Conservation of the 5'-terminal nucleotide sequences of ribosomal 18-S RNA in eukaryotes. Differential evolution of large and small ribosomal RNA.

The 5'-terminal nucleotide sequences of ribosomal 18-S and 28-S RNA of seven species of eukaryotes including three mammals, one bird, one amphibian, one echinoderm and one slime mold, were analyzed either by means of terminal phosphorylation of RNA with polynucleotide kinase of by fingerprint analysis of uniformly labeled RNA. The following conclusions were obtained. 1. The 5'-terminal sequences of the 18-S RNA of the mouse, chicken and Dictyostelium discoideum were pUpApCp(Cp,Up)Gp---, suggesting strongly that all the eukaryotes had this same sequence at the 5'-terminus. Preliminary analysis of the 5'-termini of the 18-S RNA from human, rat, Xenopus and sea urchin cells revealed the same pUp(Np)Gp--- type 5'-terminal structure, supporting the above hypothesis. 2. The 5'-terminal sequences of the 28-S RNA of the human, rat, mouse and chicken cells were all pCpGp---, whereas those of the lower animals such as Xenopus, sea urchin and Dictyostelium were different.


Poly(A)-associated RNA from the mitochondrial fraction of the fungus Trichoderma.

Total RNA was extracted from purified mitochondrial and cytoplasmic fractions of germinating conidia of Trichoderma viride and bound to oligo(dT)-cellulose at 22 and 4 degrees C. Under chromatographic conditions which retained very short poly(A) segments (i.e., 4 degrees C), up to 10% of short-term 32PO4-lebeled RNA from the mitochondrial fraction were selectively bound. The poly(A)-associated RNAs from the mitochondrial and cytoplasmic fractions showed the following characteristics. (a) On polyacrylamide gels mitochondrial fraction RNA had a distinctive pattern with a major peak at about 22 S and a smaller one at about 29 S; in contrast, cytoplasmic fraction RNA was heterogenously distributed along the gel. (b) The poly(A) segment released by RNAase digestion of mitochondrial fraction poly(A)-associated RNA migrated on polyacrylamide gels as molecules 20-25-nucleotides long, while that of the cytoplasmic fraction showed an apparent size of 50-60 nucleotides. (c) Mitochondrial fraction RNA bound to oligo(dT)-cellulose in the cold had a guanine + cytosine content of 21% versus 34% for bulk mitochondrial RNA and 48% for cytoplasmic poly(A)-associated RNA; the oligo(dT)-bound RNAs were further identified by their high percentages of adenine residues (46% for the mitochondria and 30% for the cytoplasm). (d) The poly(A)-associated RNA fraction was translated, in vitro, in a cell-free protein-synthesizing system from wheat germ. The products induced by cytoplasmic RNA showed a complex pattern on polyacrylamide gels of many polypeptides ranging in molecular weights from 10000 to 40000. The pattern induced by mitochondrial fraction RNA however, was much simpler, revealing two discrete, main products: a major one at Mr approximately 13000 and a minor one at Mr approximately 20000.


Acute tolerance to barbiturate in the rat.

3 experimental approaches to the quantitation of acute barbiturate tolerance have been compared in the rat. There was no difference between the brain hexobarbitone or barbitone concentration found at the time of loss of righting reflex compared with the concentration found on return of the righting reflex following the period of anaesthesia produced by a single i.p. injection of the drug. However, tolerance was induced by a 7 hr infusion of pentobarbitone which kept rats anaesthetized for approximately 8 hr. Such rats awakened with a significantly higher brain pentobarbitone concentration compared with rats awakening after a single i.p. injection. Repeated i.p. injections of pentobarbitone, sufficient to keep animals anaesthetized for 12 hr, also induced a tolerance to pentobarbitone, as indicated by a reduced sleeping time and higher brain barbiturate concentration on awakening following intracerebroventricularly administered pentobarbitone injected 12 hr after the last i.p. injection. The possible relationship between acute cellular tolerance and physical dependence is discussed.


Postnatal development of dopaminergic and cholinergic catalepsy in the rat.

The cataleptic response to various doses of the dopamine-receptor antagonist spiperone and the cholinergic agonist pilocarpine was investigated in rats of different ages. Spiperone produced catalepsy in rats 1, 5 and 10 days old, and also in adults. Pilocarpine produced catalepsy in 15- and 20-day old rats, as well as in adults, but not in 10-day old animals. These results suggest that dopaminergic neurons involved in catalepsy are already functional in neonates. Cholinergic substrates of catalepsy, on the other hand, appear to reach functional maturity after the second week of life.


The effect of carbon disulphide on the stereotypic effect of dopamine agonists.

Exposure to CS2 increased the intensity of apomorphine-induced stereotypy in male rats without increasing the reaction time. With amphetamine, an indirect agonist of dopamine, exposure to CS2 had a more intensive effect and significantly prolonged the length of reaction.


Inhibition of naloxone-induced withdrawal in morphine dependent mice by 1-trans-delta9-tetrahydrocannabinol.

The effects of various doses of 1-trans-delta9-tetrahydrocannabinol (delta9-THC) on naloxone-induced withdrawal were studied in mice rendered dependent on morphine by the pellet implantation procedure. When administered i.p., 30 min prior to naloxone, delta9-THC, inhibited the naloxone-induced withdrawal jumping response. Two other signs of morphine withdrawal (defecation and rearing behavior) were also suppressed by deltapTHC. It is suggested that delta9-THC or some of its derivatives may have potential use in narcotic detoxification.


Morphine tolerance and physical dependence: influence of cholinergic agonists and antagonists.

The effects of centrally acting agents which alter cholinergic activity were assessed in mice rendered tolerant to and dependent on morphine (M mice) and in naive mice (N mice). In both N and M mice, physostigmine potentiated morphine analgesia slightly, and this action was blocked by atropine and scopolamine. When administered 10 min before naloxone in dependent mice atropine enhanced precipitated withdrawal jumping; when given 30 min before naloxone, atropine produced an inhibition of the response. Physostigmine abd oxotremorine greatly inhibited the jumping response, while echothiophate had no effect. The inhibitory effect of physostigmine on naloxone precipitated withdrawal jumpimg was reversed by atropine and scopolamine but atropine did not alter morphine tolerance and dependence development. Brain acetylcholine (ACh) levels in both N and M mice were increased by physostigmine, the increase being greater in M mice. This increase was blocked by prior administration of atropine or scopolamine. When atropine was administered to M mice 10 min before sacrifice, brain AC-h levels decreased. However, when brain ACh levels were determined 30 min after atropine, no change was found. It was concluded that ACh does not play a major direct role in the development of tolerance and dependence, but that ACh is involved in the manifestations of acute morphine effects and in some of the withdrawal signs in the dependent state.


[Improved procedure for hypophysectomy of the mouse (author's transl)].

A practical procedure for hypophysectomy of the mouse by paraphyaryngeal approach has been developed by modifying the technics of Motizuki [5] and Lostroh and Jordan [4]. Postoperative care in C3H/He strain of female mice was also studied. The main points improved are as follows: (a) The dental drill bar made of a needle with 2mm outer diameter was devised for making a hole in the cranium (Fig. 2). The bar does not grind the cranium, but cuts it in the circle, resulting in speeding up of the operation and in little bleeding, since the hole is very small. (b) Special attention was paid in breathing of mice during the operation. A longitudinal midline incision of about 1cm was made in muscle encircled the trachea and a pinhole was made by sewing needle into the trachea. A small piece of cotton wool was put on the pinhole and covered by the muscle. It admirably keeps the tracheal hole open for breathing during operation (Fig. 1). (c) After the operation, the mouse was placed in a chamber filled with an atmosphere of 95% O2-5%CO2 gas until recovered, otherwise, all mice died in a few days after operation with inflamation of the lung. The temperature of the recovery chamber is recommended to be kept at about 28 degrees C for ensuring the resuscitation. The intraperitoneal injections of hydrocortone-acetate (0.25mg/0.1ml) just before and 2 days after operation further ameriolated the survival rate.


[Efficiency of microbe filtration of air filter for rearing germfree animals (author's transl)].

Filtration efficiency of 3 types of air filter frame and cylinder (Fig. 1) was examined by culture of the air obtained from the operating isolators at intervals of 3 to 21 days. The air of isolator was bubled in 30 ml of nutrient broth for 30 or 120 minutes (4approximately15 l/min.) and each of 1 ml of the broth was inoculated into thioglycollate medium (TGC), cooked meat medium (CMM), heart infustion broth (HIB) and glucose peptone water (GPW). The media were incubated for 7 to 14 days at 30 or 25 degrees C. As seen in Table 1, microbes could be effectively removed through all types of filter for over 10 months, though there were a very few positive cases suggesting technically acidental contamination at sampling.


[Bacteriolgical survey on Bordetella bronchiseptica in various animal species (author's transl)].

Bordetella bronchiseptica was examined on the respiratory tract of mice, rats, Mongolian gerbils, golden hamsters, guinea pigs, rabbits, household dogs and cats and cynomolgus monkeys imported from Asian countries. The organisms were detected in rats, guinea pigs, rabbits, dogs, cats and monkeys, but not in mice, Mongolian gerbils and golden hamsters. In rats, the organisms were isolated from 7 of 25 breeding colonies, and isolation rates ranged from 10.0 to 61.3% by colonies. In guinea pigs, 22 of 60 breeding colonies were positive, showing 6.7 to 58.2% in isolation rates. Two groups of rabbits were examined, one was collected from many non-closed colonies of small size and another was obtained from 3 closed colonies of large size consisting of more than 100 rabbits. Isolation rates were 3.0% in the former and 66.8% in the latter. The organisms were also detected in 5.3% of dogs and 3.2% of cats, respectively. Isolation rate of the organisms in the trachea of 48 healthy monkeys was 6.3%, but in 39 monkeys with pneumonic lesions, 16 (41.0%) harbored the organisms in their lungs.


Animal models of ethanol dependence and liver injury in rats and baboons.

A model has been developed for the administration to rats and baboons of ethanol as part of a nutritionally adequate liquid diet. With this regimen, ethanol intake was much higher than with conventional procedures. All animals gained or maintained their body weight, and liver morphology was normal in the controls. Isocaloric substitution of carbohydrate by ethanol (36% of total calories in rats and 50% in baboons) resulted in the production of fatty liver in all animals, while the baboons also developed alcoholic hepatitis and cirrhosis with increased activities of serum glutamic oxaloacetic transaminase. Inebriation and manifestation of dependence on withdrawal of the diet were observed in baboons and quantitated in the rat. Chemical alterations produced by ethanol at the fatty liver stage were characterized by hyperlipemia, striking triglyceride accumulation in the liver, and enhanced activities of microsomal drug metabolizing enzymes, including the microsomal ethanol oxidizing system (MEOS). In showing that all aspects of liver injury observed in alcoholics can be reproduced in animals by the feeding of pure ethanol with an adequate diet, this study incriminates ethanol itself as a cause for the hepatic complications. This new experimental model is proposed as a tool for the study of the pathogenesis and treatment of alcoholic liver injury and dependence.


Problems in the diagnosis of bovine brucellosis.

In any disease eradication program, it is the unusual animal which assumes the greatest importance. There are no easy formulae for the diagnosis of brucellosis and many problems remain to be solved. A large variety of diagnostic methods has been studied and each has advantages and limitations. Simple agglutination tests will surely remain the basis for examinations of large numbers of sera and they should often be used only for screening. Selected supplemental tests are often necessary to confirm preliminary test findings. Any diagnostic procedure should not fail to correctly identify infected cattle and interpretations of results should not lead to excessive overcondemnation. Serologic methods must always be evaluated through bacteriologic attempts. There is no substitute for expertise to constantly study disease patterns in individual cattle and herds.


The epidemiological situation of brucellosis in Africa.

Brucellosis, as a geomedical literature survey has shown, is spread to a higher of lesser degree of incidence virtually over the whole African continent. Its epidemiological spectrum of host animals is especially rich amongst the domestic and wild animal species. All domestic animal species and 21 of 26 herbivorous and 5 of 12 carnivorous wild animal species screened yielded positive brucella antibody serotitres. Thus self-maintaining natural foci independent of the domestic stock have firmly been established. The mapping of the epidemiological situation must be based on survey data which should have been planned, exactly performed, analyzed and reported according to statistical rules. Unfortunately Africa is especially badly covered in the world literature in the field of brucellosis. Representing itself 32.0% (49/153) of the countries of the world, their Medical and Veterinary Departments contributed only 2.1% of the computerized world literature on brucellosis in the period 1969-74. This picture can be considerably changed by including the non-computerized "grey literature" of Department and Laboratory Annual Reports into the screening process. By introducing objective, mathematical criteria for determining the degree of incidence from the available data, the following results were obtained from the literature survey: brucellosis is known or suspected to exist in 40 of the 49 African countries (82%). In 20 (41%) of these countries it represents a major problem, in 10 (20.4%) a moderate problem in the other 10 countries a minor problem to human health and economy. Following the rule that brucellosis can be expected to exist everywhere in the world (with the exception of a few islands) where cattle, sheep and/or goats are kept unless it has been eliminated by vigourous measures of control, it may be expected that the remaining 9 African countries not yet reporting also harbour this chronic, zoonotic disease. 35 of the 40 countries reporting have found brucellosis regularly, 1 exceptionally among domestic animals, 5 among game animals. Only 17 of these 35 (48.5%) have scheduled the disease, even if its incidence has been reported to be high. Only 32 of the 49 countries report on human brucellosis. The main reservoirs of disease and risks of infection vary from place to place with the different main kinds of domestic stock, the animal husbandry and human consumption methods and habits. Thus mainly the cattle herds are the source of infection for those countries where large numbers of cattle are kept and the drinking of raw milk is the custom; however, there is no strict correlation between these two factors. Goats and sheep fill the epidemiological place in all those countries where the lack of marketable milk curtails its consumption; the small ruminants are kept as the main source of meat supply and in close contact with the farmers family within the compound or house.


Outbreak of a Brucella canis infection in a beagle colony in West Germany.

Brucella infections in dogs were caused by the more frequent strains of brucellae i.e. Br. abortus, Br. suis, and Br. melitensis. Since 1966 it is known that in dog colonies, mostly beagle, in the United States, a new brucella species caused infections. This species was called Br. canis. The infection showed similar effects with dogs as the other brucellae with other domestic animals. With the dogs abortions occurred on the 40th to 50th day of gestation and the infection often resulted in sterility. In 1973 the author detected Br. canis for the first time in Europe; shortly afterwards the same bacteria was isolated in Japan. It is known how the disease spread to Japan, but how it came to Europe is still a mystery. Here it was first detected in a beagle colony with approximately 200 animals used for breeding. Within a few months the disease spread in the colony and finally the birthrate of inseminated bitches was only 29%; 50% had abortions and the rest had not conceived. In this communication characteristics of Br. canis are discussed.


[Immunization of ewes against experimental Brucella melitensis infection: comparison of eleven vaccines].

A comparative study of 11 antibrucellic vaccines has been carried out in the Limousin region of 360 ewe-lambs divided into groups of 30, a 12th group serving as control. After being vaccinated at 8 months, the ewe-lambs were covered between 9 1/2 and 10 1/2 months, then infected at 11 months with Br. melitensis strain 53 H 38 by instillation of 4 x 10(6) germs on the conjonctiva. Six of these vaccines reduced the number of abortions and the excretion of brucella at parturition: three consisted of an inactivated suspension of a virulent S strain of Br. melitensis in oily adjuvant, another consisted of an inactivated suspension of a modified non-agglutinogenic strain of Br. melitensis also in oily adjuvant, the fifth was prepared from Br. melitensis H 105 and Br. abortus B 112 with saponin and the sixth from a strain of Br. melitensis modified with aluminium hydroxide as adjuvant.


Gastrins in tissue. Concentration and component pattern in gastric, duodenal, and jejunal mucosa of normal human subjects and patients with duodenal ulcer.

The total concentration of gastrin and distribution of gastrin components were examined in mucosal biopsies from corpus, antrum, duodenum, and jejunum from normal subjects and patients with duodenal ulcer. The concentration was highest in the antrum, being 12.1+/-1.9 nmol per g of mucosa (mean +/-SEM) for normal subjects, and 9.0 +/-1.6 nmol per g of mucosa for duodenal ulcer patients (P eaual to 0.03). A steep gradient was found distally: in the proximal duodenum the concentration was 0.1; in the distal duodenum, 0.02 to 0.01; and in the proximal jejunum, less than 0.01 of the antral concentration. In corpus of the stomach, the concentrations were similar to those found in the jejunum. Gel filtrations showed that most gastrin immunoreactivity was eluted in positions corresponding to serum component II (gastrin-34-like) and III (gastrin-17-like), but immunoreactivity corresponding to all the components present in serum was found. No interference from cholecystokinin was observed in duodenal biopsies. In corpus, antrum, and jejunum component III was the predominant form, whereas component II made up half of immunoreactive gastrin in the duodenum. No major differences were observed between normal subjects and duodenal ulcer patients. There was no simple relationship between acid secretion and mucosal gastrin concentration, but ulcer patients with the highest acid secretion had the lowest antral content and the highest duodenal content.


The influence of body temperature on the production of ulcers of restraint in the rat.

It has been observed that gastric ulceration after restraint in rats is accompanied by a marked drop in body temperature. This investigation seeks to determine whether hypothermia is causally related to the restraint ulcer. Experimental animals were restrained for 18 hr while rectal temperatures were monitored with a telethermometer probe. Body temperatures of rats restrained at room temperature fell 5.0 degrees C in the first 5 hr. Gastric ulceration in this group was 100%. When body temperatures were mainatined at 38 degrees C, only 26% developed ulcers. Ulcer induction is not only accompanied by a marked temperature drop, but prevention of this phenomenon reduces the incidence of ulcers.


A genetic study of aggregation in the cellular slime mould Dictyostelium discoideum using complementation analysis.

A series of aggregation-deficient (aggregateless) mutants were isolated in genetically marked haploid strains of the cellular slime mould Dictyostelium discoideum. Diploids were produced from pairs of such haploid mutants by a fusion system based on this organism's parasexual cycle. The diploids were isolated from the haploids by using complementation of non-allelic growth-temperature-sensitive mutations and selection at the restrictive temperature. Complementation between the aggregateless mutations uas then assessed in 419 diploids so formed. The non-complementing aggregateless mutations fell into five complementation groups (ago A, B, C, D, and E) and a dominant aggregation class that allowed little or no aggregation when present in a diploid with any of the other mutations tested or the parental wild type. Complicating factors, including partial dominance, multiple mutations, and possible interallelic conplementation, are discussed.  Data on the linkage of the aggregateless mutations was obtained by using recessive drug resistance mutations on three linkage groups to segregate haploids from the diploids. Calculations from our results suggest a genetic complexity of about 50 genes that are specific and essential for aggregation.


Diurnal variation in blood sugar and serum insulin in response to glucose and/or glucagon in healthy subjects.

The role of insulin secretion in the diurnal variation of glucose tolerance has been investigated. In ten healthy subjects, at 08.00 and at 18.00 after 10 hrs of fasting, a combination test of glucose and glucagon was performed. 1 mg glucagon was injected intravenously 40 min after the intravenous infusion of glucose (0.5 g/kg b.w.). Samples for blood sugar (BS) and serum immunoreactive insulin (IRI) were taken before and 2-5 min following the glucose and glucagon loads, and thereafter at 10 min intervals up to 85 min. In the afternoon test, the mean blood sugar values were higher, the differences in the 20-85 min values being statistically significant: the IRI values were statistically lower after glucose, while after glucagon, the increase of serum  IRI was apparently similar in both morning and afternoon tests. However, the insulin/glucose ratio (I/G) was significantly lower at 18.00 at 55-85 men. Corresponding results were obtained in six additional healthy subjects when only glucagon (1 mg i.v.) was injected. In this case also, the mean insulin levels were lower in the afternoon after 5 min, while the BS values during the maximal insulin release (2-30 min) were comparable in both the morning and afternoon tests. In the 40-60 min interval, the BS levels were significantly higher in the afternoon. The existence of a diurnal variation in the blood sugar after intravenous glucose load, as well as after glucagon, seems to be correlated to a simultaneous diurnal variation in the insulin response, suggesting decreased pancreatic beta-cell activity in the afternoon.


Choriocarcinoma in Ibadan: clinicopathologic studies.

The host tissue reaction to choriocarcinoma was studied in 81 Nigerian patients. A mononuclear cellular reaction, observed in about 42 per cent of the patients, was composed mainly of lymphocytes, plasma cells, histiocytes, and eosinophils in varying quantities around tumor deposits. No correlation was found between the survival of the patients and the intensity of the cellular reaction. Late presentation by our patients for medical advice and treatment may partly account for the relatively poor response to chemotherapy. The syncytiotrophoblast appears to play a primary role in vascular invasion by the neoplastic trophoblast.


Comparison of exogenous energy sources for in vitro maintenance of follicle cell-free Xenopus laevis oocytes.

The purpose of these experiments was to determine which exogenous energy sources are suitable for isolated follicle cell-free oocytes from the frog, Xenopus laevis. In order to compare prospective energy sources, follicle cell-free oocytes from 0.4 to 1.3 mm in diameter were incubated in a 1 mM concentration of each of a variety of energy sources and scored daily for the maintenance of morphological characteristics. Vitellogenic oocytes placed in succinate or fumarate deteriorated at the same time as those in saline alone. Oocytes incubated in oxaloacetate (OAA) appeared to remain in the best morphological condition, followed by oocytes maintained in pyruvate or glucose. Fully grown oocytes were tested at various times of incubation for their ability to respond to progesterone by undergoing germinal vesicle breakdown. These experiments showed that oocytes placed in OAA or pyruvate retained the ability to respond to progesterone longer than those in the other energy sources. Increased respiratory rates were stimulated in isolated oocyte mitochondria by succinate as well as pyruvate and OAA. However, oocytes incubated in labelled pyruvate evolved 80 to 140 times as much labelled CO2 as oocytes incubated in labelled glucose or succinate. In addition, it was found that the rate of uptake of pyruvate is 20 to 25 times greater than the rate of uptake of glucose or succinate. It is concluded from these experiments that OAA and pyruvate are the most effective exogenous energy source for the in vitro maintenance of Xenopus oocytes. On possible explanation for the ineffectiveness of glucose or succinate as exogenous energy sources is a restriction in their uptake into the oocytes.


Surveillance projects for selected diseases.

Disease surveillance systems constitute the foundation of appropriate health plans. Surveillance data collection components at best are dependent on a series of contingencies. In developing countries scattered static health centres may result in biased and practically unusable data. A system is here described for collecting data from a sample of persons chosen for their statistical representation of the entire population. Monthly interviews can provide both prevalence and incidence data at low cost using paramedical personnel. Continuing work in this area could provide developing countries with alternative methods of defining their population-nutrition-communicable disease problems.


Effect of dietary fat on pancreatic lipase activity in chicken.

Pancreatic lipase activity was measured in young chicks receiving experimental diets for 18 to 24 days. The addition of 15% soybean oil to a commercial-type diet, without changing the calorie-protein ratio, produced a slight but significant increase in lipase activity. No differences in lipolytic activity were found when chicks received a semipurified diet with or without the addition of 10% partially hydrogenated soybean oil, nor did fasting and fasting-refeeding affect the activity. Pancreatic lipase activity in chicks appears to depend on factors other than the amount or type of fat consumed.


Quantitation of pilocarpine delivery across isolated rabbit cornea by noncross-linked high viscosity polymer gel.

The effect on pilocarpine flux across rabbit cornea in vitro by a noncross-linked polymeric gel vehicle was measured. A closed system transport chamber was used. Its design featured continuous flow of a tear analog but excluded variables of the internal eye. Results were compared to previously determined data in the same chamber system for cross-linked hydrogel buttons and for free pilocarpine fluid. Gel-mediated flux was equal to that with lens buttons to 90 minutes in the case of a 30 per cent gel (viscosity approximately 70,000 centipoises). Elution by the tear analog system limited flux duration of gels relative to lenses. Greater viscosity of 30 per cent gel relative to 25 per cent gel (approximately 15,000 centipoises) was associated with prolonged transcorneal drug flux. The congruence of flux slopes for 30 per cent gel and lens button vehicles despite the difference in available dose suggests saturable mediation of pilocarpine transport across the cornea, but a greater "flux efficiency" through 90 minutes for 30 per cent gel.


Sequence of molecular events involved in induction of allophanate hydrolase.

Addition of urea to an uninduced culture of Saccharomyces at 22 C results in appearance of allophanate hydrolase activity after a lag of 12 min. We have previously demonstrated that both ribonucleic acid (RNA) and protein synthesis are needed for this induction to occur. To elucidate the time intervals occupied by known processes involved in induction, temperature-sensitive mutants defective in messenger RNA transport from nucleus to cytoplasm (rna1) and in protein synthesis initiation (prt1) were employed along with an RNA polymerase inhibitor in experiments that measure cumulative synthetic capacity to produce allophanate hydrolase. These measurements identify the time within the lag period at which each of the above processes is completed. We observed that RNA synthesis, rna1 gene product function, and protein synthesis initiation are completed at 1 to 1.5, 4, and 9 to 10 min, respectively.


Study on development of Agaricus bisporus by fluorescent microscopy and scanning electron microscopy.

Two strains of Agaricus bisporus have been investigated by fluorescent microscopy and scanning electron microscopy. Somatic nuclei, stained with auramin O and examined by fluorescent microscopy, appear to be randomly distributed, divide asynchronously, and assume a nonclassical or "two-track" configuration during mitotic metaphase. A similar configuration has been observed for nuclei during meiosis, but early meiosis in A. bisporus appears to be classical, usually with nine pairs of chromosomes evident during prophase I. Scanning electron microscopy has been used to document developmental stages in the formation and germination of basidiospores. Two-spored basidia were predominant, but occasionally one- or three-spored forms were observed. Four-spored basidia were absent, and uninucleated basidiospores were exceedingly rare to absent.


Dissociation of developing slime mold cells does not inhibit the developmentally regulated rise in alkaline phosphatase activity.

The rise in alkaline phosphatase activity after the resumption of development of dissociated slime mold cells is comparable to that found in non-dissociated aggregates.


Relationship between cortex content and properties of Bacillus sphaericus spores.

The muramic lactam content of spores of Bacillus sphaericus mutants defective in meso-diaminopimelic acid synthesis increases almost linearly with an increase of  meso-diaminopimelic acid concentration in the medium. Since muramic lactam content is a measure of cortex content, the amount of cortex in spores of the mutants can be easily varied by changing the meso-diaminopimelic acid concentration in the medium. Characteristic properties were tested in spores containing different amounts of cortex. Critical amounts of cortex were associated with different spore properties. Refractility and dipicolinic acid accumulation in the spores both required about 20% of the maximum cortex content (although refractility is independent of dipicolinic acid content). For xylene octanol resistance, about 25% of the maximum cortex content was required.


Respiratory-deficient mutants of Torulopsis glabrata, a yeast with circular mitochondrial deoxyribonucleic acid of 6 mu m.

Purified mitochondria from the petite positive yeast Torulopsis glabrata contain a circular deoxyribonucleic acid (DNA) with a length of 6 mum and a buoyant density of 1.686 g/cm3. This DNA is absent from ethidium bromide induced respiratory-deficient mutants.


Arrangement and conformations of substrates at the active site of pyruvate kinase from model building studies based on magnetic resonance data.

Seventeen distances from two paramagnetic reference points, as determined by nuclear relaxation studies of six active complexes of rabbit muscle pyruvate kinase, have been used to construct molecular models of two composite enzyme complexes. In the model of the hypothetical pyruvate kinase-M(I)-M(II)-ATP-Cr(III)-P-enolpyruvate complex, overlap of the transferred phosphoryl groups of the two substrates, which is required to explain the observed competition, is incomplete, allowing greater than or equal to 1 A for the transition state to form. In the active enzyme-M(I)-M(II)-ATP-Cr(III)-pyruvate complex, the gamma-phosphoryl phosphorus of ATP is in molecular contact (3.0 +/- 0.5 A) with the carbonyl oxygen of pyruvate, consistent with direct phosphoryl transfer, indicating no need for intermediate phosphorylation of the enzyme. The enzyme-bound divalent cation, which forms second sphere complexes with the phosphoryl groups of P-enolpyruvate and ATP, may activate the transferred phosphoryl group indirectly, through a water ligand. By analogy with the position of Cr(III), a second divalent cation may participate more directly by coordination of the triphosphate chain of ATP.


Characterization of porcine neurophysin. III. Its resemblance and possible relationship to porcine neurophysin I.

Homogeneous porcine neurophysin III has been obtained from slightly contaminated neurophysin material by rechromatography on diethylaminoethyl-cellulose. The purified protein binds both oxytocin and lysine vasopressin. Gel filtration on a calibrated column of Sephadex G-75 gives an estimate of the molecular weight of 10,000. Amino acid analyses establish the composition Lyla8, 1/2Cys14, Val2, Met1, Ile2, Leu7, Tyr1, Phe3. The total number of amino acid residues is 95. This composition exceeds that of porcine neurophysin-I by 1 alanine and 2 arginine residues. It has an NH2-terminal alanine and the COOH-terminal sequence- Arg-Arg-Ala. Results of peptide maps, the amino acid composition of tryptic peptides, and the sequences of two small tryptic peptides suggest that porcine neurophysin III contains the entire molecule of porcine neurophysin I plus a tripeptide -Arg-Arg-Ala connected the COOH terminus. It is threfore possible that porcine neurophysin I may have been derived from porcine neurophysin III by the proteolytic removal of the last 3 or 4 amino acid residues from the COOH terminus, and that the porcine hypothalamic tissue synthesizes only two neurophysins, II and III.


Molecular hybridization of iodinated 4S, 5S, and 18S + 28S RNA to salamander chromosomes.

4S, 5S, AND 18S + 28S RNA from the newt Taricha granulosa granulosa were iodinated in vitro with carrier-free 125I and hybridized to the denatured chromosomes of Taricha granulosa and Batrachoseps weighti. Iodinated 18S + 28S RNA hybridizes to the telomeric region on the shorter arm of chromosome 2 and close to the centromere on the shorter arm of chromosome 9 from T. granulosa. On this same salamander the label produced by the 5S RNA is located close to or on the centromere of chromosome 7 and the iodinated 4S RNA labels the distal end of the longer arm of chromosome 5. On the chromosomes of B. wrighti, 18S + 28S RNA hybridizes close to the centromeric region on the longer arm of the largest chromosome. Two centromeric sites are hybridized by the iodinated 5S RNA. After hybridization with iodinated 4S RNA, label is found near the end of the shorter arm of chromosome 3. It is concluded that both ribosomal and transfer RNA genes are clustered in the genome of these two salamanders.


Actomyosin content of Physarum plasmodia and detection of immunological cross-reactions with myosins from related species.

The content of myosin in plasmodia of the myxomycete Physarum polycephalum was measured by an immunological technique, quantitative microcomplement (C') fixation. Migrating plasmodia (starved after growth on rolled oats) contained 0.60 +/- 0.08 (SD) mg myosin per g fresh plasmodia. Myosin comprised 0.77% +/- 0.05 (SD) of the total plasmodial protein. When total plasmodial proteins were separated by electrophoresis on SDS-polyacrylamide gels, a large amount of protein appeared in a band comigrating with muscle actin. Densitometry performed after Coomassie blue staining indicated that as much as 15-25% of the total protein in the plasmodium could be actin. This gives an actin/myosin ratio by weight in the myxomycete plasmodium as high as 19-33, a very "actin-rich" actomyosin compared with rabbit skeletal muscle actomyosin with an actin/myosin ratio of 0.6. Starvation stimulates rapid migration and is correlated with a higher percent of both myosin and actin in the total protein of the plasmodium compared with normally growing cultures. Immunological cross-reaction of myosins from a variety of species was measured by C' fixation using an antiserum produced against purified native myosin from P. polycephalum. Although myxomycete and vertebrate striated muscle myosins have very similar morphological and biochemical properties, and apparently possess similar binding properties to F-actin, only myosins from myxomycetes in the order Physarales, rather closely related to P. polycephalum, gave detectable cross-reactions. This finding suggests that many amino acid sequences in myosin have been variable during evolution.


Fine-structural studies of the gametes and embryo of Fucus vesiculosus L. (Phaeophyta). I. Fertilization and pronuclear fusion.

In the marine brown alga, Fucus vesiculosus L., the sperm pronucleus is delimited by an envelope following penetration of the eff by the sperm. This envelope disintegrates as the pronucleus begins its migration through the cytoplasm of the egg. The highly condensed chromatin of the sperm pronucleus disperses slightly following disintegration of the envelope. Microtubules of unknown origin are associated with the sperm pronucleus during its migration. The flagellar microtubules remain in the peripheral cytoplasm but lose their tight 9 + 2 configuration. The sperm eyespot and mitochondria follow the pronucleus through the cytoplasm toward the egg pronucleus. The mitochondria of the sperm are distinguished from those of the egg by their longitudinally oriented cristae and by electron-opaque material in the intracristal space. The pronucleus of the egg becomes convoluted along the surface nearest to the advancing sperm pronucleus. Immediately prior to pronuclear fusion, many egg mitochondria aggregate in the vicinity of the sperm pronucleus. At this time, only the portion of the sperm pronucleus facing the egg pronucleus is surrounded by an envelope. The egg mitochondria disperse rapidly after pronuclear fusion. The sperm mitochondria and eyespot are still in the perinuclear region in 16-h-old embryos. At this time, the osmiophilia of the sperm eyespot has increased, and the sperm mitochondrial membranes are less distinct than in earlier stages. The fine-structural features of fertilization in Fucus are discussed in relation to the fertilization patterns in other cryptogams and marine invertebrates and to polar axis determination in the Fucaceae.


Fine-structural studies of the gametes and embryo of Fucus vesiculosus L. (Phaeophyta). II. The cytoplasm of the egg and young zygote.

Following fertilization, there are rapid changes in the appearance of the Fucus egg. Large electron-translucent vesicles (V1) accumulate fibrillar material, and following pronuclear fusion, they are largely electron-opaque. These vesicles (V1) are formed originally in unfertilized eggs by smooth endoplasmic reticulum (SER) after release of the eggs from the oogonium. Golgi complex hypertrophy follows fertilization, and this increased activity continues throughout early embryogenesis. Wall formation begins after penetration of the egg by the sperm. Vesicles (V2) of unknown origin, which have homogeneously fibrillar contents, and Golgi vesicles (V3) merge with SER-derived vesicles (V1) after wall formation begins. Osmiophilic bodies are a prominent feature of the egg and embryo. They are penetrated by SER, and subsequently there is a loss of electron-opaque material. Alternatively, they discharge concentrically whorled material into the cytoplasm. The nuclear surface of the egg is convoluted in the period close to fertilization, and electron-opaque material is segregated in the cytoplasmic matrix lying within the nuclear invaginations.


Elimination of bacteriophages from tissue culture serum by affinity chromatography.

Use of immunoadsorbents to remove bacteriophages from tissue culture serum was investigated. Immune globulins from rabbit antiserum prepared against phi V-1 phage were immobilized by covalent linkage to activated porous silica glass derivatives of p-aminoarylamine and to Sepharose-4B. Chromatographic columns of each material were used to filter samples of a fetal bovine serum into which had been introduced 8100 plaque-forming units of the phage per ml. Efficiency of removal was determined by plaque assays of phi V-1 phage recovered in the effluent fluids. Activated but uncoupled matrices nonspecifically removed from 49 to 59% of the phages introduced into the experimental serum. A reduction of 35 to 37% in phage content occurred in the serum after filtration through columns coupled to nonantibody protein. With specific immune globulins attached, the Sepharose-4B matrix reduced the concentration of phage in the serum below a detectable quantity. Noapparent alterations occurred in the growth-promoting property of serum filtered through the Sepharose-4B immunoadsorbent as measured by cloning efficiency of BHK-21, WI-38, and FRhL-2 cells. These experiments serve as a model system for use of immunoadsorbents for selective removal of bacteriophages and perhaps other extraneous microbial agents from tissue culture serum.


Circulating and intra-articular immune complexes in patients with rheumatoid arthritis. Correlation of 125I-Clq binding activity with clinical and biological features of the disease.

The correlation between the incidence and level of immune complexes in serum and synovial fluid and the various clinical and biological manifestations of rheumatoid arthritis has been studied. Immune complexes were quantitated using a sensitive radioimmunoassay, the 125I-Clq binding test, in unheated native sera and synovial fluids from 50 patients with seropositive (RA +) and 45 with seronegative (RA -) rheumatoid arthritis, 17 with other inflammatory arthritis, and 37 with degenerative and post-traumatic joint disease. The following observations were made: (a) when compared to the results from patients with degenerative and post-traumatic joint diseases, the 125I-Clq binding activity (Clq-BA) in synovial fluid was found to be increased (by more than 2 SD) in most of the patients with RA + (80%) and RA - (71%) and in 29% of patients with other inflammatory arthritis; the serum Clq-BA was also frequently increased in both RA + (76%) and RA - (49%) patients, but only exceptionally in patients with other inflammatory arthritis (6%); (b) a significant negative correlation existed between the Clq-BA and the immunochemical C4 level in synovial fluids from patients with RA + and RA -; (c) neither the serum nor the synovial fluid Clq-BA in rheumatoid arthritis significantly correlated with the erythrocyte sedimentation rate, the clinical stage of the disease, or the IgM rheumatoid factor titer; and (d) the serum Clq-BA in patients with rheumatoid arthritis and extra-articular disease manifestations (40 +/- 34% in those with RA +,32 +/- 29% in those with RA -) was significantly increased as compared to the serum Clq-BA in patients with joint disease alone (24 +/- 30% in those with RA +, 10 +/- 13% in those with RA -). Experimental studies were carried out in order to characterize the Clq binding material in rheumatoid arthritis. This material had properties similar to immune complexes: it sedimented in a high molecular weight range on sucrose density gradients (10-30S) and lost the ability to bind Clq after reduction and alkylation, or after acid dissociation at pH 3.8, or after passage through an anti-IgG immunoabsorbant. DNase did not affect the Clq BA. These results support the hypothesis that circulating as well as intra-articular immune complexes may play an important role in some pathogenetic aspects of rheumatoid arthritis. The 125I-Clq binding test may also be of some practical clinical value in detecting patients who have a higher risk of developing vasculitis.


Retest reliability of the Halstead Impairment Index in a normal, a schizophrenic, and two samples of organic patients.

In a 1974 study Matarazzo, et al. reported the test-retest reliability of the Halstead-Reitan Neuropsychological Battery for a sample of normal young men and a comparison group of older Ss with cerebrovascular disease. The present study extended this earlier one by addition of comparable test-retest findings from two additional comparison groups: a sample of chronic schizophrenic Ss and a sample of organic patients who underwent endarterectomy. Despite the lack of comparability across the four samples on many dimensions, including age and test-retest interval, the results again reveal a high degree of clinical as well as purely psychometric reliability for most of the tests in the neuropsychological battery and the additional suggestion for further research that the test-retest instability found for some of the Ss in the schizophrenic sample may, itself, hold promise of differential clinical significance in the diagnosis of a "schizophrenic" vs. "organic" process.


Some problems of therapeutic trials in hypertension.

It is strongly recommended that a scientific protocol for controlled therapeutic trials in hypertension should include, inter alia, the following: 1. A definition of the level(s) of blood pressure which indicate hypertension (systolic and/or diastolic), preferably related to age and sex. 2. The criteria for defining the type of hypertension (e.g., essential, renovascular, etc.). 3. A statement relative to which diastolic level is to be recorded: phase IV ("muffling") and/or phase V ("disappearance"). 4. Information on the sizes of sphygmomanometer cuffs to be used. 5. A statement of which arm is to be used (throughout the study). 6. A statement of postures in which blood pressure is to be measured (supine, sitting, standing). 7. Information on the conditions under which pressures are to be recorded (e.g., "casual," "near-basal," etc.) and the duration of rest before recording. 8. Details of the times of day at which measurements are to be taken.9. A statement on the method of establishing baseline readings (e.g., mean of three successive readings) and the acceptable degree of variability (e.g., +/- 10 mm Hg). 10. A definition of "endpoints" (e.g., diastolic pressure less than upper limit of normal; reduction in diastolic pressure greater than 10 mm Hg).


Artificial induction of lactation by hypothalamic implantation of perphenazine in virgin goats.

Perphenazine (0-8-1 mg) caused udder growth and artificial induction of lactation, when stereotaxically implanted into the median eminence of virgin female goats. Sham implantations into the median eminence or implantation of perphenazine into sites of the hypothalamus not in the immediate proximity of the median eminence were ineffective. Fourteen-twenty-two d after implantation the goats were milked for the first time. Maximal milk yields of 250-1050 ml/d were achieved 3-5 months later. Udder development and induction of lactation during the premilking period were exclusively due to the action of perphenazine. It is likely that after implantation the milking stimulus played a synergic role with perphenazine in the progressive increase and the maintenance of lactation. Apparently no side effects were caused by the drug. Implantation of small doses of perphenazine in the hypothalamus might be a suitable technique for studying the physiological effects of increased levels of endogenous prolactin in goats.


Increasing polyunsaturation of milk fats by feeding formaldehyde protected sunflower-soybean supplement.

A practical means of protecting fats of a feed concentrate containing high polyunsaturated fatty acids is described. A ground mixture of 30% soybeans and 70% sunflower seeds was treated with 1% formaldehyde to protect the unsaturated lipids from microbial hydrogenation in the rumen. This was fed as a supplement to two Holstein cows in amounts that were doubled weekly. These ranged from 524 to 8384 g/day and provided successively increasing intakes of 100, 200, 400, 800, and 1600 g of linoleic acid daily. Percent milk fat increased by more than one, and linoleic acid (C18:2) of milk fat increased from 2.5 to 20% with compensatory declines in myristic (C14:0) and palmitic (C16:0) acids. Cholesterol and vitamin E of plasma both doubled at the highest supplementation. Milk yield, solids-not-fat, protein and milk cholesterol were unaltered. Fat in feces doubled from about 3 to 6%. Daily linoleic acid content of feces increased from 25 g to 120 g, indicating a dietary loss of 7 to 10% of this polyunsaturated acid. These cheaper feed ingredients elevated the polyunsaturated fats in milk as effectively as the expensive purified casein and safflower oil supplements in previous experiments.


Impact of social disorganization on behavior, milk yield, and body weight of dairy cows.

To measure the effect of intergroup transfer, four cows were added to a group of 20 cows at 28-day intervals in five trials. The two groups of cows were housed in adjoining lots and fed identical rations from opposite sides of a feed bunk which provided .9 m linear feeding space per cow. Means of the number of agonistic encounters per transferred cow were 9.4, 4.4, 4.3, 3.8, 3.3, and 2.6 during the 1-h period immediately following the first feeding on days 1, 2, 7, 14, 21, and 28. The average dominance values of the transferred cows during the 28 days (.19, .14, and .32) showed no perceptible trend, and mean body weight (567, 569, and 571 kg) was not limited. On day 1 the mean 4% fat-corrected milk yield of the transferred cows decreased .51 kg or 3%, and nontransferred cows increased .01 kg. The decrease in milk yield of the transferred cows was not associated with number of agonistic encounters per se. After day 1 regrouping had no effect on milk yield.


Influence of human chorionic gonadotropin on pregnancy rates in lactating dairy and beef cows.

Single subcutaneous injection of 1500 IU human chorionic gonadotropin or placebo injections were given at the time of insemination in lactating dairy and beef cows to determine their effects on rates of pregnancy. Pregnancy rates at first service in 161 control and 145 treated dairy cows were 52.8% and 44.8%, respectively. Similar rates for 136 control and 145 treated beef cows were 54.4% and 54.5%. Injections of human chorionic gonadotropin were not effective in stimulating conception rates in lactating dairy or beer cows under field conditions.


Studies on Alternaria allergens. I. Establishment of the radioallergosorbent test for measurement of Alternaria allergens.

The ability to covalently couple Alternaria allergens to microcrystalline cellulose particles has permitted not only the measurement of IgE antibodies to Alternaria in patient serums but also the identification of allergenic fractions from crude Alternaria extracts. Crude aqueous Alternaria extracts from 3 commerical suppliers were coupled to cellulose but failed to bind more than 5% of total radioactive counts (TRC) when reacted with serums from highly sensitive patients. Fractionation of a commercial extract through Sephadex G-25 showed that almost all allergenic activity was located in a protein- and carbohydrate-containing peak eluting at the column void volume. These fractions were pooled and coupled to cellulose to yield a RAST polymer which produced up to 20% TRC binding when tested with serums from over 100 Alternaria-sensitive patients, and only up to 1% TRC binding with 17 nonallergic serums. The study of commercial Alternaria extracts by chromatographic and Rast inhibition techniques showed that present extracts are neither qualitatively or quantitatively comparable.


Volumetric studies of aeroallergen prevalence. I. Pollens of weedy forbs at a midwestern station.

Volumetric levels of pollens derived from broad-leaved herbaceous plant species heve been determined at a midwestern urban site with suction and rotating arm samplers. The resulting data confirm an abundance of ragweed and nettle emanations but suggest that those of plantains, chenopods, and amaranths achieve modest levels, at best, despite their prominence in gravity slide recoveries. Regular seasonal occurrence periods for pollens, including those of entemophilous composites, the hophemp group, wilg grape, and the mustard and pea families, were evident in volumetric recoveries. In general, prevalence peaks of the most prominent pollen types correlated with intermediate, rather than extreme, values for air speed and relative humidity.


The total eosinophil count in asthmatic children.

The diurnal variation in total eosinophil count (TEC) in asthmatic children not on medications or on thophylline-containing bronchodilators orally every 6 hr is similar to that reported in normal subjects, with a decrease in TEC in the morning and an increase in the evening. Asthmatic children taking prednisone in 8:00 A.M. on alternate days have diurnal variations in TEC on the "day off" prednisone similar to those on normal children. On the "day on" prednisone, administered either on a daily or alternate-day basis, TECs approach zero 4 to 8 hr after prednisone is taken. The TEC then increases in the evening as it does in children not taking prednisone.


[Use of filter paper to identify antibodies against Myxovirus influenzae].

A total of 165 sera and 142 eluates from filtration papers impreggnated with whole blood were examined in reaction of complement fixation against A/Hong Kong 1/68 (H3N2) and B/Johannesburg 3/56 virus. To perform HIT 152 sera and 155 eluates were used. The results obtained were elaborated statistically. The method of filtration papers does not seem to be suitable for HIT, whereas the CFT was in several cases practicable.


Factors influencing serum cholesterol levels in swine.

Factors that influence serum cholesterol levels in swine were examined. Body weight and dam had significant influences on the serum cholesterol levels. No effects of age of pig (50-59 days of age), sex, farrow, sire, or litter size on serum cholesterol levels were detected. The heritability of serum cholesterol in swine estimated in this study is about 25 percent. Two generations of selection appear to have produced lines of pigs characterized by serum cholesterol levels that are genetically distinct with an estimate of realized heritability of 0.22.


Single - dose immunization of human subjects against tetanus.

A study was performed on human subjects to assess the effectiveness of single-dose immunization with 20 CU (1 ml) of adsorbed tetanus toxoid followed by revaccination with 10 CU (0.5 ml) 1 year later. Out of 1187 students, only those were selected for observation whose blood serum did not contain tetanus antitoxin (titre less than 0.001 IU/ml); this group counted 283 students. After administering the 20 CU (1 ml) of toxoid the antitoxin titre was repeatedly checked on days 10--15 and persons whose titre had risen to over 0.01 IU/ml were excluded from observation. The remaining 109 persons were tested for the antitoxin level 1 year later and revaccinated with 10 CU of tetanus toxoid. After 10--15 days their postrevaccination titre was determined. The single-dose immunization with 20 CU of tetanus toxoid in human subjects not given tetanus antigen previously was accompanied by a gradul rise in the antitoxin titre up to the protective level and its maintenance for 1 year (observation time) until revaccination. Revaccination with 10 CU of toxoid provided in 10--15 days a multiple (100--197fold) increase of the antitoxin titre, many times exceeding the protective level. The usefulness of transition to the shortened immunization scheme for tetanus prophylaxis of the adult population is discussed.


Predicting selection response for growth of channel catfish.

Estimates of heritability, phenotypic and genetic correlations were obtained for body length and weight at 5 months and body length and weight at 15 months in channel catfish. The estimates were obtained from a half-sib analysis by mating 20 males to two females each, producing 20 half-sib and 40 full-sib progeny families. Mortality of fish during the study reduced the number of families to 17 half-sib and 34 full-sib. Comparisons of selection methods were made for body length at 5 months and body weight at 15 months. The results of the study show: 1) heritability estimates for body length and weight at 5 months was 0.12 and 0.61, respectively,  and body length and weight at 15 months was 0.67 and 0.75, respectively; 2) from the magnitude of the estimates of heritability, it can be inferred that large amounts of additive genetic variance exist in three of the traits (length at 5 months and length and weight at 15 months) and that selection for these traits should be successful; 3) estimates of phenotypic correlation among the four traits ranged from 0.90 to 0.30, and genotypic correlation among the four traits ranged from 1.47 to 0.71; 4) the magnitude and positive nature of the genetic correlations indicated that simultaneous selection for the four traits in channel catfish would be effective; and 5) comparisons of predicted response under individual, indirect and index selection, show that selection on an index based on all four traits gives maximum response in length at 5 months and weight at 15 months.


Experimental studies on the protective effect of the M. bovis BCG against tumors in mice.

Experiments on white mice demonstrated a certain protective effect of M. bovis Prague strain when using Krebs ascitic tumor cells in various dilutions. The survival of vaccinated mice was significantly higher as compared with non-vaccinated controls. Similar results were obtained in experiments with the Bulgarian preparation F. 70.


Study of inhalation toxicity of performic, peracetic and perpropionic acid in mice.

The acute and subacute inhalation toxicity of laboratory performic, peracetic and stabilized aqueous peracetic acid solution. The differences in the toxicity of the studied of the commercial preparation Persteril for mice was studied. Persteril is a 40% peracids were not statistically significant. The histological findings in the lung tissue of intoxicated mice show that the effet of the given peracids is qualitatively the same. Although their toxicity is not very high, in repared inhalation they can induce temporary pathomorphological lesions in the lung parenchyma and have a negative effect on the development of mice in concentrations of about only 70 mg/m3 air. As regards their inhalation toxicity, performic and perpropionic acid have no advantages over peracetic acid for practical use in the air disinfection. The findings show that it is necessary for persons carrying out spatial disinfection with one of the studied peracids to wear an protective mask.


[On the epidemiology of Dientamoeba fragilis Jepps and Dobell 1918. 4th communication: evidence of Dientamoeba fragilis in Enterobius eggs using isoelectric point determination].

By means of the method of determining the isoelectric point, the same conditions of absorption and stain intensity as in Dientamoeba cultivation forms were determined in cells found in Enterobius vermicularis eggs of Dientamoeba fragilis carried. By that way, identity of both stages, as well as function of pinworms as Dientamoeba fragilis vectors were confirmed.


European suslik as a possible carrier of plague in natural foci in eastern Europe.

It is possible that the outbreaks of plague observed in Roumania and Bulgaria in the 19th century were of local origin because marmots and susliks--known as the main carriers of plague in nature--were widely spread on the territory of these countries. In the subsequent years, marmots died out in consequence of the economic activity of man and the habitats of susliks became sporadic and occurred in small foci. However, data obtained in the last few decades point out the possibility of long-term preservation of plague infection in the populations of rodents occupying small areas of land. The presence of the European suslik in the countries of Eastern Europe and the fleas parasitizing on the rodent, capable of transferring plague infection, permit the authors to raise the question of a possible occurrence of natural foci of plague in Roumania and Bulgaria. Data are given demonstrating the suitability of an extensive epidemiological reconnaissance in these countries.


An epidemic of trichinosis after ingestion of wild pig in Hawaii.

Forty-five percent of young adults who ate roast wild pig at a  barbecue in Hawaii experienced an illness compatible with trichinosis. Eosinophilia was present in all of those who were ill and in none who remained well. There were no positive results in skin tests with commercial skin-test antigen. Latex agglutination and counterelectrophoresis were equally good methods for the diagnosis of trichinosis and were more sensitive than the bentonite flocculation test. Levels of IgE in those with illness and eosinophilia were not significantly different from the levels in persons who remained well. It is concluded that skin tests should be abandoned until an improved antigen becomes available, that the relative value of diagnostic serologic methods require continued evaluation, and that levels of IgE may not rise significantly after trichinosis.


The requirement for C3 receptors on the precursors of 19S and 7S antibody-forming cells.

The main conclusion from this study is that C3 receptors are not required for the generation from B cells of a thymus-dependent 7S antibody response. The requirement for C3 receptors on the precursors of antibody-forming cells was studied in an adoptive transfer system using thoracic duct lymphocytes (TDL) from primed rats as a source of precursors and irradiated recipients as hosts. 7S precursors were found in both the CR+ and the CR- fractions of TDL and it was established that the response transferred by CR- cells did not arise from either a raidoresistant B cell in the host or from CR+ cells contaminating the CR- population. Thus, the C3 receptor is not obligatory for B-cell-T-cell cooperation in the 7S response. The precursors of 19S antibody-forming cells were found only in the CR+ subpopulation. The CR-Ig+ subpopulation was shown to contain all the B blasts in rat TDL and a very small number (approximately 1% of all TDL) of small lymphocytes. This latter population contained the CR- 7S precursors and contributed approximately 20% of the total adoptive secondary 7S response transferred by CR+ and CR- subpopulations combined. This observation suggests that the percentage of rat TDL committed to carry 7S memory is small, a conclusion which is confirmed and extended in the following paper.


Tryptophan biosynthesis in Coprinus lagopus: a genetic analysis of mutants.

Thirty-one tryptophan-requiring mutants of Coprinus lagopus have been assigned by genetic and complementation analyses to four loci designated trp-I, trp-2, trp-3 and trp-4. The trp-1 and trp-3 loci were located in group III and trp-2 in group G of the linkage map. The trp-4 locus showed no linkage to the other trp loci or to markers in three additional linkage groups tested. From auxanographic tests and a study of accumulated biosynthetic intermediates, the enzymes controlled by each locus have been provisionally assigned. The trp-2 and trp-3 loci both appear necessary for anthranilate synthetase activity since mutants accumulated no intermediates. Only the trp-3 mutant could utilize anthranilic acid, therefore the trp-2 locus must also be involved in a subsequent step in the pathway. The trp-4 mutants utilized indole and accumulated anthranilic acid, and hence this locus is involved in the conversion of anthranilic acid to indoleglycerol phosphate. The trp-1 mutants utilized only tryptophan and accumulated indoleglycerol phosphophate and anthranilic acid. They are therefore blocked in the final steps of the pathway catalysed by tryptophan synthetase.


Lability of RNA from the large cytoplasmic ribosomal subunit of the protozoon Crithidia oncopelti.

Cytoplasmic ribosomalRNA extracted from Crithidia oncopelti and analysed by gel electrophoresis at 4 degrees C consisted of two components, with molecular weights (relative to E. coli rRNA) of 1-30 X 10(6) and 0-83 X 10(6) daltons, present in equimolar amounts. On heating briefly at 51 degrees C followed by rapid cooling, the 1-30 X 10(6) RNA completely dissociated into two components of molecular weights 0-70 X 10(6) and 0-56 X 10(6) (present in equimolar amounts). Fifty per cent dissociation of the molecule occurred at 28 degrees C. That the integrity of the RNA molecule at low temperatures is maintained by its secondary structure was confirmed by electrophoresis under denaturing conditions (98%, v/v, formamide). To account for these phenomena, latent cleavage of the molecule in vivo is proposed.


The mechanism of beta-bungarotoxin action. I. Modification of transmitter release at the neuromuscular junction.

The protein, beta-bungarotoxin, a presynaptic neurotoxin isolated from the venom of the snake Bungarus multicinctus, is known to inhibit mitochondrial function. Within 30 min after adding the toxin to a rat diaphragmphrenic nerve preparation, the quantal content increased tenfold and the frequency of miniature endplate potentials increased fourfold. No increase in miniature endplate potential frequency was seen in the absence of extracellular calcium. Since mitochondria may be involved in regulating intracellular calcium levels, the rate at which the transmitter release is turned off was studied by measuring delayed release in the presence and absence of toxin. Delayed release is elevated about eightfold by the toxin. If delayed release is due to residual calcium, as has been hypothesized, these data may be explained if the toxin does not alter the amount of calcium which enters the terminal, but rather the rate at which that calcium is removed. Alternatively, a calcium-dependent modification of the release process itself might be produced. The eventual reduction in transmitter output did not appear to result from depletion of the terminal of releaseable packets of transmitter, but does require extracellular calcium.


Membrane marker movement on sympathetic axons in tissue culture.

In cultures of dissociated chick sympathetic ganglia, retrograde (someatopetal) movement of concanavalin A receptors in the axolemma can be observed directly. Such movement was visualized by using concanavalin A coated red blood cells (ConA-RBCs) as membrane markers. Forty-eight percent of all ConA-RBCs which bound to sympathetic nerve fibers moved somatopetally at rates ranging from 11-84 mu/hr with a mean and standard error of 49 +/- 6 mu/hr (n = 18). On nongrowing nerve fibers, the ConA-RBCs within 60 mu of the cell body showed retrograde movement, while on elongating neurites only those markers within 30 mu showed such movement. The rate of retrograde ConA-RBC movement appeared to increase with distance from the cell soma. The binding of ConA-RBCs to sympathetic neurites was specific for concanavalin A receptors since pretreatment with either concanavalin A or alpha-methyl-glucopyranoside prevented this binding. Untreated polystyrene beads (1.1 mu) which bound nonspecifically to the neurite membrane also showed retrograde movement. These beads moved somatopetally at rates similar to those of the ConA-RBCs but did so regardless of their initial distance from the soma. These data suggest that retrograde movement of surface elements might be a general property of cultured sympathetic nerve fibers.


Spontaneous bioelectric activity of cultured Purkinje cells during exposure to glutamate, glycine, and strychnine.

The addition of glutamate to the bathing medium increased the average firing rate of cerebellar rat Purkinje cells in vitro. At concentrations lower than 10(-6) M, there was no deviation from controls in the firing pattern or rate that was detectable. At 10(-3) M glutamate, the amplitude of the action potentials was gradually decreased until all activity was abolished. The action of glutamate was rapid in onset and reversible. Glycine produced sustained depression of firing at concentrations higher than 10(-3) M. This inhibition was strychnine-insensitive and considered nonspecific. Strychnine, on the other hand, exerted an excitatory influence on Purkinje cells when applied at low concentrations (10(-8) TO 10(-6) M). The firing became more irregular and complex discharges appeared. Higher concentrations of strychnine (greater than 10(-5) M) inhibited the spontaneous activity. The effect of strychnine was partly reversible. The data suggest that low concentrations of strychnine lower the threshold for inputs at excitatory as well as inhibitory synapses.


Eales' disease with neurological involvement Part 1. Clinical features in 9 patients.

Nine patients with characteristic changes of Eales' disease in the eye in whom there was neurological involvement, have been described. The characteristic neurological picture comprised an acute or subacute myelopathy occurring at an interval of a few weeks to a few years after the eye episode; in only 1 patient was there cerebral involvement without any evidence of myelopathy. Besides the involvement of spinal cord at the dorsal level in the 8 patients, there was evidence of additional lesions in the brain stem in 1 patient and in the cervical cord in another.


Subsequent fertility and birth histories of children and adolescents treated with 131I for thyroid cancer.

Forty patients aged 20 years or less who had been treated with 131I after surgery for papillary-follicular thyroid carcinoma were contacted for followup study. Five had died and two were unmarried; the remaining 33 were studied with respect to their subsequent reproductive histories and the health of the offspring. The mean age at the time of the first 131I therapeutic dose was 14.6 years (range 6-20), and the average followup interval, from that first dose until followup, was 18.7 years (range 14-25). The mean total dose of 131I was 196 mCi (range 80-691). The incidences of infertility (12%), miscarriage (1.4%), prematurity (8%), and major congenital anomaly (1.4%) found in this series are not significantly different from those in the general population. Thus, our study offers no overt evidence of genetic damage in children and adolescents treated with high doses of 131I for thyroid carcinoma.


Effects of a single intoxicating dose of ethanol on the vitamin profile of organelles in rat liver and brain.

The effects of a single, oral, intoxicating dose of ethanol (EtOH, 9 g/kg body weight) on the distribution of water- and fat-soluble vitamins in various subcellular fractions of eight rat livers and eight rat brains was surveyed. Results were compared to eight other rats receiving a similar dose of saline (controls). Both organs showed redistribution of vitamins among the various organelles after EtOH was given. In saline-treated animals the nucleus and cytosol of the liver contained the highest proportion of all vitamins and the microsomes and lysosomes contained the least. As compared to controls, EtHO ingestion generally caused the mitochondria and microsomes to accumulate vitamins, while vitamins in the lysosomes were decreased. A different pattern was seen in the brain after EtOH administration. Except for thiamin and niacin, the whole brain vitamins were higher than those in controls; they were primarily concentrated in the brain nucleus and mitochondria. It was concluded that changes in the organelle vitamin content of the liver were the result of EtOH injury. The simultaneous attempt to repair the injury was manifested by the by the sequestration of vitamins in the organelles of EtOH-treated animals as compared to controls.


Yolk lipids of developing atherosclerosis susceptible White Carneau and atherosclerosis resistant Show Racer pigeon embryos.

The lipid composition of yolks of developing embryonic atherosclerosis-susceptible White Carneau (WC) and -resistant Show Racer (SR) pigeons was analyzed to determine whether embryonic nutrition might be a factor in the difference in susceptibility to aortic atherosclerosis. The yolks of 1-day and 18-day old embryos were analyzed, and the amounts of phospholipid, sterol, non-esterified fatty acid, triglyceride, cholesteryl ester, and hydrocarbon were determined. On the first day of development in both breeds, triglycerides composed 80% of the total lipid content of the yolk; phospholipids, cholesteryl ester, sterols and non-esterified fatty acids comprised the rest. There was no difference between breeds in the amount of lipid in each class or in the total lipid. Therefore, the initial lipid diet of these embryos is not a factor in development of the disease. Examination of the yolk just prior to hatching, revealed that in both breeds there was a significant decrease in total yolk lipids, but unequal utilization of lipid constitutents between breeds. Significantly higher amounts of phospholipids remained in the yolk of the WC pigeons. During embryogenesis, the SR pigeons consumed significantly more of each lipid than the atherosclerosis-susceptible breed. This may indicate that there is a difference between the two breeds in lipid metabolism.


Dietary calcium, calcium kinetics and plasma parathyroid hormone concentration in cows.

Kinetic analysis of radiocalcium data was combined with radioimmunoassays of plasma parathyroid hormone in nonpregnant nonlactating cows 4.5 to 7.8 years of age whose calcium intake was varied from 0.05% to 1.4% of the diet. Calcium intake had no significant effect on plasma concentration of calcium or parathyroid hormone. It had a slight but significant effect on the plasma phosphorus concentration. As calcium intake increased, calcium absorption increased but calcium removal from bone decreased so that total calcium transport into the exchangeable pool remained fairly constant. A decline in calcium clearance with age was accompanied by a fall in plasma parathyroid hormone concentration, and a decrease in calcium transport into the pool. These observations are consistent with feedback controls between plasma calcium, parathyroid hormone and calcium transport operating to maintain plasma calcium homeostasis as calcium clearance declined with advancing age.


Alterations in peripheral blood leucocyte distribution in response to local inflammatory stimuli in the rat.

Changes in peripheral blood leucocyte distribution were monitored following subcutaneous injections of turpentine and subcutaneous and intrapleural injections of dextran. The responses in all three groups were similar; marked increases in total counts occurred at 6 hr, due largely to significant increases in neutrophil counts. Increases in lymphocyte counts also occurred and were more marked in the dextran-treated animals. By 12 hr, total counts fell, due to drops in both neutrophil and lymphocyte counts. In both dextran groups, neutrophil counts rose again between 24 and 72 hr, but in the turpentine group the fall persisted until 96 hr before counts reached a second peak at 14 days. In all groups lymphocytes showed an increase again at 18-72 hr. The rise in neutrophil counts observed 6 hr after the injection of turpentine was shown to be due principally to premature release of neutrophils from the bone marrow maturation compartment. Depletion of this compartment resulted in a drop in numbers of circulating neutrophils between 6 and 12 hr, in spite of the continued release of progressively less mature cells. The recovery in neutrophil counts between 72 and 96 hr was thought to be the expression of an increase in the rate of stem cell division. The continued rise to a second peak at 7 days probably resulted from increased marrow cellularity. It is suggested that the fluctuations in peripheral blood leucocyte counts may influence the initial colonisation of the local inflammatory lesion. The increase in neutrophil counts at 6 hr corresponds with the time of maximum neutrophil emigration reported by other workers and the fall in counts at 12 hr corresponds with the time of decreased neutrophil emigration.


A comparison of the effect of two regimens of infestation on the development of resistance by cattle to the cattle tick, Boophilus microplus (Can.).

The development of resistance to Boophilus microplus by cattle was studied using sets of cattle twins, in stalls. One twin from each set received 3 infestations of 40,000 larvae and the other a continuous infestation of 1,000 larvae a day over the same period. Sets of twins were then challenged with 1,000 larvae a day for 40 days and 2 field infestations of 20,000 larvae. Correlations of ranking for resistance made at 40-day periods during daily infestations of 1,000 larval ticks or for corresponding intermittent infestations of 40,000 larvae were low until animals had received 120,000 larvae. Thereafter irrespective of method of infestation correlations of ranking were relatively high (r = 0.61-0.96) between periods of infestations or method of infestation including 2 field infestations. Fewer adult female ticks matured on the daily infested animals than on the intermittently infested animals during the treatment period, but animals developed a similar resistance level whether infested with either technique.


Maternal and postnatal hypermagnesemia and the meconium plug syndrome.

Thirty dated pregnant Srague-Dawley rats received IM MgSO4 (750 mg/kg/ X 5 days) until birth. Fifteen untreated pregnant Sprague-Dawley rats of similar gestation served as controls. A total of 453 rats were born. Ninety neonates (two from each of 45 liters) were randomly removed before suckling, sacrificed, and the water content of the meconium and serum magnesium determined. The remaining 363 bewborn rats were observed for delayed passage of meconium or abdominal distention. Hypermagnesemic (6.3 +/- 0.5 mg/100 ml) neonates had neither abdominal distention nor delayed passage of meconium. The water content of meconium in hypermagnesemic rats (84.7 +/- 4.2% and in untreated controls (85.5 +/- 3.8%) were statistically similar. Dated pregnant mongrel dogs were given magnesium sulfate by continuous intravenous infusion and by bolus intravenous injection. The water content of meconium, transit time, and basic electrical rhythm (BER) of treated neonates were similar to untreated neonatal controls. The water content of meconium, transit time, and BER of neonatal dogs made hypermagnesemic (12.0 +/- 1.2 mg/100 ml) in the postnatal period were similar tp untreated neonatal controls. In adult and newborn pupies, receiving a continuous intravenous magnesium sulfate infusion, deep tendon reflexes ceased at serum magnesium levels of 9.0-10.0 mg/100 ml, spontaneous respiration at 14.0-15.0 mg/100 ml, and BER was suppressed (transiently) at 20.0-25.0 mg/10 ml. These data suggest that high (sublethal) doses of MgSO4 in pregnant and newborn animals have little effect on BER, meconium transit time or water content of the neonates. No correlation between MgSO4 treatment and the meconium plug syndrome was observed in the experiments.


Biosynthesis of deuterated riboflavin: structure determination by NMR and mass spectrometry.

The riboflavin-producing fungus Eremothecium ashbyii was cultured in various growth media containing high concentrations of deuteriuj, and the product was isolated. The structures of highly deuterated riboflavin, in which at least 13 of 15 nonexchangeable hydrogens were replaced by deuterium, and fully deuterated riboflavin, in which all 15 nonexchangeable sites contained deuterium, were established by NMR and mass spectrometry. The aromatic protons (C-5 and C-8) wer partially substituted in the highly deuterated molecule. Information regarding three areas of the biosynthetic pathway within the microorganism was obtained as a result of the formation of these compounds. Extensive solvent interaction, possibly due to passage of sugar through the transaldolase-transketolase pathway, occurs during formation of the ribityl chain. Limited solvent participation takes place during formation of 6,7-dimethyl-8-ribityllumazine, the immediate precursor of riboflavin. Deuteration of the riboflavin C-6 and C-7 methyl groups indicates significant solvent exchange during the final step of the biosynthetic process.


Changes in sensitivity to apomorphine during morphine dependence and withdrawal in rats.

Stereotyped behavior induced by injection of apomorphine hydrochloride (10 mg/kg i.p) was measured in control rats, rats made dependent on morphine and dependent rats undergoing naloxone-precipitated withdrawal. The dose of apomorphine chosen was approximately the ED50 dose, so that changes in sensitivity to apomorphine in either direction could be determined. Rats which had received a subcutaneous morphine (75 mg) pellet implant 72 hours previously demonstrated an increased sensitivity to apomorphine when compared with placebo-implanted controls. During withdrawal precipitated by injection of naloxone hydrochloride (0.2 mg/kg i.p.) this increased sensitivity disappeared. Naloxone alone, in a dose of 1.0 mg/kg but not 0.2 mg/kg, significantly antagonized apomorphine-induced stereotyped behavior and these effects of apomorphine were also reduced by an acute injection of morphine sulfate (10 mg/kg). The significance of these findings with regard to changes in central dopaminergic systems during dependence and withdrawal is discussed.


The production and characterization of antibodies reactive with meperidine.

Meperidinic acid was converted to O-meperidinyl-glycollic acid and covalently attached to bovine serum albumin. Rabbits injected with this conjugate produced antibodies reactive with meperidine which were measured by the ammonium sulfate method. The specificities of these antisera were studied by competitive inhibition of the binding of 100 pmol/ml of 3H-meperidine to antibody by the prior addition of increasing concentrations of various unlabeled compounds. The concentrations in nanomoles per milliliter of various unlabeled opiods required to inhibit 3H-meperidine binding by 50% (I50) were: meperidine, 0.08; O-meperidinyl-glycollic acid, 1.7; methadone, 580; heroin, 1750; codeine, 2600; and morphine, 4200. Several psychopharmacologically active compounds were found to have I50 values comparable to the nonmeperidine opioids: hydroxyzine. HCl, 460; propoxyphene, 4,500; diazepam, 6,500; and cocaine, 10,800. The metabolites of meperidine exhibited the following I50 values: normeperidine, 0.7; meperidinic acid and normeperidinic acid, 210. A radioimmunoassay for meperidine which employs this antiserum was shown to be approximately 100 times more sensitive than the spectrophotometric method of Burns et al. (J. Pharmacol. Exp Ther. 114: 289-293, 1955). In this assay only normeperidine and some of the meperidine congeners might be expected to interfere with the measurement of meperidine. The degree of normeperidine interference was shown to be comparable to that present in the existing assay method.


[Lactation and sensitivity to corticotropicaxis to stress].

1. The plasma corticosterone levels were measured in nursing female rats which had been removed from their pups for 12 hrs, at 9 a. m. every day till weaning (day 22). The mean value found in this condition (14.6 +/- 2.7 mug/100 ml) does not differ significantly from that found for the cyclic female (13.7 +/- 4.2 mug/100 ml). 2. Suckling for a period of either 3 or 30 min increases the content of plasma corticosterone to the same value ; this value is maximal (+ 22.8 mug/100 ml) 30 min after suckling has started. 3. When mothers have been anaesthetized by a pentobarbital injection 40 min before suckling, plasma corticosterone increase, measured in the same conditions, is lower (+ 12.3 mug/100 ml). 4. The response to psychic (+ 25.5 mug/100 ml) or systemic (+ 46.6 mug/100 ml) stresses in mothers which have been removed from pups for 12 hr is impaired with respect to cyclic females (+ 62.7 mug/100 ml and + 83.8 mug/100 ml respectively). 5. Psychic stress applied immediately after suckling does not increase the plasma corticosterone level ; systemic stress does so slightly (+ 25 mug/100 ml). 6. In lactating rats the response to stress of the hypothalamo-pituitary-adrenal axis seems to be the same as that of intact or castrated males or ovariectomized females ; but differs from the response of cyclic females or of pregnant females when their basal corticosterone level is low.


Synthesis and dopaminergic activity of (+/-)-, (+)-, and (-)-2-dipropylamino-5-hydroxy-1,2,3,4-tetrahydronaphthalene.

In an effort to identify further the structural requirements for central dopamine receptor agonists, some monohydroxyl analogs of the known agonist 5,6-dihydroxy-2-dipropylamino-1,2,3,4-tetrahydronaphthalene were synthesized. They were examined for production of emesis in dogs and stereotyped behavior in rats. The most potent was 5-hydroxy-2-dipropylamino-1,2,3,4-tetrahydronaphthalene, which was more potent than apomorphine but less so than the dihydroxyl analog. The two enantiomers of the monohydroxyl analog were synthesized by conventional methods from an optically active intermediate, 2-benzylamino-5-methoxy-1,2,3,4-tetrahydronaphthalene. The resolution of this amine was performed with the aid of mandelic acid. Dopaminergic activity was found to be confined to the levo enantiomer. Requirements for both substitution and chirality in the tetralines were found to correspond closely to those known for the dopaminergic aporphines.


Drugs derived from cannabinoids. 3. Sulfur analogs, thiopyranobenzopyrans and thienobenzopyrans.

Sulfur analogs of cannabinoids corresponding to DMHP (1) were prepared utilizing the Pechmann condensation between the appropriate keto ester and (5-(1,2-dimethylheptyl)resorcinol, followed by Grignard reaction. Compounds of various structural types (2-6), which had different ring size and position of the sulfur atom substituted in the alicyclic ring, were found to be active CNS agents in pharmacological tests in mice, rats, and dogs. They showed profiles qualitatively similar to those of the nitrogen and carbocyclic analogs. Basic esters of the most interesting parent phenols 2 and 4 were also prepared and tested.


The role of the academic medical center in the PSRO program.

The professional standards review organization (PRSO) program offers both a challenge and an opportunity to the academic medical center. Application by the local PSRO of objective measures of the quality and medical necessity of services challenges  the medical center to demonstrate that its self-image of excellence is correct. Educating and training medical students and house staff in methods of self-evaluation and peer review could have a major impact on both the success of the PSRO program and the quality of medical care. Evaluation of the educational programs of the medical center through review of actual practice behavior presents an unparalleled means for improvement in undergraduate, graduate, and continuing medical education.


Drugs derived from cannabinoids. 4. Effect of alkyl substitution in sulfur and carbocyclic analogs.

Various CNS-active cannabinoids in which the alicyclic ring was thiopheno, cyclopenteno, or cyclohexeno with the alkyl substituent in various positions (structural types 1-6) were synthesized by procedures described previously. These compounds were compared in selected pharmacological tests in mice, rats, dogs, and cats. The results suggested that methyl substitution in the close proximity of the phenolic hydroxyl group strongly influenced the activity of some cannabinoids, particularly of those which had a planar five-membered alicyclic ring rather than a six-membered ring.


Quality assurance in undergraduate medical education at the Medical College of Ohio.

This paper reports a four-year experience in teaching evaluation of care at a three-year medical school, the Medical College of Ohio at Toledo. Informal patient care evaluation evolved to more structured medical care evaluation in seminars and by chart audits. The introduction of professional standards review organizations prompted the teaching and evaluation of the quality and cost of primary care, especially as it applies to learning clinical tasks.


Some assay restrictions on inferences made from determining hormones in horses, cows, and their fetuses.

Often in developing hormone assays, hormones that may interfere with the assay by cross-reaction are not available for testing the validity of the assay. For example, horse TSH was unavailable to test for cross-reaction in an LH radioimmunoassay (RIA). The authors devised an indirect means of accomplishing the same goal, and the evidence from the indirect test of cross-reaction was at least as persuasive as a direct test might have been. Other examples are given of experiments where extensive effort was devoted to validation of steroid RIA, but there were substantial quantitative differences in the results among experiments and among laboratories. Differences of this kind probably would be intolerable in an assay used to monitor hormone residues in food-producing animals.


Combined electromyographic and gas urethral pressure profilometry.

Combined electromyographic and gas urethral pressure profilometry provide for rapid assessment of urethral function in neurological dysfunction of the detrusor muscle and urethra.


External sphincter spasticity syndrome in female patients.

The external sphincter spasticity syndrome is described with regard to diagnosis, etiology, pathophysiology and treatment. Use of urodynamic techniques (especially urethral pressure profile and diagnostic pudendal blocks) and adrenolytic agents and diazepam in the treatment of the dysfunction is discussed. We consider this clinical entity to be much more common than perviously reported.


Pharmacokinetic studies on the hepatotoxicity of luteoskyrin. (III) quantitative determination of luteoskyrin in the liver.

A method for the quantitative determination of luteoskyrin in mouse liver is described. Luteoskyrin was extracted with ether from the liver homogenate after acidification with with HCl, purified by thin-layer chromatography and determined by spectrophotometry. Five mug of luteoskyrin added to the liver homogenate which was equivalent to one gram tissue was determined with a recovery rate of 97% and 1 mug, under the same conditions, with a recovery rate of 70%. Luteoskyrin in the amount of 0.5 mug could be detected on the chromatogram, but could not be determined quantitatively. A radioactivity corresponding to 0.92 mug/g tissue of 3H-luteoskyrin in the livers from the mice injected intravenously with this compound was extracted into ether with a recovery rate of 93% and separated on the thin-layer chromatogram with a recovery rate of 81%. The lower limit of quantitative determination of luteoskyrin in one gram of liver was 1 mug. Amounts of luteoskyrin in the livers of mice poisoned with this mycotoxin were estimated. Luteoskyrin was recovered in a large quantity in livers from male mice while detection in the liver of females was nil.


[Modern aspects of thyrotoxicosis in childhood (author's transl)].

3 children aged 4, 7 and 12 years with severe thyrotoxicosis were observed. Though symptoms had existed for at least 6 months, the disease had not been diagnosed earlier; therefore clinical symptoms and diagnostic possibilities are discussed in detail. Carbimidazole was used for therapy because of the low incidence of side effects. Furthermore, an imidazole type drug allows to control underlying thyroid function during antithyroid drug therapy by measuring the 20 min. uptake (trapping). Results of long term observations are discussed.


[Familial vesicoureteral reflux (author's transl)].

One family with all four children affected by vesicoureteral reflux is reported. The mother of children has shrinking kidneys. The possibility, that the congenital abnormality of vesicoureteral reflux is inherited, is discussed. The awareness, that reflux may be familial, led to search for the abnormality in close relatives.


[Kidney anomalies in Ullrich-Turner-syndrome (author's transl)].

Intravenous urography was performed in fourteen children with Ullrich-Turners syndrome. Renal abnormalities have been noted in twelve cases (85,7%). The most frequent kidney anomalies were malrotations (28,5%), horseshoe kidneys (21,4%) and double kidneys (21,4%). Malformations of kidney are thus a very frequent feature in Ullrich-Turners syndrome. It is therefore recommendable to perform in any case of Ullrich-Turners syndrome an intravenous urography, since these abnormalities are clinically latent.


[Parameters of the elimination of phenolsulfonphthaleine (phenolred) in children (author's transl)].

The elimination of phenol-red was examined in 124 children without renal diseases. The normal values of the kinetic parameters were determined after intravenous injection of 3-4 mg dye per kg bodyweight. The elimination-half-life, which is independent from bodyweight and length was used as measure for the renal tubular secretion. In newborns (85,8 min) and young infants up to the age of 6 months (25,4 min) elimination-half-lives were longer than in older ones. After the second year of life (19,7 min) normal values of adults could be determined. The total clearance of phenol-red is smaller in newborns (185 ml/kg/h) than in children older than one year (643 ml/kg/h). Prematures had a longer elimination-half-life and a smaller total clearance than mature newborns.


[Development after respiratortreatment during the newborn period (author's transl)].

There were 17 survivors of severe neonatal respiratory distress treated with IPPV for more than 24 hours (36-520 hrs, mean duration of IPPV 6 days) followed into the second year of life. 11 of these young children were physically and neurologically normal. 3 were developmentally retarded (3 months or more), 2 had neurological defects without mental subnormality. These defects (Hemiplegia and Diplegia) were correlated with low gestational ages (32 and 33 weeks respectively) 1 child was severely defective. This one was treated because of apnea caused by seizures in postmaturity syndrome (44 weeks gestation). The overall incidence of defects was 3/17 (= 17%).


[Septicaemia in the neonatal and infant period (author's transl)].

The paper reported about septicaemia in the neonatal and infant period. Continuing former investigations by Kienitz in the same pediatric clinic we have got a survey from 1933 to 1974. In the last years we saw increasingly more infections with gram-negative organisms, especially by Pyocyaneus with a severe prognosis. The prognosis did not improve during the last 10 years. The over all mortality was 34-35%. Frequency, symptoms, problems of species and resistance were described. Besides that we reported about an outbreak of enterobacter in our neonatal unit.


[Comparison of the phenylalanine determination by ion exchange column chromatography and the guthrietest in treated phenylketonuric children (author's transl)].

Simultaneous measurements of phenylalanine by ion exchange column chromatography and microbiologal inhibition test according to Guthrie were performed on 22 treated children with phenylketonuria within two years. The results coincide in 40,3% (229 of 569 estimations), in 15,8% the real phenylalanine concentration by the method of Guthrie were overestimated, in 43,9% underestimated. Bacterial inhibition assay is successful in routine screening of phenylketonuria in the newborn, but not suitable for dietary control of phenylketonuria.


[Leptospirosis epidemic (L. grippothyphosa) in the Mainz area, concerning the pediatric age group (author's transl)].

31 children, presenting with rather uncharacteristic symptoms of an infectious disease and being referred to this clinic mostly because of lymphadenitis of the neck (81%) and/or signs of meningitis (45%), were seen within a period of only eight weeks and proved to suffer from Leptospirosis (L. grippotyphosa). The majority of the patients belonged to the age group of one to six years and lived in rural environs.  Our observation is considered to relate to a Leptospirosis epidemic and suggests, as opposed to the general acceptance, a much higher incidence of Leptospirosis in this country and, moreover, in children.


[Clinical further development of children after surgery for subdural effusions (author's tranls)].

Follow-up examinations of 82 children after surgery for subdjral effusions show a varied degree of retardation of motor- and speech-development. This corresponds to neurologic signs of varying severity. Preoperative EEG findings are improved both in pre-school- and school children. Disturbance of motor and intellectual development as a rule corresponds to severe EEG changes. Among pre-school children 35% had an IQ below 69%, among school-children 36%. But their occupational chances cannot yet be finally assessed. Children with large effusions (over 50 ml) and extensive capsules show a higher percentage of retardation. Present results do not establish relations between site of effusion, frequency of recurrence and mental development.


[Autistic syndrome (Kanner) and vaccination against smallpox (author's transl)].

3-4 weeks following an otherwise uncomplicated first vaccination against smallpox a boy, then aged 15 months and last seen at the age of 5 1/2 years, gradually developed a complete Kanner syndrome. The question whether vaccination and early infantile autism might be connected is being discussed. A causal relationship is considered extremely unlikely. But vaccination is recognized as having a starter function for the onset of autism.


[Hypomelanosis cutis ITO (author's transl)].

Report on a 9 year old girl exhibiting the typical features of Ito's syndrome: systematized bilateral depigmented nevus associated with various nonspecific dysplasias. The pathogenesis is not known. The syndrome geems to be transmitted by an irregularly dominant gene.