Regulation of the central metabolism in relation to citric acid production in Saccharomycopsis lipolytica.

The mechanism of the massive extracellular production of citric and isocitric acids by Saccharomycopsis lipolytica grown on n-paraffins has been studied. When growth stops, because of nitrogen limitation, the intracellular concentration of ATP sharply rises whereas that of AMP and ADP decreases to a low level. At the same time production of acids begins. The activity of the NAD-dependent isocitrate dehydrogenase which requires AMP for activity becomes very low and prevents the oxidative function of the citric acid cycle whereas isocitrate lyase is not inhibited. As citrate synthase inhibition by ATP appears to be insufficient to stop n-paraffin degradation, citric and isocitric acids accumulation can take place. Massive excretion of these acids, however, probably still involves other physiological changes brought about by nitrogen limitation, possibly some permeabilization of the cell to these acids.


[Water and salt retention in low birth weight infants. Physiopathogenic discussion].

Thirty-nine cases of salt and water retention have been observed in low birth weight infants, preterm or small for dates, during the past five years. The onset on the oedema was delayed and appeared on average at the age considered to be term, that is at about 40 weeks corrected gestational age. The iatrogenic nature of the oedema is shown by the evidence in the population at risk of preterm and small for dates infants: It is frequent when the milk is non-modified cow's milk which contains 21-25 mEq/1 of sodium, less common with modified cow's milk containing 11 mEq/sodium1 and and never with breast milk (7 mEq/1). In the absence of treatment neurological signs appeared, as showed by intracranial hypertension. One injection only of frusemide was often sufficient to interrupt the vicious circle.


[The scimitar syndrome in children. Apropos of 3 cases].

The authors describe three new cases in children of abnormal right pulmonary venous drainage into the inferior vena cava, associated with sequestration of the right lower lobe and dextrocardia caused by right pulmonary hypoplasia with a scimitar sign. The term scimitar syndrome used in the literature is to some extent inaccurate as it is neither constant nor pathognomonic. The authors have reviewed 45 paediatric cases reported in the literature and compared the different clinical, diagnostic and therapeutic aspects with their patients. To their knowledge they report the first case in childhood with right lobar sequestration, which received its blood supply from an abnormal artery arising from the right internal mammary artery.


[Schilder's disease with adrenal insufficiency (adreno-leukodystrophy). Apropos of 5 cases].

Five cases of Schilder's disease with adrenal insufficiency are reported (adrenoleucodystrophy) one of whom has a first cousin with Addison's disease. The principle clinical features of the disorder are outlined and particularly the great variability in the severity of the adrenal insufficiency. The current understanding of this disorder is reviewed.


[Hepato-diaphragmatic interposition of the colon in children. Chilaiditi's syndrome].

The interposition of the colon between the diaphragm and the liver is reported in an infant aged 12 days who presented in the neonatal period with intestinal obstruction. The syndrome which was described by Chilaiditi in 1910 under the name of hepatoptosis or diaphragmatic-hepatic interposition of the colon, is rare in adults and exceptionally rare in children. Nevertheless it is important to recognise at it is part of the differential diagnosis of pneumoperitoneum and a right sided diaphragmatic hernia. The treatment was surgical in our case.


[Pancreatico-peritoneal fistula in the newborn infant revealed by a hemorrhagic ascites].

Chronic haemorrhagic ascites in an infant is reported. After much hesitation without a definite diagnosis the first laparotomy was carried out and the estimation of amylase, lipase and proteolytic enzyme activities in the ascitic fluid suggested a pancreatic origin for the ascites. This was conformed at a second laparotomy when the condition was correted. This emphasises the importance of the estimation of pancreatic enzymes in unexplained ascites in children.


[The anti-epileptic drugs].

It is no longer acceptable to prescribe anticonvulsants on the basis of empirical rules. Pharmacological studies have made it possible to measure the absorption, distribution and excretion of these drugs. Complete understanding of this data is neccessary if anticonvulsant prescribing is to be fully effective and to avoid iatrogenic disease.


[Still another cause of hypermethioninemia in children: S-adenosylmethionine synthetase deficiency].

One case of hypermethioninaemia discovered on systematic neonatal screening examination is reported. This metabolic disorder was associated with growth retardation, anorexia, digestive disturbances, and a strong smell of "boiled cabbage" in urine and sweat. With a 6-year follow up, psychomotor and growth developments were excellent under a low methionine containing diet, in spite of a persistent pathological hypermethioninaemia. A deficiency in S-adenosyl-methionine synthetase and an abnormal kinetics of this enzyme were found in a liver tissue sample obtained by biopsy. Otherwise, the excretion of alpha-keto-gamma-methyl-thiobutyric acid was increased with, however, no abnormality in the metabolism of folates. Finally, the probability of an autosomal recessive transmission is discussed.


[2 cases of solitary pulmonary arteriovenous fistula presenting in the neonatal period].

Two case reports of pulmonary arterio-venous fistulae presenting in the neonatal period are described. One child had severe respiratory distress with cardiac failure and the other presented with cyanosis and a continuous murmur. In both, chest X-ray demonstrated a localised lesion and the presence of an arteriovenous fistula was confirmed by pulmonary angiography. Lobectomy cured both children.


The treatment of sexual dysfunction: a review.

In this article we describe and contrast the psychodynamic and directive approaches to the treatment of sexual dysfunction. We have also summarized and critically reviewed published reports with ten or more cases. No firm conclusions can be drawn on the efficacy of the psychodynamic approach with this population because of the absence of controlled studies. Fairly conclusive evidence for the efficacy of the directive approaches is now available, but solely with highly selected populations. Success rates in studies with unselected psychiatric outpatient populations are much less favorable. The effect of characteristics of the patient population on outcome with the directive sex therapies has received dangerously little attention.


The components of rapists' sexual arousal.

The erections of rapists and nonrapists were measured during audio descriptions of rape and nonrape sexual scenes. On the basis of their erection measures, rapists were separated from nonrapists in that the former developed erections to rape descriptions while the latter did not. The method also discriminated those rapists with the highest frequency of rape, those who had injured their victim, and those who chose children as victims.


Cognitive mediators between patients' social class and therapists' evaluations.

Previous research has shown that therapists are more likely to accept middle-class than lower-class persons for psychotherapy and to rate middle-class patients more favorably than lower-class patients. One explanation that has been offered is that lower-class patients may not conceptualize their experiences in a manner compatible with traditional kinds of therapy. This study investigated several cognitive variables that could theoretically serve as mediators between patients' social class and therapists' differential evaluations--specifically, verbal intelligence, psychological differentiation, and locus of control. Therapists evaluated patients after the initial therapy session. Results indicated that psychological differentiation was a mediator for therapists' judgments of both patients' desire for structure and their suitability for psychotherapy. Similarly, a locus of control orientation emphasizing the role of chance functioned as a mediator of therapists' judgments of suitability.


The goal-attainment scale: an instructional guide for the delivery of social reinforcement.

Goal-attainment scaling, a method for evaluating treatment programs, has been reported to benefit therapeutic encounters. In order to evaluate its effect on staff therapeutic behavior, raters were trained to rate the appropriateness of inpatient behavior and the staffs' responses to it. General distribution of the goal-attainment scale on a psychiatric inpatient unit influenced the delivery of positive social reinforcement for appropriate behavior.


Compliance with psychiatric emergency room referrals.

An attempt was made to identify some of the major variables, such as age, sex, ethnicity, and diagnosis, that might be determinants of compliance with psychiatrists' recommendations to enter outpatient treatment after emergency room visits. In general, it was found that older Puerto Rican and white women, usually those diagnosed as having some kind of depression, had the highest rate of compliance. Black patients, as well as all patients diagnosed as schizophrenic, had the lowest probability of outpatient follow-up. A telephone survey of those patients who did not go for outpatient treatment within six months after referral was conducted to elicit their reasons for not going. Several hypotheses were developed concerning reasons for lack of compliance with recommendations for outpatient follow-up, and a number of suggestions were made about possible methods for increasing the compliance rate.


Decriminalization of public drunkenness: the response of suburban police.

In 1973, Massachusetts abolished the crime of public drunkenness, with the intent that many of the persons who formerly had been arrested on this charge would now be treated at detoxification centers. We studied the effects of this law in the Boston suburbs, with an emphasis on the police response. We found that there has been a paradoxical increase in drinking-related jail cell detentions, and that the police and detoxification centers are dealing with two essentially different and unrelated populations. Police and detoxification officials agree that the suburban detoxification system is irrelevant for dealing with most of the public intoxicants whom the police have always dealt with and whom they continue to deal with.


Extrapyramidal side effects in chlorpromazine recipients: emergence according to benztropine prophylaxis.

The frequency of extrapyramidal symptoms (EPS) attributed to chlorpromazine among 86 patients who received benztropine for the prevention of EPS (9.3%) was similar to that of the 568 patients who received chlorpromazine alone (10.6%). The data in this small sample indicated that the prophylactic use of benztropine had no effect in reducing the rate of EPS.


Catatonic reactions to high-potency neuroleptic drugs.

Eight patients developed a syndrome marked by features of catatonia (including posturing, waxy flexibility, withdrawal and regression) and parkinsonism (including bradykinesia and rigidity) while receiving high-potency neuroleptic drugs. The syndrome had a gradual onset, responded slowly to withdrawal of the neuroleptic or use of an anticholinergic agent, but seemed to respond more rapidly to amantadine. The syndrome may easily be confused with a worsening of schizophrenic symptoms.


Successful suicides with thioridazine and mesoridazine: a result of probable cardiotoxicity.

Five cases of successful suicides from thioridazine and mesoridazine occurred. The clinical course and management are outlined. A sixth case of reversible total heart block associated with thioridazine is presented giving further evidence that the deaths from overdose probably resulted from drug cardiotoxicity.


Countersymbiotic suicide.

In the course of studying the outcome of treatment for severely disturbed schizophrenics on a special ward, the authors encountered three instances of suicide with many features in common. All three cases involved young Hispanic male patients who demonstrated pathologically symbiotic relationships with their mothers. None had a history of overt suicide attempts prior to their actual death by jumping. These incidents occurred while the patients were en route to, or at, the maternal home on an unauthorized leave from the hospital. We present the case histories and offer a dynamic interpretation. In each case, it is likely that the underlying desire was to kill the mother. This either was not permissible or, alternatively, the patients' ego boundaries were not sufficiently clear to permit differentiation of self and mother. The patients saw any attempt, short of suicide, to loosen the symbiotic bond as being futile, hence, our terminology of the event as "countersymbiotic suicide."


Persisting personalities among depressed women.

Descriptions of patients' premorbid personalities were provided by family informants at the time of the depressive episode, and one year later at follow-up the informants were asked to describe the current personalities. A comparison of the initial and follow-up descriptions for a sample of 190 depressive women showed that personality characteristics traditionally ascribed to depressive patients tended to provide a persisting characterization for most of the sample. There was a diminution in the incidence of certain personality characteristics for a small but significant portion of the sample.


Depressive symptoms in patients and normal subjects in India.

A survey of symptomatology of depressed patients and normal subjects in  India was conducted, using a previously developed operational definition for depressive disorders that had been converted into a Self-Rating Depression Scale (SDS). Results obtained from 430 depressed and 97 normal subjects showed that depressed patients scored significantly higher on 18 of the 20 individual items of the SDS, as well as the SDS index, than did normal subjects (P= less than .01). Correlation between the physician's global rating of the patient's depression and patient's own self-rating was 0.74 (P= less than .01). A comparison of these results in India with those previously obtained in the United States, Japan, Czechoslovakia, England, Germany, and the Netherlands showed that depressed patients scored similarly in all the countries studied.


Thyroid function in depression and alcohol abuse: a retrospective study.

Admission thyroid function tests were reviewed in 115 euthyroid patients with depression (66), depression and alcohol abuse (30), or alcohol abuse (19). Estimated free thyroxine (EFT) levels ranged from 0.7 to 2.7 ng/100 ml (normal, 1.0 to 2.1). Levels above 2.1 ng/100 ml were associated with agitation and values under 1.1 with alcohol abuse. Mean EFT levels differed significantly among six diagnostic subgroups and paralleled rank order for severity of depression (none, secondary, reactive, single uncategorized, recurrent, psychotic). Alcohol abuse negatively affected EFT: there was a significant decrease of mean EFT level from nonabusers to abusers and, further, to intoxicated abusers. A positive association between EFT level and severity of depression, and a negative one with alcohol use, were significant when other variables considered were controlled. These two factors accounted from 28.2% of variability in EFT levels, with a minimal additional contribution of medication effect.


Sensitivity of automated red cell antibody detection.

The principle of detecting red cell antibodies by automated technique using the two-channel Technicon Auto-Analyser with some modification is described. The sensitivity of automated methods in detecting antibodies of different specificities was determined. The study was carried out with 76 diagnostic human sera produced by the Institute of Hematology, Transfusion Centers and commercial firms: anti-RhD, -C, -E, -CW, -c, -e, anti-K, -k, Kpa, anti-Fya, -Fyb, anti-Jka, -Jkb, anti-M, -S, -s, anti-P1, anti-Lua, anti-Lea, -Leb, anti-H, -A1, anti-I, anti-Lua and anti-Vel. A majority of the antibodies were detected by both automated methods with greater sensitivity than by manual methods. Greatest sensitivity was observed in the detection of anti-S, -Vel and antibodies of the Rh system. Anti-Leb and anti A1 antibodies were not detected. The studies are the basis for introduction of the automated technique into routine use for antibodies in blood donors and recipients.


The action of cysteine on PHA-stimulation of lymphocytes. I. Influence of DNA synthesis.

The influence of short-time preincubation of rat lymphocytes in solutions of L-cysteine reduced glutathione, and dithiothreitol on PHA stimulation of these cells was studied by measuring incorporation of 3H-thymidine. Thirty-minute preincubation in cysteine solution enhanced PHA-induced incorporation of 3H-thymidine. One-hour incubation caused earlier peak of incorporation by one day; and two-hour incubation distinctly inhibited spontaneous incorporation of 3H-thymidine. Incubation in solutions of glutathione and dithiothreitol had no effect on the course or intensity of 3H-thymidine incorporation. However, constant presence of these compounds in cultures was toxic for lymphocytes.


The action of cysteine of PHA-stimulation of lymphocytes. II. Influence on incorporation of 3H-uridine and 14C-leucine.

The influence of short-term preincubation and continuous cultivation with L-cysteine hydrochloride on incorporation of 14C-leucine nad 3H-uridine in cultures of PHA-stimulated and unstimulated lymphocytes was studied. Preincubation during 1 and 2 hours in presence of cysteine inhibited incorporation of these compounds during the first few days of incubation. After 2-hr preincubation, incorporation was first somewhat depressed and then markedly enhanced. Continual presence of cysteine in the medium markedly inhibited incorporation of 3H-uridine and 14C-leucine from the first to last day of incubation.


The effect of antibody on the migratory pattern of peritoneal macrophages.

51Cr-labeled peritoneal macrophages which interiorized sheep erythrocytes (SRBC) injected i.p. into syngeneic recipients accumulate in a typical fashion in different organs. The pattern of distribution can be altered by two maneuvers--when animals at the time of macrophages transfer are injected i.v. with cytophilic antibody, or when macrophages are fed with IgG-SRBC complexes instead of native SRBC. The possible role of modified migratory pattern of macrophages in antibody-induced suppression of the immune response is discussed.


Dynamic adhesion of erythrocytes to glass. Comparative study of the influence of serum in low concentrations.

Adhesion of 51Cr-labeled rat erythrocytes was examined in a layer of glass beads in a dynamic system. The kinetics of erythrocyte retention in the bead layer was found to change with time. Adhesion decreased with time at all the studied rates of suspension flow through the layer (within the range 1-5--0-4 cm/min), both in presence and absence of serum in the medium. Serum in low concentrations of 20--200 microgram of protein per ml considerably inhibited dynamic adhesion of erythrocytes to glass. The higher the serum concentration in a medium (at a definite flow velocity), the quicker the decrease of adhesion with time, and the stronger the dependence of the kinetics of erythrocyte retention on the flow velocity of the cells. Mean adhesion of erythrocytes after 17-min perfusion of the layer (at 200 microgram of serum protein per ml of medium) seems to be independent of the concentration of the cells in the suspension flowing into the layer within the range of studied concentrations, 2 x 10(6)--20 x 10(6) cells/ml. However, mean adhesion of erythrocytes deprived of serum seems to be dependent on the cell concentration.


Activities of some peptidases and glycolytic enzymes in cells of the amniotic fluid. II. Pregnancies complicated by threatening intrauterine fetal asphyxia.

Activities of leucylaminopeptidase, aspartyl aminopeptidase, gamma-glutamyl transpeptidase, oxytocinase, phosphohexoisomerase, phosphofructokinase and aldolase were studied in amniotic cells from cases of pregnancy complicated by threatening intrauterine fetal asphyxia. Leucylaminopeptidase and oxytocinase activities were much higher in the group of pregnancies complicated by threatening fetal asphyxia than in the control group. It was concluded that elevated activity of the aforementioned enzymes in cells of the amniotic fluid from pregnancies complicated by threatening intrauterine asphyxia is due to acute hypoxia of the fetus.


Effect of menstruation on academic performance among college women.

Many studies report that women's performance and affective patterns fluctuate with their menstrual cycle. Poor mental performance is generally more common during menstruation and for several days prior to onset. Research on academically advanced women, however, has shown that their scholastic performance is less likely to exhibit the usual menstrual decline. Presumably, they are motivated enough to exert a compensatory effort on "off-days." Thus the current research was designed to test whether, among college women, academic performance fluctuates with the menstrual cycle. The academic performance of volunteers in and introductory college psychology course was followed. Biweekly course tests were used to measure performance. The subjects filled out menstrual calendars, indicated their SAT scores, and answered questions from a standardized test of academic motivation. Following the convention of past research, the "paramenstruum" (the time of menstrual stress) was defined to be the 4 days prior to onset and the first 4 days of menstruation. The other days in the cycle comprise the "intermenstruum." On all eight tests, the difference between paramenstrual and intermenstrual performance (adjusted for aptitude and motivation) was insignificant.


Gender identity change in a female adolescent transsexual.

Two years of individual and milieu therapy are described of a 14 1/2-year-old girl who had presented with the persistent request to have a sex-change operation since age 12. Her past history was obtained from her parent and the records of the child guidance clinic which evaluated her at 3 years of age. She gives a history of remarkable tomboyism during her latency years and increasing withdrawal from peers and family during early adolescence. The patient's personal and family dynamics are explored, and these major therapeutic themes are discussed. The individual and milieu therapy are described and discussed with some speculation about the reasons for her positive response to psychotherapy. It would appear that this is a rare case of postpubertal female transsexual reported to have made a gender identity change.


Investigation of human sexual response using a cassette recorder.

A cassette recorder (Medilog miniature analogue tape recorder) initially developed for prolonged recording of ECG and EEG has been adapted for monitoring physiological change during sexual response. The recorder is small, portable, and reliable. Recording can be done by the subject in private. By avoiding the problem of invasion of privacy, it may prove practical to obtain data from patients when information about their ability to cope with the stress of sex response is neeeded for medical counseling. Additionally, a larger population than would ordinarily be available for sex research may become available for study. Tracings from a recording of EEG, ECG, and vaginal photoplethysmography during sex response are presented.


[Influence of vitamin B 6 deficiency in early weaned piglets on the digestibility and conversion of protein and energy].

Early-weaned piglets were subjected during 2 metabolic periods (11th-18th and 32nd-39th days of the experiment) to conversion experiments to study the influence of vitamin B6 depletion on the digestibility of the crude nutrients, metabolizable energy and on nitrogen conversion using the difference procedure. The depleted piglets (0.4 mg vitamin B6/kh diet) and the pair-fed control animals raised under equal conditions (6.5 mg vitamin B6/kh diet) were first fed a pre-starter ration, and from the 24th experimental day, a starter feed. As the period of depletion increased, the vitamin B6 sub-provided piglets revealed deficiency symptoms such as reduced appetite, lethargic behaviour and less movement. Whilst in the first half of the experiment the control animals reached significantly higher weight gains at lower expenditure of dry matter and digestible energy per kg of weight gain, no differences were observed between both groups in the second period. On the other hand, during the 1st metabolic period the digestibility of all crude nutrients and energy in the depleted piglets proved slightly, but significantly higher than in the pair-fed control animals. In the second half of the experiment ther were just casual differences. After a 2-week vitamin B6 deficient nutrition, the piglets had a 4.1% lower nitrogen retention as compared with the pair-fed control. After a depletion period of 5 weeks, this difference reached 14.4%. As nitrogen excretion in the urine increased, a higher renal energy excretion was observed. Thus the vitamin B6 deficient animals had available less metabolizable energy (in % of digestible energy) than the control piglets.


[Studies on the determination of the part of bacterial nitrogen in relation to total nitrogen content in the duodenum of cows].

A method for estimation of content of bacterial nitrogen in duodenal intestine was described. The method of HUTTON et al. (1971) in modificated form for the own research was the best method. In two trials roughage (chopped dried forage) and ground corn were given to cows with duodenal bridge fistula in different order (90 min-intervall). Portion of bacterial nitrogen to total nitrogen was 72.5% (corn leads to roughage) and 64.7% (roughage leads to corn).


[Some methodical problems in the determination of the true amino acid digestibility in swine].

Five castrated males bridge-fistulated at the end of the small intestine and fed a wheat-casein ration were used to study the influence of the microflora in the determination of the true amino acid digestibility applying the fecal analysis method. The experimental results allow to conclude that the influence of the microflora may be regarded as a very small one if certain parameters are taken into account in applying the fecal analysis methods.


[Proof of sex-dependent effect of lambdamycin in mice].

The juvenile mouse is used as screening model to test feed additives for their potentially ergotropic effects. Weight development in 20-day old mice was found to be much more strongly influenced than in animals being 25 to 30 days old. The antibiotic lambdamycin inhibited weight gain in female mice, whilst males were promoted in weight development following lambdamycin application.


A comparison of Saint Louis encephalitis and Sindbis virus RNA.

RNA isolated from purified St. Louis encephalitis and Sindbis virus particles was compared by cellulose CF-11 chromatography, and RNase T1 and pancreatic RNase A digestion. SLE RNA eluted from the cellulose CF-11 column as a molecule with very little secondary structure, while Sindbis appears to have some internal bonding. Ribonuclease digestion indicates that SLE RNA contains 2.4 per cent polyadenylic acid.


RNAs of influenza virus recombinants derived from parents of known virulence for man.

Extensive use of recombinants made from A/PR/8/34 (H0N1) and wild, virulent H3N2 viruses as live influenza vaccines has provided a number of viruses of defined virulence for man. Clinical symptoms produced by these strains have ranged from febrile influenza to local coryzal symptoms or nil. A study was therefore made of the extent to which the PR8 genome had been incorporated into that of a number of the recombinants. By RNA--RNA hybridization it seemed that recombinants which had 55 per cent of greater homology with the PR8 parent were likely to conform an acceptable standard of attenuation. Those with lesser homology were frequently, but not always, clinically virulent. The technique seemed potentially useful, therefore, for screening PR8 live vaccine recombinants in vitro before giving them to volunteers.


Isolation and characterization of further defective clones of a temperature sensitive mutant (ts-1) of respiratory syncytial virus.

After exposure of the temperature sensitive ts-1 mutant of respiratory syncytial virus to the chemical mutagne, nitrosoguanidine (NG), 2 clones of virus were recovered which were more temperature sensitive and stable genetically than the ts-1 mutant. The initial criterion used for selection of the 2 clones was decreased ability to produce plaques at 36 degrees C. Subsequently it was shown that the 2 clones grew less well at the restrictive temperatures of 37 degrees and 38 degrees C than did the ts-1 parent. Peak titers of the NG derived clones were decreased 10--30 fold at 37 degrees C and over 100-fold at 38 degrees C compared to ts-1. Complementation analysis indicated that the NG mutants retained the same complementation pattern as the ts-1 parent.


Influenza virus infection of hamsters. A model for evaluating antiviral drugs.

Inoculation of hamsters with influenza virus [A/PR/8/34 HON 1] produces an inapparent infection which can be monitored by virus titrations of nasal washes or of homogenates prepared from trachea or lung. Antibody can be detected in the serum within 7 days following virus inoculation. Hamsters previously infected were found to be resistant to challenge with the same virus. The utility of this model for evaluating anti-influenza drugs was demonstrated with two compounds. Calcium elenolate, a virucidal agent, reduced the virus titers of nasal washes when the drug was given as nose drops near the time of virus inoculation so as to affect high drug concentrations in the nasal passages. Virazole, an inhibitor of virus replication, reduced the virus titers of the nasal washes when multiple drug treatments were given as nose drops in an effort to provide drug during the time of virus replication. The model described may provide a useful means of evaluating potential antiviral during candidates inasmuch as the drug can be delivered directly into the nasal passages in a non-fatal influenza infection in a convenient laboratory animal.


A spontaneous temperature sensitive mutant of Japanese encephalitis virus: preliminary characterization.

A spontaneously arising temperature sensitive (ts) mutant of Japanese encephalitis virus (JEV), ts104, was isolated from chick fibroblast (CF) cell cultures of JEV strain M 1/311. Strain ts104 was plaque purified and characterized to ascertain its potential as a candidate for a live vaccine. Parameters of its growth, temperature lability, immunogenicity and virulence were examined. Ts104 has been shown to be stable ts JEV strain, multiplying as well as the parent strain in CF cultures at 35 degrees C, but not mutiplying at 39 degrees C. It was avirulent for embryonated chicken eggs incubated at 39 degrees C and of reduced virulence for intracerebrally (i.c.) inoculated mice as measured by LD50 in weanling mice and average day of death in weanling and suckling mice. Intraperitoneal injection of adult mice with either parent or ts strain resulted in similar levels of protection against challenge with either strain. The potential of ts104 as a candidate live JEV vaccine strain is discussed.


The kinetics of adenovirus infection and spread in cell cultures infected with low multiplicity.

The cause for the long "incubation period" required till the appearance of the CPE in cell cultures inoculated with small amounts of adenovirus was investigated with adenovirus type 5 in HeLa cell cultures. The spread of virus in a culture from cell to cell is minimal, as shown in cultures with antiserum in the medium. The spread by spontaneously released virus via the medium is more important. It can be accelerated by repeated subcultivation after freezing and thawing the cells in 2 or 3 days' intervals. The quantity of virus produced by one infected HeLa cell was found to be 200 TCID50 within 48 hours, independent of the MOI. The growth cycle too is largely independent of the virus dose. The data suggest that the long duration of the "incubation period" is fully explained by a burst size of 200, a cycle length of 40 to 48 hours and the assumption of a slow and steadily working process of spontaneous release of virus into the medium. Some other possible causes, like impurities in the inoculum or slow and asynchronous early stages of infection, have been ruled out by appropriate experiments.


Development of a modified immunoelectroosmophoresis method for Uukuniemi and Runde virus serology.

In search for a suitable method for sero-ecological screenings for arboviruses in Norway, efforts were undertaken to make the immunoelectroosmophoresis technique more sensitive than here to fare in detection of antibodies. The aim was to make it comparable to haemagglutination inhibition test in sensitivity, retaining the advantages in specificity, simplicity and capacity. This has been achieved by: 1. Using concentrated virus as antigen. 2. Performing electrophoresis in a gel consisting of an agar-agarose mixture in optimal concentrations. 3. "Sandwiching" the first specific electrophoretic run with an anti-species antiserum to the tested sample.


West Nile virus infection of adult mice by oral route.

Adult Swiss albino mice were fed orally with suspensions of a strain of West Nile virus isolated in Nigeria. Most of these mice became sick and died 7 days post feeding and virus was recovered from organs of such infected mice. Histological lesions were observed in some tissues and antibody to the strain of West Nile virus developed in mice that survived infection.


Results of chromosome analysis of rabies virus infected human diploid cells (WI-38).

Fixed rabies virus strains did not induce mitotic or chromosome abnormalities in infected WI-38 cultures. Infected cells were shown to undergo mitosis thus indicating an endosymbiotic type of infection.


Quantitative analysis of interictal behavior in temporal lobe epilepsy.

Patients with unilateral temporal epileptic foci were contrasted with normal subjects and patients with neuromuscular disorders in the evaluation of specific psychosocial aspects of behavior. Eighteen traits were assessed in equivalent questionnaires completed by both subjects and observers. The epileptic patients self-reported a distinctive profile of humorless sobriety, dependence, and obsessionalism; raters discriminated temporal lobe epileptics on the basis of circumstantiality, philosophical interests, and anger. The right temporal epileptic displayed emotional tendencies in contrast to ideational traits of left temporal epileptic. Right temporal epileptics exhibited "denial," while left temporal epileptics demonstrated a "catastrophic" overemphasis of dissocial behavior. The results support the hypotheses that sensory-affective associations are established within the temporal lobes, and that, in man, there exists a hemispheric asymmetry in the expression of affect.


The clinical link between migraine and cluster headaches.

We describe seven patients with vascular headaches. Five of them had cluster headaches, which were preceded by migrainous scotamata (two patients), weakness contralateral to the pain (one), accompanied by ipsilateral photopsias (one), or by contralateral paresthesias (one). The other two patients had "clusters" of daily common migraine headaches separated by long free intervals. The symptoms of these patients suggest a common root for cluster and migraine headaches.


Neuropathy presenting as prolonged dyspnea. Case report and review of literature.

Polyneuropathy presented as isolated respiratory muscular paralysis. Transdiaphragmatic pressure measurements, nerve conduction studies, electromyography, and biopsy of intercostal muscle confirmed the nature of the process. Patients with unexplained respiratory insufficiency must be carefully evaulated for underlying neuromuscular disease.


Lead neuropathy in adults and children.

All parts of the nervous systems can be affected, depending on the level and duration of exposure, by increased levels of lead. The occurrence of motor neuron disease, peripheral neuropathy, and encephalopathy are not mutually exclusive disorders for those individuals suffering from the toxic effects of lead. We present data that support the concept that increased absorption of lead produces changes in both central and peripheral nervous systems. Clinical and electrical evidence of subclinical involvement of peripheral nerves appears to be common to adults and children who are exposed to lead. These observations, accumulated from several possible sources of environmental hazard, also suggest that measurement of motor nerve conduction velocity may serve as an additional factor in the diagnosis of otherwise unrecognized toxic effects of lead.


Antibodies to varicella zoster in cerebrospinal fluid.

The neurologic complications of varicella-zoster (VZ) virus infections are manifested as zoster with or without CNS involvement, encephalomyelitis, or ocular involvement. Usually the association of VZ virus in these conditions has been determined by finding VZ antibodies in the serum. In a few instances, VZ antibodies have been detected in the CSF. We report two cases of VZ virus infection followed by neurologic complications involving the CNS in which VZ antibodies were present in the CSF. These two cases underscore the need and value of determining the presence of VZ antibodies in the CSF in certain instances.


Auditory evoked brain stem potentials in a case of "locked-in" syndrome.

Auditory evoked brain stem potentials were measured in a patient with occlusion of the basilar artery about 7 mm above its origin, resulting in the "locked-in" syndrome due to infarction at the junction of the lower one third and upper two thirds of the pons. The first three waves of the evoked response originating from the acoustic nerve and auditory nuclei in the caudal pons were normal in wave form, peak latency, and voltage level. Waves IV and V, generated in the region of the lateral lemniscus and inferior colliculus in rostral pons and caudal midbrain, demonstrated prolonged peak latency and reduced voltage, indicative of slowed neural conduction in the pons above the level of the superior olivary complex. These findings suggest that auditory evoked potential recordings may have considerable value in the localization of brain stem disorders.


Stapedius reflex decay in myasthenia gravis.

Stapedius reflex decay, in response to a one-minute sound stimulus of 500 Hz occurred in six patients with myasthenia gravis. This decay is analagous to the decremental response of muscle action potentials to rapid nerve stimulation. Edrophonium chloride decreases the degree of decay. This represents a useful test in the diagnosis of myasthenia gravis.


Hypothermia and persisting capacity to develop fever. Occurrence in a patient with sarcoidosis of the central nervous system.

A patient with central nervous system and systemic sarcoidosis had profound hypothermia and dementia with associated lymphadenopathy and hypernatremia. His capacity to develop fever remained; despite the persistent marked hypothermia, sweating and shivering in response to peripheral heating and cooling were maintained. Postmortem neuropathologic studies indicated that the hypothalamic region, generally considered to contain the primary temperature control, had been severely damaged by granulomatous sarcoid disease. These results confirm and extend previous findings of temperature disturbance in hypothalamic sarcoidosis and suggest that the integrity of the primary control of body temperature is not essential to fever production and "broad-band" regulation against environmental temperature extremes.


Unusual cause of relapsing hydrocephalus. Congenital intracranial teratoma.

We add clinical and pathological details of one male and one female  infant with congenital pineal teratomas who died before reaching 3 months of age to the small number in the world literature. Each had a nonresectable, enormous neoplasm at the time of diagnosis, and shunting procedures were of no significant value. The pathological features of the tumors conformed in all respects to those classically described as true teratomas. An epidermal cyst, possibly metastatic, was found in the spinal subarachnoid space in one patient. There is currently no effective therapy for these neoplasms, although both were diagnosed during life. Whenever recurrent shunt insufficiency occurs in a hydrocephalic neonate, the possibility of a congenital brain tumor should be considered.


Bony and vascular anomalies of the head. Their possible relation to anencephaly.

This study links a midfacial anomaly in an 8-year-old boy, with underlying bony skull defects and abnormalities of the cerebral vasculature, with an earlier spontaneous miscarriage and the subsequent birth of a frankly anencephalic sibling. We believe that the midfacial and vascular anomalies in the second child could represent a forme fruste of anencephaly, which should alert the physician to monitor subsequent pregnancies for the complete anencephalic phenotype.


Evoked response and after-discharge thresholds to electrical stimulation in temporal lobe epileptics.

The records of electrical stimulation of 30 psychomotor epileptics were examined for threshold levels of evoked responses and after-discharge production. Comparisons were made between anatomical sites, operated and nonoperated structures, and different disease states. It was found that patients with hippocampal sclerosis (HS) had higher thresholds in structures on the operated side. The patients with lesions other than HS were found to differ from those with hippocampal sclerosis in that there were no differences found between their diseased and nondiseased structures. For both patient groups, the amygdala had a much higher threshold for after-discharge production than either the hippocampus or the hippocampal gyrus.


Amaurosis fugax from disease of the external carotid artery.

Three patients with proved internal carotid artery occlusion and diseased external carotid artery or common carotid artery had amaurosis fugax. Evidence for retinal embolization through external carotid collaterals is retinal emboli and infarction after carotid artery manipulation, amaurosis during external carotid angiography, and relief of amaurosis by endarterectomy of this vessel. The abundance of external carotid collaterals, their size, and natural incidence are discussed. Reports clinically support embolization to the central retinal artery and ophthalmic artery through these collaterals.


Hyperhydrosis in  paraplegia.

A 20-year-old man suffered head, chest, and abdominal trauma in an auto accident resulting in a traumatic dissecting aneurysm of the thoracic aorta. Hypotension developed. The aneurysm was resected and replaced with a prosthetic graft. Postoperatively, the patient was found to be paraplegic below T-9, areflexic and anesthetic to pain and temperature, with preservation of vibration and position senses. In the ensuing nine months, the patient regained considerable sensory function in his lower extremities and had severe constant hyperhydrosis below the T-9 dermatome. The exaggerated sweating was unaffected by temperature change and anxiety. It was diminished by methantheline bromide treatment but never abolished. The spinal cord lesion is postulated to be anterior horn cell loss, with preservation of interneurons and intermediolateral gray columns. Disinhibition of sympthetic circuits or sprouting of axons are proposed mechanisms.


Hemorrhagic complications of cerebral arteritis.

Intracranial hemorrhage occurred in two patients with cerebral arteritis. One patient with methamphetamine-induced necrotizing angitis had a spontaneous subarachnoid hemorrhage without an aneurysm. A second patient with ulcerative colitis developed an intracerebral hematoma. Carotid angiography demonstrated a diffuse arteritis in each patient. The risks of bleeding associated with cerebral arteritis are discussed. The use of anticoagulants should be avoided. Cerebral arteritis should be suspected as a cause for intracranial hemorrhage.


Acute hypokalemic myopathy in alcoholism. A clinical entity.

Two cases of an acute myopathy without muscle pain, tenderness, or swelling are described in alcoholic patients. Both were associated with severe hypokalemia and were largely reversible with potassium repletion. Hypokalemia may be the cause of some cases of acute myopathy in alcoholism, particularly those in which muscle cramps are absent.


Motor performance after unilateral hemisphere damage in patients with tumor.

Hemispheric asymmetry of sensory-motor control has been hypothesized on the basis of clinical and experimental data, but discrepant data indicate asymmetry may vary with task requirements. To examine this possibility, the performance of normal controls and patients with right or left hemispheric tumors were compared on a variety of motor tasks of varying complexity. Group differences were significant only for the two most complex of six tasks; since these two tasks differ in quality (proximal steadiness and distal dexterity), it is unlikely that quality differences are crucial. On these tasks, the group with left hemisphere damage demonstrated bilateral impairment while the right hemisphere group's deficits were contralateral to lesion site. These results support previous data and Liepmann's hypothesis of hemispheric asymmetry of sensory-motor control. Task complexity and the more specific hypothesis of sensory-motor sequencing are important factors influencing hemispheric asymmetry of control.


Neonatal meningitis. The ventricle as a bacterial reservoir.

We reviewed autopsies of neonates who had died of meningitis. Plexitis and ventricular exudate were usually present. While the pathogenetic relationship between these two phenomena is uncertain, it is possible that the glycogen-rich choroid plexus of the lateral ventricles not only facilitates local bacterial growth but also acts as a bacterial reservoir relatively resistant to antimicrobial agents. We suggest that more drastic approaches than parenteral antimicrobial therapy may be indicated to reduce further the morbidity and mortality of neonatal meningitis.


Guillain-Barré syndrome with hydrocephalus in early infancy.

Guillain-Barré syndrome (GBS) is a self-limited and uncommon acquired neurologic syndrome in childhood. It is not thought of as a problem of infancy and is not always included in the differential diagnosis of the floppy infant. This case report describes GBS ina 1-month-old infant. In addition this infant developed hydrocephalus concurrent with the appareance of high CSF protein levels. This patient is described to demonstrate that GBS can occur at all ages and that hydrocephalus may occur particularly when the CSF protein is at an unusually high level.


Perinatal intracranial hemorrhage. Incidence and clinical features.

Birth and perinatal records from all medical facilities serving the Rochester, Minn population from 1965 through 1974 were reviewed for cases of intracranial hemorrhage. Among a total of 10,850 live births, 12 documented cases of hemorrhage were found, yielding an average rate of occurrence of 1.1/1,000 live births. To investigate the role of some 30 potential risk factors, a case-control study was undertaken. Only prematurity and respiratory distress syndrome (RDS) were significantly associated with intracranial hemorrhage. This study demonstrates that neonatal intracranial hemorrhage is relatively common, associated with prematurity and RDS, difficult to recognize clinically, and characterized by poor prognosis.


Vertebral artery occlusion complicating yoga exercises.

Vertebral artery occlusion developed in a young adult shortly after he had performed neck manipulations during yoga movements. Yoga exercises are a rare cause of acute medullary or cerebellar infarction.


Facial myokymia in the Guillain-Barré syndrome.

Facial myokymia, a unique involuntary movement of facial muscles, is described in a patient with Guillain-Barré syndrome. Although this involuntary movement is most often described with intramedullary lesions of the brain stem, it may also appear with lesions external to the neuraxis. We review the literature and propose a more widespread distribution of potential lesions along the facial nerve pathway, which may produce facial myokymia.


Paroxysmal atrial tachycardia and frontal lobe tumor.

We describe a patient who experienced repeated episodes of paroxysmal atrial tachycardia. He was found to have an epileptogenic focus within the right frontal lobe adjacent to a frontal lobe glioma. Subsequent to excision of the tumor, no further attacks have occurred.


Tonography and projection perimetry. Relationship according to receiver operating characteristic curves.

Previous large scale tonographic studies revealed a significant overlap of coefficient of outflow (C) values for normal and glaucomatous eyes, but their differential diagnosis rested primarily on tangent screen visual field tests. To determine whether projection perimetry would make a difference in the correlation of outflow coefficients with glaucoma, 434 eyes from normal, ocular hypertensive (those without scotomas but with elevated intraocular pressure) and glaucomatous categories were evaluated. Results support the conclusions of earlier work concerning C value overlap and demonstrate the relatively better specificity of the initial intraocular pressure over one coefficient of outflow (Po/C) in distinguishing normal from glaucomatous eyes. It also shows that ocular hypertensives as a group are no different from glaucoma patients with regard to their aqueous outflow. Tonographic tests are, therefore, useful in identifying those eyes that need to be watched closely for the development of glaucomatous change.


Corneal endothelial changes with long-term topical epinephrine therapy.

Corneal thicknesses and endothelial cell densities were studied in nine patients with ocular hypertension receiving long-term unilateral topical epinephrine hydrochloride therapy. No difference was noted in corneal thickness in the treated eyes. There was a significant (P less than .02) reduction in endothelial cell count in the treated eyes compared to their untreated fellow controls. Those patients who had the most marked intraocular pressure response to epinephrine also had the greatest endothelial cell loss.


The visual field of low tension glaucoma and shock-induced optic neuropathy.

The visual fields of patients with shock-induced optic neuropathy with excavation, low tension glaucoma, and chronic simple glaucoma were analyzed. True altitudinal defects are seldom found. The three disease states showed identical field defects. Subtle defects can occur in all three disease states. The preponderance of defects occurred in the upper field. There are obvious differences from ischemic optic neuropathy.


Ocular manifestations of toxic epidermal necrolysis associated with allopurinol use.

A 54-year-old man was receiving allopurinol therapy to treat hyperuricemia that followed an inferior wall, myocardial infarction. After three weeks of allopurinol therapy, the patient developed signs and symptoms of toxic epidermal necrolysis that included pseudomembranous conjunctivitis with ulcerative lesions on the lids and conjunctiva, and punctate corneal staining with subsequent corneal abrasions. Treatment with topical antibiotics and artificial tears relieved the symptoms somewhat, but punctate staining and dry eyes persisted after 14 months of follow-up. Bilateral corneal ulcers developed and necessitated conjunctival flaps in each eye. Visual acuity in each eye was 20/40.


A computerized glaucoma data base.

The MISAR data base system was modified for ophthalmic use. Approximately 1,165 subject records from the Glaucoma Center of Washington University were entered into this computerized registry. The system has provided a compact, accurate, and well-organized storage of medical data. Searches of the registry for specific diagnoses or for subjects who meet specific criteria have aided the performance of clinical research.


Clonidine. Effects of a topically administered solution on intraocular pressure and blood pressure in open-angle glaucoma.

A double-blind crossover study to determine the effects on intraocular pressure (IOP) and blood pressure of topically instilled 0.125% and 0.25% solutions of clonidine hydrochloride by comparison with a 2% pilocarpine hydrochloride solution and placebo was carried out in a total of 21 patients with open-angle glaucoma, each of whom received a single drop of each preparation in the same glaucomatous eye on separate days. Both clonidine solutions were effective in lowering the IOP; the 0.25% solution was more effective than the 0.125% solution, and the former was slightly less potent than pilocarpine. Pupil diameter was essentially unchanged in all but one of the patients after clonidine. Pilocarpine reduced pupil diameter in all patients. One eye treated with placebo also showed a reduction in pupil size. Both systolic and diastolic blood pressure showed a statistically significant reduction after clonidine, but the magnitude of the change was small. We do not regard the minor blood pressure changes as being a threat to the optic nerve but further studies in this aspect of topical clonidine therapy are required.


Trabeculectomy and the progression of glaucomatous visual field loss.

Twenty-four eyes of 20 patients with chronic open angle glaucoma who had a trabeculectomy were studied retrospectively. Trabeculectomy resulted in a significant lowering of mean intraocular pressures and improvement of pressure control for the group. Progression of visual field defects occurred in all 24 eyes preoperatively, while postoperatively, the fields of 14 eyes showed no change, but the other ten showed further progression. A comparison of the pressures of the eyes showing continued progression after surgery with the eyes showing no further progression revealed no significant difference in the mean preoperative or postoperative pressure or the mean pressure reduction after surgery. Measurements of the quality of the control, however, showed that the quality of pressure control was significantly better in the eyes that did not show progression of field loss postoperatively. Careful postoperative follow-up observation of the visual field remains necessary even after successful surgical pressure reduction.


Carbonic anhydrase inhibitor side effects. Serum chemical analysis.

Multiple serum chemical values were examined in 92 patients with chronic glaucoma who were treated with the carbonic anhydrase inhibitors (CAIs) acetazolamide or methazolamide, seeking relationships between serum composition and symptomatic side effects. Of the 92 patients, 44 complained of a symptom-complex of malaise, fatigue, weight loss, depression, anorexia, and loss of libido, which we have found most commonly to threaten continuation of therapy. Patients who had this symptom complex were significantly more acidotic than those without it. Ten of 24 patients who had chemical evidence of excessive acidosis reported a dramatic alleviation of symptoms when sodium bicarbonate was administered, although their serum CO2-combining power changed little. There was no correlation of the symptom complex with serum potassium concentration, except in a few patients who were simultaneously receiving chlorothiazide diuretics for systemic hypertension and who became frankly hypokalemic.


Regression of orbital hemangioma detected by echography.

Two infants had orbital cavernous hemangioma that showed impressive regression documented by ultrasound follow-up. In a 15-week-old infant the hemangioma regressed from a size of 11.49 mm to 5.36 mm in prominence during a six-month period. In a 9-month-old infant the mass regressed from 8.53 mm to 4.6 mm during a six-month period. These cases demonstrate that orbital cavernous hemangioma in infancy occasionally shows impressive regression. Furthermore, they illustrate the value of orbital ultrasonography in defining the natural history of orbital hemangioma. Similar follow-up studies in large numbers of infants with orbital hemangioma are needed to further our understanding of the natural history of this tumor.


Echography and histological studies in various eye conditions.

A correlation between A-scan echograms recorded clinically in vivo and histological studies of corresponding sections has been made in 42 eyes with intraocular pathological conditions. This study yielded both new and little known acoustic differential criteria for the diagnosis of retinoschisis, funnel-shaped vitreous detachments, serous as well as hemorrhagic retinal and choroidal detachments, intravitreal hemorrhages, and intraocular tumors.


The ocular tilt reaction. A paroxysmal dyskinesia associated with elliptical nystagmus.

The ocular tilt reaction, a synkinesis of ocular torsion, skew deviation, and head tilting, was a paroxysmal disorder in a patient with multiple sclerosis. In this distinctive pattern of eye and head motion, the 12 o'clock corneal meridians of both eyes are rotated conjugately in the direction of the lower skewed eye and the head is inclined laterally in the same direction. Paroxysmal activation of brain stem otolithic vestibular projections is proposed responsible for the dyskinesia. Coincident attacks of vertical and horizontal low amplitude pendular oscillation of the eyes produced elliptical nystagmus. This ocular motor disorder was treated effectively with carbamazepine.


Normal saccadic structure of voluntary nystagmus.

Infrared oculographic recordings in three cases showed that voluntary nystagmus is composed of rapidly alternating small-amplitude saccades with normal velocity-amplitude characteristics. These bursts of reciprocating saccades are routinely associated with oscillopsia. This means in terms of oculomotor control theory that the brain stem mechanism mediating voluntary nystagmus must bypass the level in the oculomotor path where the saccadic corollary discharge (efferent copy) is initiated.


Swimmer's goggles for keratoconjunctivitis sicca.

Swim goggles with a moist chamber effect have been used successfully in seven patients with severe keratoconjunctivitis sicca unresponsive to the conventional means of therapy including artificial tears, mucolytics, and occlusion of the puncta. The longest follow-up is three years, the shortest six months. There have been no complications, and in all cases the patients have been subjectively and objectively improved.


Conjunctival transplantation.

A method to transplant healthy conjunctiva onto eyes with damaged ocular surface epithelium and superficial vascularization, as are often seen after chemical or thermal burns is described. Conjunctival resection and lamellar keratectomy were followed by grafting of healthy conjunctival patches. In three of five eyes with total corneal involvement, successful reepithelialization of the cornea from the conjunctiva was accompanied by improved vision and decreased vascularization. Results in two other eyes were less successful due to deep stromal vascularization.


The levator aponeurosis. Attachments and their clinical significance.

A detailed knowledge of the anatomy of the levator aponeurosis is required for the aponeurotic approach to ptosis. Yet, many misconceptions regarding the insertional attachments of this important structure are found in the literature. The levator aponeurosis inserts via a fan of fibers. The first insertional attachment curves anteriorly around the orbital septum to form the lid crease. Approximately the anterior half of the aponeurosis inserts into pretarsal orbicularis and the overlying subcutaneous tissue. The remaining posterior half inserts firmly on the lower portion of the tarsus.


Experimental hyphema clearance in rabbits. Drug trials with 1% atropine and 2% and 4% pilocarpine.

The effect of topical 1% atropine sulfate, 2% pilocarpine hydrochloride, and 4% pilocarpine hydrochloride on the clearance rate of RBCs labeled with chromium 51 (51Cr) that were injected into the anterior chamber of rabbits was determined by monitoring sequential radioactivity counts. Counts were made directly over the anterior chamber. One eye of each animal was treated with either 1% atropine, 2% pilocarpine, or 4% pilocarpine, and the other eye served as a control. None of these drugs significantly altered the clearance rate of 51Cr-labeled RBCs injected into the anterior chamber.


[Present situation of hinge-type artificial knee joints (author's transl)].

The introduction explains the general problems of knee joint replacement by artificial hinge-type prostheses, due to the reduction of the physiological "degrees of freedom" to only rotational movements around a horizontal axis. These problems are compared with the advantages of this type of prosthesis. Subsequently a description of some significant constructional characteristics of the hinge-type prosthesis, 13 given as there are placement of the joint, size of the contact surface, safety of the rotational device, design of the hinge-mechanism, the patella shield and the prosthetic stems as well as the breaking of dynamic forces, which all are subsequently compared in their values. Finally a hinge-type prosthesis is described with characteristics judged optimal according to our present scientific knowledge. We statistically evaluated our material of hinge-type prostheses with regard to final results and frequency of serious complications.


[Results of animal experiments with an implantable femur distractor for operative leg lengthening (author's transl)].

A new femur distractor for operative leg lengthening has been developed. The new instrument consists of an electronically controllable distractor set including a power unit and a two-part guide rail. The whole system can be implanted totally and gives rigid fixation throughout the period of distraction. The operations "forward motion", "stop" and "backward motion" can be regulated transcutaneously by radio control. A prototype especially developed for animal experiments has been tested successfully in sheep.


[On the stress state of bone cement fixing a hip joint prosthesis (author's transl)].

Using a simplified model, tests were made to investigate the shear stress distribution at a hip joint prosthesis. A marked increase of stress at the tip of the prosthesis was found through photoelasticity. This peak stress resulted in a safety factor of 3 against exceeding the shear strength of bone cement. Since the calculation of the stress is based on unfavourable assumptions, the actual factor of safety should show a higher value still.


[Fractures of the neck of femur in young children (author's transl)].

The problems of femoral neck fractures in young children are discussed. Results of 12 own cases are reviewed with an average age of the patients of 7.5 years at the time of accident. The average time between accident and last examination was 12 years. The operative technique, pre- and postoperative care, indications for conservative treatment and late complications are discussed. All types of fractures should be treated operatively. K-wire fixation is sufficient in most cases and does not damage the epiphyseal plate. Immobilization in POP spika is advisable for 6 weeks. With delayed operative treatment of intracapsulare fractures the intraarticular haematoma should be aspirated. Traumatic epiphyseolysis should be reduced by manipulation or operatively and stabilized by K-wires. The treatment of pseudarthrosis is by internal fixation and bone grafting. Late valgus and especially varus deformations should be corrected by intertrochanteric osteotomy.


[Chronic fibular instability of the ankle-joint -- x-ray diagnostic and ligamentous graft (author's transl)].

It was tried to find out how many radiographs are necessary to show instabilities of the ankle-joint with ruptures of the ligamentum talofibulare anterius alone (which is the most common ligamentous lesion) and in combination with other fibular ligaments. Therefore stress views of anatomical speciems of ankle-joints with previous artifically coused lesions were done. It was found that one lateral view with the talus stressed in subluxation and one a.p. view with stressed pes equinus and supination with slight internal rotation of the foot are enough in comparison with the other side. The mostly used plastic reconstructions of old fibular ligament teares by Watson-Jones and Evans act as a tenodesis for the subtalar joint, because the natural anatomical position of the ligamentum calcaneofibulare, which should be replaced, is not respected. We looked for the best positioning of a graft as a replacement of the ligamentum calcaneofibulare by help of a string model in anatomical speciems. Only the straight graft of this ligament gives the best chance of free mobility in the subtalar joint. Other directions of this ligamentous graft lead either to a tenodesis or to an outwear of the graft without a stabilizing effect. Postoperative examinations of nine patients with ligamentous grafts stress this point.


[Electromyographic investigations about operative and conservative treatment after rupture of the long tendon of m. biceps brachii (author's transl)].

After conservative respectively operative treatment of two exactly comparable patients who suffered from rupture of the long head of the biceps tendon of the arm, the myoelectric activity of both muscle heads was investigated on the injured arm and compared to the uninjured side. There was a significant diminution of activity in the ruptured long head as well as a reactive hyperactivity in the short head after conservative treatment in contrast to the operative treated patient, where these alterations in muscle activity were less marked. The operative treatment therefore shows a better functional result when compared with the conservatively treated rupture.


[Results of surgical correction of valgus deformity in childhood (author's transl)].

After surgical correction of valgus deformity in childhood by varus-rotations-osteotomy an increased incidence of recurrence of valgus is reported. The present analysis was performed to defind the indication for varus-rotations-osteotomy. 152 cases with operated hip joints were reviewed with regard to the clinical and radiological development. We found out that "postoperative insufficiency of the gluteal muscles = pathological revalgisation" does not induce revalgisation as postulated by other authors. Also discharging limping of the hip joint does not cause revalgisation. Postsurgical insuffiency of adductor muscles is not an obligatory but a potential cause for development of pathological revalgisation. And there is not correlation between the less frequent recurrence of anteversion and the pathological revalgisation, also there could not be found a correlation to lesions of the a trochanteric epiphysis due to the operation, or to the time of metal removing. According to our results the complication rate of recurrence of valgus becomes less frequent by age corresponding alteration of the CCD angle, even when it cannot be prevented.


[Results of the Ender-nailing method in Austria. With special reference to the cases of the Lorenz-Böhler-Hospital (author's transl)].

The problems of the method are briefly analyzed by the early results of together 2137 patients, who were operated in 10 different traumatological departments or accident-hospitals and by the late results of 109 patients, who were followed up in the Lorenz-Böhler-Hospital. The advantages of the Ender-method are: 1. relatively minimal operative stress to the patients (there are nearly no contraindications); 2. the low infection rate of 1.9%; 3. the favorable mechanical principle of these osteosynthesis, so that in 2137 there was no case with broken nails and no case with nonunion. 4. Rotational stability is better, than by Küntscher's trochanteric nail, because of the diverging tips of the nails in the head of the femur. Furthermore the insertion of the Ender nails does not injure the medial collateral ligament of the knee. 5. External rotation failures of the femur can be avoided by bending the nails in a second plane corresponding to the antetorsion angle of the collum femoris.


[Experience on Guepar-hinge-prosthesis (author's transl)].

Total replacement of the knee joint by the G.U.E.P.A.R. hinge prosthesis has been performed in 72 patients suffering from severe gonarthrosis combined with ligamentous instability. Follow-up examination over a period of 1/2-5 years were made in 65 cases considering pre- and postoperative findings (pain, range of motion, ability to walk). This paper reports on problems of joint replacement surgery especially on details of operative technique to restore free gliding of the patella and muscular force as well. The G.U.E.P.A.R hinge posthesis has given good or excellent results in the great majority of cases.


Benign osteoblastoma: quantitative histological distinction from osteoid osteoma.

The author performed on 10 cases of benign osteoblastoma and osteoid osteoma a comparative quantitative histological analysis using an optical line-mesh grid for sampling. Tissue components under the line crossing were counted five hundred times in every case making a total of five thousand counts for each group. It was demonstrated that 1. in osteoblastoma the amount of stroma is roughly by 10 per cent elevated and the amount of osteoid about 10 per cent less in comparison with osteoid osteoma. 2. As far as the osteoblast lining, capillaries and giant cells are concerned, there is no basic numerical difference between the two lesions. Experiences gained by qualitative histological comparison are also described. His results are favouring the concept of benign osteoblastoma as an entity with true tumour nature.


[Osteotomies of the forearm in the treatment of ulnar dysmelia (author's transl)].

The syndrome and classification of ulnadysmelia--which shows considerable analogy to fibuladysmelia--is described on the basis of two cases. The therapy of the milder form of this deformation which includes our two patients is discussed. Correction osteotomy of the bones of both forearms with excision of the radial head is recommended for inveterate cases. In younger children, a result which is both cosmetically and functionally successful can be achieved by lenghtening osteotomy of the ulna. The operation is to be repeated if necessary.


[Osteosynthesis with hinge joints and methylmethacrylate (author's transl)].

Six cases have been described where an osteosynthesis was performed using the stem of a hinge knee joint in combination with methylmethacrylate and other osteosynthetic devices (screws, wires). Need for an osteosynthesis existed because of pseudarthrosis after supracondylar and high tibial osteotomies, intraoperative fracture for implantation of a total knee, reimplantation after deep infection, and fatigue fracture after a total knee. The advantage of the procedure lies in early mobilisation and weight bearing. We do not believe in reimplantation after an infected prosthesis. Instead, we recommend fusion after implant removal.


[Standardization of implants shown by "bone-screws" (author's transl)].

The increasing use of orthopaedic implants makes international efforts of standardization with their objectives unification and benefit of the patient necessary and sufficient. In 1975 an ISO-Draft for "bone-screws" has been finished. To get experimental data there was a test series of breaking bone-screws of five producers by torsional stress. Comparable screws showed considerable differences. The control of conformity to standards gave partially distinct differences to the standard profile and different hardness values, what affects to the screws' security of twisting off.


[The force flow in hip joint-endoprostheses (author's transl)].

The mechanical force flow distribution produced by the hip joint endoprosthesis in the remaining, living femur and its deviation from that of the natural bone have a considerable influence on the quality of the bone-endoprosthesis compound and its duration of life. The loads are calculated for the natural bone as the reference system as well as the compound with conventional endoprostheses and a new type, the Tension-band-Endoprosthesis (R-G). For the calculation the finite element method is used by application of three-dimensional tetrahedron elements. It becomes apparent that in the case of the R-G-Endoprosthesis the induced stresses within the medial range of the remaining bone are far less unphysiological than in the case of the conventional endoprosthesis.


[Human joint capsule in osteoarthrosis (morpholocical changes) (author's transl)].

Morphological investigations of the joint capsules in osteoarthrotic-changed joints have given rise to doubts about the present theory of the causal aetiology of the osteoarthrosis. In every inspected and demonstrated illustration beside the partly normal capsules segments could be found every transition between mild regressive alterations and most massive proliferative changes of the conective tissue and the lining cell layer. It was extraordinary, that the strongly dilated vessels were filled with red blood cells. In another part of the same case was found a massive stricture caused by concentrically deposited substances, which were impregnated with collagenous fibers. Regeneration of the vessels frequently happened adjacent totally obstructed ones. Round-cell infiltrations, granulocytes or other indications of an inflammatory synovitis are found only in a few cases. The intracartilaginous enzymatic reactions, which have been much talked of and which were explained as characteristic of the osteoarthrosis cannot be the cause of the degradation of the cartilage, particularly, because of the normal cell count which is to be found in the synovial fluid. We can answer this problem, if we can prove that the substrates of the chondral metabolism themselves exert a direct or indirect influence on the interstitial connective tissue with induction of the powerful proliferation of the same tissue. The changes in the transit zone would be secondary and their effect on the lining cell layer would increase the progression of the arthrotic events.


Meitens' syndrome.

This paper reports on Mietens' syndrome which is characterized by mental retardation, growth failure, flexion contracture of the elbows, dislocation of the radius, abnormally short ulna and radius, bilateral corneal opacity, horizontal and rotational nystagmus, strabismus and a small pointed nose with depressed root. This is the second on the Mietens' syndrome.


[Measurements of stability of operative osteosynthesis on the proximal femur (author's transl)].

Bending burdening of stable and unstable per- and subtrochanteral fractures after osteosynthesis with Y-nails (Küntscher), Ender-nails, 130 degrees and 95 degrees angled plates of the AO were tested in a comparative experimental study. The unstable fractures were also tested after treatment with osteosynthesis and additional application of bone cement in the artificial defect. The essential results were as follows: in the group of stable pertrochanteral fractures the Ender-nails bear in the mean 147 kp, the 130 degrees angle plate 200 kp. In the fracture-group with lacking medial support a highly burdening osteosynthesis could only be achieved by filling up the defects with bone cement. The 95 degrees-angled plate-osteosynthesis combined with bone cement bearing more than 300 kp was superior to the other procedures in the unstable per- and subtrochanteral fractures. In our investigation the stabilizing forces of muscles and fascia have not been taken into consideration.


Estimations of body composition by various methods.

Body composition was measured in 38 young men all of whom were overweight by standard height-weight tables. The techniques used were body volumetry, determination of total body water by tritium dilution, whole body 40K counting, and anthropometric measurements required for an equation by Wright and Wilmore, the biceps-height formula, and a complex anthropometric model. Body volumeter and total body water dilution results agreed closely. 40K counts gave lower means for the lean mass (higher means for fat mass and percent body fat), while the Wright-Wilmore equation and complex anthropometric model gave high mean values for lean mass (low means for fat mass and percent body fat). Among the five methods correlation coefficients ranged from 0.81 to 0.94 for lean body mass, from 0.74 to 0.89 for fat mass, and from 0.60 to 0.86 for percent body fat. Although all subjects were overweight, only six (16%) were obese.


Alterations in brain electrolytes during acceleration in mice.

Calcium, magnesium, sodium, and potassium levels were determined in brain tissues of mice subjected to gravitational acceleration in the longitudinal direction. Although no significant changes occur in calcium and magnesium levels, potassium levels markedly increase while sodium levels decrease following exposure to 5 and 10 Gz for 5 min. The electrolyte changes are of long duration and remain for periods greater than 5 h.


Behavioral analyses of killifish exposed to weightlessness in the Apollo-Soyuz test project.

Two groups of killifish, Fundulus heteroclitus, which were flown aboard Apollo-Soyuz, were subjected to postflight behavioral testing. The first group examined consisted of a graded series of embryos representing key developmental stages at orbital insertion (32-h, 66-h, and 128-h stages; pre-liftoff fertilization times). The tests revealed that the young adults from the flight 32-h stage had a significantly decreased positive geotaxis and increased negative phototaxis when compared with ground controls. These findings suggested a greater sensitization of the least-developed flight stage to post-hatching environmental influences. The second group consisted of 21-d old juveniles which were subjected to light orientation tests soon after recovery. No significant differences were detected.


Ten-year survey of altitude chamber reactions using the FAA training chamber flight profiles.

The Federal Aviation Administration since 1962 has trained nonmilitary government-employed flightcrews and civilian pilots in aspects of altitude and its effects on the human body. The standard military altitude chamber flight profile was not used and the reasons are explained. Two different chamber profiles were used for a 10-year period and both included a rapid decompression, but the altitudes attained were limited to 25,000 ft (7,620 m) and 29,000 ft (8,839 m). During the 10-year period cited in this report, 4,759 students were exposed to these altitudes and none experienced an evolved gas problem.


Altitude decompression sickness: hyperbaric therapy results in 145 cases.

Most cases of decompression sickness that occur at altitude resolve upon descent to lower altitudes. Before the use of hyperbaric therapy, cases that did not resolve accounted for some of the most difficult medical management problems in military aerospace medicine. On 27 March, 1941, the U.S. Navy Diving School successfully used hyperbaric therapy for a case of altitude-induced decompression sickness that did not resolve on return to ground level. Since then, over 145 such cases have been treated by hyperbaric therapy. At first, treatments involved using compressed air, with varying success. Current medical management of altitude-induced decompression sickness requires immediate compression to 2.8 ATA, equivalent to 60 ft of sea water (FSW) pressure, and a series of intermittent oxygen and air breathing periods during the subsequent slow decompression to surface. This report confirms the treatment recommendations set forth by Behnke and Downey, and crystallized by Goodman in 1964. Conclusions are based on treatment experience in the management of 120 cases in U.S. Air Force hyperbaric chambers, and a survey of hyperbaric facilities which have treated 25 other cases.


Femur-bending properties as influenced by gravity: II. Ultimate load, moment, and stress for 3-G mice.

Material strength as approximated from bending studies of fresh femurs grew during 1 to 8 weeks of hypergravity at rates which were not measurably affected, even though the animal's body growth was measurably slower. As a result, femurs could support greater ultimate loads, moments, and stresses when compared to control bones of comparable rotational moments of their cross-sectional areas. Chronic centrifugation simulated 3.1 G for 45 male. Swiss Webster mice compared to 37 control animals. Effects were most noticeable after the first week of exposure and for younger animals. Effect were only about 50% that noted in comparable treatment of rats. This suggests that four times more mice than rats may be necessary for space-experiments designed to test the effects of weightlessness.


Selective induction of liver drug-metabolizing enzymes in rats exposed to a 21 ATA He-O2 environment.

The effects of prolonged exposure to a hyperbaric environment (21 ATA He-O2, 200 +/- 300 mm Hg O2, 32.5 +/- 1 degrees C) were investigated on the activity of rat liver drug-metabolizing enzyme systems, as monitored by O-dealkylation and N-dealkylation reactions. Continuous exposure of different groups of rats to a hyperbaric environment for 8, 22, 39, 57, or 84 d significantly increased the in vitro activity of drug-metabolizing enzymes in liver preparations obtained from rats subjected to prolonged exposures. The increase in the in vitro O-dealkylation of p-nitroanisole was selective; and the percent increases were 27, 146, 58, 40, 49, and 44 in liver preparations obtained from rats exposed continuously for 8, 22, 39, 57, 72, or 84 d, respectively. On the other hand, no statistically significant increase was observed in the in vitro activity of rat liver drug-metabolizing enzyme preparations during N-dealkylation of morphine and cocaine.


Naval aviators admitted to a Naval hospital.

This paper discusses the hospitalization of aviators at the Naval Regional Medical Center, San Diego, Ca. The areas covered include cancer, trauma, cardiac cases, alcoholics, and the effect of hospitalization on the flying status of aviators. The variety of diagnoses accumulated in 2 years was suprising. Further follow-up of cardiac cases must be pursued, especially post-coronary artery bypass. Alcoholism as a diagnosis in hospitalized patients may be a larger problem than elicited in this series. Hopefully this paper will not be just a statistical study. We should think of prevention and care to decrease the number of aviators who have their wings clipped due to medical problems.


Coronary heart disease index based on longitudinal electrocardiography.

A coronary heart disease index was developed from longitudinal ECG (LCG) tracings to serve as a cardiac health measure in studies of working and, essentially, asymptomatic populations, such as pilots and executives. For a given subject, the index consisted of a composite score based on the presence of LCG aberrations and weighted values previously assigned to them. The index was validated by correlating it with the known presence or absence of CHD as determined by a complete physical examination, including treadmill, resting ECG, and risk factor information. The validating sample consisted of 111 subjects drawn by a stratified-random procedure from 5000 available case histories. The CHD index was found to be significantly more valid as a sole indicator of CHD than the LCG without the use of the index. The index consistently produced higher validity coefficients in identifying CHD than did treadmill testing, resting ECG, or risk factor analysis.


Post-mortem blood alcohol in general aviation pilots.

Blood alcohol concentrations are reviewed from a series of 250 consecutive fatal accidents, involving 259 pilots, for the years 1962 through 1975. BACs were obtained in 150 of 213 fatally injured pilots whose bodies were recovered. Positive BACs were 18% of total estimations. Impairment by alcohol was probably a factor in about 9% of accidents in which valid BACs were obtained. These percentages are not significantly different from lumped U.S. data. Comparison with fatal accidents in other modes of personal transportation shows alcohol plays a part in the following descending order: cars in single-vehicle accidents, all cars, motorcycles, general aviation aircraft.


The significance of the hairpin counter-current principle in the pathogenesis of toxic kidney lesions. An investigation of the influence of antidiuretic hormone and papaverine on hydroxyquinoline nephropathy of the rat.

The influence of antidiuretic hormone (ADH) and papaverine on hydroxyquinoline-induced nephropathy in rats was tested, using histotopochemistry, enzyme activity measurement and morphometric investigation. Hydroxyquinoline causes a marked increase in renal weight, the development of wedge-shaped foci with severely dilated tubule segments, and a simultaneous reduction in dehydrogenases, alkaline phosphatase, and alpha-naphthyl esterase. Both ADH and papaverine produced a significant inhibition of renal damage. The subjective findings were quantitatively confirmed by measurement of enzyme activity, using the microscope photometer, and by morphometric studies with the Leitz-Classimat (determination on the basis of the alkaline phosphatase reaction) of the surface percentage of brush border in the proximal tubules. A disturbance of the hairpin counter-current system is to be considered as the cause of the renal lesion. This disturbance is caused by hydroxyquinoline-induced impairment of Na+/K+ transport, especially in the thick ascending limb of Henle's loop. Our results show that the hydroxyquinoline nephropathy can be favourably influenced both by stimulation of water re-absorption and possibly also transepithelial Na+ transport (ADH), and by increasing the blood flow of the arteriolae rectae with a resultant lowering of the intratubular urine concentration (papaverine). The dependency of hydroxyquinoline nephropathy on the phylogenetically determined concentration capacity of the kidney, and the effective influencing of the condition by ADH and papaverine indicate the importance of the degree of efficiency of the medullary countercurrent system in the pathogenesis of this renal lesion.


Fresh, dried, and sterilized manure of chicks, sheep, and cattle as feedstuff for growing chicks.

The ration of growing chicks was supplemented by chick, sheep, and cattle excreta in fresh, dried (45-50 degrees C) and sterilized (90 degrees C, 30 mins.) form with 4%, compared with a control ration. The development of the live weight was better in all supplemented ration groups than in the control group. It decreased in this order: fresh - dried - sterilized - (control). Chick excreta were most favourable, least favourable were those of cattle. Feed conversion (food consumption/unit live weight (increase) showed the same trend as the development of the live weight, the rations with fresh excreta being most favourable. 10 data are presented from the results of slaughtering. Slaughtering results were between 70 and 76%, and gave most favourable values in supplementation with fresh excreta and dried excreta from chicks and sheep. A marked influence was found on the length of the intestine (cm/100 g live weight). The mortality rate varied between 0 and 5% in the groups; it was 5% in the control group.


3-O-methyl sugars as constituents of glycoproteins. Identification of 3-O-methylgalactose and 3-O-methylmannose in pulmonate gastropod haemocyanins.

In addition to the already knownonosaccharides fucose, xylose, mannose, galactose, glucose, N-acetylgalactosamine and N-acetylglucosamine, the carbohydrate part of the haemocyanin from Helix pomatia (Roman snail) contains 3-O-methylgalactose, and that from Lymnaea stagnalis (a freshwater snail) 3-O-methylgalactose and 3-O-methylmannose. The 3-O-methyl sugars were identified by g.l.c.-mas spectrometry of the corresponding trimethylsilyl methyl glycosides and the alditol acetates, and by co-chromatography with the synthetic reference substances.


The covalent linkage of protein to carbohydrate in the extracellular protein-polysaccharide from the red alga Porphyridium cruentum.

The extracellular anionic polysaccharide isolated from cultures of a unicellular red alga, Porphyridium cruentum, contains a small amount of protein after extensive purification. The polysaccharide and protein are recovered in the same fraction after isopycnic CsCl-density-gradient centrifugation in 4M-guanidinium chloride, under conditions designed to separate proteins from polysaccharide. The peptide portion of the protein-polysaccharide is released from the polysaccharide by alkali under conditions for beta-elimination. The released peptide is non-diffusible, but in can be separated from the polysaccharide by precipitation of the polysaccharide as the cetylpyridinium complex. Under conditions for beta-elimination of certain O-glycosidic carbohydrate-protein linkages, selective destruction of serine and threonine occurs. The addition of a reducing agent to the alkali mixture produces a selective increase in alanine and alpha-aminobutyric acid. Addition of a tritiated reducing agent to the alkali mixture produces radioactive alanine and alpha-aminobutyric acid, and xylitol as the only sugar alcohol. Similar results are obtained from glycopeptides isolated from partial acid hydrolysates. A macromolecular structure of the protein-polysaccharide is suggested by a comparison of the intrinsic viscosity of material before and after treatment with alkali and proteolytic enzymes.


An evaluation of ways of using equilibrium dialysis to quantify the binding of ligand to macromolecule.

1. The effect of systematic error (loss of ligand, complex or macromolecule) on three of the experimental designs by which equilibrium dialysis may be used to quantify the interaction of ligand and macromolecule is examined theoretically, and the design that is least sensitive to systematic error is identified. 2. Thirteen methods for fitting the binding isotherm to experimental data are compared by using them to analyse simulated data containing random error, and the most reliable method is identified.


Characterization of the extracellular haemoglobins of Artemia salina.

The following factors were measured for extracellular haemoglobins of Artemia salina: a minimal molecular weight of globin chain per haem group (based on the iron and haem contents), the absorption coefficients, the absorption spectra of various derivatives and the amino acid compositions. These were compared with those of the haemoglobins of other invertebrates. Three Artemia haemoglobins (I, II and III) had similar molecular structures, constructed from two-globin subunits of 122000-130000mol.wt. Since the minimal mol.wt. was determined to be 18000, this suggests that one globin subunit was bound by seven haem groups, and hence one haemoglobin molecule (240000-260000mol.wt.) should contain 14 haem groups. A successful identification of this high-molecular-weight subunit required first the denaturation of haemoglobin in 1% sodium dodecyl sulphate before sodium dodecyl sulphate gel electrophoresis. Denaturation by prolonged incubation (12-36 h) at room temperature in the presence of 0.1% sodium dodecyl sulphate [Bowen, Moise, Waring & Poon (1976) Comp. Biochem. Physiol. B55, 99-103] was accompanied by extensive proteolysis, resulting in low recovery of the stainable protein and heterogeneous gel patterns. Regardless of which electrophoretic system was used, the high-molecular-weight subunit was always present provided that 1% sodium dodecyl sulphate was present during denaturation. These results contrast with those obtained by Bowen et al. (1976). However, preferential cleavage of the globin subunit (alpha) seemed to occur in vitro when standard conditions were used, producing two specific fragments having mol.wts. of 80000 (beta) and 50000 (gamma).


Affinity chromatography and inhibition of chorismate mutase-prephenate dehydrogenase by derivatives of phenylalanine and tyrosine.

Several derivatives of phenylalanine and tyrosine were prepared and tested for inhibition of chorismate mutase-prephenate dehydrogenase (EC 1.3.1.12) from Escherichia coli K12 (strain JP 232). The best inhibitors were N-toluene-p-sulphonyl-L-phenylalanine, N-benzenesulphonyl-L-phenylalanine and N-benzloxycarbonyl-L-phenylalanine. Consequently two compounds, N-toluene-sulphonyl-L-p-aminophenylalanine and N-p-aminobenzenesulphonyl-L-phenylalanine, were synthesized for coupling to CNBr-activated Sepharose-4B. The N-toluene-p-sulphonyl-L-p-aminophenylalanine-Sepharose-4B conjugate was shown to bind the enzyme very strongly at pH 7.5. The enzyme was not eluted by various eluents, including 1 M-NaCl, but could be quantitatively recovered by washing with buffer of pH9. Elution was more effective in the presence of 10 mM-1-adamantaneacetic acid, a competitive inhibitor of the enzyme. This affinity-chromatography procedure results in a high degree of purification of the enzyme and can be used to prepare the enzyme in a one-step procedure from the bacterial crude extract. Such a procedure may therefore prove useful in studying this enzyme in a state that closely resembles that in vivo.


Oxidation of human haemoglobin by copper. Mechanism and suggested role of the thiol group of residue beta-93.

Addition of Cu(II) ions to human oxyhaemoglobin caused the rapid oxidation of the haem groups of the beta-chain. Oxidation required binding of Cu(II) to sites involving the thiol group of beta-93 residues and was prevented when these groups were blocked with iodoacetamide or N-ethylmaleimide. Equilibrium-dialysis studies showed three pairs of binding sites, two pairs with high affinity for Cu(II) and one pair with lower affinity. It was the second pair of high-affinity sites that were blocked with iodoacetamide and were involved in haem oxidation. Cu(II) oxidized deoxyhaemoglobin at least ten times as fast as oxyhaemoglobin, and analysis of rates suggested that binding rather than electron transfer was the rate-determining step. No thiol-group oxidation to disulphides occurred during the period of haem oxidation, although it did occur subsequently in the presence of oxygen, or when Cu(II) was added to methaemoglobin. It is proposed that thiol oxidation did not occur because there exists a pathway of electron transfer between the haem group and copper bound to the beta-93 thiol groups. The route for this electron transfer is discussed, as well as the implications as to the function of the beta-93 cysteine in the haemoglobin molecule.


A carbohydrate-deficient membrane glycoprotein in human erythrocytes of phenotype S-s-.

1. We investigated the membranes of human erythrocytes which completely lack the blood-group antigens S and s (denoted as S-s-) as part of a study of the structure and function of the surface glycoproteins of the human erythrocyte. 2. The S-s-erythrocyte-membrane glycoprotein PAS-3 band was much less intensely stained in comparison with that of the glycoprotein from normal erythrocyte membranes. The S-s-membrane glycoprotein PAS-4 band also showed decreased staining. 3. Examination with the lectins from Maclura aurantiaca (Osage orange) and Arachis hypogaea (groundnut) showed that the PAS-3 glycoprotein of S-s-erythrocyte  membranes lacked the receptors for these lectins that are present on glycoprotein PAS-3 from normal erythrocytes. 4. Radioiodination with lactoperoxidase showed the presence of the polypeptide of glycoprotein PAS-3 in S-s-cells, although it was more weakly labelled than the protein in the normal erythrocyte. 5. Our results show that the PAS-3 glycoprotein of S-s-erythrocytes is deficient in some of the carbohydrates present in the protein from normal erythrocytes. Glycoprotein PAS-4 of normal erythrocytes is shown to be a complex containing both glycoproteins PAS-1 and PAS-3.


Modification of the kinetic parameters of aldolase on binding to the actin-containing filaments of skeletal muscle.

The kinetic parameters of fructose bisphosphate aldolase (EC 4.1.2.13) were shown to be modified on binding of the enzyme to the actin-containing filaments of skeletal muscle. Although binding to F-actin or F-actin-tropomyosin filaments results in relative minor changes in kinetic properties, binding to F-actin-tropomyosin-troponin filaments produces major alterations in the kinetic parameters, and, in addition, renders them Ca2+-sensitive. These observations may be relevant to an understanding of the function of this enzyme within the muscle fibre.


Estimation of gene reiteration from hybridization kinetics in moderate deoxyribonucleic acid excess.

Theoretical calculations were carried out to clarify how the DNA/RNA or the DNA/cDNA (complementary DNA) ratio in the hybridization reaction mixture affects the kinetics of DNA-RNA or DNA-cDNA reassociation, and theoretical formulae were derived as a function of these ratios. From these formulae, it was found that the DNA/RNA of the DNA/cDNA ratio did not much affect the initial reaction rates of hybridization, but greatly affected the terminal value for the extent of hybrid formation. Therefore the results obtained when one normalizes the experimental data for hydridization and derives the reiteration frequency from a number called the 'half Cot'  (Cot 1/2) are not accurate, especially in the presence of a moderate excess of DNA. A simple method for the estimation of gene reiteration was demonstrated that did not use the half Cot value in the determination. This simple method is useful even if DNA-RNA or DNA/cDNA hybridization are done with a moderate excess of DNA. With mouse myeloma cells as a model system, the gene reiteration of the 28S rRNA cristron was determined.