[The mechanism of the chronic supraventricular tachycardia: an intracavitary electrophysiological study (author's transl)].

Chronic Supraventricular Tachycardia (CST) or Chronic Atrial Tachycardia is a relatively rare arrhythmia. Because of very poor number of cases studied with electrophysiologic techniques its mechanism is still debated. Three cases of CST, one of persistent type and two of repetitive type, are reported. His bundle electrogram, high and low right atrial electrograms and atrial stimulation were performed in every case, ventricular stimulation in only one case. The Amiodarone, Pindolol, Verapamil and vagal manoeuvres effects were evaluated in all cases. The site of origin of tachycardia, atrial in cases 1 and 3 and junctional in case 2, was estabished by atrial map. The electrophysiologic findings suggested the presence of an ectopic focus in cases 1 and 3 and of an AV nodal re-entry circuit in case 2. Our results and those of the literature indicate that the site and the mechanism of CST, as in paroxysmal supraventricular tachycardia, is not univocal. Their electrophysiologic evaluation by means of endocavitary techniques can allow a more satisfactory therapeutic approach.


[Selective ventricular and coronary denervation (author's transl)].

A technique for selective ventricular denervation is described and functional documentation of the effectiveness of this method is presented. Further evidence is presented to demonstrate that selective ventricular denervation interrupts the alpha-adrenergic coronary vasoconstriction fibers and significantly decreases the myocardial oxygen demands during sympathetic nerve stimulation.


[Urinary excretion of adrenaline, noradrenaline and 11-hydroxycorticoids under job stress (author's transl)].

The role of the sympathoadrenomedullary and adrenocortical systems has been assessed by measuring serially the urinary excretion of free adrenaline, noradrenaline and 11-hydroxycorticosteroids in 32 healthy men under two conditions of job stress: piece-work and assembly line. The urinary levels of two catecholamines and 11-hydroxycorticosteroids rose significantly in piece work and assembly line workers, compared with the values observed respectively during salaried and "ordinary" work. Identical results were obtained in the same workers after six months of stressor exposure to piece-work and assembly line conditions. The results support the assumption that long-term exposure of conditions of work stress significant effects on the function under study, this being in the same direction and of the same order of magnitude as that described during short-term exposure in other types of every-day stress and distress. The methodological and clinical implication of these results are discussed.


[Quantitative cineangiography. Part I. Computerized volumetry of ventricular models (author's transl)].

A computerized system for cineangiograms analysis is described. Each selected frame is displayed by a TV camera on a TV monitor, allowing the physician to draw the left ventricular contour using a light-pen. The coordinates of selected points are sent to a small size digital computer to be processed. The processing techniques are outlined, while particular evidence is given to the operating procedure. Left ventricular volume is evaluated using both area-length and slice methods. Results obtained on models yield an estimation of the accuracy of the volume measurements.


[The biological prostheses of Hancock in our experience of 250 subjects underwent a valvular replacement (author's transl)].

In this study we present the results of 5-years Follow-up of Clinical experimentation with biological prostheses of Hancock in 250 patients underwent a valvular replacement at the Cardiovascular Surgery Institute of Padua University in Verona. We report the immediate and long-term results with the death causes and the complications related above all with thrombo-embolic events. For such complications it was done a comparison relatively to the cases with mitral and aortic prostheses, with the results obtained from another Cardiovascular Surgery Center where are always applied artificial prostheses. From this comparison results that Hancock's biological prostheses has a major tendency to give incidence of embolic in the first months following the valvular replacement, but successively it is clearly to be prefered to artificial prostheses.


[The bicycle electrocardiographic test for secondary prevention of coronary insufficiency. Results of a screening on 11,362 Italian workers (author's transl)].

A series of multi-phase mass screenings has been carried out in a number of working communities for locating, in their early stage, some socially important disease. The bicycle electrocardiographic test has been used for diagnostical purposes in order to single out all subjects affected by latent coronary heart disease and to evaluate the method as a means of prevention for the population. In the whole case-history, consisting of subjects free from coronary disease and with normal blood-pressure, mostly young or middle aged, the prevalence of positive electrocardiographic tests has been of 0.96%. The incidence of ischemic heart disease in 39 subjects with positive exercise test controlled after two-five years has been of 19%. Since the percentage of subjects with positive exercise test is extremely low on account of the not high occurrence of ischemic heart disease in our country as well as of the limited sensitivity of this method, it is believed that the electrocardiographic exercise test is not a satisfactory tool for secondary prevention of coronary disease in the Italian population.


[The atrial stimulation programmed for the research of dual A-V nodal conduction pathways (author's transl)].

Several techniques of premature atrial stimulation were used in a group of 28 not selected patients admitted to electrophysiological investigations of different rhythm troubles. The purpose of this study was the demonstration of dual A-V nodal pathways. The method consisted in the delivery of one or two atrial extrastimuli at every sixth beat, with or without atrial pacing at increasing rate, up to the either atrail or nodal refractory period. Then a curve of intranodal conduction was plotted. The different techniques led us to a curve reproducible in the 89% of the cases. Its main features are the steady increase of the A-H interval, the subsequent sudden "jump" of the same at critical shortening of the coupling stimulation interval and finally a third segment of steady increase until the atrial or nodal refractory period is reached. We believe that this behaviour is common in the man. The significance of the "jump", of the morphology of the curve and their possible relationship with the existence of dual A-V nodal pathways is discussed. Finally the different stimulation techniques are compared.


[Subxiophoyd echocardiography: pulmonary artery or aorta (author's transl)].

Six patients with chronic obstructive pulmonary diseases, have been examinated by subxiophoyd echocardiography associated with ultrasonic contrast of right heart. It is detected that the vessel placed behind anterior cavity is aorta. This is confirmed by study of calcific aortic stenosis too, where the calcifications allows sure localisation of the vessel. Main pulmonary artery, or its branches, is instead visible behind aorta.


[Ventricular septal defect and valvular aortic insufficiency. Our experience with nineteen patients (author's transl)].

Nineteen patients with ventricular septal defect (V.S.D) and valvular aortic insufficiency (A.I.), who underwent surgical repair, were reported. In the majority of patients the V.S.D. was localized in the supracristal region and the most frequent aortic valve abnormality was a prolapsing right cusp. Closure of the V.S.D. was effected with a patch in 15 patients and by direct suture in 4. Surgical management of A.I. consisted of: a) replacement of the aortic valve in 12 patients; b) no procedure on the aortic valve in 6 patient; c) plastic repair of the aortic valve in 1 patient. Only one patient died. Conservative management of the A.I. is advocated, but this is possible only if early repair is attempted. In adults, replacement with a prosthesis is indicated for severe A.I.


[General anesthesia in patients with intraventricular conduction abnormalities (author's transl)].

This study was undertaken to assess the risk of developing complete heart block during general anesthesia in patients with bundle branch block. His bundle electrograms were recorded during sinus rhythm and after atrail pacing in 11 patients (5 LBBB, 2 RBBB, 3 RBBB and LAH, 1 RBBB and LBH) before and after administration of Pentothal 0.20 g e.v., Succinylcholine 1 mg/kg e.v., and breathing of fluothane 1%or Ethrane. Minimal effects on sinus functions and A-V node conduction was observed during anesthesia; Fluothane only increased slightly AH intervals (+11%). Both Fluothane and Ethrane effects on HV conduction was insignificant. In 9 patients HV intervals increased of 5% after Succinylcholine; 2 patients developed a complete heart block distal to his after the drug. Possible causes of the complete heart block are discussed and a direct effect of Succinylcholine is hypothesized.


[Sublingual isosorbide dinitrate-induced severe hypotension, bradycardia and prelypothymia in patients with acute myocardial infarction (author's transl)].

100 patients with acute myocardial infarction were given 5 mg of sublingual isosorbide dinitrate within 36 hours by the onset of their symptoms. 86 patients did not show any unusual effect after the administration of the drug; their heart rate was only slightly increased and their arterial pressure slightly reduced. 14 patients developed severe systemic arterial hypotension, associated with absolute or relative bradycardia, within 30 minutes of receiving the drug. All the patients complained of fainting and sweating, 1 patient developed a syncope. Symptoms were relieved by raising patients legs in 10 cases, by 0.5 mg Atropina e.v. in 4 cases, 1 case required also external cardiac massage. There was no significant difference between the two groups as regard to the location of myocardial infarction nor to the functional class (according to Killip classification). Possible mechanism producing bradycardia, hypotension and lipothymia after nitrates administration are considered. A vagally mediate reflex possibly elicited by a fall in venous return is the most acceptable hypothesis. The study emphasizes the importance of carefull observation of patients receiving sublingual nitrates during acute myocardial infarction, and the rapid response of bradycardia, hypotension and lipothymia following nitrates administration, to a simple therapy, which avoids other potentially hazardous treatments.


Intraoperative measurement of the bile flow resistance in the terminal portion of the common bile duct and its clinical significance in biliary surgery.

A practical method, safe and relatively simple to perform, which we have developed for the intra-operative measurement of the resistance to bile flow in the terminal portion of the common bile duct is described. This method performed routinely in conjuction with the operative cholangiography in the operating room, proved to be a powerful diagnostic acid for detecting abnormalities in the terminal portion of the common bile duct. In gallstone disease, the results by this method were compared with the operative results. It was found that minimal organic changes or functional disturbances in the terminal portion of the common bile duct, even those without jaundice, can be detected, and unnecessary choledochotomy or sphincteroplasty avoided. This method has a further advantage in that it gives universality to the resistance R and the residual pressure P as quantitative discriptive indices for the qualitative state of bile flow in the terminal portion of the common bile duct, and, if adopted as a standard and routine method, should make the comparison of works by different investigators easier and more significant.


The diagnostic evaluation of ERCP in pancreatic and biliary carcinoma.

Endoscopic retrograde cholangiopancreatography (ERCP) was performed in 77 cases of pancreatic carcinoma, 47 cases of carcinoma of the common bile duct and 45 cases of carcinoma of the gall bladder. In order to evaluate ERCP in pancreatic and biliary carcinoma, success rates of desired duct cannulation and some problems in the interpretation of ERCP findings were discussed. In 2 cases (2.6%) of pancreatic carcinoma, 6 cases (13.0%) of carcinoma of the common bile duct and 8 cases (17.8%) of carcinoma of the gall bladder were failed to visualized the desired ducts by ERCP. In pancreatic carcinoma, false negative cases in the interpretation of ERCP findings were encountered in 4 cases (4.6%). Similarly, false positive cases were encountered in 12 patients (13.6%). On the other hand, 4 false negative were encountered in cases of which carcinoma of the gall bladder could not detected and 4 false positive cases were encountered in cases with inflamatory disease of the common bile duct.


Experimental study of transductal dissemination of cancer of the pancreas.

Experimental studies on the mechanims of transductal dissemination of the pancreas carcinoma was made in rabbit by injection of VX2 carcinoma suspension into the pancreatic duct. Ductal occlusion was conductive to nidation and growth in the pancreas of intraductal floating cancer cells, but tumor growth also occured in 40% of animals in which the duct was not occluded. The mechanisms of nidation in the pancreas of intraductal floating cancer cells were direct embedding into the ductal wall, and leakage of cancer cells from the duct in the process of pancreatic fibrosis due to ductal obstruction. Expansive tumor growth in the pancreas was more vigorous the smaller the degree of fibrosis of the pancreas, and was most active where associated acute pancreatitis was seen or where the pancreas was X-irradiated one week before injection of carcinoma suspension.


The clinicopathological features of the alcoholic liver injury in Japan and its etiological relationship to hepatitis B virus.

Clinicopathological features of 73 patients with alcoholic liver injury were investigated and its etiological relationship to HBV was examined. The results obtained are as follows: 1) the symptoms and histologic changes observed in this study were slightly differed from that of acute alcoholic hepatitis reported in the United States and European countries and only few cases showed similar symptoms and histologic changes compatible to acute alcoholic hepatitis. 2) Histologically, the pattern of hepatic fibrosis extending from the protal tracts into the lobule with scanty inflammatory changes was supposed to be the most characteristic features in this study. 3) Evidence of the exposure to HBV has been presented in 19 of 55 examined cases. Three cases with persistent HBs antigenemia were occasionally associated with severe hepatic changes. However, positive tests for antibodies presumably reflect the previous infection of HBV and no continuous damage due to the infection was supposed in these cases.


An ultrastructural study of the Brunner's cyst.

A Brunner's cyst, removed from a 54-year-old woman, was studied by light and electron microscopy. The cyst was spherical, measured 1.5 cm in diameter and was located in the duodenal bulb. Histologically, the cyst, confined in the submucosa, consisted of a single layer of epithelial cells and connective tissue. The epithelial cells were composed of an orderly array of tall columnar cells containing basal round nuclei and fine granular cytoplasm. Ultrastructurally, the epithelial cells contained many secretory granules in the cytoplasm. Each secretory granule was membrane-bound and appeared electron-lucid with a dense core. They were small and sparse around the Golgi apparatus but large and numerous in the apical region. Multinucleated cells were intermingled with cells of the epithelial lining.


[Urological complications following gynecological surgery (author's transl)].

Lesions of the urinary tract occur in a constant percentage no matter what type of gynecological operation is performed. In the last 11 years we saw 150 immediately postoperative complications, 85 of which involved the ureter, 58 the bladder and 7 the urethra. 8 lesions of the ureter healed spontaneonsly. 15 ureters were mounted with a stent. Surgical treatment had to be performed on 62 ureters. 50 of which were ureteroplasties: 21 ureteroneocystostomies, 28 ureteroplasties with a bladder flap (Boari-Küss), 1 uretero-ureteral-anastomosis. The results were good in 80%. Therapy of vesical-fistulae consisted in operative closure 3 month after the primary lesion. (54 cases: 30 vaginal approaches, 7 transvesical approaches, 14 transvesical a. with a peritoneal flap and 3 transvesical a. with interposition of the omentum.) Continence was achieved in all but one cases. Two cases required a second intervention. 4. fistulas were treated only conservative, in 3 times successfull, one event of bladder abdominal-wall fistula. The 4th case was not closed because of the rejection of the operation from the patient. All urethral fistulae could be closed successfully.


[Critical observations on the rate of "False Negative" findings in gynecologic cytology (author's transl)].

In order to obtain a resonable approach to the rate of false negative findings in gynecologic cytology, all cases available to the authors for analysis with cervical carcinoma, carcinoma in situ and dysplasia during 1971 to 1973 were examined for any previous history of negative cytologic findings during the years preceding the detection of these pathologic conditions. It was found that negative results had been obtained in 11% of the patients suffering from cervical carcinoma, whereas the corresponding percentage figure was 18% negative results in carcinoma in situ patients. However, in about half of the cases, repetition of the smear had been recommended. Among the possible causes of false negative cytologic findings, the laboratory error (screening and evaluation) is the only one which can be accurately determined; in the present analysis, one-third of the false findings were found to be due to laboratory error. It is probable that the majority of the other false negative cytologic findings are mainly due to errors in sampling. As a matter of fact, rapidly growing carcinomas and carcinomas in situ are probably rare.


[A casuistic contribution to therapy with gestagen in metastasizing corpus carcinoma (author's transl)].

Casuistic contribution of a sucessfully with Gestagen treated stage IV corpus carcinoma which previously had been operated and undergone radiotherapy. Ten years after the primary treatment the patient presented herself asymptomatic and clinically free of a tumor. The possible mechanism of the effect of the Gestagen-therapy is discussed as well as the indication for the administration of Gestagen in a corpus carcinoma.


[The surgical treatment of pelvic thrombosis during pregnancy (author's transl)].

Pelvic venous thrombosis during pregnancy is a rare event. The treatment discussed in the literature consists mostly of recommendations for therapeutic fibrinolysis. The surgical alternative is the retrograde operative thrombectomy with concommitant Caesarean Section. Two cases were successfully treated by this method at 33 and 39 weeks gestation. The cases are reported. The operative technique is described. The advantages and disadvantages of this treatment are discussed.


[Sudden maternal death in late pregnancy: congenital diaphragmatic defect causing prolapse of the intestine into the thoracic cavity (author's transl)].

Near the end of her first pregnancy, a 17-year-old patient developed sudden epigastric pain followed shortly afterwards by restlessness, paleness and respiratory distress. A diagnosis of pneumothorax was made from the chest radiogram. Shortly after this examination the patient died from cardiocirculatory failure. Autopsy revealed a congenital defect of the diaphragm with prolapse of abdominal organs into the thoracic cavity and displacement of the heart and mediastinum. The strangulated, gas-filled stomach was situated in the thoracic cavity and showed hemorrhagic erosions of the mucosa and a circumscribed mural defect which had obviously developed in the prefinal stage. This case as well as similar ones reported in the literature underline the necessity for a rapid diagnosis of unclear epigastric pain in late pregnancy. In the case of "diaphragmatic hernia" early surgery is indicated.


[Classification and estimation of risks as a preoperative requirement for risk patients (author's transl)].

The increase in gynecologic surgery for groups of risk patients, who, heretofore, have been considered as inoperable, forces us to systematize our procedures by estimating the surgical risk. The general surgical risk was high in 158 patients (10%). None of these patients died as a result of surgery. Suggestions were made, based on our own experience, for the extent of preoperative diagnostics, and for the form of the classification and estimation of risks. The improved possibilities for surgery can be extended to high-risk groups only when the existing risks are correctly estimated.


[Questions of liability in unsuccessful voluntary sterilization (author's transl)].

Since the June 29, 1976, decision of the Federal High Court of the Federal Republic of Germany, voluntary sterilization is permitted under certain, limited, circumstances. After the physician has thoroughly instructed the patient, the patient must give written consent in agreement with S 226 of the penal code. The physician cannot then later be charged with commiting bodily injury according to S 224 of the penal code. Recently, the German courts have tended more and more to consider the unplanned birth of a child following unsuccessful sterilization as a damage case for which the attending physician is held responsible under civil law. For most physicians, this means that the financial compensation set by the court is not, or at least not fully, covered by their medical indemnity insurance. A corresponding increase in the medical indemnity coverage or a release from all damage claims overagainst the attending physician signed by the patient is urgently indicated.


[Pelviscopic surgery in gynaecology (author's transl)].

Surgery of the fallopian tubes has today developed into pelviscopic surgery. The development of suitable instruments such as the tube set, a new endocoagulation method were prerequisites for this development. Operative therapeutic pelviscopic surgery is a development past laparotomy. It is now possible to treat adhesions in the abdomen with this method, to coagulate and divide fallopian tubes for sterilization, to aspirate ovarian cysts and resect walls of ovarian cysts, to coagulate endometriosis and to perform salpingolysis and salpingostomy. In selected cases ovariectomy and myomectomy are possible through the pelviscope. Tables and statistics on 3300 pelviscopies are presented. The indications are discussed. The use of pelviscopy following previous laparotomy (1831 cases) is discussed. The complication rate was 1.10% without death, without injury to large vessels, without embolic phenomenon. The operative risk is therefore less than that of laparotomy. The operative therapeutic pelviscopy can replace the classical laparotomy in about 25% of the cases. For the operation of tubal infertility, a laparotomy is eliminated in about 80% of the cases.


[Critical evaluation of clinical and hormonal parameters for the optimal timing of induction of ovulation with gonadotropins (author's transl)].

In 9 hypogonadotrophic, normoprolactinemic women with primary or secondary amenorrhea, who were infertile, 16 treatment cycles with menopausal gonadotropin and chorionic gonadotropin (HMG-HCG) were carried out. Nine treatment cycles were monitored indirectly with the cervical factor and hormonal cytology. The concomitant serum estradiol and progesterone values were later determined by radioimmunoassays. The other 7 treatment cycles were monitored by daily serum estradiol determinations. There were 4 pregnancies. Successful induction of ovulation with subsequent pregnancies was only obtained in the treatment cycles monitored by serum estradiol determinations (pregnancy rate 60%). Classical signs of overstimulation with ascites and hydrothorax occurred twice in treatment cycles which were monitored by clinical means only. Neither the maturation index nor the cervical factor reflected a quantitative overstimulation of the ovaries. The daily radioimmunological determination of estradiol prevented overstimulation of the ovaries, and permitted optimal timing of the induction of ovulation with HCG. In our experience, the maturation index determined from vaginal cytology and the clinical determination of the cervical factor are inappropriate parameters to monitor individually a successful induction of ovulation with HMG-HCG.


[The purity degree of the vagina containing mycoplasmosis urogenitalis (author's transl)].

In 156 women with mycoplasmosis urogenitalis the degree of purity of the vagina was determined. In none of the patient's a first degree of purity (containing lactobacilli only) was found. This is an additional sign that mycoplasma has an optional pathogenetic importance in the female urogenital system. In order to restore a normal vaginal flora of lactobacilli, the mycoplasma has to be eliminated.


[Vaginal metastasis of renal carcinoma (author's transl)].

Four cases of vaginal metastases of renal carcinoma are reported. This is an incidence of 1.3% in 313 operated patients (from 1/1/70 to 12/31/76). A surgical treatment of primary renal carcinoma and vaginal metastasis seems to be reasonable in there cases. Since in accordance with the literature metastatic involvement of vagina and vulva seems not to be a very rare finding, the diagnostic in renal carcinoma should imply a gynecologic examination. Although in carcinoma of the left kidney metastatic spreading into the external female genitalia most probably occurs by a retrograde venous pathway (left ovarian vein), the way of dissemination in carcinoma of the right side is unclear.


[Pregnancy after conisation for atypical epithelial processes of the uterine cervix (author's transl)].

At the First Department of Obstetrics and Gynecology, University of Vienna Medical School, 148 females aged under 35 years at the time of conisation were examined between 1963 and 1974 to determine their desire for children, their fertility status and the course of pregnancy. After conisation a total of only 42 females (28,4%) wanted children. Of 104 patients with preinvasive carcinoma, a desire for children was reported by no more than 21 (20,2%); among the cases with dysplasia, the number of women desiring children was equally 21 (47,7%). By the end of 1976, after a followup period of 1 to 13 years, 16 of 42 females wanting children failed to conceive, while the remaining 26 gave birth to 20 children. Judging from our admittedly small material, conisation thus apparently has no effect on conception. However, the course of pregnancy was found to be impaired in some cases by the incompetent cervical function. Twelve patients required a Shirodkar operation, which failed to prevent late abortion in 2 cases and premature delivery in 4. Nine women gave birth at or at best 3 weeks before term without preventive methods.


Effects of ancestral X irradiation followed by random mating on body weight of rats.

Effects of nine generations of 450r per generation of ancestral spermatogonial X irradiation of inbred rats on body weight were examined. After six generations of random mating (avoiding inbreeding) following the termination of irradiation, descendants of irradiated males (R) were significantly lighter than their controls (C) at 3 and 6 weeks, but not at 10 weeks of age. However, differences in growth between R and C populations were small. Among-litter and within-litter variance estimates were generally larger in the R lines than in the C lines, suggesting that selection responses would be greater in R than in C lines. In conjunction with previous evidence--obtained during the irradiation phase of the experiment--this suggested that more rapid response to selection for 6-week body weight, in particular, might accrue in the R lines.


Estimates of genetic parameters of body weight in descendants of X-irradiated rat spermatogonia.

Effects of nine generations of 450r per generation of ancestral spermatogonial X irradiation of inbred rats on genetic parameters of body weight at 3, 6, and 10 weeks of age and of weight gains between these periods were studied. Covariances among relatives were estimated by mixed model and regression techniques in randomly selected lines with (R) and without (C) radiation history. Analyses of the data were based on five linear genetic models combining additive direct, additive indirect (maternal), dominance and environmental effects. Parameters in these models were estimated by generalized least-squares. A model including direct and indirect genetic effects fit more closely to the data in both R and C lines. Overdominance of induced mutations did not seem to be present. Ancestral irradiation increased maternal additive genetic variances of body weights and gains but not direct genetic variances. Theoretically, due to a negative direct-maternal genetic correlation, within full-sib family selection would be ineffective in increasing body weight at six weeks in both R and C lines. However, progress from mass selection would be expected to be faster in the R lines.


Evaluation of the culling variate used by breeders in actual selection.

The theoretical basis and computational procedures for estimating the culling variate utilized by breeders in actual selection are presented. The essential part of this procedure is to derive the unknown culling variate in terms of a linear combination of traits based on realized indirect selection differentials of those traits and phenotypic variances and covariances among traits in the population. Special emphasis is placed on the distribution of the variables involved. The accuracy of the culling variates is estimated by use of the biserial correlation with some modifications. Numerical illustrations are given for different types of selection.


Persistence of common alleles in two related populations or species.

Mathematical studies are conducted on three problems that arise in molecular population genetics. (1) The time required for a particular allele to become extinct in a population under the effects of mutation, selection, and random genetic drift is studied. In the absence of selection, the mean extinction time of an allele with an initial frequency close to 1 is of the order of the reciprocal of the mutation rate when 4Nv less than 1, where N is the effective population size and v is the mutation rate per generation. Advantageous mutations reduce the extinction time considerably, whereas deleterious mutations increase it tremendously even if the effect on fitness is very slight. (2) Mathematical formulae are derived for the distribution and the moments of extinction time of a particular allele from one or both of two related populations or species under the assumption of no selection. When 4Nv less than 1, the mean extinction time is about half that for a single population, if the two populations are descended from a common original stock. (3) The expected number as well as the proportion of common neutral alleles shared by two related species at the tth generation after their separation are studied. It is shown that if 4Nv is small, the two species are expected to share a high proportion of common alleles even 4N generations after separation. In addition to the above mathematical studies, the implications of our results for the common alleles at protein loci in related Drosophila species and for the degeneration of unused characters in cave animals are discussed.


Age-correlated changes in expression of micronuclear damage and repair in Paramecium tetraurelia.

In Paramecium, age is defined as the number of mitotic divisions which have elapsed since the previous cross-fertilization (conjugation) or self-fertilization (autogamy). As the mitotic interval between fertilizations increases, the percentage of nonviable progeny clones increases. In the current study, resolution of conflicting previous reports on the pattern of increase of death and reduced viability in progeny from aging parent cells is found. Some exautogamous clones exhibit a high mortality at young clonal ages, others show no mortality throughout their life span, but most (73%) show an abrupt increase in the percent death and reduced viability in progeny from cells 50-80 fissions old. Ultraviolet-irradiation-induced micronuclear mutations, repairable by photoreactivation, increased with increased clonal age when monitored by percent death and reduced viability of exautogamous progeny of irradiated cells. Loss of dark repair is considered a contributor to the increased expression of micronuclear mutations with increased clonal age.


A comparison of survival and repair of UV-induced DNA damage in cultured insect versus mammalian cells.

Survival and unscheduled DNA synthesis (UDS) were measured in a cultured insect cell line, TN-368, and a cultured mammalian cell line, V-79-4, following exposure to several fluences of ultraviolet light. TN-368 cells were approximately seven times more resistant to the lethal effects of UV than V-79 cells, as determined by colony formation. The amount of UDS per unit amount of DNA is about the same in both cell types 4 hr after 10-50 J/m2 UV irradiations.


Histochemical investigations of thyrosine in normal and pathological glia cells.

Investigations on thyrosine content in normal and pathological glia cells are the continuation of researches on occurrence of protein functional groups in abnormal glia cells (Szydlowska, 1970a, 1970b). The investigations carried out with the use of Caselli, Glenner and Lille methods have shown that fluctuations of thyrosine level in nuclea and cytoplasm of glia cells pathologically changed correspond to quantitative changes of other functional groups of proteins. Hence it may be assumed that the observed increase of thyrosine in pathologically changed glia cells is not connected with the change of protein composition of a cell but with the general increase of proteins in its nucleus or cytoplasm.


Deoxyribonuclease I purification from protease contaminations.

Affinity chromatography as a tool in purification of commercial DNA-ase I preparation from protease contaminations by the use of insoluble--protease inhibitors is described.


Electronmicroscopy of the replication of the ISU-2 strain of IBR/IPV-herpes virus in inoculated cultures of bovine embryo kidney (BEK) cells.

Studies on the replication of the ISU-2 strain of IBR/IPV-Herpes virus and on its behaviour in inoculated BEK cultures have shown that the replication of viral DNA as well as the production of icosahedral particles occur within the cell nucleus. Similarly like in each Herpes virus group, while passing through the nuclear envelope and the cell membrane the virus obtains an additional envelope that enlarges its diameter. The viral particles produced in a large quantity, may pass through the cell membrane into the extracellular spaces or may be caught by the cytoplasmic vacoules, where they are decomposed.


Histochemical and autoradiographic studies of abnormal spermatozoa in mice of the inbred KE strain.

Abnormal spermatozoa in mice of the KE strain, with defective chromatin condensation, are induced by disturbances in the process of spermiogenesis. When stained with methyl green-pyronin, spermatozoa with elongated heads reveal a staining pattern characteristic of the 13th stage of development of spermatids, indicating that they are not totally transformed molecularly, like normal spermatozoa. Labeling with L-arginine-5-H3 showed a weaker incorporation of arginine in the heads of the abnormal spermatozoa particularly those with elongated heads. Errors in the process of differentiation of spermatozoa leading to abnormal shapes may be related to atypical composition of deoxyribonucleoproteins (DNP).


[Glycerol-induced hemolysis of mammalian erythrocytes and inhibition of the lysis by fructose (author's transl)].

The mechanisms of glycerol-induced hemolysis and inhibition of the lysis by fructose were studied. Energy of activation, entropy of activation, and free energy of activation for the hemolytic process were calculated from the data on temperature change in the rate of hemolysis. The values of the thermodynamic quantities thus obtained indicated that the temperature change in the rate of hemolysis is brought about mainly by that in the viscosity of liquid. The presence of fructose in the hemolytic systems caused a reduction in both energy of activation and entropy of activation while free energy of activation remained almost unchanged. Pretreatment of erythrocytes with glycerol gave rise to complete hemolysis of the cells in hypotonic as well as hypertonic saline solutions. Thus, it appears that glycerol releases a portion of the lipids of the cell membrane into the surrounding medium and dehydrates the membrane, thereby promoting hemolysis. Fructose was considered to prevent dehydration of the membrane by glycerol.


[Effects of dobutamine on the respiration, blood pressure, and several blood components in dogs (author's transl)].

In anesthetized Beagle dogs, intravenous bolus administration of dobutamine (DOB) caused an increase of systolic pressure and a decrease of diastolic pressure--increase of pulse pressure. These effects of DOB were not so pronounced as the marked depressor effect of isoproterenol (Iso) and pressor effects of epinephrine (Epi), norepinephrine(NE) and dopamine (DA). The degree of the positive chronotropic effect of DOB was the same as that of DA. Incidences of ventricular extrasystole observed at the maximal dosages of catecholamines, intravenous administration of 300 microgram/kg of DOB, 3 of Iso, 10 of Epi, 10 of NE, and 300 of DA, were 1/4, 1/4, 4/4, 4/4, and 2/4, respectively. With no evidence of ventricular extrasystoles, an increase of pulse pressure was also observed in conscious dogs given an intravenous infusion of DOB (10 or 30 microgram/kg/min for 20 min). Iso infusion resulted in an increase of serum free fatty acid, and a decrease of serum Na and K. Although DA infusion increased blood glucose and serum free fatty acid, DOB infusion produced no significant concentration change of blood components. These experimental results indicate that effects of DOB on the blood pressure, heart rate, and several blood components are weaker than other catecholamines.


[Paper disk granuloma method for experimental granuloma in rats (author's transl)].

The paper disk granuloma (PDG) method is a newly devised procedure for the screening of antiinflammatory drugs and was compared with the cotton pellet (CP) method. Results obtained were as follows; in the CP method, formation of granuloma was observed on the 1st day after the implantation of CP. On the 3rd day, maximum weight, protein and nucleic acids in granuloma were observed. The granuloma produced by PDG method was too small to collect on the 1st day. Weight and protein content of granuloma reached the peak on the 2nd or 3rd day. With respect to nucleic acids, maximum amounts were found on the 6th day. The incorporation of 3H-uridine into RNA was increased in the early stage of the formation of granuloma in both methods. The maximum incorporation of 3H-thymidine into DNA was noted on the 2nd day in CP method, and on the 3rd day in PDG method. Development of granuloma in the PDG method was different from that in CP method with respect to the synthesis of DNA. Antigranuloma action of fluocinolone acetonide (FA) was more marked in the PDG method than in the CP method, suggesting that the PDG method is more sensitive for screening of antiinflammatory drugs. Granuloma produced by the PDG method was also prevented and therapeutically suppressed by certain non-steroidal antiinflammatory drugs. ED50 values of applied FA, phenylbutazone, and 3-o-phthaloxy glycyrrhetinate were 27 microgram/kg, 91 mg/kg, and 66 mg/kg, respectively.


[Pharmacological studies on expectorants (author's transl)].

Perry and Boyd's method described in 1941 appears to be the most suitable for evaluating the efficacy of expectorants. In this method, changes in volume of respiratory tract fluid (RTF) collected by postural drainage from animals breathing air kept at a constant temperature and humidity are used as criteria. We attempted to improve on the method and to establish the optimum experimental conditions for rabbits. Accordingly, an air conditioning apparatus and tracheal cannula were re-designed and basic experimental conditions essential for quantitative collection of RTF were studied. Using this method, the effects of drugs on the volume of respiratory tract fluid (VRTF) were determined. Bromhexine and emetine as expectorants increased VRTF, and the former showed far more remarkable effects. Codeine and dextromethorphan as antitussives, isoproterenol, clorprenaline and C-78 as bronchodilators decreased VTRF. On the other hand, fominoben and eprazinone as antitussives increased VRTF. Our findings with application of this new approach indicate that this method is applicable for evaluating not only the efficacy of expectorants which increase VRTF but also that of other drugs which decrease VRTF.


[Effects of morphine on evoked potential recorded from pain-afferent pathways (author's transl)].

Effects of morphine (1 mg/kg i.v.) were examined on evoked potential of somatosensory afferent pathways elicited by tooth pulp stimulation in cats. Results were as follows: In central gray (CG) of the midbrain which has a triphasic evoked potential with a short latency, morphine decreased the amplitude. In nucl. lateralis posterior(LP) and nucl. medialis dorsalis(MD) of the thalamus, association relay nuclei, which have a late component followed by a fast component with a relatively short latency, morphine decreased the amplitude of the late component but not that of fast component of the evoked potential. In nucl. centralis lateralis(CL) of the thalamus, intralaminar nuclei, and pre-central association area(PCA) of the cortex, which have monophasic and triphasic evoked potentials with a long latency, respectively, morphine markedly decreased the amplitude of both evoked potentials. In nucl. ventralis posteromedialis(VPM) and somatic sensory area I (SI), lemniscal system, which has biphasic and mutiphasic evoked potentials with a short latency, respectively, morphine had no effect on these evoked potentials. As these depressant effects of morphine on evoked potentials were antagonized by naloxone (0.2mg/kg i.v.), a specific morphine action is suggested.


[In vivo cytogenetic studies of 10-chloro-11b-(2-fluorophenyl)-7-(2-hydroxyethyl)-2, 3, 5, 11b-tetrahydrooxazolo-(3, 2-d) (1, 4) benzodiazepine-6(7H)-one (MS-4101) on rat bone marrow cells (author's transl)].

Chromosome aberrations induced by MS-4101, diazepam, and nitrazepam were studied in Sprague-Dawley rats. Female rats were administered orally via stomach tube daily doses of 200, 500 and 2000 mg/kg of MS-4101, 200 and 500mg/kg of diazepam, 40 and 200mg/kg of nitrazepam and 20 and 50 mg/kg of cylcophosphamide as the positive control for one, 5 and 10 days. In this study, we used bone marrow cells derived from rat femur at 6 or 24 hours after the last drug administration. No significant chromosome aberrations were seen in the treated groups with MS-4101, diazepam, and nitrazepam when compared with the nontreated control. The increase of structural aberration on gap and break was observed in the group of cyclophosphamide as the positive control. These findings indicate that MS-4101, and diazepam and nitrazepam as similar comparative drugs, do not have the potential of induction of chromosome aberrations in rat bone marrow cells.


[Effects of dantrolene sodium on some types of visceral muscles (author's transl)].

Twitch contraction height of the outer layer of esophagus was reduced by 5 X 10(-6) g/ml of dantrolene to 7% of the height observed before the application. High-K induced contracture of this preparation and of cremaster muscle were also depressed to 14% and to 18% of the control, respectively. When dantrolene (25 X 10(-6) g/ml) was applied during the contracture induced by 9.7 X 10(-4) g/ml of caffeine, a complete relaxation was observed. Dantrolene had no effect either on the evoked twitch contraction of the smooth muscle of vas deferens or on spontaneous contractions of the taenia coli. High-K induced contracture of these smooth muscles was not affected by dantrolene. Electron micrograph showed that the outer layer of esophagus and cremaster muscle were composed of striated muscle cells in which the sarcoplasmic reticulum, transverse tubulus, and triadic junctions were well developed. In smooth muscle preparations, although sarcoplasmic reticula were observed, neither transverse tubula nor triadic junctions comparable to those in the striated muscle were evident. These morphological differences may explain differences in the action of the drug.


[A preliminary study on the changes of calcium (Ca) and phosphorus (P) contents in serum following intravenous administration of lead acetate (author's transl)].

We investigated the mechanisms of interaction between lead acetate (Pb-Ac) and bone minerals. One hundred and eighteen male rats were used and the following experiments were carried out: (1) determination of changes in serum Ca and P following intravenous injection of Pb-Ac or sodium acetate(Na-Ac) as the control for acetate, (2) to ascertain the deposition of lead at the calcifying site of bone immediately after Pb-Ac administration. The serum Ca and P levels increased with time after Pb-Ac administration and the maximum values were noted after 1 hour in Ca (17 mg%) and 30 minutes in P (13.5mg%), respectively. Both Ca and P levels reverted to the normal range within 12 hours. The net increasing rates in both Ca and P were calculated from each value in the Pb-Ac and Na-Ac groups. Those maximum rates were found immediately after the Pb-Ac administration (0 approximately 30 sec). At the same time, deposition of lead was evident at the calcifying site of bone and insicor dentine.


[Influence of inflammation on prostaglandin metabolism in rat skin (author's transl)].

Influence of inflammation on prostaglandin metabolism in rat abdominal skin was studied. Prostaglandin F2alpha content was determined by the radioisotope dilution method. Prostaglandin F2alpha content in rat abdominal skin was increased by thermal burn and application of 2, 4-dinitrochlorobenzene. The incorporation of 3H-arachidonic acid into prostaglandin F2alpha in rat abdominal skin was not increased by inflammation. Indomethacin caused a significant reduction of prostaglandin F2alpha content. These results suggest that the prostaglandin may play an important role in the inflammatory process of rat skin.


Strain improvement in Streptomyces galilaeus, a producer of anthracycline antibiotics galirubins.

The production of epsilon-pyrromycinone glycosides in Streptomyces galilaeus increased 12-fold, with respect to the wild strain, as a result of a sequential procedure including both natural selection and treatment with mutagens (nitrous acid, UV light and gamma-irradiation). Nitrous acid exhibited the highest mutagenic effect, both in increasing the productivity and in inducing blocked mutants. A mutant strain blocked in the biosynthesis of glycosides and accumulating free epsilon-pyrromycinone as the principal metabolite was obtained.


Origin and morphology of atypical forms of Streptomyces granaticolor.

Nonfilamentous forms of Streptomyces granaticolor are formed in a medium with amino acids and glucose. They form filaments again after transfer to a medium with glucose and peptone. The nonfilamentous forms do not produce granaticin. Formation of nonfilamentous forms depends on the concentration of the inoculum, on the cultivation temperature and on the presence of simple sugars. Ultrathin sections revealed atypical septation in the nonmycelial forms and non-uniform accumulation of the wall material.


Transport of ribitol and D-glucose in the yeast Candida guillermondii.

The uptakes of the linear polyol ribitol and of D-glucose by Candida guillermondii were found to be carrier-mediated and to require metabolic energy. In glucose-grown cells ribitol possibly enters by simple diffusion but after an induction period a specific transport system is synthesized, inhibitable by higher concentrations of arabinitols, xylitol, mannitol and sorbitol. Actidione blocks the synthesis of the inducible ribitol transport system. Two systems of different affinity for substrate were found to operate in the uptake of both glucose and of ribitol. Counter-transport experiments with ribitol, D-glucose and 3-O-methyl-D-glucose support the carrier nature of the uptake system.


Biochemical dehydrogenations of saccharides. IX. D-lyxo-5-hexulosonic acid from D-mannose by Acetomonas oxydans fermentation.

Fermentation of nutrient media by a selected strain of Acetomonas oxydans with a continuous pH control gave D-lyxo-5-hexulosonate in the form of a calcium or potassium salt with a yield equal to 95% of theory. The media contained up to 20 g D-mannose per 100 ml and a small amount of a readily assimilated monosaccharide.


Microbial activity in soil enriched with preparations of AS-lignin and lignofulvonic acid.

In chernozem soil, enriched with preparations of AS-lignin or lignofulvonic acid, an increased production of carbon dioxide was observed during a 4-week incubation, and, as compared with the non-amended control, an increased number of bacteria but not of actinomycetes was detected. Increased numbers of fungi were detected only in the variant with AS-lignin at the end of the incubation. The relative incidence of bacteria utilizing vanillin, syringic acid or protocatechuic acid as the only carbon sources increased in the enriched medium. Oxidation of vanillic acid, syringic acid and to a lesser extent of coumarin increased in suspensions of soils incubated with AS-lignin or fulvic acid. The results obtained indicate that bacteria are involved in the mineralization of the added substrates and confirm the relationship between metabolism of these compounds and simple aromatic derivatives.


Population dynamics of Fusarium spp. in pea rhizosphere as affected by soil amendments.

In nonamended soil, vegetative growth and sporulation of Fusarium spp. were higher in the rhizosphere than in the soil. Sporulation was favoured by young plants and decreased with increasing plant age. Amendments with low C/N oil-cakes enhanced vegetative growth and sporulation in root-free soil. The extent of stimulation varied with the nature of organic matter used and the stage of its decomposition. Sporulation was suppressed by castor cake and sawdust with urea amendments. Rhizosphere cf pea altered the effect of different amendments.


Effect of rifampicin on tryptophanase induction in normal and rifampicin-resistant Vibrio el tor.

The induction of tryptophanase was not affected by rifampicin in the rifampicin-resistant mutant of Vibrio el tor while the antibiotic inhibited the induction of tryptophanase in the normal strain at level of ribonucleic acid and protein synthesis.


Production of L-aspartic acid from fumaric acid by Alcaligenes metalcaligenes CCEB 312.

Among 23 microbial strains, Alcaligenes metalcaligenes CCEB 312 was found to be most suitable for the conversion of fumaric acid to L-aspartic acid. In a growth medium containing 4% peptone, the strain produced as much as 50 g L-aspartic acid per litre.


Ultrastructure of the dikaryotic form of Cyathus bulleri Brodie.

The fine structure of the dikaryotic form of Cyathus bulleri Brodie was generally found to be similar to that of other hyphal forms of the Basidiomycetes. The nuclear walls were doubled, porous and in some cases connected to the endoplasmic reticulum. The presence of typical as well as filamentous and U-shaped mitochondria was confirmed. Other cellular structures and organelles, among them vacuoles, vesicular and myelinoid-like bodies, often associated with the cell membranes, glycogen and ribosomes were also observed in the cytoplasm. The presence of the dolipore/parenthesome apparatus and clamp connections typical of the Basidiomycetes was established.


Equipment for germ-free caesarean section and baby care.

A germ-free isolator system was designed and constructed. It permits a sterile caesarean section and rearing of an infant under germ-free conditions. The system includes a plastic surgical and rearing isolator and two supply isolators; one of the supply isolators served as a transport mobile unit of staff participating in the sterile caesarean section and in the postnatal care of the germ-free newborn underwent to a special training and all of them were able to meet the high requirements of this work. The surgery itself was without complications. The newborn was absolutely sterile up to the age of 1 month; afterwards the infant was gradually colonized with selected strains of bacteria and thus prepared for conventialization. In the course of this work further possibilities of application of gnotobiological techniques in pediatrics were proposed (e.g. care of premature, high-risk neonates).


[Euthanasia--Polish scientistś viewpoint and in the light of the laws of the people's Republic of Poland].

Euthanasia has for a long time been the object of very lively discussions in Poland. This article contains the views of scientists from various fields of science, especially medical doctors of different specialities. All of them have very serious objections to euthanasia and are against its practical application not only from the medical point of view but first of all for purely humanitarian reasons. Polish penal law regards murder on request as delictum sui generis, i.e., as a kind of privileged crime as compared with common murder. Article No. 150 of the Polish penal law demands two features to characterise euthanasia: (1) the delinquent must act on grounds of compassion towards his victim, and (2) on the victim's request. The patient must be in such a state that gives reason for compassion. The request to shorten somebody's life must be very distinct, direct, firm, conscious and convincing. Perosns under age, mentally defective or unconscious cannot express such a wich. Polish penal law punishes with utmost severtity perpetrators of active euthanasia even in such cases in which the delinquent was moved by the most noble feelings. Only when it comes to penalty is distinction made between such a delinquent and a common murderer.


[Passive euthanasia].

After having been acquainted with the historical development of euthanasia, the following steps for assitance in dying, called passive euthanasia are being discussed. a) Assistance during dying without speeding up death is the self-evident duty of a doctor. b) Assistance during death and speeding up the same as an unavoidable result of therapeutical treatment, more or less desired or more or less unavoidable. c) Assistance through letting the patient die by abandoning all therapeutical means, when these would only lead to a short extension of life time. No doctor is compelled to take measures to extend life if it is against the will of the patient. He is not even entitled to do so. A special problem is the abandoning of extended operative treatment, this borders on the so called active enthanasia. The dying patient always has the same right of treatment by a docter as well as nursing like all other suffering human beings. The decision to let a patient die should not result in leaving him by himself and to abandon all nursing as well. Such steps would include letting him lie in dirty linen, not sucking off the mucous secretion from the trachea, refusal to assist during mealtimes, non-assistance during cathetering, and the removal of the dying person to the bathroom, or any other remote orner of the hospital. No dying person should stay without help Loneliness especially is the greatest pain of a dying patient.


Concentration levels of 2,4-D and 2,4,5-T in forensic material.

Concentration levels, of 2,4-D and 2,4,5-t in blood and viscera in a case of fatal intoxication with "Tributon" are given. Since the toxicity of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-t), widely used as herbicides in domestic and agricultural situations is very low, little information exists on human toxicology and particularly on analytical data in forensic material in cases of fatal poisoning. The reason of this paper is to provide further information on the concentration levels of these compounds in viscera in cases of fatal, accidentally or suicidal, poisoning.


Application of polar stationary phases OV-225 and OV-275 in the detection of drugs in urine samples.

A procedure for fast screening of urine sample is described. TLC and GC equipped with NPD enable detection of therapeutic doses of drugs to be made in a short time. Tables of retention values for TLC and GC are also presented. TLC detects drugs with a sequence of three reagents. GC screening is carried out with a temperature programmed run of 30 degrees C/min up to 290 degreesC. For the determination of retention indices new polar phases with suitable thermal stabilities such as OV-225 and OV-275 are used.


Identification of blood stains by non-genetic characteristics: the HBs antigen of viral hepatitis B.

In forensic cases, until recently, identification of biological stains was based on the use of genetic markers, such as blood groups. In this paper, we show that another acquired characteristic, even if not immutable during life, may afford similar possibilities. As an example, we have demonstrated that the HBs antigen, associated with the hepatitis B virus, can help in the identification of bloodstains. The requisite condition for using this new marker, is that not too much time should elapse between the time the biological stains are formed and the moment when victim and suspected individual are examined for comparison of their blood with the stain. We have shown that in a dried state, the HBs antigen is very stable for a least six months. In vivo, it persists for a few week to 6 or 7 years according to thecase. HBs antigen is a relatively rate factor, its frequency being 0.5%ew marker, is that not too much time should elapse between the time the biological stains are formed and the moment when victim and suspected individual are examined for comparison of their blood with the stain.  We have shown that in a dried state the, HBs antigen is very stable for a least six months. In vivo, it persists for a few week to 6 or 7 years according to the case. HBs antigen is a relatively rate factor its frequency being 0.5% in the Belgian population; the frequency reaches 2 to 3% in the Mediterranean population who constitute most of the immigrants in Belgium.


[Septic temperatures in questionable ascites].

The case history of a 40 year old male with septical temperatures and ascites is presented. Because of skin-pigmentation, hypotension, low rate of electrolytes, augmented renin-activity, and septical temperatures there was a suspicion of Addison's disease. A protein-rich ascites without tumor cells and erythrocytes, but with lymphocytes gives the diagnosis of peritonitis tuberculosa. Addison's disease and peritonitis tuberculosa are late manifestations of an organ tuberculosis, about 20 years after pulmonal tuberculosis.


[Ultrastructure of neuronal ceroid-lipofuscinoses].

The ultrastructure of autofluorescent residual bodies in the Jansky-Bielschowsky and Spielmeyer-Sjögren types of neuronal ceroid-lipofuscinoses (NCL) is variegated though the curvilinear profiles encompass the basic pattern. The infantile and Kufs' types are marked by granular cytosomes. Deposition of the lipopigments in NCL simulates the distribution of "wear and tear" lipofuscin enabling diagnosis by biopsy and electron microscopy in peripheral organs such as skin, rectum, and especially striated muscle. Pathological findings in the retina of the associated retinopathia pigmentosa entail typical NCL residual bodies in almost every type of retinal cells, a loss of photoreceptors, atrophy of pigment epithelial cells and displacement of melanin into inner layers of the retina. This retinopathia pigmentosa seems to be a regular finding of only the classic late infantile and juvenile human types of NCL since it is mostly absent in the adult human type and the canine NCL. As long as an enzyme deficiency of this autosomal recessive disorder remains unproven, the clinical diagnosis of NCL can only be morphologically confirmed by electron microscopy.


[Hemodialysis without risk of hemorrhage. Introduction of an APTT bedside method for exact heparin monitoring--a review].

A summarized account of our experiences over 1 1/2 years is given, in relation to a minimum heparinisation technique during haemodialysis. This novel technique was made possible by the introduction of an APTT bedside method. In a comparison between the techniques employed so far for preventing a heparin-caused risk of haemorrhage and our method, the clear advantage of our method was apparent. In addition to a discussion of our methods, we describe the cases treated so far. The amounts of heparin required for dialysis are so small that a necessary coagulation can occur even in a part of the organism where there is a danger of haemorrhage. Thereby it was possible to extend the range of indication for haemodialysis substantially. By using minimum heparinisation, it is possible to perform an immediate postoperative haemodialysis. The healing of wounds, which is impaired in cases of renal insufficiency, may be improved by early dialysis without the risk of haemorrhage. Our results show that the minimum heparinisation signifies a decisive achievement in acute dialysis therapy.


Sex determination of severely burned bodies.

Kidney, thyroid gland, liver, striated muscle and cerebral cortex from ten males and six females who died with severe burns were examined with regard to sex determination using Y-chromosome detection. A control group of sixteen persons was compared. Only the kidneys offered a reliable sex determination. Thyroid gland presented high false positive values, the liver one false-negative and striated muscle and cerebral cortex both false negative and positive values. When heating liver and kidney it was demonstrated that temperatures higher than 150 degrees C made the detection difficult.


[Treatment of chlamydial urethro-adnexitis with erythromycin].

Besides mycoplasmas and ureaplasmas chlamydias are able to cause an urethro-adnexitis in men. Jeasts, trichomonas and herpes-viruses are in our patients of less importance. Therapy with erythromycine of chlamydial urethroadnexitis is successful.


Case report of deaths caused by freon gas.

A report of two autopsies which is thought to be the first case of its kind in Japan is presented here. The cause of death was concluded to be oxygen deficiency from the filling of a compartment by Freon gas escaping from a cylinder. However, the authors suspect that Freon per se is not a non-toxic substance as had been believed but has some toxicity because of the existence of fat droplets in hepatocytes of mice exposed to reon gas and because of the behavioral findings on them during experiments.


[Vulvar neoplasms and preoperative lymphography].

20 patients with histologically verified carcinoma of the vulva fulfilled the following conditions: general operability, preoperative lymphography, radical vulvectomy with inguinal lymph node resection and histological examination of all lymph nodes. It was studied how far the preoperative lymphography plays a role for the strategy of operative treatment of carcinoma of the vulva and eventually in the limitation of risks of operative treatment. A survey of the lymphatic drainage of the vulva underlines the importance of the knowledge of the lymphatic pathways for the operation and for the lymphography as performed in this hospital since 1972. The results suggest that lymphography shows an unacceptable high number of false-negative results in cases of metastatic involvement of the inguinal nodes (7 out of 10 cases), whereas it is reliable for the judgment of the iliac and paraaortal nodes. For this reason the resection of the inguinal nodes remains a necessary part of radical vulvectomy. The additional removal of intrapelvic lymph nodes has been restricted to patients with lymphographic signs of positive nodes. In our opinion preoperative lymphography is of considerable value to minimize the operative risk for patients with carcinoma of the vulva by means of a more precise preoperative diagnosis, stage-oriented therapy and postoperative control.


[Pregnancy in diabetic patients. A calculated risk].

In general, a diabetic woman may count upon delivering a healthy child--provided optimal antenatal care. Success or failure of pregnancy will in the individual case decisively depend on the experience and efforts of the attending physician. The directives for the care of pregnant diabetic women as practiced at the II. Univ.-Frauenklinik München are demonstrated.


[Hormonal regulation mechanisms during puerperium].

The regulation of the hypothalamic-hypophyseal-ovarian axis during puerperium is reviewed. The lactotrophic hormone prolactin is necessary for the growth of the milk producing system, initiation and maintenance of lactation. Inappropriate responsiveness of the hypothalamic-hypophyseal-ovarian system causes independent of the actual prolactin serum values postpartum amenorrhea during early puerperium. However, the duration of amenorrhea depends on the duration of breast-feeding. The prolactin peaks induced by suckling interfere with the reappearance of normal cyclic ovarian regulation.


[The ball deformation method, a new method in oryhopedics for the quantitative threedimensional force flow determination in bone models].

The long term results of 1135 followed up patients after coxarthrosis-operations showed, besides being very effective, typical complications and problems. The bone bearing strength and strain has to be known exactly. In the past there was no method known for quantitative 3dimensional measurement of strength flow in case of biomechanical alteration by operations. The ball deformation system is introduced which was tested on bone models.


[Mechanisms of bronchial self-cleaning. Surface studies on the bronchial mucosa, bronchial basement membrane and subepithelial connective tissue. A scanning electronmicroscopic study].

Bronchial mucosa and bronchial basement membranes of man and of healthy slaughter animals were examined with the scanning electron microscope. The surface relief of the normal human bronchus mucosa is composed of a system of bulge-like prominences and valleys. There are parallel recesses and narrow valleys which run parallel to the longitudinal axis of the bronchus. Man and pig have the same kind of surface relief in bronchus. A fundamental different type of surface area relief is exhibited by the cow and the sheep. The bronchial basement membrane is a homogeneous plate with dune-like prominences and trough-shaped depressions. Often one can see perforations of variable size. The structures of the basement membranes have a great variability and no species-specifity. There are the same types of dysplasias in the bronchus mucosa in man and in animals. The differences are based upon in the wideness of the expansion and in the grade of the dysplasias in man.


[Classification of bronchial asthma].

The bronchial asthma disease is divided into 5 groups: 1. bronchial asthma caused by allergy, 2. bronchial asthma caused by infection, 3. bronchial asthma caused by physicochemical irritants, 4. bronchial asthma caused by exercise, 5. combination between the groups 1--4. Etiological factors, immunologic phenomena so far as known and pathogenic mechanisms are listed for each group and discussed.


[The thrombocyte aggregating effect of phosphatidic acids and their lyso-derivatives (DAS)].

In aged plasma or serum phosphatidic and lysophosphatidic acids (DAS) may occur which have been found to induce platelet aggregation in human and feline PRP (platelet rich plasma). Experiments performed on cats demonstrate that the lethal effect frequently following the i.v. injection of these substances into cats with high platelet counts is mediated via massive pulmonary microembolization. It remains to be elucidated whether the in vivo formation of these phospholipids may be of clinical interest.


[Corpus luteum function and female sterility. Comparative studies of endometrial biopsy and pregnanediol secretion within the same cycle].

In 129 patients with sterility or endocrine menstrual cycle disturbances the pregnandiol concentrations in the urine were measured and in the same cycle the endometrium of the 1st day of menstruation histologically examined. The length of the corpus luteum phases was classified into 6 groups (over 14, 11--14, 9--10, 7--8, 1--6, 0 days), also the endometrial findings (over stimulated, normal, slightly, moderately, significantly retarded secretory transformation, no secretory signs). In 77.5% of the cases a complete accordance between the pregnandiol output and the endometrial biopsy was found, in 18% a difference of one step between the two parameters. Only in 4.5% great discrepancies were found, which partly could be explained by simultaneous medication in the same cycle. The two methods do not compete with each other but complete each other, because pregnandiol output is a parameter for corpus luteum function and endometrial histology reveals the reaction of the target organ to the hormonal stimulus. A statement about the etiology of the corpus luteum insufficiency is not possible by these two methods. For that further examination, i.a. serial evaluation of the sexual steroids and gonadotropins in serum are necessary.


[The interaction of Ca2+ and heparin in the activation of lipoprotein lipase from adipose tissue (author's transl)].

The effect of calcium on the activation of lipoprotein lipase by heparin was studied using ammonia buffer extracts of acetone powder from guinea pig adipose tissue as the lipoprotein lipase source. Lipase activity was assayed with an artificial triglyceride emulsion that had been activated with rat high density lipoproteins. The addition of Ca2+ (2mM) alone increased the lipoprotein lipase activity about 2.5- to 3.5-fold, but heparin (1 unit/ml) alone had little effect. When both Ca2+ and heparin were added to the assay medium, the activity was increased to 4- to 5- fold above control values. When Ca2+ in the assay medium was sequestrated by EGTA, these increases by Ca2+ and heparin were completely abolished. The results suggest that the presence of Ca2+ is a prerequisite for the activation of lipoprotein lipase by heparin. Gel filtration of the mixture of acetone poder extracts and [3H] heparin showed the enzyme bound [3H] heparin whether Ca2+ was present or not. In addition to lipoprotein lipase, there were proteins in adipose tissue extracts which had an affinity for heparin.


[Evaluation of percutaneous transhepatic cholangiography (PTC) in the diagnosis of biliary diseases (author's transl].

Procedures of PTC and evaluation of this technique in the diagnosis of disorders of the pancreas and the biliary tract were described. The combination of PTC with superselective angiography proved to be an effective approach to cover the weak point of PTC and to ensure the diagnosis of the infiltrative changes outside the biliary tract.


[Study on the surgery of malignant biliary tumors (author's transl)].

The principle of the surgical therapy of malignant biliary tumor lies, as in other cancers, in the extensive removal of the tumors and lymph nodes in the regional area. Nevertheless, many problems remain unsolved with biliary carcinoma because of the anatomical structure and ensuing various symptoms depending on the degree of expansion. Seventy-two cases of biliary cancer were recorded during the past 13 years of observation in our clinic. The overall removal rate was 28%, which was extremely low as compared with other cancers. The regional removal rate was 62% in the ampulla, 25% in the gallbladder and 19% in the bile duct. In the bile duct carcinoma jaundice was most frequently seen and the degree and duration of jaundice were well correlated with the operative prognosis.


On the role of glucocorticoid in glucose-induced insulin secretion.

To explore the role of endogenous glucocorticoid in insulin secretion, the plasma concentrations of insulin in the fasting state and in response to intravenous administration of glucose were determined in adrenalectomized and sham-adrenalectomized rats. Adrenalectomy produced a decrease in the fasting plasma insulin two days after the operation when there was found no change in the blood glucose levels. Likewise, plasma insulin response to glucose was clearly reduced in adrenalectomized rats, although there was no difference among the two groups in increment of the blood glucose after the glucose load. At this moment, a stimulatory action of insulin on glucose metabolism was rather decreased in the adipose tissue from the adrenalectomized rats when compared with that from the control rats. The pancreatic tissue from the adrenalectomized rats secreted much less amount of insulin in response to perifused glucose not only in the early phase but also in the second phase of release pattern. The pancreas from the adrenalectomized rats treated with dexamethasone showed the opposite changes. These findings support the hypothesis that the endogenous glucocorticoid may play a role in maintaining sensitivity of the B cell to insulinogenic stimuli.


Heterogeneity of extractable gut glucagon-like immunoreactivity (GLI) and its lipolytic activity.

Gut glucagon-like immunoreactivity (GLI) was extracted from the mucosa of the canine intestine and was separated into two peaks by gel filtration; Peak I (7,000 daltons) and Peak II (3,500 daltons). These two peaks were purified by means of affinity chromatography using an anti-glucagon antibody as a ligand substance. These purified gut GLIs were not composed of single component, when applied to ion exchange chromatography. These partially purified Peak I and Peak II showed lipolytic activities, though very weak in potency, in vitro on the rat fat tissue at pharmacologically high concentration (5 ng eq/ml in final). It was concluded that gut GLI, even though purified, showed heterogeneity and that gut GLI revealed lipolytic activity although weak in potency compared with pancreatic glucagon.


Metabolic effect of high environment temperature on non-diabetic and diabetic rats.

Blood lipids and glucose were studied in streptozotocin diabetic rats during hyperthermia. Blood glucose, free fatty acids (F.F.A.) and glycerol of diabetic rats with a rectal temperature of 42 degrees C (hyperthermic) were elevated significantly above those values found in normothermic (TR = 38 degrees C) diabetic or normothermic non-diabetic rats as well as hyperthermic non-diabetic rats. Streptozotocin diabetes caused an elevation in blood triglycerides of normothermic rats, but this hypertriglyceridemia was depressed in diabetic rats during hyperthermia. As in the case of diabetic animals, hyperthermia also caused a depression in the blood triglycerides of non-diabetic rats. However, unlike in the diabetic animals, the blood F.F.A. of non-diabetic rats were depressed during hyperthermia. Although hyperthermia caused a significant increase in the blood glucose of the diabetic animals, no significant change in blood glucose was shown in the hyperthermic non-diabetic rats. Blood cholesterol did not change significantly in the non-diabetic or diabetic animals during hyperthermia. The blood changes of these "energy substrates" are discussed with respect to their possible role in the extreme sensitivity of diabetics to high environmental temperature and "heat stress".


Metabolism of thyroid hormones by the isolated perfused rabbit kidney.

The metabolism of thyroxine and triiodothyronine in the isolated perfused rabbit kidney was monitored by specific radioimmunoassay for each hormone. The amount of thyroxine catabolised was proportional to the amount added initially and no saturation effects were observed over a wide range (3.9-82 nmol). After addition of thyroxine alone, triiodothyronine could be detected in the perfusion medium within 10 minutes but only much later in the urine. It was proposed that circulating thyroxine contributes indirectly to the level of urinary triiodothyronine.


Influence of rifampicin treatment on the metabolic fate of [4-14C] mestranol in women.

[4-14C] Mestranol was administered to 2 rifampicin treated and to 3 untreated hysterectomised women with normal liver functions. The urinary excretions of mestranol, ethynylestradiol, 2-hydroxy-ethynylestradiol and of the total radioactivity were measured within the following 5 days. After this period the total urinary excretion of radioactivity amounted to approx. 43% (38%-50%) of the administered dose and no difference was found for the rifampicin treated and untreated women. Moreover, in the urines of both of these groups the same amounts of radioactive mestranol (1.1%-6.3% of the urinary radioactivity) and 2-hydroxy-ethynylestradiol (0.9%-3.9% of the urinary radioactivity) were measured. In contrast, the urinary excretion of ethynyl-estradiol was definitely lower in the rifampicin treated women (3.5% and 4.9% of the urinary radioactivity) as compared to the control group (15%-23%).


Effects of estradiol on in vitro nucleoside incorporation and methylation of rat uterine ribonucleic acid.

The in vitro nucleoside incorporation and methylation of uterine RNA was examined by incubating immature rat uteri with either 3H-uridine, 3H-uridine-3H-cytidine, and/or 14C-methyl-methionine. Radioactivity was determined in extracted RNA which was fractionated by gel electrophoresis or by differential solubility in zine acetate or lithium chloride. Estradiol (E2)-treated uteri respond by showing a maximum in vitro incorporation of nucleosides into total RNA and high M.W. RNA within one hr of in vivo treatment. Nucleoside incorporation into low M.W. RNA increased gradually throughout the first 3 hrs of a 4-hr hormone treatment period. E2 in vivo also caused increased in vitro methylation of total, high, and low M.W. uterine RNA fractions. Methylation of all fractions increased through the first 3 hrs of hormone treatment, but greater methylation of low M.W. RNA was apparent. The data indicate that in vivo E2 treatment stimulates an initial transitory stage of in vitro nucleoside incorporation into uterine RNA followed by a more prolonged interval of RNA methylation.


Circulatory and lipolytic effects of parathyroid hormone. An experimental study in dogs.

Parathyroid hormone (PTH) was given intravenously to anesthesized adult dogs. Blood flows were measured with electromagnetic probes in different vascular areas concomitant with analysis of glycerol, free fatty acid, calcium, glucose, sodium, potassium, albumin, carbon-dioxid and creatinine. PTH consistently caused an immediate increment in blood flow in the celiac vasculature and a following, less pronounced increase in the renal artery. These changes were effectuated by a vasodilatation. The degree and duration of the flow increments were dose dependent; The celiac artery was more sensitive to the effect of PTH than the renal artery. In celiac artery maximal increase above basal flow was 58 +/- 27% (Mean +/- S.D.), in renal artery 25 +/- 12%. A significant lipolytic action of PTH was consistently notable within minutes after the administration of PTH. The other parameters analysed in blood remained unchanged sixty to ninety minutes after the PTH injections. Then a hypercalcemic effect of PTH appeared. A lipolytic action of PTH could be demonstrated with PTH doses which did not induce hypercalcemia.


Radioimmunological determination of cyproterone acetate.

A sensitive and specific radioimmunoassay for cyproterone acetate in serum has been developed. Antiserum was raised in rabbits by immunization with a conjugate of cyproterone acetate-11 alpha-hemisuccinate and bovine serum albumin. Radioactive tracers with high specific activities were synthesized by coupling the hemisuccinate with [3H]-tyrosine methyl ester of [125I]-iodohistamine. Competition studies with substances structurally related to cyproterone acetate have revealed that the structures of ring A and B are mainly responsible for binding to the antibody.


Triiodothyronine-producing metastatic follicular thyroid carcinoma.

Thyroid hormone serum concentration was determined in a thyroidectomized patient with functional follicular thyroid carcinoma with metastases. Marked diminution of circulating serum T4 and FT4 with normal T3 serum concentration was found. The clinical implications of this shift in secretory activity are discussed.


Induction of precocious puberty in newborn female guinea pigs by a positive feedback action of estrogens.

The existence of a positive feedback of estrogen on the gonadotrophin-releasing mechanism at birth, was tested in the female guinea pig. Estradiol benzoate (100 ng during the first 5 days of life) or HCG (100 RU during the first 5 days of life) induced a true precocious puberty, with similar characteristics to the control animals (60% of the animals ovulated at puberty age: corpora lutea present at the ovaries). The uterus was larger in ovulating than in nonovulating animals. Reserpine (2.5 mg/kg) on 15, 17 and 19 days of age did not modify the precocious puberty induced by estradiol at birth. It is concluded that exogenous or endogenous estrogen (induced by exogenous gonadotrophin administration) have a positive feedback action on the newborn female guinea pig to release gonadotrophin and develop puberty. These results are very different than those observed in the rat and differences can be related to the stage of somatic and nervous maturation attained by the animals at birth.


[On the preparation of intermediates in cobyrinic acid biosynthesis by suspensions of Propionibacterium shermanii (author's transl)].

The preparation of a dimethyltetrahtdrouroporphyrin (Faktor II or sirohydrochlorin) using suspensions of Propionibacterium shermanii as well as a promising method for the isolation of tetrapyrrols with at least four carboxy substituents from cell-free extracts and growth media are described. Also a Faktor II-analogue with three methyl groups which are derived from L-methionine is reported. Incorporation experiments indicate that this is an intermediate in cobyrinic acid formation. Because of this, and from spectroscopic (field desorptionmass, visible absorption) studies it is concluded that the "extra" methyl group is located at the meso-carbon between two methylated reduced rings.


Enzymatic and chemical synthesis of 3-dehydroecdysterone, a metabolite of the moulting hormone of insects.

3-Dehydroecdysterone, a less polar metabolite of ecdysterone, was synthesized in vitro using either an enzyme (edcysone oxidase, EC 1.1.3.16) or the chemical catalyst platinum. 3-Dehydroecdysterone was purified and characterized by its chromatographic behaviour, its staining properties and by UV, IR, NMR and mass spectroscopy. The compound is 1/15 as active as ecdysone in the Calliphora moulting hormone bioassay. Its biological relevance is discussed.


[The estradiol and estrone esters of [103Ru]ruthenocenecarboxylic acid. Synthesis, excretion and organ distribution (author's transl)].

The synthesis of the estradiol-17beta and estrone esters of ferrocenecarboxylic acid is described. The exchange reaction of these compounds with [103Ru]RuCl3 produced the corresponging [103Ru]ruthenocene compounds. The excretion and organ distribution of these estrogen esters in mice were quite different from those of [103Ru]ruthenocenecarboxylic acid and its methyl ester. The 103Ru-labelled estrogen esters are compared to 125I or 135I-labelled derivatives with respect to possible applications.


Complex formation of crosslinked fibrin oligomers with agarose-coupled fibrinogen and fibrin.

Soluble oligomers of fibrin were produced by limited incubation of fibrinogen with thrombin in the presence of calcium2 positive earth, cysteine and factor XIII. They were separated from fibrinogen by gel filtration. Gamma-gamma dimers were demonstrated in fractions from the void volume and the shoulder prior to the fibrinogen peak. These fractions were subjected to affinity chromatography on agarose-coupled fibrinogen and fibrin. Cross-linked oligomers of fibrin were adsorbed to agarose-coupled fibrin, whereas no adsorption occured during affinity chromatography on agarose-coupled fibrinogen. This indicates that crosslinked fibrin oligomers have no affinity to fibrinogen, yet readily form complexes with fibrin.


The influence of oxygen deficiency and electrical stimulation on the concentrations of ATP, ADP, AMP and phosphotaurocyamine in the body-wall musculature of Arenicola marina.

1) Concentrations of ATP, ADP, and AMP, as well as phosphotaurocyamine in the body-wall musculature of Arenicola marina were determined enzymatically and by means of isotachophoresis after 12, 24, and 48 h of experimental anaerobiosis and after electrical stimulation under aerobic and anaerobic conditions. 2) Freshly collected lugworms contained 3.5-3.8 mumol ATP, 0.8-1.0 mumol ADP, and 0.3-0.5 mumol AMP, as well as 4.5-4.7 mumol phosphotaurocyamine per g wet weight (energy charge 0.81-0.85). 3) After 48 h of anaerobiosis the concentration of ATP was decreased to one half, that of phosphotaurocyamine to one third of the initial value, while the content of ADP on the other hand nearly doubled and that of AMP trebled (energy charge 0.60-0.63). 4) Electrical stimulation in the absence of oxygen caused a rapid decrease of the ATP and phosphotaurocyamine to low levels corresponding to those found after long-term anaerobiosis; the ADP and AMP concentrations were slightly higher than those found after long-term anaerobiosis (energy charge 0.55-0.58).


[Imidazole nucleosides, III. Nucleosides of 4(5)-aminoimidazole-5(4)-carboxamide (author's transl)].

The synthesis and properties of 13 nucleosides derived from 5-aminoimidazole-4-carboxamide and from 4-aminoimidazole-5-carboxamide are described. The isomers were oriented by comparison of their spectra and colour reactions. All compounds were tested for anticancer activity. 4-Amino-1-(alpha-D-arabinopyranosyl)-imidazole-5-carboxamide significantly inhibits the growth of Ehrlich ascites carcinoma (fluid form) in mice.


A novel semisynthetic route to insulin analogues modified at the N-terminus of the A-chain.

We report a novel route for the semi-synthetic production of insulin analogues modified at the amino-terminus of the A-chain. The route proceeds from insulin via [Nalpha-Boc-GlyA1]-insulin to [Nalpha-(Z-methionyl)-PheB1, Nepsilon-(Z-methionyl)-LysB29]des-GlyA1-insulin. We have replaced residue A1 with glycine, to give a fully crystalline resynthesized insulin, and with D-lysine.


Synthesis and properties of [11-serine]alpha-melanotropin.

[Ser11]alpha-melanotropin has been prepared and its melanotropic activity compared with that of alpha-melanotropin and several known analogues. Full activity does not depend on the positive charge of 11-lysine in alpha-melanotropin but on the hydrophilic character of the amino group or a corresponding residue. A shift, or even more, a loss of such a group decreases the melanotropic activity.


Human alkaline phosphatases. II. Metalloenzyme properties of the enzyme from human liver.

Human liver alkaline phosphatase is a metalloenzyme requiring Zn2 and Mg2 for full activity. Zn2 cannot be replaced by manganese, cobalt or calcium, whereas Mg2 can be replaced by manganese or calcium. The binding constants of the enzyme for different divalent cations were determined by the use of complexing agents. The enzyme is inhibited by a number of reducing and complexing agents such as 2-mercaptoethanol, cyanide, nitrilotriacetic acid and EDTA. From studies using these inhibitors it is suggested that there are different mechanisms of inhibition. Reversible inhibition occurs if the free Zn2 concentration is not significantly lower than 10(-12)M. Inhibition is irreversible at lower Zn2 concentrations. Evidence is given, that the human liver alkaline phosphatase possesses different zinc binding sites, which are responsible for the catalytic function and for the integrity of the enzyme structure.


Partial purification of L-ascorbate:ferricytochrome b5 oxidoreductase from rat liver microsomes.

L-Ascorbate:ferricytochrome b5 oxidoreductase from rat liver microsomes was enriched about 750-fold after treatment with a non-ionic detergent with a yield of about 15%. The enriched enzyme still shows four bands in sodium dodecylsulfate polyacrylamide-gel electrophoresis and is a hydrophobic membrane protein.


The anatomy of cooperative binding between protamines and DNA.

DNA was titrated with protamine under equilibrium conditions while binding was simultaneously followed by electron microscopy and the fluorescamine technique. Positive cooperativity concluded from the binding assays was shown to be correlated with an aligned association of DNA fibres. Subsequent structural modifications, dependent upon the protamine/DNA ratio, suggests a mechanism for DNA compaction by protamines. In the framework of this model, protamine phosphorylation appears to promote formation of DNA interstrand links yielding a very pronounced filigree structure.


Purification and properties of the pyruvate kinase isoenzymes type L and M2 from chicken liver.

A procedure for the simultaneous purification of both isoenzymes of pyruvate kinase (type M2 and L) from chicken liver has been worked out. Each isoenzyme produces a single band in dodecylsulfate gel electrophoresis. Each has a molecular weight of 190 000 and contains four apparently identical subunits of Mr = 50 000. The isoenzymes differ in their isoelectric points (type L: 6.3; type M2: 8.3) and their kinetic behaviour. Pyruvate kinase type L had an S-shaped phosphoenolpyruvate saturation curve (K 0.5=0.79 mM) which was transformed into an hyperbola in the presence of fructose 1,6-bisphosphate, while type M2 had a phosphoenolpyruvate saturation curve of the Michaelis-Menten type (K0.5=0.2mM). Antibodies against pyruvate kinase type L from chicken liver inactivated type L from rat and partially inactivated type M2 from chicken and rat; but the antibodies against type L did not react with type M1 from chicken breast muscle. It is therefore concluded that, contrary to a previous report (Strandholm, J.J. et al. (1975) Biochemistry 14, 2242-2246), avian liver contains pyruvate kinases type M2 and L as the mammalian liver does.


[Preparative isolation of mono- and di-pyrimidine nucleotides from depurinated herring sperm DNA (author's transl)].

The preparative isolation of DNA fragments with defined sequences from hydrolysates of naturally occuring DNA is proposed as an alternative to their complicated synthesis and has been partially realised. Starting with herring sperm DNA which was depurinated in 100 g batches, one obtains 35-40 g of a pyrimidine-oligonucleotide mixture which is separated into high and low molecular weight fragments via column chromatography on DEAE cellulose. The low molecular weight pyrimidine-nucleotide mixture thus obtained is then selectively separated on a preparative scale into fragments with one and two monomer units by means of a three-step separation procedure on QAE-Sephadex.


[Scope and limitations of the analytical use of dansyl chloride, I: The reaction of aromatic sulfonyl chlorides with aliphatic tertiary amines: the microanalytical aspects of the Hinsberg test (author's transl)].

Contrary to the present understanding of the Hinsberg test, aliphatic tertiary amines (N,N-dimethylethylamine, bufotenin, hordenine, tropan alkaloids) are shown generally to react with aromatic sulfonyl chlorides yielding the N-substituted sulfonamide derivatives of the monodealkylated amines as the result of oxidative dealkylation of the aliphatic tertiary amines. Possible errors resulting from the indiscriminate use of either dansyl chloride, bansyl chloride or other aromatic sulfonyl chlorides for the direct analytical determination of secondary amines, secondary amino acids, noralkaloids etc., are pointed out.


[Scope and limitation of the analytical use of dansyl chloride, II: Formation of secondary dansyl amines by the reaction of dansyl chloride with N-oxides of aliphatic tertiary amino derivatives according to the Polonovski reaction (author's transl)].

The general validity of the Polonovski reaction with sulfonyl chorides is demonstrated by the reaction of bansyl chloride and dansyl chloride with pseudotropine-N-oxide and the isomeric tropine-N-oxides yielding the corresponding N-Bansyl derivatives and N-Dansyl derivatives of the noralkalois. The consequence of this reaction for the analytical determination of secondary amino derivatives with bansyl chloride, dansyl chloride and corresponding fluorophors is that secondary amino derivatives cannot be determined in the presence of the N-oxides of these amino derivatives.


Purification and characterization of animal porphobilinogen synthases. I. Bovine liver porphobilinogen synthase.

Porphobilinogen synthase was purified from ox liver by ammonium sulfate fractionation, heat denaturation and column chromatography (purification: 400-fold; specific activity 4.72 nkat). The molecular weight of the native enzyme obtained by thin-layer gel filtration is about 280 000. Using 8M urea in the presence of dithiothreitol as reducing agent, the molecule breaks down into 8 subunits of molecular weight 36 000 (dodecylsulfate gel electrophoresis); the preparation of aminoethylated subunit is described. According to the above-mentioned molecular weight and to the above-mentioned molecular weight and to the quantitative amino acid analysis after total hydrolysis, the following compositon of the enzymes subunit was calculated ASX23-25 Thr7 Ser23-24 Glx29-31 Pro22-23 Gly22-24 Ala36-37 Val23-26 Met7 Ile9 Leu34-35 Tyr10 Phe11-12 Lys11-12 Cys6-7 His6-8 Arg22 Trp1-2. The subunits, having two free sulfhydryl groups, therefore consists of a chain of about 306 amino acids. The Dansyl-Edman procedure did not enable identification of any free N-terminal amino acid. The acyl group blocking the N-terminus is an acetyl group. It was identified, after hydrazinolysis of the enzyme, by means of chromatographic comparison with 1-formyl-2-dansyl-hydrazine and 1-acetyl-2-dansylhydrazine, whose syntheses and UV spectra are described.


Isolation and characterisation of a low molecular weight inhibitor (of chymotrypsin and human granulocytic elastase and cathepsin G) from leeches.

Two protein proteinase inhibitors were isolated and purified from the leech Hirudo medicinalis by means of gel filtration and ion-exchange chromatography. They inhibit chymotrypsin, subtilisin and the granulocytic neutral proteases elastase and cathepsin G. They proved to be homogeneous in polyacrylamide and dodecylsulfate gel electrophoresis and by end group analysis; only threonine was found as N-terminal amino acid residue using the dansylation technique. These inhibitors, which we call eglins, are stable in neutral and weakly acid (pH 3) solutions and resist non-specific proteolysis. From the amino acid compositions, a molecular weight of 6 600 - 6 800 is calculated for both inhibitory proteins, which is in good agreement with a value of about 6000 estimated by dodecylsulfate electrophoresis. The eglins contain an unusually large amount of hydrophobic amino acid residues but no methionine, isoleucine or--a rarity--cysteine residues or disulfide bridges. To our knowledge, the eglins are the first examples of proteinase inhibitors of the protein type which are not stabilized by disulfide bridges.


Labelling of histones and nonhistones in lung nuclear matrix and chromatin fractions.

Rat lung tissue is labelled in vitro with [3H]leucine and nuclei are prepared. They are digested with deoxyribonuclease II and four subfractions are isolated after differential centrifugation: MgCl2-soluble (active) and MgCl2-insoluble (inactive) chromatin, nuclear matrix sediment and matrix extract using 2M NaCl. The matrix extract fraction is found to be enriched in radioactive DNA after a short pulse of [3H]thymidine. The labelling kinetics of histones are similar in each subfraction, suggesting that histones are not preferentially incorporated onto nascent DNA. Nonhistones isolated from the subfractions, except for the matrix sediment fraction, also follow closely similar incorporation kinetics with [3H]-leucine. The matrix sedimnent fraction is three times more actively labelled than nonhistones of the other fractions and displaying a unique protein composition, suggesting distinct functional properties.


Membrane sialic acid and behaviour in vivo of rabbit "stress" macroreticulocytes.

Membranes of rabbit reticulocytes obtained by phenylhydrazine stimulation have a chemical composition different from that of normal erythrocytes; sialic acid/protein and cholesterol/protein ratios are in fact lower than normal. In vivo study of 51Cr-labelled reticulocytes show that these cells are quickly removed from blood and, after a short "homing" in liver, return to peripheral blood. During "homing" in the liver, the sialic acid/protein ratio seems to increase.


Computer provides definite linen distribution and control mechanism.

For the past 10 years or so, large laundries have been concerned with productivity. While productivity has increased 10 to 20 percent, the linen replacement cost in these same laundries has more than doubled. It will not suffice for these laundries to point toward the hospitals they serve and imply that linen service and control is solely a hospital management problem. As long as proven technology is available, these laundries have an inherent responsibility to provide hospital management with the data necessary to pinpoint and correct linen consumption and replacement problems.