Spontaneous labor and elective induction--a prospective randomized study. I. Effects on mother and fetus. In a prospective randomized study spontaneous and oxytocin induced labor "for convenience" have been compared with respect to uterine activity, duration of labor, the condition of the fetus and the newborn infant. The study consists of 84 normal patients, of whom 43 were induced at full term by amniotomy and oxytocin infusion using the Cardiff Infusion System Mark II; 41 patients served as controls. No difference in maternal age, number of previous pregnancies and pelvic score one week before the day of delivery were found between the groups. The following parameters were calculated: duration of labor, uterine activity, amount of bleeding in the third stage of labor, number of early and late decelerations as well as number of episodes of bradycardia in the CTG-recordings, birth weight, Apgar score one and five minutes post-delivery and blood gases in mother and child 60 seconds after delivery. No significant differences between the two groups were found. It is concluded that there are no increased risks to mother or fetus compared to normal labor provided that there is cephalic presentation and normal pregnancy, careful selection with respect to the length of pregnancy and the condition of the cervix and that the Cardiff infusion system is used with intrauterine pressure recording and continuous fetal heart monitoring.


Hemodynamic effects of somatostatin in insulin-dependent diabetic subjects. The aim of the present study was to evaluate possible hemodynamic effects of somatostatin in insulin-dependent diabetic subjects. For this purpose, 7 insulin-requiring juvenile-onset diabetics were submitted to a short-term infusion of cyclic somatostatin (250 micrograms/h, over 2 h) or saline in randomized order. Somatostatin infusion resulted in a progressive and significant decrease in heart rate, stroke volume, cardiac index and velocity circumferential fiber; on the other hand, left ventricular ejection time was augmented by somatostatin. None of these effects was seen in the saline control study. We conclude that somatostatin exerts a negative inotropic effect in insulin-dependent diabetes.


Somatostatin and insulin secretion in man. II. The effect of theophylline. This study was aimed at evaluating the effect of theophylline, a drug that increases the intracellular concentrations of cAMP by inhibiting phosphodiesterase activity, on somatostatin (SRIF)-mediated inhibition of insulin secretion in man. Acute insulin response (AIR) to i.v. glucose (mean change 3-10 min) was almost totally suppressed by SRIF (500 micrograms/h) and glucose utilization was reduced (p less than 0.0001). These SRIF-induced decreases failed to be eliminated by a concurrent infusion of theophylline (100 mg as a loading dose followed by a constant infusion of 5 mg/min). Theophylline alone resulted in a significant increase in both AIR (p less than 0.01) and glucose removal rates (p less than 0.05). Thus, our data disprove the involvement of the phosphodiesterase enzymes in the inhibitory action of SRIF on glucose-induced insulin secretion in man.


[Neurovegetative regulation of the heart and use of beta-adrenergic blocking agents]. Dynamic adaptation of cardiac activity to respond to various physiological and pathological situations involves the autonomic nervous systems by means of negative feed-back. Beta-blocking drugs are very effective in changing cardiocirculatory regulation equilibria by altering the intensity of the negative feed-back mechanism, or by converting positive feed-back into negative feed-back. A strict and specific indication for the use of these powerful drugs is therefore required. Treatment should also take the form of courses, and be limited in terms of time wherever possible.


Benzodiazepines: some aspects of their clinical pharmacology. Benzodiazepine derivatives are the most commonly prescribed anti-anxiety agents in clinical practice. Six benzodiazepine anxiolytics are now available in the United States. Additional drugs are used in other parts of the world, and many others are in various stages of clinical testing. All these benzodiazepine derivatives have similar neuropharmacological properties--they reduce anxiety, produce sedation and sleep, have anticonvulsant effects, and can produce muscle relaxation. Faced with this bewildering array of drugs from the same class which are very similar in intrinsic effects upon the brain, the clinician may well ask how best to make a rational choice among the available derivatives. Despite neuropharmacological similarities, there are differences among benzodiazepines in patterns of absorption, distribution, and elimination by the human body. These pharmacokinetic differences may in turn lead to apparent differences in clinical action. This review summarizes pertinent pharmacokinetic characteristics of benzodiazepine anti-anxiety agents.


Isolation, purification, and study of certain properties of diacetyl(acetoin) reductase in the yeast Saccharomyces vini. A highly active preparation of diacetyl(acetoin) reductase was isolated from cell-free extracts of the yeast Saccharomyces vini. Since the activity ratio of 2,3-butanediol dehydrogenase and diacetyl(acetoin) reductase was practically unchanged in the process of 65-fold purification, it can be assumed that the yeast cells contain one enzyme, which catalyzes both the reversible oxidation of 2,3-butanediol to acetoin by NAD and the practically irreversible reduction of diacetyl to acetoin by NAD-H2. Some properties of this enzyme were studied.


[In vitro activity of cefaclor (author's transl)]. A comparative study was conducted on the in vitro activity of cefaclor and other oral cephalosporins against a large number of freshly isolated clinical strains of gram-negative and gram-positive bacteria. The activity of cefaclor against gram-positive pathogens is very similar to that of cephalexin. The action of cefaclor against Streptococcus pneumoniae is superior. Cefaclor is the most active antibiotic against strains of Haemophilus influenzae, and is also more active than cephalexin and cephradine against non-beta-lactamase producing strains of Escherichia coli, Klebsiella species and Proteus mirabilis.


Summary of laboratory studies on the antibacterial activity of cefaclor. Laboratory aspects of cefaclor, a new orally-effective cephalosporin antibiotic, are summarized. On the basis of data from a variety of studies, the useful antibacterial spectrum of cefaclor is shown to include all classes of bacteria that are generally susceptible to cephalothin and cephalexin. Cefaclor has a significant potency advantage over cephalexin against many Enterobacteriaceae, Haemophilus sp. and Streptococcus pneumoniae. Bacteria that are susceptible to cefaclor are killed by concentrations at or near the inhibitory concentration. In vitro enzymatic hydrolysis experiments have shown that cefaclor is a relatively good substrate for several beta-lactamases. Orally administered cefaclor is effective in protection of mice from the lethal effects of intraperitoneal challenges with cefaclor-susceptible bacteria. The chemical instability of cefaclor, test medium composition and inoculum density influence the results of in vitro susceptibility tests with cefaclor. Methods for routine susceptibility testing are described.


Sperm quality in adult diabetic men.

Sperm quality in adult diabetic men. In 65 adult diabetic men and 77 control men without diabetes, both groups without any problems as to fertility, the following characteristics of ejaculate have been compared: volume of seminal fluid, sperm concentration per milliliter, total sperm count, sperm morphology, and motility at 1, 3, and 5 hours after ejaculation. In the entire diabetic group, sperm morphology and motility at 1 hour after ejaculation was statistically significantly worse. In 15 diabetics without sexual disurbances only sperm morphology was statistically significantly worse compared with an equally large control groups. In 50 diabetics with erection disturbances, sperm volume and motility in three successive observations were statistically remarkably lower. In younger age subgroups, the differences between diabetics and nondiabetics were more marked than in older age subgroups. The patients' age, when diabetes was discovered in them, did not essentially influence the quality of the ejaculate where diabetes lasted 8 or more years. Diabetics over 40 years' age displayed a significantly lower sperm volume. The total sperm count and motility at 3 and 5 hours after ejaculation, with 12 or more years' duration of diabetes, differed from diabetes of 2 years' duration. On the basis of these observations a negative influence of diabetes on the quality of the ejaculate seems unquestionable. There exists great variability in the adverse effect on the individual diabetic. Also, the individual characteristics of the ejaculate are affected, usually, to a different extent: the most frequently and markedly affected being the sperm motility, then morphology and/or volume of ejaculate, and the least often and the least conspicuously, the sperm count.


Endocrinological analysis of environmental menstrual disorders. In 139 new student nurses, a change of menstrual cycles after school entry was studied, recording their basal body temperature over more than 4 months. In some of these students, serum FSH, LH, prolactin, estradiol, and progesterone were assayed every day or every other day throughout the second cycle after entry. Forty-six out of 72 students with previously normal menstrual cycles changed the length of their cycles. In most of the cases with a change in menstrual cycle, LH seemed not to be released in adequate amounts judging by the peak of estrogen and ovulation did not occur; the lack of sufficient LH stimulation resulted in anovulatory shortened cycles, amenorrhea or prolonged ovulatory cycles, followed by delayed ovulation. Also, in these cases, corpus luteum insufficiency persisted even when the ovulation returned. Prolactin was not considered to be involved in the mechanism of environmental menstrual disorders because serum prolactin did not increase in the cases with menstrual change. It can be concluded that environmental change or stress influences LH-RH cells in the hypothalamic centers simultaneously with the stimulation of ACTH secretion, and suppresses ovulation by decreasing LH secretion, and causes the different types of menstrual disorders.


Psychological reactions of couples to artificial insemination with donor sperm. The case histories of 62 couples successfully treated by AID were established through nondirective interviews, and were surprisingly similar in all cases. Several distinct stages were regularly observed: the awareness of wanting a child while the woman cannot become pregnant; the investigation of the couple's sterility with as a result, the announcement that the husband is sterile; a period in which the couple adapt to this situation; the disappearance of the feeling of guilt both of the husband, wounded in his "virility," and of the wife, ashamed of her desire for a child; acceptance of the idea of AID; request for AID; conflict with the medical profession; the disturbing seances of AID, usually in the presence of the husband; uneasiness at the beginning of pregnancy; euphoric continuation of pregnancy; uncomplicated delivery of a child whose father is very involved in its upbringing, and then request for a second child by AID.


An attempt to explain occurrence of patent reproductive tract in azoospermic males with tubular spermatogenesis. Twenty-two azoospermic males with no hormonal disturbances who revealed tubular spermatogenesis in testicular biopsy, were further surgically explored. Eight of these patients did not show any obstruction of the seminal ducts. This paradoxical finding is explained by the possibility of a low sperm production rate much below the absorption rate of sperm, mainly by the epididymis. A threshold theory is suggested in which sperm appear in the ejaculate only when their production rate is above a certain level. This threshold cannot yet be expressed quantitatively and there is no other way except through surgical exploration by which real obstruction can be differentiated from low sperm production rate in azoospermic males with tubular spermatogenesis.


Surgical correction of cervical incompetence. Results obtained with a modified surgical cerclage technique in 80 patients suffering from isthmic cervical incompetence are analyzed. The operation was performed once in 58 patients and twice in 22, giving a total of 102 pregnancies treated. The technique is described in detail, emphasizing its advantages. In 73 pregnancies (71.5%) the outcome was satisfactory (the newborn babies survived) despite the fact that in 66 instances (65%) cervical modifications were present at the time of the operation.


Semen separation technique monitored with greater accuracy by B-body test. A fluorescent staining technique, the B-body test, is utilized to ascertain the proportion of male and female spermatozoa in separated semen. This test is also used to monitor progress of Thermal Convection Counterstreaming Sedimentation and Forced Convection Galvanization processes for separating heavier electropositive (female) and lighter electronegative (male) spermatozoa into the two constituent fractions. Biological field tests using separated semen with 1,115 cows resulted in 510 progeny showing close correlation in the percentage of male versus female and B-body positive in the male spermatozoa fractions, while a control group with nonseparated semen, usually 46% B-body positive, yielded 55% male offspring and 72.0% pregnancy. Thus, the accuracy of the separation techniques has been established to the extent of producing more females with heavier and electropositive and more males with the lighter and electronegative spermatozoa fractions. However, the pregnancy rate slopes downward as the positive electropotential and density of the spermatozoa are successively increased.


Autoproteolysis in human seminal plasma under acidic condition. The existence of both neutral and acidic proteases in human seminal plasma suggests a possible autohydrolysis of the proteins in the fluid. By means of polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, the autoproteolysis in human seminal plasma was shown to occur at pH 3.5 but not at pH 5.0--7.5 conditions. At pH 3.5, most proteins of large molecular weight, except one of 28,000 daltons, were completely hydrolyzed into peptides of 13,000 daltons or smaller. The autoproteolysis was due to the action of the acidic protease since it can be blocked by 1 mM of p-bromophenacyl-bromide or 1,2-epoxy-3-(p-nitrophenoxy) propane, the specific inhibitors of the acidic protease.


Techniques for laparoscopy on patients with previous abdominal surgery. Many clinicans are hesitant to perform laparoscopy on patients with previous intra-abdominal surgery, because of increased risk of hemorrhage or intestinal perforation in the presence of abdominal adhesions. Experiences and techniques used in Grady Memorial Hospital to increase the safety of laparoscopic procedures performed on patients with extensive abdominal adhesions are discussed.


Experimental design for the surgical relocation of the ovary into the vaginal fornix. After translocation into the vaginal vault while attached to a pedicle consisting of the infundibulo-pelvic ligament, the ovary was found to maintain its function in laboratory primates. In the majority of the baboons the ovulatory pattern returned within a few weeks after the surgical procedure. The only significant complication was a transitory, and self-limited, infection which was evident on inspection and on the biopsy specimens, but caused no clinical symptoms. By comparing the surgical outcome in two primate species, namely Papio Cynocephalus and Macaca Arctoides, it could be deduced that the Homo Sapiens would be a more suitable experimental model than either of the laboratory primates used in this research. Because there are potentially effective methods for reducing the likelihood of postoperative infection in the relocated ovary, the experience gained by this new method suggests the possibility that it could be utilized in the future for the purpose of collecting ova for in vitro fertilization in carefully selected, and otherwise untreatable, cases of female sterility.


Hyperprolactinemia and polycystic ovarian syndrome. Prolactin and pituitary gonadotropin levels were studied in eight patients with polycystic ovarian syndrome. All women were of reproductive age and had had menstrual disorders since menarche. Three patients had hyperprolactinemia with or without galactorrhea and tomograms of the sella turcica revealed pituitary microadenomas. The remaining five patients with normal baseline prolactin levels had a prolactin stimulation test which used 25 mg of thorazine per os, and a prolactin suppression test using l-dopa 500 mg per os. Analysis of the results of these tests and a comparison with tests performed in five normal individuals used as controls showed significantly different responses in the two groups of women. The preliminary information obtained indicates that an abnormal prolactin secretion status may exist in the polycystic ovarian syndrome.


Spontaneous motility of isolated mesosalpinx-free isthmic and ampullar segments from human oviducts, and the influences of indomethacin and prostacyclin (PGI2). The spontaneous contractile activity of isolated mesosalpinx-deprived isthmic and ampullar segments from estrogen dominated human oviducts and the influences of indomethacin, prostaglandin F2-alpha, (PGF2-alpha), E1 (PGE1), E2 (PGE2) and prostacyclin (PGI2) on their motility, were explored. Indomethacin enhanced significantly the Isometric Developed Tension (I.D.T.) of the isthmic but not the ampullar region. On the other hand, a single and identical concentration (10(-6) M) of PGE1 and PGI2 depressed the ampulla whereas PGE2 and PGF2-alpha enhanced its contractions. In the isthmus, PGE1, PGE2, and PGF2-alpha augmented whereas PGI2 diminished the I.D.T. Dose-response curves of PGI2 demonstrated a dose-dependent depression of I.D.T. and contractile frequency of both ampullar and isthmic regions. Furthermore, in the isthmus PGI2 resulted in a biphasic action on resting basal tone (depressing at low and augmenting at high concentrations), whereas in the ampulla only a progressive dose-dependent decline, was observed. The results suggest that a prostaglandin with inhibitory capacity, presumably PGI2, may be synthesized by the human isthmus and play some role in the reduced spontaneous activity observed under estrogenic dominance.


Inherent ranges of seminal prolactin in pre- and postvasectomy subjects. Seminal immunoreactive prolactin (i prolactin) was studied in 14 healthy subjects, ages 31 +/- 2 SEM, before and after undergoing elective vassectomy for birth control. Seminal plasma was separated within 2 hours of ejaculation, and prolactin was measured in duplicate by radioimmunoassay. The difference between the prevasectomy (mean +/- SEM 11.1 +/- 0.8 ng/ml) and postvasectomy seminal i prolactin (mean +/- 9.9 +/- 0.7 ng/ml) was statistically significant (mean +/- SEM 1.21 +/- 0.53 ng/ml, paired t-test, t = 2.36, P < 0.05). The mean prevasectomy seminal prolactin correlated with the corresponding mean postvasectomy value of the same subject (linear regression analyses, r = 0.77, P < 0.001). This study suggested that the accessory sex organs were the major source of seminal immunoreactive prolactin, and that a minor contribution might come from the in vivo presence of spermatozoa and/or testicular secretions. It also suggested that the magnitude of seminal immunoreactive prolactin was characteristic for each individual.


Fertility in women after age forty-five. Pregnancy after age 45 years is infrequent and the mother and baby should be considered as a high risk. There is a greater incidence of spontaneous abortion, gestational trophoblastic disease and chromosomal abnormalities in the fetus. Birth control practices should be discontinued after 49 years of age in the best interest of the woman's sexuality if abortion is acceptable to her. The patient should be completely informed of the risks and, in the event of pregnancy, abortion should be advised.


The use of donor mucus and insemination for cervical factor. In a case of infertility due to cervical factor, application of donor mucus into the cervical canal was effective. The donor mucus with the first fraction of the husband's split ejaculate were incubated at 37 degrees C for 20 minutes. The mucus was then introduced into the cervical canal and a cervical cap for insemination was applied. A positive postcoital test was demonstrated after 6 hours. The patient conceived following a second such treatment. Donor cervical mucus aplication and insemination seem to be of value in the treatment of cervical factor.


A method for the in situ measurement of the electrical quantities in frog skin. A method allowing the measurement of the electrical quantities related to the physiological functions of the frog skin in situ is presented. The method allows the performance of several experiments on the same pithed animal, which remains alive for a number of days. The preparation is very stable, and the electrical potential difference and short-circuit current values are higher than in isolated skin. The theory of measurement and the possible systematic errors are discussed. The possibilities of the method are evaluated on comparing the pH and temperature dependence of the electrical quantities in situ with previous measurements on isolated skin.


Catecholamines in fetal blood during birth in man. Catecholamines and pH were determined simultaneously in human fetal scalp blood during parturition and in umbilical artery blood at birth. During the course of six normal vaginal deliveries with relatively small changes in blood pH about a ten-fold increase in catecholamine concentration was found. During six deliveries complicated by falls in blood pH to < 7.25 much higher values were often encountered.


The role of the physician's assistant in a university-based pediatric surgical service. Physician's Assistants (P.A.), recent additions to the health profession, have proved valuable as "extenders" for primary physicians in relatively remote rural areas. More specialized surgical assistants have been trained for the community-practicing surgeon. The introduction of physician's assistants into university centers has been proceeding at a slower pace. A need has existed for an accurate assessment of the role of the P.A. in a residency-training program. In subspecialties, such as pediatric surgery and thoracic surgery, an increasing patient load has usually required a corresponding increase in junior resident staff. This resident coverage is usually dependent upon the availability of general surgical house staff since pediatric surgical trainees are currently fixed in number. Foreign medical graduates are no longer available in large numbers and general surgical programs themselves are being reevaluated and the number of trainees decreased. In this setting physician's assistants can be used to augment patient coverage by acting as junior surgical residents.


Abnormalities of the vas deferens and epididymis in cryptorchid boys with congenital rubella. Cryptorchidism was present in 12% of 316 boys with congenital rubella (CR) followed by The Roosevelt Hospital Rubella Project. Eight of these patients, age 4 through 16 yr, had a recent orchiopexy, 4 on the left, 2 on the right, and 2 bilaterally. The vasoepididymal system was absent or apparently obstructed in 60% of the 10 sides. The epididymis was abnormal in 6 instances and the vas deferens in 5. Sixty-one boys of the entire series had an intravenous pyelogram (IVP) that was significantly abnormal in 18%. The 8 patients described all had a normal IVP except for 2 who had a malrotated kidney on the involved side. In 5 of the 8, a known maternal rubella infection has occurred during the first 8 wk of gestation. As the rubella virus is known to interfere with cellular growth and tissue differentiation in early pregnancy, it apparently altered the developing testis and mesonephric duct system. Similar vasoepididymal abnormalities have been described previously in patients with uncomplicated cryptorchidism, inguinal hernia, kidney defects, cystic fibrosis and male sterility. Their presence should alert the clinician to perform an IVP and also consider a diagnosis of congenital rubella.


Tumour promoter alone induces neoplastic transformation of fibroblasts from humans genetically predisposed to cancer. Neoplastic transformation is a multi-phase process apparently caused by carcinogens and subject to the influence of promoters. The naturally occurring phorbol esters such as 12-O-tetradecanoyl phorbol-13-acetate (TPA) are potent tumour promoting agents. Through the use of phorbol esters a two-stage process of malignant transformation has been demonstrated in the mouse skin model and, more recently, in cell culture systems. Studies in vitro suggest that TPA reversibly inhibits terminal differentiation in most, but not all model systems, and that its function is presumably to increase the probability of expression of the malignant phenotype. We have studied the effects of TPA on mutant human fibroblast cell strains derived from individuals with hereditary adenomatosis of the colon and rectum (ACR), an autosomal dominant trait. We have previously demonstrated in these fibroblasts abnormal phenotypic expressions which often appear in transformed cells. In these studies, we have assumed that the ACR cell exists in an "initiated state" due to a dominant mutation and that expression of the malignant state might only require treatment with a promoting agent. This single experimental protocol provided a novel system for the study of cancer promotion in vitro. We have now demonstrated, for the first time, the growth in vivo of human mutant cells exposed to TPA alone.


Factors affecting the bluetongue virus neutralizing antibody response and the reaction between virus and antibody. A study was made of different aspects of the bluetongue virus neutralizing antibody response and the reaction between the virus and antibody. Optimum neutralization was obtained in a 2mM Tris-HCl buffer, pH 9,0, at a temperature of 4 degrees C. The reaction of virus and antibody could be demonstrated by electron microscopy in the formation of clumps which were shown to be serotype specific. It was found that both IgM and IgG antibodies can neutralize the virus, but that IgM reached its maximum level sooner after infection than IgG.


Trypanosoma brucei infection in nude mice: B lymphocyte function is suppressed in the absence of T lymphocytes. B lymphocyte function was assessed in outbred nude mice and nu/+controls infected with Trypanosoma brucei brucei. On day 10 of the infection in outbred nu/nu mice in which the initial wave of parasites was strongly controlled, B cell function was unaltered on enhanced compared with uninfected animals or infected nu/+. In other nu/nu mice unable to control the initial parasitaemia, thymidine incorporation and Ig secretion by spleen cells were increased on day 10 and their response to lipopolysaccharide in vitro negated. By day 15 however, even the spleen cells of infected nu/nu which controlled the initial wave of parasites were proliferating and secreting Ig on removal from the mice and they were unable to respond to LPS in vitro. These experiments confirm results of a previous study of B cell function in T cell-depleted mice (Askonas et al. 1979). T. b. brucei infection of mice causes both enhanced Ig production and suppression of the ability of B cells to respond to mitogen even in the absence of T cells, but the presence of T cells may accelerate the changes which occur in B lymphocytes following this infection.


Immunodepression and the course of infection of a chronic Trypanosoma brucei infection in mice. The relationships between course of infection, antigenic variation, and immunodepression of antibody responses to heterologous antigens have been investigated in mice chronically infected with Trypanosoma brucei. T. brucei Brunel University Trypanosomiasis (BUT) 64 produces a fluctuating parasitaemia lasting about 80 days and ending fatally. It is demonstrated that recurring peaks of parasitaemia are associated with the appearance of new variant antigenic types. At 21 and 31 days of infection, IgG responses to the heterologous antigen, sheep red blood cells (SRBC), are absent and IgM responses are less than 5% of normal. When a single dose of cyclophosphamide (300 mg/Kg) was injected into mice on day 31 of infection, the parasitaemia rose sharply in an uncontrolled fashion and the treated mice died in about 10 days. Cyclophosphamide, given in this way, is known to ablate antibody production completely but temporarily. It is therefore concluded that even though infected mice make extremely poor antibody responses to heterologous antigens, they are still capable of producing sufficient antibody to control peaks of parasitaemia associated with the emergence of new variant antigenic types. The significance of these findings is discussed in relation to recurrent hypotheses of trypanosome-associated immunodepression.


Patients' awareness of extrapyramidal reactions to neuroleptic drugs: possible evidence for the role of catecholamines in perception. The awareness of extrapyramidal reactions during initiation of neuroleptic treatment was studied in 14 patients. Only one patient spontaneously identified the presence of dystonia. The other 13, including 3 who had experienced extrapyramidal reactions during previous hospitalizations, did not fully identify the presence of symptoms, although several had vague discomfort. There was marked variability in acknowledgement of symptoms in response to prompting by staff members. The findings are similar to reports of agnosia for hemiparesis after parietal lobe injury and also to descriptions of agnosia in animals caused by destruction of dopaminergic neurons. Since extrapyramidal reactions represent blockade of dopaminergic neurotransmission, patients' inability to perceive the reactions may represent evidence for catecholaminergic modulation of sensory perception.


Serum levels of neuroleptics measured by dopamine radioreceptor assay and some clinical observations. A new dopamine radioreceptor assay was used to measure serum concentrations of neuroleptics during treatment of 58 patients. Results of this assay are expressed as chlorpromazine equivalents. Serum concentrations varied with different drugs, with extremely high levels in patients receiving thioridazine or mesoridazine. No detectable serum levels were found in 11 patients, probably either due to low drug doses or noncompliance in taking medication. Best results with the assay were obtained in the 22 patients treated with haloperidol. Serum concentrations of haloperidol were correlated with dose and were related to the Brief Psychiatric Rating Scale (BPRS) total pathology score, as well as to BPRS factor scores for thinking disturbance and paranoid disturbance. Serum concentrations of haloperidol were not different among patients with or without the presence of extrapyramidal symptoms or among patients receiving or not receiving concurrent antiparkinson medication.


Demonstration of two new endogenous "benzodiazepine-like" compounds from brain. The recent report that purines are competitive inhibitors of specific [3H] diazepam binding to brain membranes has prompted further work concerning the characterization of possible endogenous ligands for the benzodiazepine receptor. In this report, two previously undescribed fractions capable of apparent competitive inhibition of [3H] diazepam binding are reported. Both factors are heat stable and resistant to proteolytic degradation. The larger factor (approximately 700 to 30,000 daltons) is present only in brain and pituitary. The smaller factor (500 to 600 daltons) is found in pituitary, liver, and muscle, but the highest levels are found in brain.


Serum prolactin levels following intramuscular chlorpromazine: two- and three-hour response as predictors of six-hour response. Neuroendocrine studies that examine the changes in serum prolactin levels following intramuscular (im) neuroleptics have usually monitored prolactin levels before and for 90 minutes to 3 hours after neuroleptic injection. Recent studies have suggested that this may be an inadequate period of time. In the present study, six male and four female psychiatric inpatients, who had not received neuroleptic medication for at least 1 week before the study began, received an injection of chlorpromazine (CPZ) 25 mg im; serum prolactin levels were monitored for 6 hours after injection. Peak serum prolactin levels occurred at 60 minutes in one subject, 90 minutes in three subjects, 120 minutes in two subjects, 180 minutes in three subjects, and 240 minutes in one subject. Area under the serum prolactin curve at 2 hours and area under the curve at 3 hours after CPZ injection were found to be good predictors (r = 0.86; r = 0.95, respectively) of 6-hour area under the curve. Two-hour studies should therefore not be considered inadequate; however, a 3-hour study length results in more precise characterization of prolactin response to im CPZ.


Neuroleptic, antimuscarinic, and antiadrenergic activity of chlorpromazine, thioridazine, and their metabolites. Chlorpromazine and thioridazine are widely used antipsychotic agents that are extensively metabolized. Parent compounds and metabolites have diverse pharmacologic activities, and differences in patterns of metabolism may explain differences in therapeutic and side effects from individual to individual. Radioreceptor assays were used to determine the neuroleptic, antimuscarinic, and anti-alpha-noradrenergic potency of chlorpromazine, thioridazine, and their metabolites. The results indicate that these metabolites show a wide range of potencies. The spectrum of activity of a metabolite may be quite different from that of its parent compound. The clinical relevance of these findings to individual differences in drug response is discussed. The combined use of radioreceptor assays and chemical assays in future clinical research is proposed.


Responses of the thymus and the paracortex of draining lymph nodes to repeated applications of oxazolone to mouse skin. The oxazolone-induced response in the paracortex of draining lymph nodes is characterized by an early increase in the proliferative activity that decreases to control levels when stimulation is continued. The possibility that this may be a toxic side effect of the concentrated oxazolone solution used was investigated by simultaneous registration of the changes taking place in the thymus. These were found to be different from toxin-induced changes and compatible with cell loss due to massive emigration of cells. Repopulation of the thymus took place over the last 1 1/2 week of stimulation. It was concluded that the changes in the thymus as well as the decline of the proliferative activity in the paracortex, are most likely physiological responses. The most important factor in maintaining a high production of paracortical lymphocytes under chronic stimulation is the increase in the lymphocyte mass in the paracortex.


Dose dependency of the responses in draining lymph nodes and skin to repeated applications of oxazolone. A quantitative and histological study in mice. The skin reactivity and lymph node responses to a large scale of different doses of oxazolone, were followed under continuous stimulation for a period of 12 days. It was found that the lack of a continuous high blast cell activity in the paracortex was a physiological response that could be observed with high dosage as well as with very low dosage. Low doses gave distinct stimulation of the paracortex without any detectable reaction in the cortex and in the medulla. Manifest stimulation of these compartments required considerably higher doses. A marked paracortical response was the only lymph node change required for development of a typical delayed type skin response. When germinal centres and plasma cells had developed, the skin reactivity was also found to change characteristically.


From penicillin-binding proteins to the lysis and death of bacteria: a 1979 view. The mechanism by which interference with the biosynthesis of bacterial cell wall causes death and lysis of bacteria appears more complex than originally thought. In an earlier model of the mode of action of beta-lactams, it was assumed that, in the presence of the antibiotics, bacteria synthesize a mechanically weak (poorly cross-linked) cell wall that ruptured under the osmotic-mechanical pressure of the normally growing cytoplasmic mass. However, recent findings suggest a much more complex picture. Lysis and, in at least some bacteria, loss of viability as well, seem to be catalyzed by autolytic enzymes (murein hydrolases), the destructive activity of which is triggered in the beta-lactam-treated bacterium via a poorly understood mechanism. Furthermore, different species of bacteria respond quite differently to treatment with the same beta-lactam: some bacteria are both killed and lysed, others only lose viability, whereas still other species respond mainly by a reversible inhibition of growth (beta-lactam-tolerant bacteria). In addition, structurally different beta-lactams may cause quite different biochemical, morphological, and antibacterial effects, even within the same bacterial species. It is conceivable, therefore, that there is more than one mechanism for loss of viability and/or lysis. Most of the bacteria examined so far contain a number (four to eight) of different penicillin-binding proteins. Genetic and physiological evidence obtained in E. coli indicate that these proteins play essential roles in a variety of physiological functions, such as maintenance of structural integrity, shape, and cell division. Pneumococci with a suppressed autolytic system are resistant to he lytic (and, partially at least, to the bactericidal) effect of beta-lactams. Interference with cell wall synthesis seems to trigger autolysin activity by upsetting the cellular control of autolytic enzyme. It is suggested that the irreversible antimicrobial effect of beta-lactams may have an indirect mechanism in other bacteria as well.


Myosin and actin containing cells in the human postnatal thymus. Ultrastructural and immunohistochemical findings in normal thymus and in myasthenia gravis. Samples of normal human thymus of different ages (4-63 years old) were studied by immunofluorescence microscopy (using antibodies to smooth muscle myosin, to actin from the chicken gizzard, and antibodies to myosin from human striated muscle) as well as by routine electron microscopy. Thymus tissue from myasthenia gravis patients was also investigated for comparative reasons. Epithelial cells reacted with anti-smooth, but not with anti-striated muscle myosin, whereas myoid cells reacted with antibodies to striated, but not to smooth muscle myosin. Both epithelial and myoid cells displayed a strong immunoreactivity with antiactin. Corresponding to this immunoreactivity, both cell types contained bundles of thin, actin-like filaments. Myoid cells occurred in the rounded and elongated variety, and they were a normal constituent of all thymuses investigated in this study. Ultrastructurally, this non-innervated, striated muscle-like cell type possessed bundles of thin and thick filaments as well as Z lines in a rather disorganized arrangement, resembling striated muscle after denervation or various other pathologic conditions. There were no overt differences in the number and structure of myoid cells between healthy and myasthenic patients.


Lowered resistance to lytic agents in sucrose vacuolation. Vacuolation in fibroblasts cultivated in the presence of sucrose is associated with progressive accumulation of the undigestible sugar. In radioisotope experiments the process lasted several days, and when the cells were subcultured back into a medium devoid of sucrose the label was also lost after several days. This type of vacuolated cells is more fragile when it is challenged with lytic agents. 51Cr-labelled LS fibroblasts released more radioactivity when they had been growing in the presence of sucrose, whether they were suspended in media of decreasing osmolarity, in dilutions of various surfactants, exposed to high temperatures, or subjected to mechanical stress. It is concluded that these cells exhibit a lower resistance when exposed to unfavourable environments, but retain their viability in growth media despite some morphological and biochemical alterations.


Estimating the proportion of proliferating cells in a population. In a population of cells that proportion which is actively engaged in the proliferative cycle is often estimated from the ratio of the observed labelling index to an expected labelling index, calculated, on the basis of all cells being in cycle, from the cell cycle phase durations and the age distribution. Ignoring the variability in cell cycle times may lead to large overestimates or underestimates in the expected labelling index. A method is given of obtaining a more accurate estimate of this variable, and hence of the proliferative proportion.


Alkaline Phosphatase Activity Induction in Human Spleen Sinuses in Storage Diseases. Human splenic sinuses were observed for the induction of alkaline phosphatase (AP) activity in mucopolysaccharidoses of type I and II, in GM1 gangliosidosis, and in Niemann-Pick's disease, type A. A substantially lower degree of activity was found in Sanfillipo's disease, type A, and in hemosiderin pigmentation of the sinuses. In a number of hematological affections and in control spleens AP activity could not be proved by histochemical means. From the formal pathogenetic view, enzyme activity induction is probably related to lysosomal deposition of the material stored.


Comments on spleen sinus enzyme equipment. A histochemical study. Histochemical observations were made of the activities of nucleosidephosphatases splitting ATP, ADP, IDP, and AMP and exopeptidases splitting l-alanine, l-leucine and l-glycyl-proline in the spleen sinuses of man, mouse, rat, hamster, and rabbit. Of the exopeptidases, only glycylprolyl-naphthylamidase could be proved histochemically, and that only in man and rat. Nucleosidephosphatases showed only traces of activity except in the rabbit where there was highly active AMP-ase, the others being moderately active.


Membrane sialoglycoprotein from human erythrocytes activates lysosomal proteinases. The capacity of membrane glycoproteins to interact with proteinases was investigated in the model system: Membrane sialoglycoprotein from human erythrocytes (glycophorin) and lysosomal proteinases from rat liver. Glycophorin was found to stimulate the activity of a lysosomal proteinase mixture up to about 150% at pH 6.9. Cathepsin L was found to be the primarily stimulated proteinase. The stoichiometry in the saturation range of the dose-response curve waas about 10 to 20 molecules glycophorin per molecule cathepsin L. The mechanism of the activation is unknown. Interactions of this type may be of importance for the regulation of cell proliferation on the level of cell membranes.


The ribosomal serine proteinase: cathepsin R. As has been known for several years, thoroughly purified ribosomes contain a firmly bound serine proteinase with an optimum of activity at neutral pH. The present paper shows that the activity is found in free cytoplasmic ribosomes as well as in ribosomes detached from the membranes of the endoplasmic reticulum of rat liver. After ribosome dissociation, the proteinase activity is found only on the 40 S subunits. Recovery of the proteinase in the proteins of whole ribosomes or of 40 S subunits amounts to 44 and 65%, respectively. Ribosomes purified both from plant (Euglena) and bacterial (Acinetobacter) cells contain a serine proteinase having an activity quite comparable to that of rat liver ribosomes. In view of the recommendations of BARRETT et al. ( in REICH, RIFKIN and SHAW (eds).: Proteinases and Biological Control, Cold Spring Harbour Lab., 1975, p. 481), who no longer restrict the name "cathepsin" to acid or even lysosomal proteinases, we propose the name " ccathepsin R" for this ribosomal serine proteinase.


[Studies of the antibody heterogeneity in carp (Cyprinus carpio L.). I. Electrophoretic and isoelectric spectra of anti-DNP-antibodies]. Carp IgM as well as carp anti-DNP-antibodies migrate electrophoretically very well as a diffuse band into polyacrylamide gel of large pore size. The isoelectric spectra of the carp anti-DNP-antibodies are heterogeneous and show bands in the pI-range of 4.0 to 6.4. The activity of focused anti-DNP-antibodies could be demonstrated in the pI range between 5.4 to 6.4 even in high antibody dilutions. The investigated structural heterogeneity of the anti-DNP-antibodies of carp is a further proof for the phylogenetically early onset of a large antibody heterogeneity of lower vertebrates.


Indications of pH-induced conformational changes in phosphofructokinase from baker's yeast. The partition of phosphorfructokinase (EC 2.7.1.11) from baker's yeast between the liquid phases of an aqueous biphasic systeem changes drastically in the pH interval 7-8, in contrast to other proteins. This abnormal behaviour is correlated to changes in sedimentation coefficient and binding capacity of the enzyme in this pH region. Since the molecular weight of phosphofructokinase does not change, these findings must reflect conformational changes in the enzyme molecule.


Psychopharmacology in the secondary and tertiary prevention of mental illness. Some of the changes brought about by the introduction of therapeutically effective psychotropic drugs were reviewed in the context of secondary and tertiary prevention of mental illness. The role of maintenance therapy in lowering the prevalence of manifest psychiatric disorders and defective functioning due to mental illness, was discussed.


[Studies of the presence of enzymes in various tissues of swine. 5. Studies of the activity and properties of adenosine triphosphatases in the pancreas]. Studies were conducted into the activities of magnesium-ATPase, sodium-potassium-ATPase, and HCO3-ATPase in homogenates of pancreas of 19 foetuses, with body weights between 340 g and 1,642 g, two piglets, with body weights of 9 kg and 10 kg, and four adult pigs. While general enzyme activity was low during foetal development, highest activies usually were recordable from HCO3-ATPase. High activities were recorded from both the piglets and adult pigs. The highest data, again, were recordable from HCO3-ATPase which is essential to the secretion of HCO3 ions. Maximum activity of magnesium-ATPase was based on an ATP-magnesium ratio of 1:1. HCO3-ATPase was best activated by 25 mM NaHCO3 and exhibited high stability to temperature. The activities of magnesium-ATPase and of HCO3-ATPase were inhibited by 10 mM of Rhodanid. Calcium-ATPase reached its maximum activity in response to 5 mM calcium concentration.


Nasal secretion from normal subjects.

Nasal secretion from normal subjects. A new method of collection of nasal secretion, by dilution with condensed mositure of the exhaled air, is described. This method may be defined as a sefl-administered nasal lavage. The method permits quantitative determination of pH, relative viscosity, and electrolyte and protein composition. Concentrations of sodium, potassium, calcium, total protein, IgA, IgG, IgM, secretory compoenent and polysaccharide are reported for normal subjects. Significant correlations were noted between the relative viscosity and variables: dry weight, total protein and calcium.


Metachromatic leukodystrophy and age: a comparative study of clinical, enzymological and ultrastructural findings. The clinical findings of three cases of metachromatic leukodystrophy, one of the late infantile, one of the juvenile and one of the adult variant are described and compared with those mentioned in relevant publications. Comparison of our findings lead us to conclude that a difference exists between the late infantile case on the one hand and the juvenile and the adult case on the other hand. This conclusion concurs with the results obtained by the enzymological study of the enzyme arylsulfatase A derived from the three cases. As to the characteristics of the enzyme arylsulfatase A, a difference was found to exist between the enzyme of the late infantile case on the one hand and that of the juvenile and the adult case on the other hand. The results of the electronmicroscopic investigation of peripheral nerve biopsy specimens of the three cases are briefly summarized. It is postulated that the ultrastructural findings do not justify any such distinction.


Interactions of pharmacological agents which alter biogenic amine metabolism and depression--an analysis of contributing factors within a primate model of depression. The observation that the biogenic amine depleting agent, reserpine, could induce severe depression in a small proportion of the patients treated with it has proved to be seminal finding in what is now a much larger field of research relating the function brain biogenic amine systems to emotions and behavior. A review of the human reserpine literature suggests, however, that factors other than pharmacologically produced alterations in brain biogenic amine metabolism must have been critical determinants of the eventual mood alterations observed in conjunction with reserpine treatment. While some of these factors, such as previous history of depression, ongoing psychosocial and environmental stress, can be intuitively identified, there are practical as well as ethical problems involved in actually testing the relative contribution of these factors in precipitating human depression and thereby determining their importance in a quantitative fashion. In the present paper we have attempted to examine, in a nonhuman primate model of depression, the degree to which factors such as prior rearing condition, repeated peer separation, and housing environment can intact with the behavioral effects produced by biogenic amine depleting agents. Major emphasis will be placed on studies utilizing alpha-methyl-para-tyrosine, an inhibitor of tyrosine hydroxylase, to ostensively reduce levels of the catecholamine neurotransmitters norepinephrine and dopamine. The results of these studies provide quantitative estimates, in terms of dose-effect relationships, of the degree to which a number of factors can combine to produce despair-like behavior in rhesus monkeys. These data may be of practical importance in evaluating the contribution of similar factors to the precipitation of human depression. Analysis of some of the existing literature relating alterations in behavior to changes in biogenic amine metabolism in animals suggests that there are important differences between rodent and primate species. These differences, when fully established, may indicate that additional research examining the mechanisms whereby modest alterations in biogenic amine metabolism can interact with environmental and social stress is needed.


Rapid pH and deltamuH+ jump by short laser pulse. The excited state (S1) of sulfononaphthols has a pK value well below that of the ground state, consequently intensive illumination of their aqueous solution should lead to acidification. In this study the second harmonies of a ruby laser pulse (10 MW, 30 ns at 347.2 nm) were used for excitation of a sulfononaphthol solution, resulting in a lowering of the pH from 8 to 4. The change in pH was demonstrated by spectral changes of the pH indicators Bromocresol Green, Bromothymol Blue, Bromocresol Purple and Phenol Red. The magnitude of the pH change was calculated from the kinetics of the changes in the indicators' absorbance and from fluorescence intensity of naphtholate. Sulfononaphthols, due to their hydrophylic nature, cannot permeate across phospholipid membranes. Taking advantage of this property, liposomes containing sulfononaphthol were prepared and irradiated by the laser pulse. Evidence is given that under such conditions the change in pH was limited to the space enclosed in the liposomes. The resulting proton-motive force (deltamuH+ = 180 -- 240 mV) is adequate for perturbing the energy-coupled reactions of oxidative phosphorylation. Possible applications of this technique in chemical physics, chemistry, biochemistry and bioenergetics are discussed.


[Effect of a histamine aerosol in 20 subjects with histamine hyperreactivity. Application to a study of the protective properties of pipoxizine]. The authors made a study of the antihistaminic properties of Pipoxizine in 20 subjects with proven histaminic hyperreactivity. The design of the trial consisted in comparing the changes of VC, FEC1, expiratory airway resistance and V50 produced by a histamine aerosol given before and after administration of Pipoxizine. Pipoxizine was given by mouth to 10 patients and intravenously to the other 10 of the group. The statistical analysis of the results demonstrated an antagonist effect of Pipoxizine on the histamine induced bronchoconstriction. The data of this trial are confirmative of the results of other experimenters. It seems therefore reasonable to take into consideration the use of Pipoxizine in the preventive treatment of the paroxystic attacks of the asthmatic disease.


Acute experimental poisoning by diethylene glycol: acid base balance and histological data in male rats. Acute intoxication by diethylene glycol (LD 50) in male rats is associated with a severe metabolic acidosis which is significantly decreased by intraperitoneal (IP) hydration or IP alkalinization and eliminated by IP ethanol. Tubular necrosis and deposit of calcium oxalate crkystals constitute the histological renal lesions in 50% of rats given diethylene glycol with or without IP hydration. Groups with massive IP alkalinization and/or IP ethanol do not present any renal lesion. It could be inferred that diethylene glycol has the same metabolic pathway as ethylene glycol and the treatment of acute intoxication by diethylene glycol should be the same as that of acute poisoning by ethylene glycol.


[The quality of preserved blood].

[The quality of preserved blood]. The examinations of 30 blood samples each preserved with three Yugoslav different ACD-solutions were performed. The blood samples were stored at 2-6 degrees C and examinations were performed at the day of blood donation and after on the 7th, 14th and 21st day during the storage. Differences in hematocrit (well known dilution effect of the ACD-solutions used) and intensive morphological and chemical changes were found in all blood samples regardless the type of ACD-solution used. It was shown that the permanently increasing number morphologically altered erythrocytes (echinocytes and spherocytes) and the excessive release of hemoglobin and potassium from erythrocytes were occurred during the storage of blood samles. Too, there were noticed significant decrease of pH values enormous accumulation of ammoniac and other metabolic producta.


Characterization of the multiple forms of monoamine oxidase from chronic schizophrenic sera. Either half or one hour incubation time was enough to get a constant production of benzylaldehyde and were proportional to the amount of enzyme added. The optimal temperature of MAO, I, II, III, IV are 60 degrees, 37 degrees, 60 degrees, 45 degrees, and 37 degrees C respectively, and they follow Arrhenius equation until these optimal temperatures. Each form have optimal pH depends on substrate concentration used and the buffer used. These forms were shown to be inhibited by high substrate concentration with formation of inactive enzyme-amine complex, whereas butyl- and octylamine was found to be competitive inhibitors. Isoniazid inhibit MAO II, III, IV and V forms in a non competitive fashion, whereas MAO I inhibited competitively with respect to the substrate. Semicarbazid inhibit MAO I. III, IV and V forms in a non competitive fashion, whereas MAO II inhibited competitively with respect to the substrate.


Cross-over study of the efficacy of four beta 2-sympathomimetic bronchodilator aerosols. 1 Bronchodilator efficacy of four beta 2-sympathomimetic aerosols, fenoterol, orciprenaline, salbutamol and terbutaline has been compared in nine patients with chronic stable reversible airways obstruction using a double-blind placebo controlled cross-over design. Two puffs of each agent were given on two separate occasions to each of the patients and the forced expiratory volume in one second (FEV1) and the vital capacity (VC) were measured before and 30, 90, 150 and 210 min after administration. 2 Multivariate analysis of the data at 30 min showed FEV1 and VC in these patients to be so highly correlated that they could be considered as a single variable. 3 When absolute change in VC at 30 min was used as the response criterion, efficacy of the four drugs was significantly better than placebo (P < 0.01). It was not possible to rank all four drugs in order of effectiveness; fenoterol and salbutamol were significantly better than terbutaline and orciprenaline (P < 0.01) but this was complicated by a significant interaction effect between drugs and patients (P < 0.01). 4 Similar results were obtained when absolute and relative changes in FEV1 and VC and area under the curve were used as response variables. 5 The study demonstrates that important individual differences in patient response may be concealed if only average drug effects are considered.


Oxitropium bromide (Ba 253), an advance in the field of anticholinergic bronchodilating treatments. Preliminary results. The changes in FEV1 and in specific conductance induced by 200 micrograms oxitropium bromide given as pressurized aerosol were measured at 8 time intervals during 7 hours after inhalation in a group of 19 patients with reversible broncho-obstruction. The working of the drug was compared to the functional values observed at the same time intervals after placebo, 40 micrograms ipratropium bromide and 400 micrograms fenoterol. Both oxitropium and ipratropium were definitely and significantly superior to placebo at all time intervals. Oxitropium was superior to ipratropium at the 7th hour. At this time interval the difference was significant At the 7th hour oxitropium gave higher mean results than fenoterol, but this difference was not significant. The drug was also compared to its competitors regarding its subjective and cardiovascular tolerance. No unfavourable side-effects were observed.


[Effect of almitrine on arterial gases in patients with chronic respiratory insufficiency. Comparison with doxapram. Preliminary results]. We compared the effects of almitrine and doxapram on the arterial blood gases and ventilation of patients with chronic respiratory insufficiency and chronic hypercapnia and hypoxemia. Sixteen long-term in-patients were randomly allocated to one of the following treatment groups: the first group (8 patients) received IV almitrine 0.5 mg/kg and the second group (8 patients) IV doxapram 1 mg/kg by IV perfusion during 30 min. All gave their informed consent. Arterial blood gases and ventilation were measured 10 min and 5 min before treatment, at the 5th, 15th and 25th min of perfusion time, and 5, 10 and 15 min after infusion. There was a marked increase in paO2 in almitrine-treated patients, which was maximum at the 25th min of infusion (+ 14.6 mm Hg, p < 0.001), but only a slight improvement was observed in the doxapram group (+ 3.3 mm Hg, p < 0.05). After almitrine the maximum mean paCO2 decrease was at the 10th min after perfusion (-6.9 mm Hg, p < 0.001); after doxapram the maximum decrease, although highly significant, was much less (-2.8 mm Hg, p < 0.01). Thus, at the presently used and well-tolerated doses, almitrine is much more efficient than doxapram in improving gas exchange in patients with chronic hypoxemia and hypercapnia. However, complementary studies using higher dosage of doxapram are warranted.


On the role of the recipient cell during conjugation in Escherichia coli. To study the role of the E. coli recipient cell in conjugation recipient cell mutants deficient in conjugation (Con-) were isolated. Mutants specific for F-type E. coli donor cells (ConF-) and mutants specific deficient in conjugation with I-type donor cells (ConI-) were isolated. Both ConF- and ConI- mutants were blocked in stable mating pair formation. Biochemical analysis of the mutants suggests that the outer membrane protein coded by the ompA gene and LPS are important for recipient activity in F-type conjugation while LPS is important for recipient activity in I-type conjugation.


Characterisation and metabolic studies of Saccharomyces cerevisiae and Kluyveromyces fragilis by flow microcalorimetry. The use of microcalorimetry in the routine identification of microorganisms is critically discussed and assessed. By use of flow microcalorimetric studies on Saccharomyces cerevisiae and Kluyveromyces fragilis the role of physical parameters and that of oxygen tension are discussed. The conclusion reached is that identification of microorganisms by microcalorimetry and subsequent discussion of metabolic events revealed by the thermogram, except under restrictive conditions, is inappropriate. However flow microcalorimetry, in contrast to batch microcalorimetry which has been used in the published material on microorganism identification, may allow characterization of yeasts suitable for particular industrial processes.


Regulation of biosynthesis of aminoacyl-transfer RNA synthetases and of transfer-RNA in Escherichia coli. We have isolated temperature resistant revertants from temperature sensitive E. coli strains containing either a thermolabile glutaminyl-tRNA synthetase or leucyl-tRNA synthetase. Among the revertants which still contained the thermolabile leucyl-tRNA synthetase we found two classes of regulatory mutants (leuX and leu Y) which have elevated levels of this enzyme. The leuX mutation specifies an operator-promoter region adjacent to the structural gene (leuS) for the enzyme. The leuY gene maps away from the leuS gene and codes for a protein. Using these mutants we demonstrated that the levels of leucyl-tRNA are related to the derepression of the leucine and isoleucine-valine operons. Among the revertants which still contained the thermolabile glutaminyl-tRNA synthetase were characterized three classes of mutants, glnT, glnU, and glnR. The glnT and glnU mutants contain elevated levels of tRNAgln, while the glnR mutant possesses elevated levels of glutaminyl-tRNA synthetase. The level of glutamine synthetase, the enzyme responsible for the formation of glutamine, is also derepressed in the glnT and glnR mutants.


[Cell-mediated immunity after blocking of the H2 lymphocyte receptors]. The effects of cimetidine have been evaluated in 10 normal subjects on cutaneous delayed reactions in vivo, and on E rosette forming cells in vitro, in order to define the significance of the lymphocytes H2 receptors in cell-mediated immunity. The results show the immuno-suppressive activity of histamine, but do not allow us to hypothesize an immuno-regulatory action of cimetidine.


Effect of pH and buffers on insulin binding to normal and neoplastic mammary cells, fat cells and membrane preparations. As a function of buffer pH, [125I]-insulin binding to rat mammary cells, rat adipocytes, or membranes prepared therefrom, at 4 degrees or 20 degrees C, showed 2 peaks in different buffers. Specific insulin binding at the pH 7.7. peak (100 +/- 11%) was lower than at pH 8.8 (140 +/- 17%) with no change in nonspecific binding. Although insulin stimulation of glucose uptake into fat cells was highest at pH 7.5, this response was also seen at pH 8.6. Scatchard affinity profiles, or in the kinetics of dissociation. Insulin degradation (< 10%) and binding to insulin antibody were similar over the pH range of 7 to 9.


Bicarbonate ATP-ase in ciliary body and a theory of Diamox effect on aqueous humor formation. Bicarbonate was found to stimulate ATP breakdown by rabbit or cat ciliary body-iris homogenates. Maximum HCO3- stimulation of ATPase with Tris-Hepes buffer occured at pH 8.0. Acid pH and chloride ions in the media reduced the activity of the HCO3--stimulated ATPase. The Km for ATP was 0.55 mmolar and for HCO3-, 20 mmlar. HCO3- ATPase was not inhibited by acetazolamide added to in vitro. It is postulated that ATPase represents the linkage step of energy donor mechanism and active CT secretion in acid aqueous humors (human, cat.) or HCO3- secretion in alkaline aqueous humor (rabbit, guinea pig). Inhibition of Cl- or HCO3- secretion by acetazolamide results from decreased intracellular HCO3- levels which, in turn, reduces the stimulation of the HCO3- ATPase.


[Effects of a neurotoxin isolated from the sea anemone, Anemonia sulcata, at frog neuromuscular junction (author's transl)]. ATX II is a toxin extracted from tentacles of Anemonia sulcata. It was known that this protein displays neurotoxic effects on frog isolated neuromuscular preparation (Fig. 1, 2) and that muscular contractures observed with ATX II are blocked by d-tubocurarine (Fig. 3) or on a 40-days-denervated gastrocnemius (Fig. 4). Part of these experiments has already appeared. 1. These effects of ATX II depend on calcium concentration in the bathing medium, as is the case for transmitter release. The same results were observed when we substituted strontium to calcium. 2. On an intact sciatic sartorius preparation, ATX II does not act on the amplitude of the miniature endplate potentials (mepps, Fig. 6). The muscular action potential is not modified by this toxin. 3. ATX II increases the frequency of the mepps (Fig. 5). The evoked transmitter release (quantal content) after ATX II is also largely increased (Fig. 7). 4. In conclusion, it is suggested that ATX II acts indirectly on the muscle through an increase in acetylcholine release from the motor nerve terminals.


[Evidence for a central action of CO2 ventilatory stimulus in Pekin ducks (author's transl)]. Ventilatory responses to changes in PCO2 of the blood perfusing the central nervous system were studied breath by breath by pneumotachography in Pekin ducks under transient and steady condition. 1. Transients. In conscious birds, all the arteries to the cephalic region were tied or clamped, except the right internal carotid. The blood supply via the single remaining arterial pathway was transiently replaced, for about 15 sec, by injecting 2 ml of blood previously made either normocapnic (control PCO2 = 32 Torr) or hypercapnic (test; PCO2 = 76 Torr) from a syringe thermostated at 41 degrees C, under normal oxygenation (PO2 around 110 Torr) and mean endovascular pressure (107 mm Hg). During control injections, no significant ventilatory changes were observed. In contrast, test injections provoked an early and significant 20% increase in the minute volume of ventilation. 2. Steady conditions. Using cross-perfusion between pairs of anesthetized ducks, the head of a recipient animal (R) was vascularly isolated from the trunk and perfused by a donor (D), the nervous connections with the trunk remaining intact. When giving some CO2 to breathe to D (FICO2 = 0.05) while R breathed ambient air, arterial PCO2 increased in D and in the head of R, and hyperventilation occurred in both ducks. As a consequence of this hyperventilation, PCO2 decreased in the arterial blood and the end-tidal gas of R.


Applied and theoretical significance of electrohoretic studies in mosquitoes (Diptera: Culicidae). The more relevant results obtained in the past decade with the use of electrophoretic techniques in studying mosquitoes are reviewed and discussed. These results mainly concern the evaluation of genetic variability of natural and laboratory populations; the study of the role of natural selection and genetic drift in the maintenance and evolution of enzyme polymorphisms; the estimate of genetic differentiation between populations, subspecies and species; the identification of sibling species and of their possible hybrids; the field study of precopulatory isolating mechanisms by the release of electrophoretically recognizable population samples; the elaboration of genetic maps; the study of the phenomenon of multiple insemination; and the evaluation of sexual competitiveness, particularly in connection with the planning of genetic control measures. The importance of this approach in the study of mosquito biology from the applied and theoretical points of view is stressed.


[The role of anaerobe adhesion in the colonization of the vaginal mucosa]. Some our previous research works on bacterial adhesion to vaginal cells in the different phases of the menstruum showed that adhesion changes depending on changing environmental conditions. We therefore considered interesting to extend our investigations to anaerobic flora, in the light of recent observations intended to attribute an important role to anaerobic flora in the pathogenesis of vaginitis. The results obtained so far indicate that the maximum adhesion capability is found in the middle of the menstruum. The very low adhesion of bacteria belonging to the Leptothrix genus remains substantially unaltered throughout the menstruum. Low adhesion is also found in sporogenic bacteria, whereas the coccoid ones have a stronger adhesion, particularly about the middle of the menstruum. With lower pH values adhesion of the anaerobic flora is enhanced, whereas in the final phase of the menstruum, with higher pH values, adhesion is reduced. Competition tests evidence a stronger adhesion of coccoid as compared to bacillar types.


[Effect of cadmium on the activity of alkaline phosphatase (3.1.3.1) of Venus gallina]. The marine mollusc Venus gallina was exposed to 32 days sublethal concentrations of Cadmium (0.1 microliter/ml). The activity of alkaline phosphatase was assayed every four days. In the controls the activity was also tested in different tissues and in the soft tissue for the pH dependence. Moreover the influence of direct addition of 10(-4) M Cd on enzyme preparation in vitro was assayed. From the results there are no consistent relationships between the direct in vitro effects of the metal on the enzyme, that is inhibitory, and the effect of exposing the whole animal to the same metal, in this case no inhibition was observed.


[Dehalogenation of pp'DDT to pp'DDD in the liver microsomal fraction of Mugil cephalus]. pp'DDT was converted to DDD 1-1 dichloro-2,2 bis (p-chlorophenyl) ethane, by treated 12 000 x g supernatant preparations from grey mullet livers. The anaerobic reductive dechlorination occurs whether or not exogenous NADPH and riboflavin is added after a heat pretreatment, otherwise the dechlorination is lowered when the cofactors are not added.


[Characteristics of a rat liver cellular extract protein which mediates transport of various phospholipids from liposomes to mitochondria]. The effect of pH, Ca++ and Na+ concentration on the phosphatidylethanolamine transport from liposomes to mitochondria by an aspecific soluble rat liver protein has been studied. Results obtained indicate that at pH higher than 6.5 and Ca++ ion concentrations from 5 mM on the transport is strongly inhibited. Preliminary data with ESR spectrometry concerning the nature of lipoprotein association between phosphatidylethanolamine and carrier protein during the transport are also presented.


[Biohydrogenation of erucic acid (22:1 n-9 cis) in an "artificial rumen". II) Effect of pH, potential hydrogen donors and type of anaerobiosis]. The possibility of dietary C18 unsaturated fatty acids double bonds biohydrogenation, which normally occurs in ruminants, has been investigated in the case of erucic acid (22:1 n-9 cis). The results have shown that, while oleic acid is always converted into hydrogenation intermediates and stearic acid, to various extent, erucic acid does not undergo hydrogenation process, unrelated to the incubation conditions applied. Data are discussed on the basis of the different structure of erucic and oleic acids.


[Research in experimental electrocardiography. II: effect of a beta-blockader (pindolol) on the electrocardiogram of the rat]. From the Authors' observations during this research, there emerges the fact that pindololo does not seem deprived of that cardiodepressive action, which is typical of all beta-blocking drugs.


[Chromatographic determination of arylsulfatases A and B in human gastric mucosa]. In continuation of a previous work, we have confirmed the occurrence of arylsulfatase A in 4 samples of human gastric mucosa analysed by the chromatographic procedure described by Stevens et all. By using the chromatographic method we have also evidentiated the occurrence of arylsulfatase B, which was not detected by using the method of Baum et all. The B form was lower than the A form in 3 samples while it was higher in another sample. In the latter sample of gastric mucosa it was also detected the unusual form Bm of arylsulfatase. It was concluded that both forms A and B of arylsulfatase are present in human gastric mucosa, in variable amounts and that the simple procedure developed by Baum et all., although suitable for the analysis of these enzymes in the urine, is not useful for the determination of arylsulfate B in the gastric mucosa.


Alpha-adrenergic blockade in severe asthma. Thirty-nine chronic asthmatics requiring steroids showed no response to the alpha-blocking drug indoramin during a double-blind trial.


[Mechanisms of ovulation in mammalian females]. The aim of this review was to briefly recapitulate the most important mechanisms involved in ovulation in the Mammals. The rabbit served as a model for the study of reflex ovulation. The triggering of ovulation by coitus was shown to be dependent on the activation of the hypothalamo-pituitary axis by sensory signals of multiple origin. The fundamental aspects of the hormonal and nervous machinery that governs spontaneous ovulation have been envisaged. The timing of LH ovulatory release and the mechanisms of action of this hormone at the ovarian level have been defined. Evidence was given that steroid hormones from ovarian and/or adrenal origin could evoke or modulate ovulatory processes. The structures responsible for both the tonic and clonic secretion of LH in subprimate and in primate mammals have been localized in the hypothalamus. The nervous endocrine mechanisms involving interactions between LHRH, neurotransmitters, prostaglandins and steroid hormones have been elucidated. Short loop feed back effects of pituitary hormones were shown to control LHRH secretion. Several examples were given attesting that the limbic system, the thalamus and the neocortex on one hand, and the environmental factors, on the other hand, were capable of modulating the activity of the hypothalamic structures implicated in the control of either ovulation or estrous rhythm regulation. An unitarian conception of the ovulatory mechanisms, based on the fact that coital-induced ovulation and estrogen-induced ovulation could occur in spontaneous and reflex ovulators respectively, has been proposed.


[Alkaline phosphatase activity of the bursa of Fabricius: histochemical study in the normal embryo and during allograft reactions]. Alkaline phosphatase activity allows a certain discrimination between lympho-inhibition following a direct action on the lymphoid stem cells or a modification of mesenchyme/epithelium interactions; in this study we have compared the evolution of this activity in untreated chick embryos and in chick embryos following graft-versus-host-reactions. The important decrease of mesenchyme alkaline phosphatase activity induced here, involves a localisation of allograft reaction in this tissue; this result does not agree with the former explanations about a direct action on the lymphoid stem cells.


[Transplacental passage of cells from mother to fetus: experimental approach and initial results in the rat]. The consequences of transfusion across the placenta of maternal cells to fetuses, supposed to elicit a Graft-Versus-Host-Reaction, are poorly investigated; the injection of pregnant rat whole blood cells to its own fetuses is proposed here as a convenient experimental model to improve the understanding of these consequences; indeed this technic is reliable as well as easy enough to carry out experiments on large samples. Preliminary results indicate that the injection is often followed by a runting disease, a thymic atrophy and a liver hypertrophy; splenomegaly does not occur. On the histologic level, the main features are as follows 1) modification of central lymphoïd organs, 2) blastic and/or granulocytic infiltrates of several other organs, namely the liver, the adrenal cortex and the thyroïd gland.


[Derivatives of 2,3,4,5,-tetrahydro-1H-pyrido-(3,2-b)azepine and 2,3,4,5-tetrahydro-1H-pyrido(2,3-b)azepine and their corresponding lactams. II. Synthesis and pharmacologic study of their psychotropic activity]. Preparation of the N-(2-diethylaminoethyl) derivatives of lactam (II) and of the N-(3-dimethylaminopropyl) derivative of lactam (XI) is described. Synthesis of the N-[4-(2-hydroxyethyl)piperazinylacetyl]- and 1-carbothiamide derivatives of azepine (I) and of the n-(chloroformyl)- and N-(carbamoyl) derivatives of azepine (XII) are also described. Some pharmacological results indicate a partial tranquilizing activity.


Synthesis and pharmacological activity of derivatives of exo-trimethylenenorbornane. I. Lithium aluminum hydride reduction of exo-5,6-trimethylenenorbornan-2-one oxime gave in good yield exo-5,6-trimethylenenorbornan-2-endo-amine, from which a number of amides were prepared by reaction with acyl chlorides. Lithium aluminum hydride reduction of the above-mentioned amides afforded N-substituted exo-5,6-trimethylenenorbornan-2-endo-amines in good yields. Some amides showed CNS depressant and anti convulsant activity, and an amine convulsant activity in mice.


Aminomethyl derivatives of 1-cyclohexyl-5-alkyl- and 1-cyclohexyl-5,5-dialkylbarbituric acids as potential antiinflammatory agents. The synthesis and the structure of some aminomethyl derivatives of 1-cyclohexylbarbituric acids, obtained by the Mannich reaction, are described. Acids, containing a pyrrolidinomethyl group in the position 5 were found to have the barbituric ring in the enolic form, stabilized by a hydrogen bond with the pyrrolidine nitrogen atom. Some of the described compounds displayed antiinflammatory activity.


Therapeutic efficiency of spleen or bone marrow CFU in X-irradiated 89Sr marrow-ablated mice. Experiments were carried out to compare the therapeutic efficiency (TE: number of CFU required to reduce the mortality from 100 to 50 per cent) of spleen or marrow (BM) stem cells (CFU) grafted into lethally irradiated mice (807 rad) which had been previously treated with 89Sr or splenectomized. It was found that during the reconstitution of the haemopoietic organs, the spleen does not provide more than 10 per cent of the functional cells necessary for survival. Besides, the BM-derived CFU growing in 89Sr marrow-ablated mice remain twice as efficient as the spleen-derived ones. Similarly, spleen-derived CFU transplanted into splenectomized mice are half as efficient as BM-derived ones. It may therefore be assumed that haemopoietic stem cells grafted into a foreign microenvironment retain their original kinetics of growth and differentiation during 7 to 10 days after their transplantation.


The substitutive role of ACTH in supporting aldosterone response to head-up tilt during acute renin suppression in patients with essential hypertension. The relative contribution of the renin-angiotensin system, adenocorticotrophic hormone (ACTH) and plasma electrolytes in the response of plasma aldosterone to 30 minutes of 65 degrees head-up tilt was assessed in 10 essential hypertensive patients. Studies were carried out before and during acute blockade of renin release by propranolol, ACTH suppression by dexamethasone and combined renin and ACTH blockade. In control studies orthostasis induced significant increases only in plasma renin activity and aldosterone. In contrast, when the renin response to tilt was acutely suppressed by propranolol administration, the aldosterone response was nonetheless maintained but now appeared to be under ACTH control, since concurrent increases in cortisol were observed. During ACTH suppression aldosterone increased during tilt and so did renin. However, during combined ACTH and renin blockade aldosterone failed to increase during tilt. These studies suggest that the aldosterone secretory response to head-up tilt is normally mediated by the renin-angiotensin system but, when the renin response is suppressed, an ACTH response is elicited which assumes a backup role. However, when these two systems are blocked other factors appear unable to respond during tilt to support a normal aldosterone response.


Plasma vasopressin levels during haemorrhage in mature and immature fetal sheep. In four mature chronically catheterized fetal sheep in utero arterial pressure, heart rate, arterial pH and haematocrit fell during a 16-70% haemorrhage, while Pao2 rose. Plasma vasopressin concentrations increased and were correlated with the percentage of blood volume removed. Following haemorrhage arterial pressure and heart rate were restored within 60 min, while hyperozaemia and acidaemia persisted. Plasma antidiuretic hormone (ADH) concentrations remained the same or increased and were significantly related to the degree of acidaemia. Upon return of the removed blood, pressure rose transiently and Pao2 fell; pH remained low and plasma ADH concentrations fell, but were still related to the degree of acidaemia. In three immature, exteriorized fetuses (0.4 of term) plasma vasopressin concentrations also rose during haemorrhage. The results indicate that fetal plasma vasopressin levels rise during haemorrhage in response both to hypovolaemia and the subsequent acidaemia. Further the response to haemorrhage is present at an early gestational age.


Microspectrofluorometric studies on the formaldehyde-induced reaction product of 5-hydroxytryptamine. A new model incorporating Sephadex G-25 as an inert carrier has been developed for studying the reaction between biogenic amines and formaldehyde vapour. Both the fluorescence yield and the spectral characteristics of the 5-HT formaldehyde reaction product are influenced appreciably by the relative humidity at which paraformaldehyde is equilibrated, the duration of the reaction, the glycine concentration and pH of the suspending solution and the duration of exposure to ultraviolet light. It is concluded that care should be exercised in attempting to identify or quantify 5-HT on the basis of microspectrofluorometric analysis.


Activation of phosphatidylserine synthesis: a possible mechanism of regulation of the base-exchange enzymic system. The possible relationship between phosphatidyl serine synthesis by base-exchange and nervous activity has been investigated in the rat caudate nucleus. The rate of incorporation of L-serine into the phosphatidyl serine of slices from caudate nucleus is not affected by dopamine nor is it affected by the addition to dopamine of a cyclic phosphodiesterase inhibitor which would increase the endogenous cyclic-AMP levels. However, imidazole, a phosphodiesterase activator, clearly stimulates by more than 100% the phosphatidyl serine synthesis in the slices. The activation is not due to interaction at the catalytic site(s) of the base-exchange system, since it is neither observed in homogenates of caudate nucleus nor in cerebral microsomes at various pH values.


[Reevaluation of the treatment of acute bacterial pneumonias (author's transl)]. In spite of extreme and persistent susceptibility to antibiotics, specially benzylpenicillin, the pathology due to pneumococcus remains frequent and serious. From 14 cases of pneumococcal meningitis associated with pneumonia the authors have studied the relationship between these two localizations. They conclude that meningeal seeding appears most frequently secondarily and is probably latent at the beginning. Moreover they note that treatment of pneumonia by itself does not always prevent the occurence of the meningitis. Density of bacterial population, prolunged bacteremia, resistance of pneumococcus to phagocytic mechanisms and the delay of treatment might explain these findings. For those reasons the authors recommend the use of high doses of benzylpenicillin for the treatment of lately diagnosed bacterial pneumonia.


[Effects of somatostatin upon prolactin secretion both in normal subjects and in patients presenting pituitary adenoma (author's transl)]. In normal subjects somatostatin cannot modify the plasma levels of prolactin when they are in a normal range or when they are pharmacologically increased. In the case of pituitary adenoma (prolactinic or eosinophilic), the response of prolactin to somatostatin varies widely. In some patients there is a marked decrease of the prolactin levels while in others no modification is observed.


[Pantalar arthrodesis. A follow up study of 45 operations (author's Transl)]. The authors have studied the long term results of 45 Pantalar arthrodesis realised either in one stage, or in two stages. Technical details are given for obtaining a good positioning during the surgical procedure. It was found that post operative complications were more frequent than after more limited operations. The long term results were satisfactory, provided a good positioning. Residual equinus deformities were better tolerated than deformities in pronation or supination. It was noted no consequences on neighboring joints.


Effect of beta-blocking agents in hyperthyroidism. Propranolol modifies peripheral thyroxine metabolism, in opposition to the beta blocking agent GYKI 41099 which has no such effect. Both beta-receptor blockers produce a significant fall in the serum cAMP level of hyperthyroid subjects. It is suggested that the beneficial effect of the beta-blocking agents in hyperthyroidism is partly due to their depressive effect on cAMP production. As far as the action of propranolol is concerned, it may well involve an additional effect on T4 metabolism.


[Nitroglycerin and amyl nitrite action on common bile duct during operation for vesicular lithiasis (author's transl)]. Eight patients undergoing cholecystectomy received a single injection of nitroglycerin (0,9 mg) and 8 received amyl nitrite, during a cholangio-kinesimetry. The maximum fall in common bile duct pressure was similar in both group; 3.2 +/- 0.3 torr after nitroglycerin (NTG),3.8 +/- 0.6 torr after amyl nitrite (AN). NTG caused a more persistent lowering of pressure than AN; 614 +/- 42 seconds/343 +/- 27 seconds (p < 0.001). This study showed that it is possible to produce a relaxation of biliary tract muscle fibres with an injection of nitroglycerin and then replace amyl nitrite during anesthesia.


[Hemodynamic effects of normovolemic hemodilution]. After reviewing data from the literature concerning the effects of normovolaemic haemodilution on cardiac output and regional flow rates, the authors illustrate these concepts by a personal study involving the haemodynamics of 10 subjects undergoing operation in normovolaemic haemodilution. Removal of blood was compensated simultaneously by modified liquid gelatin in electrolytic solution (Plasmion) until the haematocrit was 0.30. Measurements were performed before haemodilution in patients in a steady state (anaesthetised, intubated, normoventilated), at the end of haemodilution, at the end of the operation, then 4 hours after recovery. There was no variation in blood pressure and heart rate, showing that normovolaemia was maintained. At the end of haemodilution, cardiac index increased from 3.10 to 3.84 l.min-1.m-2 (0.0517 to 0.0638 l.s-1 . m-2) (p < 0.005); stroke volume increased from 70 to 83 ml (p < 0.005); systemic resistance fell from 1585 to 1262 dynes. s.cm-5 (158.5 to 130.4 kPa.s.l-1) (p < 0.005); arterial oxygen content decreased from 191.1 to 152.1 ml.100 ml-1 (8.535 to 6.793 mmol.l-1) (p < 0.005), whilst oxygen transport was unchanged. These various haemodynamic measurements showed no significant changes at the subsequent times when they were measured, values remaining close to those obtained at the end of haemodilution. The results confirm the fact that norvolaemic haemodilution is accompanied by a fall in systemic vascular resistance with an increase in cardiac output. Regional circulations are thus improved. Since oxygen transport is unaffected, the oxygenation of peripheral tissues is ensured normally.


[Rheological effects of normovolemic hemodilution]. Blood viscosity depends essentially on two factors: shearing rate, since the blood is not a Newtonian liquid and the hematocrit, any fall in which tends to cause the blood to become closer in its behaviour to a Newtonian liquid. Furthermore, these two factors are interdependent. When the hematocrit falls, blood viscosity decreases in greater proportions at lower shearing rates than at high shearing rates. Whilst in vitro, in hemodilution, results vary in relation to the type of replacement solution, in vivo this factor would appear to be of little importance by virtue of the adapted variations in the deformability of the red cells. However, hemodilution results in the greatest relative decreases in blood viscosity at the highest hematocrits. Below a hematocrit of approximately 30 p. cent, the gain in terms of viscosity is very low. This figure would appear to be the ideal hematocrit level from a rheological standpoint. An additional rheological advantage is provided by hemodilution the instability of red cell rouleaux, which are in fact created more readily in areas where shearing rate is low. All of these rheological changes explain the hemodynamic consequences.


[Theoretical, experimental and clinical effects of variations in hematocrit during hemodilution]. By decreasing both viscosity and maximum oxygen capacity, a fall in hematocrit has two opposing effects on oxygen transport. The resultant of these effects was studied using a mathematical model representing the circulatory system and the oxygen transport system. This simulation showed that hemodilution decreased mean aortic pressure, increased central venous pressure and cardiac output. Oxygen supply to the tissues was maximum at a hematocrit of 30 p. cent. Blood volume was an essential parameter. These theoretical concepts of an optimum hematocrit of 30 p. cent were confirmed in the isolated rat heart perfused by blood with varying hematocrits. A clinical study in general surgery involving 307 patients where the hematocrit was reduced to below 32 p. cent by replacing blood loss by Ringer lactate or a fluid gelatin type solution, showed the good tolerance of normovolaemic hemodilution when used carefully, and its value in the prevention of post-operative thrombo-embolic disease.


[Study of erythrocyte lipids after perfusion of modified fluid gelatin]. Study of changes in erythrocyte lipids after the infusion of 1,000 ml of modified fluid gelatin (Plasmion) demonstrated disturbances at the level of the lipid double layer with, in particular, a decrease in phosphatidyl-ethanolamines found in the serum. No erythrocyte deformation was seen.


[Tissue oxygenation during normovolemic hemodilution]. Limited hemodilution does not affect the respiratory function of the blood, neither in vitro nor in vivo. By virtue of the unchanged affinity of oxygen for hemoglobin and increase in nutritional flow, reduction in the O2 content of the blood is completely compensated. Tissue hypoxia does not develop as long as pulmonary and circulatory compensation is ensured. As a result, maintenance of a normal blood volume is an essential parameter. Information is not yet available concerning the relationship of O2 supplies in coronary disease. Coronary disease is presently considered to be a contra-indication since a marked reduction in the O2 content of the blood could restric coronary reserves and result in myocardial ischemia.


Pyrite oxidation by Thiobacillus ferrooxidans with special reference to the sulphur moiety of the mineral. Available cultures of Thiobacillus ferrooxidans were found to be contaminated with bacteria very similar to Thiobacillus acidophilus. The experiments described were performed with a homogeneous culture of Thiobacillus ferrooxidans. Pyrite (FeS2) was oxidized by Thiobacillus ferrooxidans grown on iron (Fe2+), elemental sulphur (S0) or FeS2. Evidence for the direct utilization of the sulphur moiety of pyrite by Thiobacillus ferrooxidans was derived from the following observations: a. Known inhibitors of Fe2+ and S0 oxidation, NaN3 and NEM, respectively, partially abolished FeS2 oxidation. b. A b-type cytochrome was detectable in FeS2- and S0-grown cells but not in Fe2+-grown cells. c. FeS2 and S0 reduced b-type cytochromes in whole cells grown on S0. d. CO2 fixation at pH 4.0 per mole of oxygen consumed was the highest with S0, lowest with Fe2+ and medium with FeS2 as substrate. e. Bacterial Fe2+ oxidation was found to be negligible at pH 5.0 whereas both FeS2 and S0 oxidation was still appreciable above this pH. f. Separation of pyrite and bacteria by means of a dialysis bag caused a pronounced drop of the oxidation rate which was similar to the reduction of pyrite oxidation by NEM; indirect oxidation of the sulphur moiety by Fe3+ was not affected by separation of pyrite and bacteria. Bacterial oxidation and utilization of the sulphur moiety of pyrite were relatively more important with increasing pH.


Production, purification and properties of a Pichia kluyveri killer toxin. Production of the killer toxin of Pichia kluyveri 1002 was stimulated in the presence of yeast extract. In a minimal medium production was optimal at pH 3.8-4.0 and 22--25 degrees C. Addition of gelatin and nonionic detergents, like Brij-58 (polyoxyethylene 20 cetyl ether) and Triton-X-100, to this medium enhanced production significantly. The killer toxin was purified 140-fold by use of a stepwise ethanol precipitation and butyl Sepharose column chromatography. The purified killer toxin, which still contained some carbohydrates, appeared to be glycoprotein with a mol wt of about 19 000 and an isoelectric point of 4.3. It was stable between pH 2.5 and 4.7 and up to 40 degrees C.


[Genesis of connective matrix of Veretillum cynomorium Pall. (Cnidaria-Anthozoa). Ultrastructural and autoradiographic study (author's transl)]. Ultrastructural study of the tissues of Veretillum cynomorium shows the presence of two mesenchymatous cellular states in the mesoglea: the nongranular mesenchymatous cells and the granular mesenchymatous cells. These latter possess, besides their cytoplasmic granules, some homogeneous fibrous inclusions, very similar to the fibrous material of the mesoglea. Granules and homogeneous fibrous inclusions are also present in the cytoplasm of some ectodermic and endodermic cells. These morphological results lead us to consider that mesoglea and epithelia can be occupied by the same granular cell type. Besides this, the digestive endodermic cells are sometimes very rich in heterogeneous fibrous inclusions histochemically identified as phagosomes. An autoradiographic study indicates two possible pathways for the synthesis of the mesoglea. The first involves the endoderm which elaborates the mesoglea at a fast rate but in small amounts. The second is due to the granular cells (mesenchymatous and epithelial) which show a slow rate of synthesis leading to the formation of the homogeneous fibrous inclusions. The heterogeneous fibrous inclusions of the digestive endodermic cell support the hypothesis of the involvement of these cells in mesogleal degradation.


Microelectrophoretic application of putative neurotransmitters onto various types of bulbar respiratory neurons. Six putative neurotransmitters and the beta-receptor excitant isoproterenol were applied to bulbar respiratory neurons classified according to their burst discharge in the respiratory cycle and, for comparison, also to "unspecific" cells. With glycine inhibition occurred in I and prevailed in unspecific neurons. With GABA inhibition preponderated in I and E neurons. Glutamate excited E neurons. With dopamine inhibition prevailed in I and unspecific neurons. The majority of E neurons remained unaffected. With NE excitation occurred in EI and preponderated in I, IE, E and unspecific neurons, while some IE and E neurons were inhibited. The effects of isoproterenol did not allow any clear statement about receptor properties. In I units, however, activation was more frequent than inhibition. With 5-HT excitation prevailed in IE neurons. About half of the I cells remained unaffected and in the remainder inhibition preponderated over activation. This suggests the existence of two 5-HT-specific receptors in I and IE neurons. Comparison of the single effects revealed differences in the receptor properties of the various cell types. Results suggest that some cell types possess dopaminergic receptors and that these differ from NE-receptors, which have been found in all cell types. NE-receptor stimulation apparently can result in neuronal activation or inhibition.