean PD was--14.4 mV (SEM +/- 0.4 mV), whereas in nine patients with histological changes of reflux mean was +9.4 mV (SEM +/- 3.0 mV). In this latter group, polarity of the PD was reversed in all but one case. Good correlation was found between these objective indices of lower oesophageal disease and the presence of symptoms such as dysphagia and heartburn. The visual appearance at endoscopy was less reliable. It is suggested that measurement of PD is a simple, rapid, and sensitive method of detecting the presence of oesophageal mucosal damage.


Motilin release in the pig.

Motilin is found in the upper intestine of pig and man and in man is released by acid. A similar release by acid has now been found in the pig and is associated with markedly reduced immunostainable motilin in the upper small intestine. Clamping the arteries and veins to the stimulated segment immediately reversed the rise of plasma motilin, indicating the motilin release to be an entirely local phenomenon. The apparent half life of endogenous motilin was 3.9 minutes. No release of motilin was seen after a meal and the possible physiological role of motilin thus remains speculative.


Effect of ulcer healing on the prognosis of chronic gastric uler. Four-year follow-up.

Eighty three patients were followed-up for four years after an admission to hospital with a chronic gastric ulcer proven by radiology (index ulcer). The index ulcer healed completely in 50 patients, but was unhealed at the time of discharge in the other 33. Significantly fewer patients whose index ulcer was healed compared with those whose ulcer was unhealed at discharge had had a recurrence by one (p < 0.05), two, three and four years' (p < 0.01) follow-up. Moreover, the rate of recurrence was significantly greater for those patients with unhealed, compared with those with a healed index ulcer (p < 0.05) and by the end of the four-year period 61% of patients with unhealed, compared with 26% of those with healed index ulcers had had a recurrence. Patients over the age of 60 years with unhealed index ulcers had a significantly poorer prognosis than those of similar age whose index ulcer was healed at discharge (p < 0.025). The sex of the ulcer patient did not significantly influence ulcer recurrence. Large ulcers (> 57 mm(2)) were less often healed on initial discharge and were more frequently associated with recurrence at one (p < 0.05), two (p < 0.025), three and four years (p < 0.01) than smaller ulcers ([unk]57 mm(2)). Heavy intake of analgesics adversely influenced the course of patients whose ulcer was unhealed (p < 0.05), but did not alter the recurrence rate in those whose ulcer was healed. Ulcer recurrence was not influenced by smoking habits or by alcohol consumption.


The two histological types of gastric carcinoma in Northern Nigeria.

Sixty-five specimens of gastric carcinoma from Northern Nigeria were classified using the criteria of Lauren (1965). Forty were intestinal, 16 diffuse, 2 mixed, and 7 unclassifiable. The intestinal type predominated in both men and women and in all age groups contrary to the expectation of a diffuse predominance because of the relatively young age groups of the population and the low risk for gastric carcinoma in this region.


On use of chromogenic substrates for studies of coagulation inhibitors.

Methodological problems encountered using chromogenic substrates on thrombin and Xa are discussed: (1) influence of substrate on inhibitor; (2) influence of heparin; (3) optimal concentrations; (4) specificity; (5) denatured enzymes, and (6) natural versus chromogenic substrates.


Fluorogenic substrates for sensitive and differential estimation of urokinase and tissue plasminogen activator.

Two fluorogenic peptide amides have been synthesized, i.e. BOC-L-valyl-glycyl-L-arginine 2-naphthylamide (I) and L-valyl-glycyl-L-arginine 2-naphthylamide (II). The kinetic parameters of plasmin, urokinase and human uterine tissue plasminogen activator on substrates I and II have been determined. Quite unexpectedly, the tissue activator appeared to require for its activity a blocked amino terminus on the substrate. This was further corroborated with other synthetic substrates. Plasmin and urokinase did not show this requirement.


Pharmacological content of hyperproteolytic states in blood by synthetic inhibitors of serine proteinases.

Proteolytic enzymes participate extensively in coagulation, fibrinolysis, kininogenesis, and complement activity. Synthetic low molecular weight inhibitors of these enzymes which belong to the group of serine proteinases allow pharmacological control of these processes. The development of such inhibitors and their therapeutic importance are reported, especially on the pattern of benzamidine derivatives.


Chromogenic substrates for horseshoe crab clotting enzyme. Its application for the assay of bacterial endotoxins.

An endotoxin-activated hemocyte lysate from the horseshoe crab (Tachypleus and Limulus) was found to hydrolyze Bz-Ile-Glu-(gamma-OR)-Gly-Arg-p-nitroanilide (PNA), Bz-Val-Gly-Arg-PNA, Boc-Val-Leu-Gly-Arg-PNA, and Boc-Leu-Gly-Arg-PNA, all of which have the COOH-terminal Gly-Arg sequence. This amidase activity was due to a clottting enzyme contained in the lysate. Furthermore, the amidase activity increased by increasing the concentration of bacterial endotoxin (E. coli, 0111-B4) added to the lysate. Therefore, the measurement of the endotoxin-induced amidase activity made it possible to determine the concentration of the endotoxin.


Designing of peptide substrates. Different approaches exemplified by new chromogenic substrates for kallikreins and urokinase.

Chromogenic peptide substrates for serine proteases have been designed by using two approaches: (1) by using the natural substrate as a model and (2) by structure-activity correlations obtained through screening of a large number of tripeptides. Some recent examples, substrates for kallikreins and urokinase are given.


Changes in plasma levels of prekallikrein, kallikrein, high molecular weight kininogen and kallikrein inhibitors during lethal endotoxin shock in dogs.

Plasma levels of prekallikrein, kallikrein, high molecular weight kininogen and kallikrein inhibitors were measured in samples from dogs infused with E. coli endotoxin. Markedly reduced levels of prekallikrein and high molecular weight kininogen were seen at circulatory collapse and free kallikrein was detected. Both 'fast-reacting' and 'time-dependent' inhibitors of plasma kallikrein were significantly reduced. Fractionation of pre-infusion and collapse samples by gel filtration together with immunological procedures indicated that both alpha2-macroglobin and alpha1-antitrypsin were the major kallikrein inhibitors in dog plasma, and that they were significantly reduced in the collapse samples.


New chromogenic peptide substrates for factor X.

The factor Xa-sensitive substrate BZ-Ile-Glu-Gly-Arg-p-nitroanilide has been made more sensitive by making ester and amide derivatives of the gamma-carboxyl group of the glutamyl residue. The morpholinyl and piperidyl amides react 2.5 times more rapidly with factor Xa.


Rat coagulation factors V, VIII, XI, and XII: vitamin K dependent.

When rats were given single or multiple doses of warfarin, the levels of prothrombin and factors VII, IX, and X were depressed, as expected. However, modest reductions of factors V, VIII, XI, and XII, but not of fibrinogen, also occurred. The levels of all eight factors promptly returned to normal when vitamin K1 was given. Warfarin-resistant rats had no depression of any of the eight factors. When vitamin K deficiency was induced by internal or external biliary fistula, factors II-VII-IX-X decreased sharply and factors V-VIII-XI-XII decreased modestly. Again, all depression were promptly reversed by vitamin K1. Isolated livers from warfarinized rats did not generate the classic vitamin K-dependent factors during 5 h of perfusion but did generate small amounts of factors V, XI, and XII, although less than normal. The isolated rat liver apparently does not generate factor VIII.


Automated antithrombin III assay with a centrifugal analyser.

The factor Xa inactivating function of antithrombin III is measured automatically by an amidolytic method, adapted to a centrifugal analyser. Plasma is diluted in buffer with heparin. In stage I, diluted plasma is incubated with excess factor Xa. Heparin accelerates the saturation of antithrombin with factor Xa. In stage II, remaining factor Xa is determined with the chromogenic substrate Bz-Ile-Glu-Gly-Arg-pNA. The precision of the present assay compares favourably with that of the clotting assays and immunoassay. There is a close correlation (r = 0.82) between the results obtained with this assay and the immunoassay of antithrombin III.


The effect of trypsin and storage on aggregation and release of human gel-filtered platelets.

Trypsin was studied as an aggregating and release-inducing agent with gel-filtered platelets (GFP) and was compared with ADP, epinephrine and collagen. GFP aggregated irreversibly with final concentrations of 0.5-4 microgram/ml trypsin, 1.6-3.2 micrometer ADP, 2.5-5 micrometer epinephrine and 40 microlite 1/ml soluble collagen. Addition of human fibrinogen to the Tyrode-suspending buffer was required for ADP and epinephrine, but was not necessary for trypsin or collagen. Release of (14C)5HT was obtained with trypsin and collagen using the same concentrations as used in aggregation. GFP stored at room temperature for 48 h were still responsive to trypsin and collagen, whereas aggregability and (14C)5HT release induced by ADP and epinephrine were already impaired 5 h after collection of blood. CP-CPK, an ADP-removing reagent, blocked aggregation and release induced by low trypsin concentrations, suggesting that ADP plays an intermediate role in the mechanism by which trypsin activates platelets. Trypsin appears to be a valuable reagent for studying platelet physiology, particulary following storage.