The effect of children on marital dissolution.

The relationship between the presence of children and divorce and separation is examined using data from the first four years of the National Longitudinal Surveys of Labor Market Experience in Women Aged 30 to 44. The data show that children were a deterrent to separation and divorce only when they were in the preschool ages. Once all the children in a family were in school, they did not seem to influence the probability of separation and divorce. It is suggested that the high costs of child care for preschool children, in terms of time, money, and effort, act as a deterrent to marital dissolution. The associations between several other social demographic variables and marital dissolution also are investigated.


Labor force participation of working mothers and family formation: some further evidence.

This paper offers additional insight and evidence on the well-documented inverse relationship between female employment and fertility. Interviews with 388 working mothers from a probability sample in Robeson County, North Carolina, provide the data for testing the hypothesized relationships. Generally, the results indicate that lower fertility, lower desires and expectations, and earlier use of birth control are associated with work before the first birth and with employment of the longest duration. The timing of the first birth was not differentiated by variations in work experience. The results are conditional in that the relationships hold more for whites than for blacks or Indians.


A two-sex nuptiality-mortality life table.

The "problem of the sexes" has been one of trying to reconcile inconsistent male and female demographic rates. The present paper deals with that question in the context of a two-sex nuptiality-mortality life table. A "rectangular" population, with equal numbers of persons in each age-sex group, is introduced as a standard, and a standardization relationship expressed in equation (9) relates changes in rectangular population rates to changes in age-sex composition. The standardization relationship is shown to satisfy a number of desirable properties and produce a realistic two-sex model. The standardization approach is then applied to data from Sweden for 1973, and the results and their implications are discussed. In particular, it is seen that the total number of marriages in a two-sex population neither is nor should be bounded by the total numbers of marriages in the associated male and female one-sex nuptiality-mortality tables.


Population forecasting standards: some considerations concerning their necessity and content.

This paper discusses the nature of population forecasting and provides guidelines for standards that are in line with good professional practice yet do not stifle creativity or technical advances.


Balsam of Peru as screening agent for essential oils sensitivity.

The standard series and 35 essential oils were tested on 450 patients with dermatitis. It was found that those simultaneously sensitive to essential oils are more frequently negative than positive to balsam of Peru. The remaining 3 balsams, however (colophony, turpentine and wood tars), are also screening agents for essential oils. All four balsams reveal sensitivity to essential oils in most of the subjects tested. In patients negative to all 4 balsams of the standard series, attempts to find an essential oil with which tests would be simultaneously frequently positive with those for other essential oils failed.


Generalized pruritus in metastatic adenocarcinoma of the stomach.

Generalized pruritus appeared 2 years following resection of an adenocarcinoma of the stomach. The appearance of the pruritus was the presenting symptom of recurrence of the malignant process in the stomach as well as of its metastatic spread to the liver and to the lungs.


Induction of multinucleate cells by 8-MOP and UV treatment in vitro and in vivo.

Fibroblast cells were treated with a single dose of 8-methoxypsoralen (8-MOP) and long-wave UV irradiation in vitro and the cytotoxic effects of the treatment followed up for 5 passages. During the first passage, there was an inhibition in cell proliferation, the induction of chromosomal aberrations and the production of macrocells as well as cells with more than one nucleus. In the subsequent passages, the proliferation rate of the cells gradually normalized but there was a concomitant increase in chromosomal aberrations and in the number of macrocells and multinucleate cells. Specimens, which were taken from the uninvolved skin of psoriatic patients who had been treated between 20 and 40 times with an oral dose of 8-MOP and black light irradiation (PUVA) also revealed the presence of binucleate, tetranucleate and multinucleate epidermal cells as well as binucleate and tetranucleate dermal fibroblasts.


Treatment of Keratoacanthomas with currettage.

The present paper reports the results of a follow-up study of 47 patients with keratoacanthomas treated solely with currettage. Only one recurrence was seen, and the cosmetic results were much better than those obtained with other types of treatment. Curettage must be considered the treatment of choice for keratoacanthomas on the face.


[Therapeutical action of urea on the skin (author's transl)].

Long-term application up to 8 weeks of a 10% urea solution provokes an epidermal thinning expressed in a decreased number of DNA-synthetizing cells. This epidermal reaction cannot be established after topical use of HTH emulsion. Even by daily application during 8 weeks no change was seen. The absence of epidermal thinning after HTH exposure can be explained as an additive effect of urea and the other constituents of the HTH emulsion. This opinion is supported by the results after application of urea together with Tween 60 in that the acanthogenic effect of Tween 60 is decreased by addition of urea. On the other side, the therapeutic efficiency of 10% 5-fluorouracil solution can be increased remarkably by preliminary treatment with HTH emulsion. These findings could reach importance in the topical therapy with regard to the possibility to improve the effectiveness of any drug by addition of, or preliminary treatment with, urea.


[Clinic, statistic and risik factors of the malignant melanoma (author's transl)].

The prognosis for malignant melanoma is dependent on the stage of the disease, sex, size respectively depth of penetration, structure (lentigo maligna melanoma, superficial spreading melanoma, nodular melanoma), location and age of the patient when the disease begins. The method of conventional treatment (X-ray then excision, excision then X-ray, X-ray alone, excision alone) is not important. The decisive factor is early diagnosis (histology) and early treatment (total excision of the tumor). The value of additional immunotherapy and chemotherapy in cases diagnosed early cannot yet be judged. Melanoma is rarer among colored races than among whites, and the frequency of the disease among Caucasians increases as one approaches the equator. Morbidity and mortality are rising throughout the world. The influence of factors such as trauma and sunlight is disputed.


Topical treatment of extended alopecia. Intralesional steroid--Kromayer lamp.

Two groups of patients with subtotal to universal areate type alopecia were serially treated, 6 with intralesional triamcinolone acetonide suspension and 6 with contact irradiation by ultraviolet light from a high-pressure mercury-arc source with a quartz envelope (Kromayer lamp). The treatment was limited to one half of the scalp while the untreated half served as a control. Triamcinolone acetonide suspension gave in 2 of the 6 treated patients a temporary  stimulating effect on hari growth; later, however, hair growth inhibition was noted in 3 patients. Contact irradiation with ultraviolet light from a Kromayer lamp gave in 4 of the 6 treated patients a stimulatory effect upon hair growth, but did not seem to initiate it.


Effect of somatostatin on plasma C-peptide immunoreactivity in normal man.

The effect of somatostatin on plasma C-peptide immunoreactivity was studied in seven normal men following an intravenous 25 g glucose load. No elevation in plasma insulin was observed and similarly no rise in plasma C-peptide immunoreactivity occurred, indicating that somatostatin inhibits glucose-induced C-peptide release as well as insulin release.


Reliability of a simple and rapid glucose measuring device in conducting oral glucose tolerance tests.

160 oral glucose tolerance tests (OGTTs) were carried out, the glucose measurements being performed with the rapid dry-lab device Reflomat/Reflotest-Glucose and the GOD-Perid method. In 151 patients (94.4%) the two methods of measuring glucose led to the same diagnoses (i.e. "normal", "suspect" or "diabetic"). This high conformity in the results suggests the reliability of the rapid device in conducting OGTTs. Only in 9 subjects (5.6%) were the clinical conclusions different, Reflotest-Glucose giving predominantly "more pathological" results. It is, however, not possible to say which method showed "falsely positive" and which one "falsely negative" results.


Evidence for genetic control of anti-insulin immunity in juvenile onset diabetes mellitus.

The role of genetic factors in humoral anti-insulin-response was studied in 87 patients with juvenile onset diabetes. A significant insulin antibody formation was found in 76 (87%) juvenile diabetics. By dividing these patients in four groups according to different heights of insulin antibody levels (non-, low-, moderate- and high-responders) a positive or negative correlation between humoral anti-insulin response and certain HLA antigens could be found. Non-responders showed a close association with HLA-B7 positivity, whereas in the insulin high-responder patients, a considerable decrease of HLA-B8 and increase of HLA-Bw15 and HLA-Cw3 was found. These findings indicate that certain genetic constellations within the HLA complex might have an important part in determining humoral anti-insulin immunity.


The HLA system and diabetes mellitus.

There is a significant positive association between insulin dependent diabetes, irrespective of age of onset, and the HLA system, whereas there is no association of HLA antigens with non-insulin dependent diabetes. There is a significant concordance value for HLA antigen frequencies in insulin dependent diabetics from three different centres, indicating that the genes (s) conferring susceptibility to this type of diabetes is possibly present in all "juvenile-onset" diabetics and is in linkage disequilibrium with all the B locus alleles.


Ambulatory treatment of psoriasis: combined use of occlusive dressings with locacorten tar at night and 'open' treatment with locasalen during the day.

Fifty patients with refractory psoriasis were treated with a combined method consisting in the application of occlusive dressings with Locacorten Tar ointment at night and of 'open' treatment (without occlusive dressings) with Locasalen ointment during the day. The aim of this trial was to obtain the benefit of the occlusive-dressing method without having to hospitalize the patients. The mean time required for the eradication of psoriatic scales was 3.46 days, while that needed for complete recovery was 14 days. The results clearly indicated that this combined approach has all the advantages of occlusives dressings but allows the patient greater freedom during the day. The very good effect of the treatment is also attributable to the triple action obtained with this combination: the anti-epidermoplastic effect of flumethasone pivalate, the squamolytic effect of salicylic acid, and the keratoplastic action of the tar compound.


A study of the local tolerance of tibicorten during long-term application.

Regular observation of 16 patients with chronic skin diseases, treated twice daily with applications of Tibicorten for 2 to 14 weeks, showed that this treatment did not give rise to development of local side-effects. Even protracted local application of Tibicorten is tolerated excellently.


Metabolic effects of the glucose tolerance factor (GTF) in normal and genetically diabetic mice.

The acute metabolic effects of glucose tolerance factor (GTF), the biologically active form of trivalent chromium, were studied in normal and genetically diabetic (db/db) mice. A single intraperitoneal injection of GTF significantly reduced the nonfasting plasma glucose level in normal mice by 38 per cent, and in diabetic mice by 14 to 29 per cent. Time course studies in normal and diabetic mice showed a maximal lowering of plasma glucose at four hours after GTF treatment. Furthermore, a single injection of GTF significantly lowered the elevated plasma triglyceride and cholesterol levels by 47 and 35 per cent, respectively, four hours after injection. Genetically diabetic mice are refractory to insulin, and treatment with exogenous insulin produced a smaller decrement in plasma glucose (11-18 per cent). The combination treatment of diabetic mice with GTF and exogenous insulin was significantly more effective in reducing plasma glucose (39-51 per cent) and triglycerides (76 per cent) than either treatment alone. These findings are consistent with the suggestion that GTF and insulin act synergistically.


Unexplained hyperinsulinemia in normal and "prediabetic" Pima Indians compared with normal Caucasians. An example of racial differences in insulin secretion.

The pattern of insulin response to oral and/or intravenous glucose has been claimed to be characteristic of diabetes and even prediabetes. To determine if differences in insluin secretion might explain the exceptionally high prevalence of diabetes in the Pima Indians, 26 genetically normal Pimas (nondiabetic offspring of nondiabetic parents), 32 genetically prediabetic Pimas (nondiabetic offspring of diabetic parents), 10 diabetic Pimas, and 29 normal Caucasians were studied. All subjects received an intravenous glucose tolerance test (IVGTT) to examine the acute-phase insulin response, and all nondiabetic subjects received an oral glucose tolerance test (OGTT) and arginine infusion (AI). The prediabetics also received a cortisone-primed oral glucose tolerance test (CGTT) and were classified by the result of this test. While acute-phase insulin release during the IVGTT was absent in the diabetics, there was a rapid response in all nondiabetics. Prediabetic Pimas with normal or abnormal CGTT had insulin levels similar to normal Indians during the IVGTT, OGTT, and AI. Thus, no evidence of impairment of acute- or late-phase insulin release was found. The normal and prediabetic Indians had fasting and stimulated insulin levels during all the tests two-to-threefold greater than the Caucasians. Differences in insulin levels between the two races could not be explained by differences in glucose level, age, or obesity.


The Prader-Willi syndrome. Regulation of fat transport.

Studies of fat mobilization and transport are reported in six patients with the Prader-Willi syndrome. Two patients had carbohydrate intolerance. One of these had a low and the other an augmented insulin response to glucose challenge. Following challenge with glucose, three of the four nondiabetics had normal insulin responses or increased responses consistent with their obesity; the other nondiabetic had insulinopenia. Measurements of the effects of norepinephrine, insulin, glucose, and 5-methylpyrazole-3-carboxylic acid on plasma levels of FFA, glycerol, and ketones provide no evidence for abnormal regulation of mobilization of fat from adipose tissue. Measurements of plasma lipids and postheparin lipolytic activity are consistent with normal uptake of fat into adipose tissue, and normal fatty acid composition of adipose tissue gives no evidence for abnormal lipogenesis.


Hypertension in acute neurological diseases of childhood.

Five children are described who developed hypertension in relation to acute neurological disease. Possible pathophysiological mechanisms for the hypertension are considered. It is thought that the hypertension may have been related to interruption of the ascending tracts in the brain stem, leading to failure of integration between, or independent action of, the baroreceptors and osmoreceptor system. Management and treatment are discussed. Diazoxide (5 mg/kg bodyweight, given intravenously) appears to be the most effective drug for use in the acute episodes.


The first-born child: patterns of development.

209 first-born infants and their mothers were studied at birth and again two months later in order to learn how they had adapted to post-natal life. Only a small minority had escaped ill-health and also achieved the ideal of a contented breast-fed baby with an established routine. At two months 33-5 per cent were still breast feeding. Difficulties with feeding were reported by 55 per cent of mothers. 24-4 per cent of the babies were having a night feed at two months and 24-8 per cent had not yet established a daytime routine. The daily number of feeds ranged from three to seven, with a median of five. Medical problems had occurred in 46-5 per cent of the babies. Bottle-fed babies had more infections, and were more likely to use a dummy than breast-fed babies. Wakefulness during the daytime ranged from less than four hours to more than 10 hours. Many of these women were over-anxious. The primary care teams and paediatric services face a major task in helping today's primiparous mothers and their infants make a good start in life together.


Problems in diagnosis and management of children with cerebral palsy and deafness.

Problems in the diagnosis, management and educational placement of 10 children with cerebral palsy and deafness are reported. Serious inadequacies revealed by the study include delays in diagnosis, poor co-ordination of decision-making between services and frequent changes of school--all leading to unsatisfactory progress by these children.


Tempo change during body rocking.

Occasional tempo change during spontaneous body rocking is described in two institutionalised mentally retarded children. Both acceleration and deceleration in moment-to-moment rate of body rocking were demonstrated under constant environmental conditions. The findings are discussed in relation to the automatism hypothesis of stereotyped behaviour.


Recovery of intellectual ability after closed head-injury.

Seven children with intellectual and personality changes after closed head-injury were followed-up with neuropsychological and psycho-educational evaluations. Two cases are presented in detail. Persistent intellectual changes documented on standardized tests were not always apparent to parents or physicians, and recovery of intellectual abilities lagged behind the disappearance of neurological abnormalities. Some of the children required special class placement for several years after the injury. Personality changes were thought to be secondary to stress on impaired perceptual and cognitive abilities, and the desirability of limiting such stress is emphasized.


Natural sleep as an aid to electroencephalographic diagnosis in young children.

A total of 300 children aged five years and under, referred for routine EEG investigations, were included in this study. It was possible to obtain recordings during natural sleep in 250 of the 300 children, using stick-on electrodes. Of the 250 with natural-sleep recordings, 110 children had normal records both awake and asleep. In 73 cases the awake record was normal but the asleep record showed abnormalities, the most common being spike discharges (60 children). Of these 60 children, 52 had a history suggestive of epilepsy or of febrile convulsions. A further 27 children had recordings which were equally abnormal awake and asleep, and 37 showed abnormalities while awake but greater abnormalities while asleep. It is concluded that useful additional information can be obtained from the EEG if young children are encouraged to sleep naturally during the recording, and that this can be done without sedation, even in a busy, routine EEG department.


Transtympanic neurectomy: a solution to drooling problems.

Thirty patients underwent transtympanic neurectomy because of severe drooling problems. Most of the group had cerebral palsy and/or mental retardation and the remainder had suffered brain damage. Their ages ranged from four to 56 years. There was improvement in drooling in 87 per cent of the group 14 months post-operatively, and there was no serious, irreversible complications. In this series of patients, transtympanic neurectomy has proved to be a safe and effective procedure for the control of drooling.


Control of drooling by translocation of parotid duct and extirpation of mandibular gland.

A modified Wilkie procedure, consisting of submandibular gland resection and parotid duct transplantation, has proven to be successful in controlling drooling in over 90 per cent of 120 patients with cerebral palsy and/or mental retardation. Follow-up ranges from one to six years. The operation is safe, effective and appears to be permanent.


Mucosal neuroma syndrome presenting in a neonate.

A case of multiple mucosal neuromata and a calcitonin-secreting medullary carcinoma of the thyroid is described. Unusual features were the neonatal presentation with large bowel obstruction and severe feeding difficulties associated with giant neuromata of the intestine; severe hypotonia; developmental delay; and the early recognition and treatment of an associated medullary carcinoma of the thyroid.


Congenital herpes simplex type II infection with extensive hepatic calcification, bone lesions and cataracts: complete postmortem examination.

True congenital herpes simplex viral (HSV) infections have been reported infrequently and have been associated with various 'congenital' malformations. Microcephaly, microphthalmia, intracranial calcifications, chorioretinitis, congenital heart disease and abnormal digits have been associated with presumed congenital HSV infection. This report describes the clinical and pathological features of an infant with a congenital type-II HSV infection. In addition to the findings previously reported with this form of HSV infection, extensive hepatic calcifications, osseous lesions and cataracts were observed for the first time. The effect of congenital HSV infection on the developing central nervous system is discussed.


Rhythmic habit patterns (stereotypies).

Rhythmic movements such as head-rolling, head-banging and body-rocking are seen in normal children in early life, but much more commonly in the mentally handicapped. Emotional disturbance and boredom tend to increase the movements. Various theories have been advanced to account for these stereotyped patterns. They appear to be intentional and may satisfy some inner need or allay frustations, but it is concluded that their true significance is unknown.


Mean transit time of solid test meals in gastric emptying.

Gastric emptying of a test meal labelled with 99Tcm-sulphur colloid has been studied in 9 healthy volunteers using a gamma-camera with on-line computer. Mean transit time (MTT) was determined by fitting the time-activity histogram to a gamma-variate, and the half-time of emptying (T1/2) was calculated by exponential fitting of the down-slope of the time-activity curve. MTT showed a smaller coefficient of variance than T1/2. This result suggests that MTT may be a more suitable parameter for definition of normal values and for the separation of normal from pathological patterns of emptying.


A modified leucocyte migration assay as indicator of malignant and non-malignant gastric mucosal alteration.

When gastric cancer patients' leucocytes were exposed to a panel of tumour extracts, leucocyte migration reactivity was "positive" before operation (90% of cases), it declined after surgery and it reappeared in patients with local recurrence or metastases. In patients with non-malignant gastric diseases, "positive" reactivity against tumour extracts was associated almost exclusively with atrophic gastritis with and without intestinal metaplasia (24/43 cases). "Positive" patients also showed a pathological migration index with an extract of normal gastric mucosa.


Biliary copper excretion in man and the rat.

The form in which copper is bound in bile was studied in bile from patients with Wilson's disease, control subjects and rats. Bile was labelled with 64Cu. Sephadex column chromatography using gels G-200--G-10 showed a major 64Cu and protein peak of about 5,000 daltons and a minor peak of about 8,000 daltons. A high-molecular-weight peak (above 800,000 daltons) which was present when the eluting solution consisted of water or saline was shown to be an artefact which could be abolished by the addition of bile salt to the eluting solution. Bile from control subjects, Wilson's disease patients and from the rats behaved in the same manner binding copper to low-molecular-weight proteins. The relationship of these findings to the pathogenesis of copper retention in Wilson's disease is discussed.


The epithelium in healing experimental standard lesions in the gastric mucosa of the rat. A light microscopical and scanning electron microscopical study.

In a series of experiments in rats, the movement of the advancing sheet of epithelial cells streaming from a border region into the woind bed of standardized defects in the glandular mucosa of the stomach was studied using the light microscope and the scanning electron microscope (SEM). A very high synthetic activity of mucus in gastric lining cells of the border region (with a typical shift in its reaction product towards a more acidly reacting product showing metachromasia with toluidine blue) was observed histochemically, together with a loss of characteristic features of glandular cells in the border region with an increase in mitotic activity. The SEM images enabled a detailed analysis of the advancing epithelial front in its relation to the border regions. Considerable local differences were noted in the moving pattern of the migrating epithelium, possibly in relation with the nature of the base on which it has to move. The lesion of 3 mm diameter appeared to close usually after 10 days; in some instances, however, small epithelial defects were later found which could easily be traced with the SEM.


"Luminal nutrition" versus "functional work-load" as controllers of mucosal morphology and epithelial replacement in the rat small intestine.

Isotonic solutions of substrate were infused into surgically prepared sacs of upper small intestine in conscious unrestrained rats which fed normally via the gut-in-continuity. Infusion of glucose, galactose or sodium chloride all caused a local increase in villus height, while alpha-methyl glucoside and mannose had no effect. Glucose, galactose and alpha-methyl glucoside all stimulated a similar increase in counts of vincristine metaphases in microdissected crypts. although the absolute level of cell production was lower throughout the gut in glucose-infused rats. Sodium chloride infusion also caused a small stimulation of cell production locally, but a considerable increase in the uninfused gut-in-continuity. Mannose infusion had a variable effect on cell production. These results do not support "luminal nutrition" as a controller of epithelial replacement in the rat small intestine, and suggest that a mechanism based on the work-load of the epithelial may be more appropriate.


Effects of chronic ethanol consumption on pancreatic response to central vagal stimulation by 2-deoxy-D-glucose in the rat.

Male Wistar rats, fed a standard normal laboratory diet, drank ad libitum a 20% ethanol solution for 3 months. Basal and 2-deoxy-D-glucose (2DG) stimulated pancreatic secretion were measured. Basal secretion of sodium (-30%, p less than 0.001), bicarbonate (-35%, p less than 0.001) and total protein (-35%, p less than 0.001) were depressed in alcoholic versus control rats. Pancreatic response was identical in both groups with the smaller dose of 2DG, dose related in controls, and identical for both doses in alcohol-fed rats. The response was thus significantly smaller in alcohol-fed rats than in controls for the larger dose of 2DG (p less than 0.01). Pancreatic concentration and contents of amylase, trypsinogen, chymotrypsinogen and lipase were all decreased in alcoholic versus control rats (40-60%, p less than 0.001). These results are consistent with the hypothesis of functional modifications in pancreatic cholinergic innervation in alcohol-fed rats.


Chronobiological study on serum innumoreactive gastrin RIA levels in patients with liver cirrhosis.

After days of standardized conditions of life and standardized diets, serum gastrin levels were measured in 6 patients with liver cirrhosis on 3 consecutive days and in 14 normal controls on 1 day. Blood samples were drawn every 4 h. In patients as well as in controls, a significant serum gastrin circadian rhythm was noted. The daily mean serum gastrin levels of patients were not significantly different from those of controls. These results suggest a secondary role of the liver in gastrin metabolism.


[Pre- and post-operative echocardiographic evaluations of mitral stenosis].

46 patients, affected by pure mitral stenosis, underwent echocardiographic study before and after mitral commissurotomy. The following echocardiographic parametres were considered: 1) closing velocity of anterior mitral leaflet (E-F slope); 2) amplitude of the mitral valve motion; 3) intensity and number of echoes coming from the mitral leaflet; 4) posterior leaflet motion; 5) left atrial diameter index; 6) right ventricolar diameter index; 7) left atrial and aorta diameter ratio. Moreover mitral diameter, mitral fibrosis or calcification, and possible mitral incontinence were evaluated intraoperatively before and after commissurotomy. The pre-operative echocardiographic examination of the mitral stenosis showed the following specific aspects: 1) reduced E-F slope, significantly correlated with the severity of the stenosis; 2) abnormally moving posterior mitral leaflet; 3) enlargement of the left atrium, directly correlated with the degree of the mitral stenosis. Correspondence was noted between the echocardiographic and the intraoperative evaluation of the anathomical pattern of mitral valve. Postoperatively the echocardiograms showed: 1) improved E-F slope, directly correlated with the surgical dilatation of the valve; 2) persistent abnormal movement of the posterior mitral leaflet; 3) disappeared correlation between the surgical diameter of mitral valve and the left atrial index. The ECHO proved to be a good diagnostic method for both a qualitative and a semiquantitative evaluation of mitral stenosis. The ECHO is also quite usefull in evaluating modifications induced by commissurotomy.


[Kinetics of beta-methyl-digoxin in various degrees of renal function].

A radioimmunologic assay method was employed for assessing the hematic and urinary levels of beta methyl-digoxin in patients with various degrees of renal function, evaluated by creatinine clearance test. Significantly elevated hematic values and reduced clearance rates of MD were observed only in patients whose creatinine clearance values were below 50 cc/min. A good correlation between values of creatinine and MD clearances and between their ratio and serum albumin levels was verified. The authors stress the usefulness of this ratio as an indirect index for the plasmatic percentage of the free and of the protein- bound fractions of MD.


[Evolutive study of the vectorcardiogram from the 14th day to the 6th month of life on the normal infant].

With the purpose of a better evaluation of the changes of cardiac potentials during the early hemodynamic arrangement of the normal heart, the authors analyze the VCG of 10 normal children periodically recorded from the 14th day to the 6th month from birth. Rotation of QRS, T and P loops in the three planes, direction and voltage of principal planar and spatial vectors were analyzed. The QRS loop showed a balanced distribution between right and left ventricular forces in the second week and developed a leftward orientation from the 4th week to the 3rd month, as demonstrated both by the loss of clockwise rotation of horizontal QRS loop and by the progressive leftward and backward direction of intermediate vectors. The initial vectors were sketched or absent in the 14th day and increased successively until the typical Q loop. The voltage of terminal vectors did not change in the course of time, but the S loop in the horizontal plane lost its original clockwise rotation and shifted to middle posterior line. The T loop progressively shifted backward so that it was always posterior after the 30th day. The P loop in the frontal plane was similar to the adult's one while in the horizontal plane it often presented a figure-of-eight. The semeiological aspects and the electrogenic considerations of these changes were discussed.


[Polysplenia. Description of a case].

A clinical and hemodynamic study of a case of polysplenia, with typical left bilateral symmetry, anomalies of systemic venous drainage and defect of the endocardial cushions. A brief revision of the literature is given and the embriological and clinical concept of the left bilateral symmetry is discussed.


[Intracardiac mycotic thrombosis in the course of permanent endocardial stimulation].

A case of intracardiac micotic thrombosis during permanent endocardial stimulation is reported. After a brief note on the pathogenesis of pocket infections, the AA. conclude that, in those cases, a medical treatment is insufficient and a surgical treatment is necessary to remove the micotic thrombus.


An in vitro study on the interaction between dimethylnitrosamine and nucleic acids via a microsomal system.

Radioactive alkylated bases, ribose or phosphate, were never found either in acid and alkaline hydrolysates of polyribonucleotides or in alkaline hydrolysates of DNA after incubation with 14C-dimethylnitrosamine (DMNA) in a microsomal system. Two radioactive compounds, which were co-chromatographed with methylamine and N-methylhydrazine, respectively, on column, paper, and thin-layer, were always detected. They differed from the compound derived from 7-methylguanosine after the alkali-mediated fission of the imidazole ring in its molecule. The in vitro system employed well represents the in vivo situation (7-methylguanine which is liberated from DNA after acid hydrolysis); however, it has given results which do not agree with the generally-accepted mechanism of DMNA alkylation at the N-7 position of guanine.


Effect of thymidine and thymidylate analogs on nucleic acid synthesis in tumor cells.

Synthetic 5'-amino-5'-deoxythymidine (5'-AdThd), alpha,beta-methylenethymidine diphosphate (alpha,beta-MTDP), and alpha,beta-methylenethimidine triphosphate (alpha,beta-MTTP) were found to inhibit thymidine kinase. Using thymidine kinase extracted from FM 3A/B cells (a strain of mouse mammary gland tumor cells), the Ki values of 5'-AdThd, alpha,beta-MTDP, and alpha,beta-MTTP against thymidine were calculated to be 9.2 X 10(-5)M, 2.3 X 10(-5) M, and 1.8 X 10(-5) M, respectively. At concentrations above their Ki values alpha,beta-MTDP and alpha,beta-MTTP did not inhibit incorporation of labeled thymidine into DNA of cultured cells, whereas 5'-AdThd did. Under the same conditions all three compounds inhibited TMP incorporation. The inhibitions of thymidine and TMP incorporation were specific, since the incorporation of deoxyguanosine was scarcely inhibired by 5'-AdThd. These results suggested that the specific inhibition of thymidine and TMP incorporation was mostly due to reduction in permeability of the cells to these substrates rather than to inhibition of thymidine kinase activity.


Summation effect of N-butyl-n-(4-hydroxybutyl)nitrosamine, N-(4-(5-nitro-2-furyl)-2-thiazoly)formamide, N-2-fluoroenylacetamide, and 3,3'-dichlorobenzidine on urinary bladder carcinogenesis in rats.

The effects of the sequential administration of 0.01% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), 0.15% N-(4-(5-nitro-2-furyl)-2-thiazoly)formamide (FANFT), 0.025% N-2-fluorenylacetamide (2-FAA), and 0.3% 3.3'-dichlorobenzidine (3,3'-DCB) on urinary bladder carcinogenesis were examined in male Wistar rats. Each chemical was administered for 4 weeks in various combinations. BBN for 4 weeks resulted in no histopathological changes, mild diffuse cell growth, and/or focal hyperplasia after 4, 8, 12, or 16 weeks of observation. No bladder carcinomas were present in rats given only BBN or any one of the other 3 chemicals. Statistically significant incidences of bladder carcinomas occurred with the sequential administration of all 4 chemicals or the first 3 chemicals without 3,3'-DCB. Bladder cancer was also present in rats administered the sequence of FANFT, 2-FAA, and 3,3'-DCB. No antagonistic effects between chemicals were observed.


Antitumor activity of a new antitumor antibiotic, sporamycin.

Sporamycin is an antitumor antibiotic isolated from the culture filtrate of Streptosporangium strain No. PO-357. Hydrolysate of the antibiotic showed at least 12 kinds of amino acid, and the molecular weight was calculated approximately as 8,500 approximately 9,000. Antitumor activities of Sporamycin were examined on murine tumors according to different schedules of treatment. After nine daily doses of the antibiotic had been given to dd mice bearing Ehrlich ascites carcinoma, significant increase of lifespan was observed at doses of 5.0 approximately 1.3 mg/kg. A marked decrease in tumor size of sarcoma-180 transplanted subcutaneously was observed when the mice were treated by daily or single injection of Sporamycin. Against leukemia P-388 and L-1210 inoculated intraperitoneally into CDF1 mice, the antibiotic increased lifespan of leukemic mice. The antibiotic also inhibited significantly the growth of human tumor cells in vitro.


Antitumor activity of N-heterocyclic carboxaldehyde thiosemicarbazone derivatives.

Antitumor activity of N-heterocyclic carboxaldehyde thiosemicarbazone derivatives was examined in ascites sarcoma-180 system. Among isoquinoline-1-carboxaldehyde thiosemicarbazone derivatives, the parent compound, IQ-1, was the most active and less toxic. On the other hand, among the pyridine-2-carboxaldehyde thiosemicarbazone derivatives tested, 5-acetoxymethyl and 5-isonicotinoyl derivatives were active, and their therapeutic indices were 190 and 54, respectively. In other tumor systems, acetoxymethyl derivative was markedly active against Ehrlich ascites carcinoma, leukemia L-1210, and leukemia C-1498, while moderately effective against Nakahara-Fukuoka sarcoma, but it was not active against adenocarcinoma-755. Isonicotinoyl derivative was markedly active against Ehrlich ascites carcinoma, leukemia L-1210, and leukemia C-1498, while moderately active against adenocarcinoma-755, and slightly active against Nakahara-Fukuoka sarcoma.


Isolation of a cell line insensitive to growth-restricting action of dextran sulfate from 3t6 cells.

In the medium containing dextran sulfate, 3T6 cells stopped growth at almost monolayer stage and showed decreased saturation density. This action of dextran sulfate is referred to as a growth restriction. About 70% of untreated 3T6 cells formed piled-up colonies whereas the remaining 30% formed monolayer colonies. Fraction of the latter increased with increasing concentration of dextran sulfate in the medium. Cell lines sensitive and insensitive to the growth-restricting action of the compound were cloned from colonical culture of the wild type cells. Sensitive cells showed a slightly less saturation density than the wild type cells in the presence of dextran sulfate. Insensitive cells grown in dextran sulfate medium showed almost the same growth rate and saturation density as the untreated wild type cells grown in the absence of the compound.


Comparative study of Corynebacterium parvum and Corynebacterium liquefaciens on antitumor activity against sarcoma-180.

Corynebacterium parvum and Corynebacterium liquefaciens were comparatively examined for their antitumor activity against sarcoma-180 in ddY mice. In the case of ascitic form, significant antitumor effect was observed when C. parvum was administered on days -4 and -2 or day -2. As for solid form, maximal effect was obtained when C. parvum was administered on day 0. On the other hand, C. liquefaciens exhibited maximal antitumor activity against sarcoma-180, both in ascitic and solid forms, when it was administered on days -4 and -2. However, no significant difference in respect to antitumor activity against sarcoma-180 was seen between C. parvum and C. liquefaciens (ascitic form, F1 118 = 0.09, P greater than 0.05; solid form, F1 53 = 0.03, P greater than 0.05).


Comparative studies on the antitumor activity and the bone marrow toxicity of 1-(beta-D-glucopyranosyl)-3-(2-chloroethyl)-3-nitrosourea and 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-glucopyranose.

Antitumor activity and bone marrow toxicity of a new nitrosourea analog, 1-(beta-D-glucopyranosyl)-3-(2-chloroethyl)-3-nitrosourea (GANU), were compared with those of 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-glucopyranose (Chlorozotocin) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). GANU was found to be highly active against mouse leukemia L-1210 when administered intraperitoneally or intravenously, being the same degree as Chlorozotocin. Even by oral route, GANU exhibited significant activities, whereas Chlorozotocin failed to show any activities by this route. Studies on the bone marrow toxicity as measured by the depression of white blood cell counts and the marrow cellularity revealed that both GANU and Chlorozotocin were less toxic than BCNU. GANU, however, weemed to be rather more toxic than Chlorotocin.


Treatment of gastric cancer, with special reference to the survivals of the cancer patients treated with multiple combination MFC therapy or immunochemotherapy of MFC plus OK-432 (NSC B116209).

Investigations were made on the survivals of 81 patients with advanced gastric cancer. Of these, 55 patients were treated with a combination chemotherapy of mitomycin C, 5-fluorouracil, and cytosine arabinoside (i.e., MFC therapy). Another 26 cases were treated with immunochemotherapy of MFC plus OK-432, an immunotherapeutic agent. Fifty percent survival times were 5.4 months for the MFC group, and 7.5 months for the MFC plus OK-432 group. One year survival rates of each group were 13 and 35 percent, respectively. The two year survival was null for the MFC group, and 13 percent for the MFC plus OK-432 group. Statistical analysis revealed that the survival curve of the MFC plus OK-432 decreased more slowly as compared with that of the MFC (p less than 0.05). In other words, the patients treated with MFC plus OK-432 showed a significantly longer survivals compared to the patients treated with MFC alone. Some cases were also presented for the better understanding of the immunochemotherapy of MFC plus OK-432.


Intestinal responses to hyperosmolar glucose infusion in dogs.

Physiological and morphological changes of small intestine after hyperosmolar glucose infusions into canine jejunum were studied using in vivo perfusion model. Infusions of 40 ml of 50% and 20% glucose solution into the jejunal loops induced biphasic osmolar degression in the lumen. Osmolarity of jejunal venous blood was rapidly increased and maintained the maximal level (approximately 320 mOM/L). Blood flow to the jejunal loop was significantly increased after 50% glucose infusion compared to 5% glucose infusion. Most characteristic electron microscopic change of jejunal epithelial cell was pseudo-pod like process projected into the jejunal lumen, which was very similar to that of cholera.


Serum glycoproteins in the liver diseases. III. Desialylated glycoproteins in the acute hepatitis.

Circulating desialylated glycoprotein level in acute hepatitis was studied by using the competitive binding assay reported by us. Statistically significant differences of the level among acute hepatitis in the peak of illness, fulminating hepatitis and normal subjects were observed. The desialylated glycoprotein level in acute hepatitis was elevated associating with S-GPT and serum bilirubin levels, and it returned to the normal range before S-GPT and serum bilirubin were normalized. The desialylated glycoprotein in a fulminant hepatitis was increasing associated with bilirubin even when S-GPT  was decreasing.


Serum glycoproteins in the liver diseases. IV. Alpha-1 acid glycoprotein level in liver cirrhosis.

Circulating alpha-1 acid glycoprotein level in cirrhotic patients was determined by radioimmunoassay, and was compared to the ones in normal subjects and chronic active hepatitis with sublobular necrosis. Serum alpha-1 acid glycoprotein levels in liver cirrhosis (p less than 0.001) and chronic active hepatitis with sublobular necrosis (p less than 0.02) were significantly reduced comparing to the normal subjects, although any statistically significant difference was not observed between the formers. In liver cirrhosis, thie serum alpha-1 acid glycoprotein level correlated negatively with serum albumin concentration but neither with serum alpha-1 globulin fraction nor with Indocyanine green clearance rate.


Experimental carcinoma of the biliary tract induced in dogs by N-ethyl-N'-nitro-N-nitrosoguanidine.

The present study was designed to produce the experimental carcinoma of the biliary tract in dogs. Tube cholecystostomy was constructed in 8 mongrel dogs and 5-10 ml of 0.7-1.0 mg/ml solution of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) was administered through the tube every day for the maximum period of 180 days. As the results: The experiment had to be cut off in 7 dogs (5 dogs: The tube was inadvertently pulled out. 2 dogs: died of general weakness). Pathological changes were observed in one dog given ENNG for 180 days and sacrificed at 372 days after the beginning of the experiment. Macroscopically, scattered foci of flat elevation of the mucosa were observed in the entire mucosal surface of common bile duct and a tiny polypoid lesion at the terminal protion. A tiny polypoid projection was adenocarcinoma confined to the mucosa, and areas of flat elevation showed marked hyperplasia of mucosa with partial atypical proliferation. No remarkable findings were noted in other organs.


Electron microscopic observation of the liver in portal hypertension following chronic exposure to vinyl chloride monomer.

Two patients with portal hypertension following chronic exposure to vinyl chloride monomer were studied histologically and ultrastructurally. Both cases showed non-cirrhotic portal hypertension accompanied by esophageal varices and splenomegaly. They proved hepatic fibrosis with conventional microscope. Ultrastructurally, there were large amounts of small myelin-like lamellar materials with electron density and remarkable proliferation and vesiculation of smooth endoplasmic reticulum in the cytoplasms of hepatocytes. The widened Disse's spaces, were the sinusoidal lining cells were arranged in multilayers, were plugged by collagenous fiber bundles. The finding may be consistent with the development of portal hypertension.


HLA-B5 associated with duodenal ulcer.

In a search for further genetic factors contributing to ulcer disease we undertook a study of the frequency of HLA antigens in patients with duodenal ulcer. Seventy-seven male patients (of two races) were typed for the HLA-A and-B loci. Thirteen of the 54 (24%) white males were found to have antigen B5 compared to 10% of controls. These results have a P value of 0.0016 which remains significant even when multiplied by the number of antigens tested (28). These results demonstrate a significant association between duodenal ulcer and HLA antigen B5 in white males, with a relative risk of 2.9, greater than that associated with the combination of blood group O and nonsecretor status.


Personality pattern of patients with chronic gastric ulcer. Study of neuroticism and extroversion in a gastric ulcer and a control population.

Forty-four patients with chronic gastric ulcer were compared with a control group matched for age, sex, and place of residence. The personality pattern was studied by the Eysenck Personality Inventory and personality assessed in terms of neuroticism and extroversion. The relevance of social class was also studied. The gastric ulcer population did not differ from the control group except among the male population, in which the gastric ulcer population was significantly more neurotic and less extroverted than their controls.


Effects of fundic distention on pentagastrin-stimulated gastric acid secretion in man.

The acid secretory effect of combined stimulation with balloon distention of the fundus and body of the stomach and intravenous infusion of pentagastrin has been studied in patients with duodenal ulcer (DU) and in healthy subjects. In 8 nonoperated DU subjects and in 5 DU patients subjected to proximal gastric vagotomy, low grade fundic distention moderately enhanced the acid output evoked by a threshold dose of pentagastrin. Fundic distention with a baloon volume eliciting a maximal acid response to distention either left unchanged or suppressed the maximal acid secretory rate produced by pentagastrin in 7 nonoperated and 6 vagotomized DU patients and in 5 healthy subjects. The heterogeneous secretory effects of maximal stimulus combination suggest that fundic distention has a complex action on acid secretion eliciting a hitherto unknown inhibitory effect as well as a cholinergic activation of the parietal cell area. This complex action may explain the failure of fundic distention to augment markedly the action of pentagastrin in the present study.


Relationship between gastric acid secretion, histopathology, and cell proliferation kinetics in human gastric mucosa.

Cell proliferation of gastric antral and fundic mucosa was studied in a series of patients with different gastric diseases. After in vitro incubation of endoscopic biopsies with tritiated thymidine, radioautographs were prepared by the dipping technique. The labeling indices were estimated, and the biopsies were classified according to the degree of gastritis. The peak acid output after "maximal" stimulation with histamine was also determined. A highly significant inverse correlation between peak acid output and the labeling indices in both antral and fundic mucosa was demonstrated. The correlation between the degree of gastritis and the labeling indices in antral and fundic mucosa was also statistically significant. The results indicate that a significant inverse relationship exists between the acid secretory capacity of the gastric mucosa and the rate of cell proliferation in both antral and fundic mucosa. Furthermore, the data suggest that an increasing degree of gastritis in human gastric mucosa is followed by an increased rate of epithelial cell proliferation.


Prospective evaluation of the pancreatic secretion of immunoreactive carcinoembryonic antigen, enzyme, and bicarbonate in patients suspected of having pancreatic cancer.

We undertook to test the recent suggestion that measurement of immunoreactive carcinoembryonic antigen (CEA) in pancreatic secretion may be useful in diagnosis of pancreatic cancer. Using duodenal intubation and a perfusion method in 57 cases, we measured the rate of pancreatic CEA secretion into the duodenum under basal saline perfusion, alone and with continuous intravenous infusion of secretin (2 clinical units per kg per hr) and of cholecystokinin-pancreozymin (CCK, 15 Crick-Harper-Raper units per kg per hr); and we compared the CEA output with secretion of trypsin, lipase, and bicarbonate under the same conditions. Subsequent laparotomy revealed pancreatic carcinoma in 25 patients, pancreatitis in 7, other intraabdominal malignancies in 6, and benign nonpancreatic disorders in 19. CEA output rates did not differentiate all pancreatic-cancer patients from other patients in any test condition. However, pancreatic enzyme outputs were abnormal with almost 90% of cancers of the pancreatic head and with 75% of cancers of the pancreatic body and tail. For detection of pancreatic cancer, enzyme and bicarbonate outputs in response to CCK are more accurate than pancreatic CEA or bicarbonate outputs in response to secretin. Since CCK-stimulated enzyme outputs can be related accurately to malabsorption (not reported here), we prefer them to bicarbonate output for assessment of pancreatic function.


Vasoactive intestinal peptide: a secretin-like partial agonist for pancreatic secretion in man.

The responses of pancreatic volume flow and bicarbonate output to intravenous vasoactive intestinal peptide (VIP, 0.8 to 3.2 microgram per kg per hr) and synthetic secretin (32.2 to 129 ng per kg per hr) were compared intraindividually in 5 healthy volunteers. Pure pancreatic juice was obtained by endoscopic cannulation of the main pancreatic duct. The mean +/- SEM observed maximal response of secretin-stimulated juice flow was 248 +/- 7 microliter per kg per 5 min, whereas the observed maximal response for VIP-evoked juice flow was 48 +/- 6 microliter per kg per 5 min. The observed maximal secretin-induced bicarbonate output was 30 +/- 2 muEq per kg per 5 min, and the maximal VIP-related response was 4.3 +/- 0.9 muEq per kg per 5 min. In addition to low efficacy, high dose requirements, and side effects (significant rise in pulse rate and cutaneous flushing at 3.2 micrograms per kg per hr) argue against a major physiological role of VIP as a hormonal stimulant of human pancreatic bicarbonate secretion.


Occurrence of gastrin in gastric juice, in antral secretion, and in antral perfusates of cats.

Large amounts of gastrin are present in vagally induced gastric juice of cats. This gastrin is secreted directly into the gastric lumen from the antral mucosa, because in experiments in which the stomach was divided into one antral and one corporeal pouch, most of the gastrin appeared in the antrum, only small amounts appearing in the acid gastric juice. When the antrum was perfused with a slightly alkaline buffer solution, parallel recordings of the gastrin release into the antral lumen and into the gastric venous outflow revealed more gastrin to be secreted per minute into the gastric lumen than into the blood (2 to 23 times as much). Electrical vagal stimulations caused an increased release of gastrin both into the antral lumen and into the circulation.


Gastric acid secretion in gastric fistula dogs after antral denervation and antrectomy.

Acid secretion in Pavlov pouches in dogs is known to increase after antrectomy in response to histamine and gastrin. Dogs with gastric fistulae were tested with histamine and tetragastrin as a control study. The vagal nerve fibers to the antrum were divided and the dogs underwent repeat testing. Finally an antrectomy was performed and final dose-response data  were collected. After antrectomy there was an increased acid response to histamine and tetragastrin. We postulate that the vagal fibers innervating the antrum are probably not a factor in this increase. Furthermore, we believe that the increased acid secretion after antrectomy observed in the dog and the decrease known to occur in the human being is a species difference and is not related to the pouch method of study used in earlier studies of the antrectomized dog.


Effects of anionic surfactants on hamster small intestinal membrane structure and function: relationship to surface activity.

The relationship of the surface properties of a group of anionic surfactants to their effects on intestinal water transport was studied. Dose-response inhibition of water transport in everted hamster jejunal segments was obtained with two long chain detergents (sodium dodecyl sulfate and dioctyl sodium sulfocuccinate), a fatty acid (ricinoleate), and dihydroxy bile salts (deoxycholate, chenodeoxycholate, and taurodeoxycholate), whereas no activity was seen with trihydroxy (cholate, glycocholate, and taurocholate) and tri-keto (dehydrocholate) bile salts. The relative effects on water transport were paralleled by their abilities to lyse the erythrocyte, a membrane model. These two biological effects were related to the surface properties of the agents, as determined by critical micelle concentration and surface tension reduction. We further characterized the action of deoxycholate on hamster small intestine, in vivo. Net water secretion was accompanied by increases in permeability of the mucosa to inulin, dextran, and albumin. These secretory and permeability changes were accompanied by both biochemical and histological alterations: exfoliation (DNA release), membrane effects (sucrase release), and shortened villi. Electron microscopy revealed extensive alteration of the brush border membrane with a decrease in binding of lanthanum and the development of permeability to tracer in villus tip cells. In contrast, taurocholate, which did not alter water transport, did not affect intestinal permeability or the brush border membrane. We believe that the surface properties of anionic surfactants cause changes in absorptive cell membranes which result in intestinal secretion.


Stimulation of mucosal growth in the rat ileum by bile and pancreatic secretions after jejunal resection.

After proximal small bowel resection, the remaining small intestine undergoes adaptive hyperplasia. The role of bile and pancreatic secretions in stimulating ileal mucosal growth after jejunectomy was studied. Male Sprague-Dawley rats were fed either standard rat chow or a liquid elemental diet, and were divided into four surgical groups: sham-operated; transplantation of the duodenal papilla (containing the bile and pancreatic ducts) into the ileum; 50% proximal small bowel resection (jejunectomy); and combined transplantation of the duodenal papilla into the ileum and 50% proximal small bowel resection. Four weeks after surgery the rats were killed and segments of ileum were assayed for total weight and mucosal weight, and for DNA and protein concentration per centimeter of segment. These measurements of mucosal mass were significantly increased in ileal segments adjacent to the transplanted duodenal papilla both in nonresected and jejunectomized rats, compared with their respective controls. Transplanting the duodenal papilla into the ileum significantly increased growth of the ileal mucosa after jejunectomy. The results indicate that bile and pancreatic secretions flowing into the ileal lumen stimulate mucosal growth and play a direct role in ileal adaptation to jejunal resection.


Acinar cell responsiveness to urecholine in the rat pancreas during fetal and early postnatal growth.

These studies were performed to determine when, during fetal or postnatal life, rat pancreatic acinar cells acquire their capacity to respond to cholinergic drugs. The release of amylase, lipase, and chymotrypsin from rat pancreas in response to urecholine was measured in vitro. Fetal and newborn pancreas did not respond to 10(-5) M urecholine; 3-day- to 15-day-old pancreas demonstrated an increasing response to this dose. Peak sensitivity when compared to adult pancreas was present between days 15 and 21. Our results indicate that the exocrine pancreas acquired a responsiveness to urecholine on the 3rd day of postnatal life and becomes more sensitive to stimulation from the 15th day.


Complications of diuresis in the alcoholic patient with ascites: a controlled trial.

Forty-three patients with decompensated alcoholic liver disease and ascites of recent onset were randomized to salt and water restriction alone (control group) or to salt and water restriction plus diuretics (diuresis group). The two treatment groups were comparable in clinical findings and laboratory results. Seven patients in the control group and 5 patients in the diuresis group died during the acute illness. Weight loss was more marked and the disappearance of ascites more common in those given diuretics. A modest decrease in serum sodium and increase in serum potassium, and readily reversible elevations of blood urea nitrogen were noted in the diuresis group. Eight patients in each treatment group developed either the hepatorenal syndrome, marked electrolyte abnormalities, or encephalopathy. Diuresis can be accomplished in these critically ill patients without serious complications that can be attributed to the diuretic treatment.


Detection of endotoxin in plasma and ascitic fluid of patients with cirrhosis: its clinical significance.

Endotoxin was measured by the Limulus assay in plasma and ascites in 46 patients with cirrhosis having demonstrable esophageal varices, of whom 29 had ascites and 17 did not. It was positive in ascitic fluid in 23 (79.3%) of the former group. In plasma, a positive test was obtained in 22 (75.9%) in the group with ascites and only 4 (23.5%) without ascites, the difference being significant (P less than 0.01). Of the 23 positive ascites specimens, 17 showed high titers (greater than or equal to 10(-3) microgram per ml). Hepatic uptake of 198Au colloid was markedly reduced in 11 of the 17 patients with endotoxemia who were studied by scanning. Death occurred within 6 months in 47.8% of the patients with a positive endotoxin test, whereas only 16.7% of those with a negative test died in the same period (P less than 0.05). No hypotension was noted in patients with toxemia and only 2 ran a fever above 37.5 degrees C. Development of tolerance to endotoxin is suspected. A follow-up study has demonstrated sustained endotoxemia in some of these patients.


Significance of suspected "chronic aggressive hepatitis" in acute hepatitis.

Transition from acute to chronic hepatitis has important prognostic and therapeutic implications. In 17 patients with acute viral hepatitis, observed during a period of 7 years, a liver biopsy showed changes compatible with chronic aggressive hepatitis and superimposed acute hepatitis. Follow-up biopsies showed normal liver in 14 cases, chronic persistent hepatitis in 1, and cirrhosis in 2. In 12 cases the initial biopsy which showed changes suggestive of chronicity was taken 1 month after onset of symptoms of acute hepatitis, or later. Cases developing chronic liver disease showed no characteristic clinical, laboratory, or histological features at the time of the first biopsy. If the diagnosis of chronic active hepatitis is based on histological findings alone in patients with prolonged acute hepatitis, the incidence of this condition will be grossly overestimated. The transition from acute to chronic hepatitis cannot be recognized with any degree of certainty by presently available methods.


In vitro studies on IgG-mediated lymphocyte cytotoxicity in chronic active liver disease.

Antibody-dependent cytotoxicity in chronic active liver disease (CALD) (10 subjects), mediated by allogeneic nonimmune lymphocytes (NL), was studied in vitro. NL in significant numbers adhered to the surface of target Chang monolayer cells, pretreated with the sera of CALD patients (immune adherence of NL) and were cytotoxic. This was blocked by anti-IgG and IgGFc. Test sera, absorbed with Chang cells or human adult liver tissues, failed to provoke target Chang cell lysis. Small amounts of granular-appearing IgG were demonstrated on the surface of Chang cells treated with the CALD sera from 8 of the 10 patients (membrane-fixed IgG). It is concluded that the antibody-dependent cellular cytotoxicity in this in vitro system is mediated by the IgG of CALD sera, most likely bound to target cell surface antigens, and that effector NL appear to lyse the target cells by direct contact through the Fc portion of the above membrane-fixed IgG. This immune cytotoxic process may play a role in the pathogenesis of CALD.


Giant multinucleated hepatocytes in an adult with chronic active hepatitis.

A case of an adult with chronic active hepatitis associated with giant multinucleated liver cells is presented. The giant liver cells in this case are widespread and the picture resembles neonatal hepatitis. The morphology, pathogenesis, and epidemiology of giant hepatocytes found in human neonates and adults and in experimental animals is discussed. Because the proliferative phase of giant hepatic cells is transient, this reaction may be more common than generally believed.


Cirrhotic pleural effusion in the absence of ascites.

A 61-year-old female presented with a right transudative pleural effusion in the absence of ascites and other stigmata of chronic liver disease. A diagnosis of cirrhosis with a secondary hydrothorax was eventually established; however, ascites could never be demonstrated clinically or radiographically until just before her death, when hypertonic saline was administered for symptomatic hyponatremia. Based on the autopsy finding of a 1-mm hole in the right diaphragm and her clinical course, a mechanism for the production of a cirrhotic pleural effusion in the absence of asictes is proposed.


Progression of Menetrier's disease with postoperative gastrojejunal intussusception.

A unique case of Menetrier's disease of the stomach with long term follow-up is presented to document progression of extent of the disease radiologically and pathologically. This observation provides an insight into the natural history of the condition and suggests that local excision is not necessarily curative. In addition, this case demonstrates the complication of preoperative direct prolapse of involved gastric mucosa through the pylorus, and subsequent postoperative antegrade intussusception of the progressively involved gastric mucosa across a Billroth II gastrojejunostomy.


Can the singularity of chronic peptic ulcers be described by catastrophe theory and explained by biofeedback?

The damaging effect of hydrochloric acid within the lumen of the stomach and duodenum should be diffuse, but chronic peptic ulcers are discrete and usually single. The search for localizing effects on acid attack, or localized defects in mucosal defense have so far been fruitless. If attacking forces increase, or mucosal defense diminishes to the point where ulceration occurs, mucosal breakdown should be progressive. In chronic peptic ulceration, however, the process usually seems to be self-limiting. The catastrophe theory of René Thom may describe the progressive change in the forces that leads to eventual breakdown in mucosal continuity. Possibly this catastrophe triggers off biofeedback mechanisms that hold in check further progress of the ulcer.


Transient neutropenia in a patient receiving cimetidine.

Transient neutropenia developed in a 62-year-old, white male on maintenance hemodialysis being treated with cimetidine for an in tractable duodenal ulcer. The probable mechanism was peripheral destruction of the granulocyte series, unlike the marrow depression reported with metiamide, another histamine H2 receptor antagonist.


The liver during and after fulminant hepatitis.

Within 5 to 14 days of onset of grade 3 or 4 coma, liver biopsies were obtained in 14 of 15 consecutive patients who recovered from fulminant hepatitis. In 9 patients, follow-up biopsy was obtained 6 to 60 months after acute hepatitis and autopsy was performed in 2 patients who died in 4 months from complications of hepatitis (aplastic anemia) or of corticosteroid therapy (sepsis). During fulminant illness the biopsy findings were: multilobular necrosis in 4 patients, confluent (bridging) necrosis in 9, and only portal inflammation in 1. The duration or the grade of coma did not correlate with the severity of necrosis on the biopsy. Follow-up biopsy showed development of chronic (active) hepatitis in 3 of 9 patients (with cirrhosis in one of these). Chronic liver disease was not found in the two autopsies. If fulminant hepatitis is the result of vigorous cell-mediated immune attack on hepatocytes, then this process cannot always eradicate chronic hepatitis B surface antigenemia, nor can it always prevent the development of chronic (active) hepatitis or cirrhosis.


Lipolysosomes in human liver: distribution in livers with fatty infiltration.

In this study we investigated whether lipolysosomes--lysosomes containing large lipid droplets--were present in livers of patients with various forms of hepatic injury. Organelles which displayed the same morphological characteristics and enzymatic activity as those originally described in the hamster and those found in the hepatocytes of patients with Wolman's or Wilson's disease were also found in hepatocytes of 13 of 14 randomly selected biopsy specimens from patients with minimal to severe fatty infiltration of the liver. The numbers and sizes of the lipolysosomes seemed to increase with the degree of fatty infiltration while their proportion in relation to the total number of lipid droplets remained below 5%. Based on these observations of a virtually constant association of lipolysosomes with excess lipid accumulation in liver cells we suggest that lysosomes probably play an important role in hepatic lipid metabolism and that various pathogenetic mechanisms may trigger their proliferation.


Idiopathic hemochromatosis and iron overload in alcoholic liver disease: differentiation by HLA phenotype.

HLA A and B antigens were determined in two groups of patients: 38 patients with idiopathic hemochromatosis (IH) and 22 patients with iron overload accompanying alcoholic liver disease (AH). As previously described, HLA A3 and HLA B14 antigens appeared more frequently in the IH group (76.3 and 28.9%, respectively) than in a control group of 204 subjects (27 and 3.4%). In the AH group the frequency of A3 (22.7%) and B14 (13.6%) was not significantly different from that observed in controls. The frequency of A3 was significantly lower in the AH group than in the IH group (P less than 0.001). On this basis a clear difference appears between the two conditions with iron overload, and genetic analysis of the results rules out the hypothesis that AH would be a heterozygous form of IH exposed by alcohol.


Diagnostic usefulness of plasma carcinoembryonic antigen levels in acute and chronic liver disease.

Raised plasma carcinoembryonic antigen (CEA) levels were found in over 90% of 71 patients with chronic liver disease and 50% of 16 patients with acute liver damage. Levels increasing chronicity and clinical severity of disease. In individual patients, the plasma CEA level fluctuated with the clinical condition. Persistently normal levels were never found in patients with chronic liver disease in poor clinical condition. A very high level suggests a bad prognosis. If CEA is considered together with SGPT, a discriminant function can be calculated, separating patients with acute liver damage and those with an acute exacerbation of chronic active hepatitis, with a high degree of certainty. In acute damage, peak CEA levels occur later than the time of maximum liver necrosis, suggesting that the rise is not owing to release of CEA from damaged cells. There is no significant difference in CEA level between patients with and without spontaneous or surgical portosystemic shunts, suggesting that high levels are not attributable to bypass of the liver. The timing of the rise in CEA in acute liver damage suggests that raised levels may be associated with regeneration. The tendency for higher levels to occur in those patients with greater disturbances of liver function suggests altered metabolism or excretion of CEA.


Survival in patients with postnecrotic cirrhosis and Laennec's cirrhosis undergoing therapeutic portacaval shunt.

Survival rates were compared in 82 patients who underwent therapeutic portacaval shunt. All patients were followed for at least 5 years after shunt or until death. Survival rates were calculated by Life Table methods. Based on a combination of currently accepted histological and clinical criteria, there were 45 patients with Laennec's cirrhosis, 29 patients with postnecrotic cirrhosis, 11 of whom had histological evidence of chronic active hepatitis, and 8 patients with primary biliary cirrhosis. Survival rates were similar in all three groups, alcoholic cirrhosis, postnecrotic cirrhosis, and primary biliary cirrhosis. Hepatic reserve, as defined by Child's classification, provided the best criteria for predicting survival. The type of shunt, end-to-side, side-to-side, or splenorenal, did not influence survival. Histological evidence of chronic active hepatitis adversely affected survival in patients with postnecrotic cirrhosis. However, histological evidence of ongoing alcoholic hepatitis in patients with Laennec's cirrhosis did not influence survival adversely. The data indicate that once a patient with cirrhosis has bled from esophageal varices, the etiology of the cirrhosis is not a major factor in determining survival after a therapeutic portacaval shunt.


Diagnostic accuracy of fiberendoscopy in the detection of upper intestinal malignancy. A follow-up analysis.

The accuracy of fiberendoscopy with directed biopsy in the detection of upper intestinal malignancies has been evaluated by studying the operative or postmortem findings or the clinical follow-up data after at least 1 year and, for relevant lesions, after 2 or 3 years. Of 1005 patients examined, a satisfactory follow-up was obtained in 990. There turned out to be no false-positive diagnoses of malignancy in the 167 patients diagnosed fiberendoscopically to harbor an upper intestinal malignancy, and only two false-negative diagnoses in the fiberendoscopically benign group. Seven of the 135 adenocarcinomas of the stomach turned out to be early gastric cancers. The two missed malignancies were interpreted initially as benign gastric ulcers. The over-all endoscopic-bioptic accuracy rate calculated for all patients amounts to 99.8%. Such a high accuracy rate can only be reached provided high numbers of biopsies are taken, and particularly at least 10 of gastric ulcers and of suspicious lesions. Endoscopy by itself is not sufficiently reliable in determining the nature of the lesion. Indeed an incorrect endoscopic interpretation was made in 7.3% of the ulcerous lesions, and in 8.2% of them no firm conclusion could be reached.


Carcinoembryonic antigen in colonic lavage.

Colonoscopic lavage was performed for assay of carcinoembryonic antigen (CEA) concentration in patients with small and large colonic adenomas, in patients with adenocarcinoma of the colon, and in normal controls. CEA concentration was considerably higher in colonoscopic lavage as compared to plasma. CEA concentration in normal controls and in patients with colonic adenomas less than 1 cm in size were not significantly different. CEA concentrations in patients with colonic adenomas greater than 1 cm in size and in patients with adenocarcinoma of the colon were significantly higher than those observed in patients with small adenomas and in the normal controls. In all except 2 patients, plasma CEA concentrations were normal. Assay of CEA concentrations in colonic lavage may have potential application in the further assessment of the mucosa at risk for colon adenomas and for colon cancer. It does not appear to be accurate enough for diagnosis of colon cancer in individual patients.


Is there an oxyntopyloric reflex for release of gastrin in man?

Plasma gastrin concentrations and gastric acid output were measured during graded balloon distention of the gastric fundus and body in 20 patients with duodenal ulcer. Acid output rose stepwise with increasing distention volumes but plasma gastrin remained unchanged. During intragastric neutralization in 5 of these subjects, fundic distention did not elicit a significant rise in plasma gastrin, whereas the acid response was similar to that observed in the control study when the gastric contents were acid. In 8 of  the 20 patients, proximal gastric vagotomy profoundly suppressed the acid response to fundic distention. Basal plasma gastrin concentrations were elevated after vagotomy but were unchanged during graded fundic distention. The results suggest that neural reflex activation of the oxyntic glands is the main mechanism by which fundic distention stimulates acid secretion in man. The failure of fundic distention to release gastrin does not, however, completely rule out the existence of an oxyntopyloric distention reflex for gastrin release in man. Fundic distention in man seems to both stimulate acid secretion and induce an inhibitory mechanism acting on acid secretion. This inhibitory mechanism may, purely speculatively, also mask the effect of an oxyntopyloric reflex for gastrin release. The present study and earlier work suggest that in man distention of the stomach is a poor stimulus for release of gastrin, regardless of whether the pyloric or the oxyntic gland area, or both, are distended.


Simultaneous measurement of basal pancreatic, gastric acid secretion, plasma gastrin, and secretin during smoking.

The effect of smoking one unfiltered cigarette every 15 min for 1 hr on basal gastric acid and pancreatic secretion was studied in 10 subjects with a history of duodenal ulcer and 10 without duodenal ulcer. Smoking induced a transient rise of basal acid output followed by a slight decrease. This effect was more pronounced in the duodenal ulcer group. Smoking markedly inhibited fluid and bicarbonate secretion during the smoking period. The bicarbonate and fluid secretion returned to control levels within 30 to 60 min in the ulcer group and in 60 to 90 min in the nonulcer group. There was no difference in the degree of inhibition of pancreatic secretion between the two groups. Immunoreactive gastrin and secretin in the peripheral venous blood did not change significantly during smoking. The degree of inhibition of basal pancreatic secretion correlated well with the plasma concentrations of nicotine. These observations indicate that smoking in the fasting state induces alterations of basal gastric and pancreatic secretions which are not related to changes in plasma gastrin and secretin concentration, but to plasma concentrations of nicotine. The implication of this study in relation to a possible causal association between cigarette smoking and peptic ulcer disease is discussed.


Clindamycin-associated colitis in hamsters: protection with vancomycin.

Clindamycin and lincomycin produced a lethal enterocolitis in 65 of 67 Syrian hamsters. The administration of oral or parenteral vancomycin to recipients of clindamycin or lincomycin was uniformly protective in 49 patients. These results suggest that certain bacteria play a role in the pathogenesis of enterocolitis in this model.


Gastric secretory effect of amino acids given enterally and parenterally in dogs.

To investigate the possible role of absorbed amino acids in the "intestinal phase" of gastric secretion, experiments were carried out in 5 mongrel dogs with Heidenhain pouches, gastrostomies, and Roux en-Y jejunostomises. A 3% solution of mixed amino acids was infused at a constant rate of 120 ml per hr throughout a 2-hr period either intravenously or intrajejunally, and the secretory response of the pouches was compared to that obtained during similar infusions of 0.9% NaCl. Intravenous administration of saline did not stimulate gastric secretion. The mean secretory responses (muEq per 2 hr) were: intrajejunal saline 37, intravenous amino acids 330, and intrajejunal amino acids 301. These results suggest that amino acids, absorbed from the gut, may play a role in the stimulation of gastric secretion which occurs when food passes through the intestine.


Pharmacotherapy of an ulcer in Barrett's esophagus: carbenoxalone and cimetidine.

A 70-year old man is described who had specialized columnar epithelium in the esophagus up to the upper esophageal sphincter, 19 cm from the incisor teeth. The patient had a small sliding hiatus hernia but the lower esophageal sphincter was located at 39-41 cm. Above the sphincter the patient had large peptic ulcers which failed to heal after 1 year of a conventional antireflex regimen. Carbenoxalone sodium administration led to healing in 3 months. However, the ulcers recurred after discontinuation of the drug. On a second attempt carbenoxalone effected modest healing but was stopped because of hypertension and hypokalemia. Cimetidine therapy led to complete healing of the the ulcer within a month. The authors concluded that both carbenoxalone and cimetidine are useful in the treatment of an ulcer in Barrett's esophagus. However, cimetidine may be more rapidly effective and does not produce dangerous side effects.


Effect of vasoactive intestinal polypeptide on basal and cholecystokinin-induced gallbladder pressure.

Studies were conducted in vivo to examine the pressure response of the opossum gallbladder to vasoactive intestinal polypeptide (VIP) alone and in combination with cholecystokinin (CCK). The following observations were made (1) VIP alone produced dose-related decreases in basal gallbladder pressure; (2) VIP eliminated spontaneous contractile activity when present; (3) VIP significantly antagonized the expected pressure response to CCK infusion. These observations lend further support to our proposal that the regulation of gallbladder motor function depends upon the actions and interactions of the gastrointestinal hormones on gallbladder smooth muscle.


Mutator mutations in bacteriophage T4 gene 42 (dHMC hydroxymethylase).

Temperature-sensitive mutations of bacteriophage T4 gene 42 produce diverse effects upon spontaneous mutation rate. G:C vector A:T transition rates are increased, often strongly; frameshift mutation rates are weakly increased; A:T vector G:C transition rates (and perhaps also A:T vector Py:Pu transversion rates) are decreased; and one G:C vector Py:Pu transversion rate is also decreased. These results, together with certain interactions between gene-42 mutator effects and both base analogue mutagenesis and the viral error-prone repair system, suggest that the dHMC hydroxymethylase coded by gene 42 affects mutation rates in a more complex manner than by the simple regulation of the concentration of the DNA precursor dHMCTP.


Virus-like particles in Ustilago maydis: mutants with partial genomes.

Mutants with partial genomes for the virus-like particles of U. maydis were recovered following treatment with nitrosoguanidine. Examination of the properties retained by progeny of genetic crosses indicates that the 2.9 X 10(6) dalton component of double-stranded RNA contains the information for capsid formation and dsRNA replication. Other components appear to contain the information for killer function and immunity to killer. The use of such mutants for studies on the evolution of viruses with segmented genomes is discussed.


Estimation of the number of sex alleles and queen matings from diploid male frequencies in a population of Apis mellifera.

The distribution of diploid males in a population of Apis mellifera was obtained by direct examination of the sexual phenotypes of the larvae. Using these data, estimates are derived for the number of sex alleles and the number or matings undergone by the queen. The number of sex alleles is estimated to be 18.9. The estimate is larger than previous ones, which have ranged between 10 and 12. However, the increase in the number of sex alleles can be explained by the large effective population number for our data. The best estimator of the number of matings by a queen is a maximum likelihood type that assumes a prior distribution on the number of matings. For the data presented here, this estimate is 17.3. This estimate is compared to others in the literature obtained by different approaches.


The evolution of epistasis and the advantage of recombination in populations of bacteriophage T4.

Experiments reported here test two hypotheses about the evolution of recombination: first, the Fisher-Muller concept that sexual organisms respond to selection more rapidly than do asexual ones, and second, that epistasis is more likely to evolve in the absence of recombination. Populations of bacterio-phage T4 were selected by the drug proflavine in discrete generations and the change in mean population fitness was monitored. Three separate selection series yielded results supporting the Fisher-Muller hypothesis. The amount of epistasis evolved was measured by partitioning the T4 map into regions and comparing the sum of the proflavine resistances of each region with the resistance of the whole. Significantly more interactions were found in phage isolated from the populations with lower total recombination than in those from populations with higher recombination. The degree to which these experiments fit preconceived notions about natural selection suggests that microorganisms may be advantageously used in other population genetics experiments.


Phylogenies constrained by the crossover process as illustrated by human hemoglobins and a thirteen-cycle, eleven-amino-acid repeat in human apolipoprotein A-I.

Examination of human apolipoprotein A-I revealed a segment of eleven amino acids that repeated itself 13 times in succession without any additional intervening amino acids between the beginning of the repeats (amino acid 93) and their end at the carboxyl terminus of the sequence. The segments are not identical, but the pattern of their physical and chemical properties is highly conserved. The pattern is shown to be suitable to the formation of alpha helices with an amphipathic character consistent with the formation of a micellar structure, a process entirely appropriate to the protein's known function in the blood stream as a lipid carrier. The simplest hypothesis to account for repeated segments is a series of unequal crossovers. But such a series implies that some segments are more closely related to each other than they are to others, that is, they have a "phylogenetic" relationship. It is shown that only a small fraction of all possible phylogenies are consistent with a set of segments arising by simple unequal crossing over. Nevertheless, it is shown that the apolipoprotein A-I segments are readily interpretable as the result of simple unequal crossing over. Moreover, the crossover constraint applies with as much force to segments larger than a gene as to segments within a gene, and this is shown to require that the human gamma (Gly) hemoglobin gene lie to the left, rather than to the right, of the other non-alpha human hemoglobin genes, a conclusion for which there is no direct genetic evidence currently available.


Three linked enzyme loci in fishes: implications in the evolution of vertebrate chromosomes.

A three-point linkage group comprised of loci coding for adenosine deaminase (ADA), glucose-6-phosphate dehydrogenase (G6PDH), and 6-phospho-gluconate dehydrogenase (6PGD) is described in fish of the genus Xiphophorus (Poeciliidae). The alleles at loci in this group were shown to assort independently from the alleles at three other loci--isocitrate dehydrogenase 1 and 2, and glyceraldehyde-3-phosphate dehydrogenase 1. Alleles at the latter three loci also assort independently from each other. Data were obtained by observing the segregation of electrophoretically variant alleles in reciprocal backcross hybrids derived from crosses between either X. helleri guentheri or X. h. strigatus and X. maculatus. The linkage component of chi2 was significant (less than 0.01) in all crosses, indicating that the linkage group is conserved in all populations of both species of Xiphophorus examined. While data from X. h. guentheri backcrosses indicate the linkage relationship ADA--6%--G6PDH--24%--6PGD, and ADA--29%--6PGD (30% when corrected for double crossovers), data from backcrosses involving strigatus, while supporting the same gene order, yielded significantly different recombination frequencies. The likelihood of the difference being due to an inversion could not be separated from the possibility of a sex effect on recombination in the present data. The linkage of 6PGD and G6PDH has been shown to exist in species of at least three classes of vertebrates, indicating the possibility of evolutionary conservation of this linkage.


The detection of sympatric sibling species using genetic correlation analysis. I. Two loci, two gamodemes.

Four models are presented describing zygotic frequencies at two loci for one or two sympatric but genetically differentiated populations of "gamodemes." Linkage disequilibrium within gamodemes is allowed in two of the models. Maximum likelihood criteria are used to fit the models to the observed numbers of zygotes in a sample. A fitting-testing sequence for choosing a best model is described and the power of the test is analyzed. The statistical characteristics of the genetic parameter estimates were examined by simulation studies. In general, estimates were reliable when allele frequency differences between gamodemes were greater than 0.30 at both loci. This method may be used to study the population structure of samples with fewer heterozygotes than expected for Hardy-Weinberg populations, including the detection and genetic description of sibling species having overlapping ranges.--An example is given for Drosophila longicornis and D. propachuca, two sibling species within the mulleri complex of the repleta group which have been studied in detail using more conventional techniques. The reanalysis using the approach derived in this paper confirmed the reproductive isolation of these two species, and hinted at the possibility of further subdivision within D. propachuca.


A model of functional epistasis and linkage disequilibrium in populations with overlapping generations.

A model of functional epistasis is proposed in which it is assumed that coupling and repulsion genotypes differ in metabolic efficiency and thus in development time and net fecundity. The implications of this model are investigated for iteroparous populations with fluctuating rates of increase. It is found that the fluctuations in rate of increase can lead to large fluctuations in gamete frequency and D, the coefficient of linkage disequilibrium, but that D will almost always have a value of zero at some point during the populations' demographic cycle. Some of the model populations would be expected to be in a state of linkage disequilibrium only fleetingly: others would exhibit D-cycles interpretable as random fluctuation. Implications of the model for interpretations of existing data on linkage disequilibrium among enzyme loci in Drosophila are discussed.


Mutation-selection balance with stochastic selection.

Diffusion theory has been used to analyze a model of mutation-selection balance in which the selection process is assumed to be stochastic in time. The limiting outcome of the mutation-stochastic selection process is determined qualitatively by the geometric mean fitnesses of the genotypes, and the conditions for fixation or polymorphism are similar to those that determine the outcome of the mutation-selection process when selection is constant. However, in the case of a completely recessive allele, detailed numerical study of the polymorphism associated with stochastic selection has shown that the average allele frequency maintained is greater than the equilibrium frequency expected when selection is constant, even when the geometric mean fitness of the recessive homozygotes is identical in the stochastic and deterministic models. Thus, allele frequencies in natural populations that are too high to be plausibly explained by a balance between mutation and constant selection can be accounted for if selection is stochastic.


Identity coefficients in finite populations. I. Evolution of identity coefficients in a random mating diploid dioecious population.

Properties of identity relation between genes are discussed, and a derivation of recurrent equations of identity coefficients in a random mating, diploid dioecious population is presented. Computations are run by repeated matrix multiplication. Results show that for effective population size (Ne) larger than 16 and no mutation, a given identity coefficient at any time t can be expressed approximately as a function of (1--f), (1--f)3 and (1--f)6, where f is the mean inbreeding coefficient at time t. Tables are presented, for small Ne values and extreme sex ratios, showing the pattern of change in the identity coefficients over time. The pattern of evolution of identity coefficients is also presented and discussed with respect to Neu, where u is the mutation rate. Applications of these results to the evolution of genetic variability within and between inbred lines are discussed.


[Cytogenetic activity of the pesticides phthalophos, chlorophos and gardona in a culture of human lymphocytes].

The cytogenetic action of three phosphoorganic pesticides, imidan, dipterex and gardona, in cultured human lymphocytes is studied. It is found that all the sunstances induce the signficant increase in the frequency of metaphases with chromosomes aberrations as compared with the control level. Maximal effects in vitro qere 6,0; 4,8 and 4,0% of aberrant cells for imidan, dipterex and gardona respectively. All investigated substances had a weak mutagenic activity in human lymphocyte culture.


[Inheritability of blood metabolite concentrations in cattle at different age periods and seasons of the year].

Coefficients of heritability of lipid, carbohydrate and protein-nitrous blood metabolites were studied through comparison of mothers and their daughters at different age periods (6, 9, 12, 15, 18 months and the 1st lactation) and seasons. The highest and most statistically significant are heritability coefficients of triglycerides, phospholipids, cholesterin, total lipids; coefficients of acetic acid, 3-hydroxybutyric acid, acetone and acetylacetic acid and blood glucose are lower. The highest coefficients of heritability among protein-nitrous metabolites are those of globulins; coefficients of albumins, total protein, blood amino nitrogen are lower. Heritability coefficients of blood metabolites, except albumins, globulins and glucose are stable enough at different age periods. No pronounced season differences are observed. The presence of high and statistically significant heritability coefficients of a number of blood metabolites, their age and season stability indicate the possibility of using these metabolites as additional tests in selection of dairy cattle.


[Further genetic analysis of mink serum Lpm-allotypes].

The results obtained by testing 3127 mink sera as well as the analysis of families completely confirmed that the Lpm allotype system of very high density proteins is under genetic control, as postulated earlier. The polymorphism of the first five allotypes is due to the genetic units Lpm1, Lpm4, Lpm1,2, Lpm3,4 and Lpm2,4,5, which behave as Mendelian alleles. The data obtained suggest the existence of an additional gene, LpmX, which, in the homozygous state, determines a very rare phenotype, negative for the first five markers.


[Isolation and preliminary characteristics of the extrachromosomal elements of Bacillus thuringiensis DNA].

Centrifugation of Bacillus thuringiensis 351 DNA in CsCl-ethidium bromide density gradient has revealed, besides the main band of chromosomal DNA (p = 1.56 g/cm2), some additional bands with higher density, which usually correspond cicle superhelix DNAs, are revealed. 6 discrete bands are observed under electrophoresis of total fraction of minor DNA bands, which suggests, that the preparation contains cicle DNAs of different size. The treatment with DNAse results in the appearance of 3 bands corresponding to opened cicle DNA forms, their molecular weight being 12-10(6)--4-10(6) daltons. Cicle super-helix and opened cicle DNA forms are found in minor fraction by means of electrone microscopy. Statistical analysis has revealed the presence of at least three types of cicle molecules of different size. The variant 351-10, free of extrachromosomal elements, is isolated after ethidium bromide treatment at high temperature. Possible mechanisms of cicle DNAs formation are discussed. Biological function of DNA extrachromosomes fragments in Bacillus thuringiensis is still obscure.


[Recombination in amber mutants of bacteriophage T4B. III. Influence of X-mutation on intragenic recombination in T4 phages].

Study was made of the influence of X-mutation on interallelic and intergenic recombination at the region of genes 34-38 of phage T4B. In the case of intergenic crosses in all studied recombinations of genes mutation X caused a 2-fold decrease in recombination frequency. X-mutation showed the same effect on integenic recombination in genes 36 and 38. In the case of crossing flank markers of gene 35 the frequency of recombination decreased 3.5-fold, that of gene 34--6 fold. Crosses of double am-X mutants mapped at different sites of gene 34 allowed to detect the gradient of the effect X-mutation on recombination in gene 34 in the direction from gene 33 to gene 35. The data obtained indicate a local anomaly of DNA structure of the region of genes 34 and 35 and allowed to draw a conclusion that the degree of suppressing recombination process under the influence of X-mutation depends nor on the original recombination frequency between markers to be crossed, that is on the internal structure of the given region of the genome of bacteriophage T4. Possible reasons for specific effect of X-mutations on the recombination in genes 34 and 35 of phage T4B are discussed.