Mutagenicity of the triazine herbicides atrazine, cyanazine, and simazine in Drosophila melanogaster.

Assays for dominant lethal mutations, sex-linked recessive lethal mutations, and chromosomal breakage, nondisjunction and loss were performed on Drosophila melanogaster males treated by injection or by larval feeding of the herbicides atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine), cyanazine [2-chloro-4-(1-cyano-1-methylethylamino)-6-ethylamino-1,3,5-triazine], or simazine [2-chloro-4,6-bis-(ethylamino)-1,3,5-triazine]. The three herbicides significantly increased the rate of apparent dominant lethals, but this reduction in egg hatch was probably due to physiologic toxicity to sperm. Atrazine significantly increased X-linked recessive lethals and X or Y loss after treatment by larval feeding. Injection of simazine elevated X-linked lethals, whereas treatment by larval feeding did not. None of these herbicides significantly increased partial loss of the Y chromosome nor sex chromosome nondisjunction. Much larger experiments are needed to determine with confidence the mutagenic potential of these herbicides.


Calcifying and osteoblastic tumors of the paranasal sinuses.

Calcifying and osteoblastic tumors of the paranasal sinuses comprise a large group of diseases, each characterized, however, by their own distinct pathologic features and correlated radiologic findings. The basic radiologic signs of such lesions comprise calcification, bone formation, and reactive bony sclerosis. It is the purpose of this presentation to define the radiologic signs which allow for appropriate diagnosis. These disorders are divided into three groups: calcifying and osteoblastic lesions simulating tumors, benign calcifying and osteoblastic tumors, and malignant calcifying and osteoblastic tumors.


Prostaglandin synthetase inhibitors in Bartter's syndrome. Effect on immunoreactive prostaglandin E excretion.

Urinary excretion of immunoreactive prostaglandin E (iPGE) was measurably increased in five of seven patients with Bartter's syndrome. The effects of indomethacin were compared with those of either aspirin or ibuprofen in four patients. Indomethacin produced notably greater suppression of urinary iPGE, greater sodium and potassium retention, greater increases in serum potassium, and decreases in plasma renin activity and in creatinine clearance than the other inhibitors. This demonstration that there is a close correlation between the suppression of urinary iPGE excretion and the extent of correction of the clinical abnormalities in Bartter's syndrome, regardless of the chemical structure of the prostaglandin synthetase inhibitor, is further evidence for the importance of prostaglandins in the pathogenesis of this syndrome.


Effect of PCB (polychlorobiphenyls) on on L-ascorbic acid, pyridoxal phosphate and riboflavin contents in various organs and on hepatic metabolism of L-ascorbic acid in the rat.

Effects of continuous oral administration of PCB (polychlorobiphenyls, 10-100 mg/kg/day, 4 weeks) on tissue levels of L-ascorbic acid (vitamin C), pyridoxal phosphate and riboflavin (vitamin B2) in various organs and on hepatic metabolism of L-ascorbic acid were examined in male Wistar rats weighing 150-250 g. Riboflavin contents in the liver, kidney, brain, heart and testis were not altered by PCB treatments, whereas the hepatic level of pyridoxal phosphate, a biologically active form of vitamin B6, was significantly reduced by PCB administration. Under the same experimental conditions, L-ascorbic acid contents in the liver, kidney, lung and testis showed a significant increase. Histochemical studied revealed that in the adrenal gland, increase of L-ascorbic acid was localized in the fasciculate and reticular zones of cortex, respectively. It was found that increase of L-ascorbic acid in the liver is caused predominantly by activation of biosynthesis at the steps of galactose to D-glucuronic acid and is not due to changes in the catabolic processes of L-ascorbic acid per se. Possible significance of these changes in tissue levels and/or metabolism of vitamins in the occurrence of PCB intoxication is briefly discussed.


[Norrie syndrome (author's transl)].

The Norrie syndrome, an x-chromosomal linked, recessive genetic disease, is described using ophthalmologic and genetic examinations of a family in three generations. The main symptom of this syndrome is retinal detachment with hemorrhages, which generally leads to blindness in early childhood. In addition to this, in 25--35% of the cases mental retardation and hearing problems are found. Special significance is to be attached to the differential diagnosis of this syndrome because the vascular proliferation on the retina is a non-specific, secondary reaction in children, which also occurs symptomatically in several other diseases.


[Epithel regeneration inhibition in the treatment of Trifluorothymidin (F3TDR) (author's transl)].

After well-defined chemical and mechanical removal of the corneal epithelium from 38 rabbit eyes 19 right eyes were treated with F3TDR (Trifluorothymidine) 6 times daily, whereas the 19 left eyes were with physiologic NaCl-solution 6 times daily. The epithelial regeneration was compared with the contralateral controll-eye. No significant difference was found between both eye-series. The short-timed high dosage of F3TDR seems to have no delaying effect on epithelial regeneration.


[Hospital infections from a bacteriological viewpoint].

In spite of the successful treatment of bacteriological infections combined with progress in hospital hygiene there remain still problems of infective hospitalism in certain sections of the hospital. Generally, the causative bacteria are nosoparasites not being dangerous to human beings in good condition. From this point of view Pseudomonas aeruginosa and Serratia marcescens are the most important species. A successful challenge against infective hospitalism is only possible under the supervision of the bacteriologist. It is his task to isolate and differentiate the bacteria and to carry out the sensitivity tests against antibiotics. Besides this, he has to treat epidemiological and hygienic problems. Special kinds of methods sometimes have to be used to find out the sources and the routes of spreading of the infections in a hospital e.g. bacteriophage typing, bacteriocin typing and analysis of the antigenic structure. Likewise, the transmission of bacteria by air has to be studied and continuous controlling measures and monitoring are required. The bacteriologist is also responsible for preparing hygiene instructions. There always has to exist a good cooperation between the bacteriologist, the clinical doctors, the nurses and the technical staff. The whole problem can only be handled by special teams.


[Comparative studies during postoperative infusion of glucose or a combination of glucose, fructose and xylitol over five days (author's transl)].

Two groups of 12 cholecystectomized or vagotomized patients were given central venous infusions of either a combination of glucose, fructose and xylitol at the ratio of 1:2:1 or of glucose alone for 5 days. The dose was increased stepwise from 1.43 g/kg/h on operation day up to 7.14 g/kg/24 h on the fourth day after surgery, which equals 100-500 g/24 h for the average 70 kg patient. On both infusion regimens mean blood glucose values ranged from 98-124 mg/100 ml. Urinary losses of infused substrates amounted to 0.2-0.8 g/24 during glucose infusion and to 2.22-13.4 g/24 h during infusions of the carbohydrate combination. Regarding mean blood or serum values of lactate, pyruvate, uric acid, sodium, potassium, phosphorus, insulin and free fatty acids, no significant differences were found between the two types of carbohydrate infusion. Side effects were not observed. The results obtained allow conclusion that in clinical situations with moderate stress, such as the selective operations mentioned above, the combination of glucose, fructose and xylitol studied offers no advantage over glucose alone. However, in severely ill patients presenting with more pronounced glucose intolerance, further studies with sugar substitutes are warranted.


The reproductive cycle of the capuchin (Cebus apella).

Six, mature female capuchins, Cebus apella, were used to study occurrence of bleeding, the length and phases of the menstrual cycle, and the gestation period. During a 3-month period the menstrual cycle was determined to be 21 days, including an average of 4 days in which bleeding was detectable. It was found that only proestrus and estrus could be reliably identified during the menstrual cycle by the use of vaginal smears. Each female was housed with a male for a sufficient time to allow insemination. Four became pregnant. Three had term pregnancies and one aborted. The other two remained barren. The average gestation period for the three normal pregnancies was 153 days.


Oxygen consumption and thyroid function in the squirrel monkey (Saimiri sciureus).

Thyroidal accumulation of 125I and the biological half-life of 131I-thyroxine were determined in the squirrel monkey. Oxygen consumption and the respiratory quotient were also measured. A peak uptake of 131I by the thyroid of 45.3% of the injected isotope occurred 4 hours after administration of the radioisotope. The biological half-life of the 131I-thyroxine was 22-24 hours. Oxygen consumption was 1.02 cm3 O2/g/hour and the respiratory quotient was 0.82. It was concluded that the squirrel monkey is hypermetabolic when compared with other laboratory animals of the same size.


Disseminated cryptococcosis in a patas monkey (Erythrocebus patas).

Cryptococcosis was diagnosed in an adult male patas monkey (Erythrocebus patas) 9 months after importation. The disease was characterized by an open lesion on the buttock and epileptiform seizures. Diagnosis was confirmed through immunologic identification of the organism in serum and cerebrospinal fluid and by mycologic procedures performed on the cultured organism. The monkey was killed and cryptococcal organisms were found in the lung, brain, subcutaneous lesions, thyroid, pancreas, adrenals, and spinal cord. Retrospective analysis of stored serum indicated that the monkey was infected at the time of importation.


The duration of gestation in the squirrel monkey (Saimiri sciureus).

A restricted mating period was used to determine the duration of gestation in the squirrel monkey (Saimiri sciureus) of Colombian-Brazilian origin. Ten pregnancies were observed. The length of the gestation period was found to range from 141 to 154 days with a mean of 146.9 +/- 3.28 SD, a median of 146.5, and a modal length of 146.


The olive babbon (Papio anubis) as an animal model for research in affective disorders of man.

Efforts were made to develop an animal model for studies of the role of biogenic amines in a group of human "mood" diseases including mania and depression. Subadult, male olive baboons (Papio anubis), both normal and psychologically disturbed individuals, were anesthetized and administered 18O-enriched air for 60-130 minutes. Afterwards blood, urine, and cerebrospinal fluid were collected every hour, for 10 hours. The samples were subsequently fragmentographically analyzed for labelled metabolites of serotonin, dopamine, and norepinephrine. The results showed that significant incorporation of 18O was found in all metabolities studied, with a peak after about 4 hours. The effect of chlorpromazine injection on 18o-incorporation was also measured. It was found that chlorpromazine caused a faster rise in labelling and indicated the stimulation of dopamine turnover in the brain. The usefulness of the animal model and the in vivo labelling technique for biogenic amine determination in the brain was demonstrated by the fact that the technique was subsequently used in human patients with neurologic disease.


The common marmoset (Callithrix jacchus jacchus) as a model for ethological research.

The uses and advantages of the common marmoset (Callithrix jacchus jacchus) as an animal model for ethological research were examined. It was found that this species had advantages over Old World primates for work on social behavior as a nearer approximation to the group structure occurring in natural conditions could be obtained in the laboratory. The small size of the common marmoset also made it easier to handle and cheaper to maintain. The adult female gave birth at five-month intervals and usually reared twin offspring. This, and the short generation time, made it an ideal model for mother-infant behavioral studies. The common marmoset was also shown to be a useful model for studies of social play, especially for categorizing the changes in playful behavior with age, and the relationship of the patterns seen in play to other behaviors. It was also suggested that it may be an ideal model for experimental studies of play. Other suggested uses included studies of the relationship of food supply and feeding habits to territory size and group structure, and of the advantages to elder offspring of helping to rear younger siblings. As a result of these observations the common marmoset was considered to have great potential as a model for ethological research, both in its natural habitat and in the laboratory.


Plantar ulcers with osteomyelitis underneath. A bacteriological study.

39 consecutive cases of plantar ulcers with underlying chronic osteomyelitis admitted in the Sacred Heart Hospital during 1975/1976 were studied for the infecting organisms and their sensitivity to easily available antibiotics. Single organism was iasolated in only 10 cases, the infection in the rest being a mixed one. The commonest organisms were Staphylococcus, Streptococcus and Proteus mirabilis. In a few cases Pseudomonas and E-Coli were also isolated. Chloramphenicol was the most effective antibiotic in general and Streptomycin the least. 70% of the staphylococcus strains isolated were found to be resistant to Penicillin. Empirical use of antibiotics especially Penicillin and Streptomycin is hence deprecated.


High-affinity phlorizin binding to brush border membranes from small intestine: identity with (a part of) the glucose transport system, dependence on Na +-gradient, partial purification.

In the presence of an NaSCN gradient phlorizin binds with a high affinity (Kd similar or equal to 4.7 micron) to vesicles derived from brush border membranes of intestinal cells of rabbits. The value for Kd corresponds closely to that of Ki determined from phlorizin inhibition of sugar transport. The apparent affinity for phlorizin is decreased if NaCl is substituted for NaSCN and decreased substantially if the gradient of NaSCN is allowed to dissipate prior to the phlorizin binding. The number of high affinity binding sites is about 11 pmol/mg protein. Additional binding to low affinity sites can amount to as much as 600 pmol/mg protein after prolonged exposure to phlorizin (5 min.). The high affinity sites are related to glucose transport based on the similarity of the Kd and Ki values under a variety of conditions and on the inhibition of the binding by D-glucose but not by D-fructose. The transport system and the high affinity phlorizin binding sites can be enriched by a factor of 2-3 by treatment of vesicles with papain, which does not affect the transport system, but considerably hydrolyzes nonrelevant protein.


Changes in ethanol consumption by pregnant pigtailed macaques.

Three out of four monkeys reduced their consumption of ethanol at conception and increased their consumption after delivery.


Gentamicin-resistant Pseudomonas aeruginosa: Mayo Clinic Experience, 1970-1976.

During the period 1970 through 1976, there were 144 patients from whom gentamicin-resistant Pseudomonas aeruginosa (minimum inhibitory concentration [MIC], more than 5 microgram/ml) was isolated. In 20(21 percent) of the 95 patients who acquired such organisms within our institutions, the occurrence was considered clinically significant. Factors that favored the appearance of gentamicin-resistant P. aeruginosa included prolonged hospitalization, previous antibiotic treatment, increased gentamicin usage, underlying disease, and instrumentation (70 percent). Virulence of gentamicin-resistant isolates appeared less than that of susceptible organisms, with bacteremia due to these isolates occurring in only three cases. Resistant isolates with MICs for gentamicin of 8 to 16 microgram/ml were more susceptible to tobramycin than to amikacin, whereas isolates with MICs for gentamicin of 64 microgram/ml or greater were more susceptible to amikacin than to tobramycin. Eighty percent of all strains were susceptible to 128 microgram/ml or less of carvenicillin. Favorable results occurred in 12 or 13 cases treated with gentamicin plus carbenicillin, whereas treatment with either of these agents alone resulted in failure or relapse in 7 of 14 cases.


Antimicrobial susceptibility of gentamicin-resistant Pseudomonas aeruginosa.

The susceptibility of 41 strains of gentamicin-resistant Pseudomonas aeruginosa to tobramycin, sisomicin, netilmicin, amikacin, and carbenicillin was determined. Amikacin and carbenicillin exhibited the greatest activity against these strains and especially against those with a high level of resistance to gentamicin. Netilmicin exhibited little activity, whereas tobramycin and sisomicin were active against approximately two-thirds of the strains. Cross-resistance to tobramycin, sisomicin, and netilmicin was frequent.


[Mammary carcinoma: radiotherapy (author's transl)].

Radiotherapy for mammary carcinoma has special indications, depending upon the TNM stage and the localization. The use of megavoltage irradiation, a well-defined technique, and consideration of radiobiologic factors are necessary. Radiotherapy is the only therapeutic possibility in cases of recurrences.


[Present status of breast cancer surgery in Italy (author's transl)].

Radical mastectomy is the most frequent surgical procedure in breast surgery in Italy. It is indicated in all stages associated or not to complementary therapies. Extended radical mastectomies are performed less frequently than previously. In initial stages of the disease partial mastectomies are performed more frequently. Generally, castration is performed as therapeutic means, not any more for prophylactic reasons. Adrenalectomy and hypophysectomy are seldom associated procedures. As postoperative treatment, Roentgen-Cobalt-Betatrone therapy is still widely used. However, chemotherapy (CMF) is progressively replacing radiation therapy, mostly in the advanced stages.


[Breast cancer: current concepts in Holland on the treatment of the primary tumor (author's transl)].

Holland is among the countries with the highest incidence of breast cancer. Increasing awareness of the danger is borne out by rapidly decreasing average diameter of primary tumors during the lase 15 years. The application of very strict pre- and peroperative criteria for operability resulted in a decrease of 15% of the clinically operable group, thereby avoiding therapeutically meaningless mutilation. Encouraging results of radiotherapy in inoperable cases are reported. Operative treatment consists of removal of the breast and axillary contents. Radiotherapy is applied only to the parasternal nodes.


[Carcinoma in Zenker's diverticulum (author's transl)].

Carcinoma arising in Zenker's diverticulum have to be thought of, if it has been present for long time, if there is blood mixed the food regurgitated, and if there are irregularities of the wall of the diverticulum to be detected radiologically. In most cases resection is the method of choice. A case of a 70 year old patient is reported, who harbored a microcarcinoma in the mucosa of a resected Zenker's diverticulum. Surgery was done 10 years ago and no recurrence or mestastases have been observed since.


Glucagon and growth hormone secretion in insulin-treated diabetics: effects of added sulfonylureas.

Eleven insulin-dependent ketosis-prone diabetics were given glibenclamide (5 mg/day) in addition to their usual insulin treatment for a period of 1 or 6 mo. There was significant reduction in arginine-induced IRG and hGH secretion and no change in blood glucose levels after either 1 or 6 mo of treatment. During that time no change in weight or insulin requirement was observed. The importance of the duration of treatment and the fact that in this type of patient the effects on IRG and hGH secretion could not be mediated by the influence on insulin secretion are stressed.


The application of an image analyzing computer (Quantimet 720) for quantitation of biological structures--the automatic counting of mast cells.

A Quantimet 720 image analyzer was utilized in order to 1) quantify mast cells automatically in gingiva and in doing so to 2) investigate the applicability and accuracy of the machine for quantitative analysis of biological structures. The mast cells of two hundred gingival sections were counted first by means of the Quantimet and then by manual count. Results indicated that a) mean counts of mast cells obtained by means of the Quantimet were comparable to that of the manual counts, b) although the spread was larger than by manual methods, the Quantimet automatic image analyzer performed quantitation more rapidly.


Correlative scanning-transmission electron microscopy of the primate infundibular recess.

This report describes a basic techinque for the analysis of subhuman primate brains with correlative scanning (SEM) and transmission electron microscopy (TEM) of the same tissue sample. The methodology is described in detail and this report characterizes the type II supraependymal histiocyte.


[Diabetic ketoacidosis: new therapeutic regimen (author's transl)].

A regimen of low-dose insulin infusion (0.1 IU/kg/h) for the treatment of children with diabetic ketoacidosis is given. The regimen is safe, simple, effective, and minimizes the dangers of hypoglycemia and hypokalemia, In addition a selective bicarbonate therapy is proposed.


Cytological analysis of X-ray-induced aberrations in spermatocytes I and the somatic ganglia of male Drosophila melanogaster.

The correlation between damage induced in somatic cells and that induced in germinal cells of the same genetic pool of individuals is important in establishing the possibility of extrapolation of this damage to the offspring. We have used Drosophila melanogaster to compare cytologically the frequency of aberrations induced in the cells of somatic ganglia and in the spermatocytes I of males irradiated with 625 R X-rays. The spermatocytes were more sensitive than the gangliar cells to radiation: the aberrations induced in the spermatocytes I were three times more frequent than those induced in the ganglia. The distribution of the aberrations was, however, similar. The most important variable element lies in our observing no symmetrical exchanges in the spermatocytes. This result seems to us to be related to the fact that in the males of D. melanogaster there is no crossing-over.


Mutagenicity of hair dye components relative to the carcinogen benzidine in Drosophila melanogaster.

A comparative assay was undertaken in Drosophila melanogaster for the assessment of the mutagenic efficiency of the hair dye components m-toluene-diamine (m-TD) and 4-nitro-o-phenylenediamine (4-NOPD) relative to the  aromatic amine human carcinogen benzidine (Bzd). The compounds were injected at equimolar dose ranges (5-20 mM) around the testes of adult males and their mutagenicities were measured separately on the various stages of spermatogenesis. Genetic activity was simultaneously assayed with respect to the overall induction of the X-chromosome recessives (lethals and visibles) relative to the specific effects on rDNA (expressed as bobbed mutations). All compounds exerted decisive mutagenicity both on the X-chromosome and the RNA genes, although their activities on the different genic sites varied between compounds and as a function of cell stage, but not in response to changes in dose, within the investigated molarity range. The mutagenicities and selectivities of the test compounds for rDNA gradually decreased in the order Bzd greater than m-TD greater than 4-NOPD, which correlated with the evidence-so far-about their carcinogenicities.


Superiority of demeclocycline over lithium in the treatment of chronic syndrome of inappropriate secretion of antidiuretic hormone.

We evaluated demeclocycline and lithium therapy in 10 patients with the syndrome of inappropriate secretion of antidiuretic hormone. Despite severe water restriction, all patients had hyponatremia (mean +/- S.E.M. serum sodium of 122 +/- 1.1 meq per liter) and elevated urine osmolality (744 +/- 59 mOsm per kilogram) before treatment. Demeclocycline (600 to 1200 mg daily) restored serum sodium concentration to 139 +/- 1.1 meq per liter within five to 14 days, permitting unrestricted water intake in all patients. In three patients given lithium carbonate (900 mg daily) the serum sodium concentration, urine osmolality and urine volume were unchanged; since two patients had adverse central-nervous-system symptoms during lithium therapy, further study of this agent was abandoned. A patient with an unusual 22-year history of the syndrome was unresponsive to lithium, whereas long-term treatment with demeclocyline was markedly effective. Demeclocycline is superior to lithium in the treatment of the syndrome and may obviate the need for severe water restriction.


Hospital discharge one week after acute myocardial infarction.

Sixty-seven consecutive patients who had suffered an acute myocardial infarction but no serious complications during the first to fourth hospital days were considered for a trial of hospital discharge at one week. Thirty-three of the 67 patients were discharged at one week, the remainder having a mean hospital stay of 11 +/- 2 days. The incidence of late complications and recurrent infarctions, as well as mortality and functional status, were determined in all patients six months after discharge. No serious complications occurred in either subgroup within three weeks after discharge. There were no deaths in either subgroup and no difference in functional status at six months. Patients without serious complications during the four days after an acute myocardial infarction can be spared the economic costs and psychologic stress of prolonged hospitalization.


Approaches to controlling the costs of medical care: short-range and long-range alternatives.

Cost containment requires changes either in patterns of consumption or in the way services are provided. Although the former includes prevention, changing social expectations and finding suitable substitutes for some types of care, the latter involves mix of personnel technologic inputs, auspices of care and the content of encounters. Ultimately, the future of medical care and cost containment depends on advances in biomedical and health-services research. In the short run, costs will be contained increasingly by rationing mechanisms. Whereas cost sharing is intended to affect consumer behavior, implicit rationing, as through capitation and prospective budgeting, is intended to encourage physicians to make tougher allocation decisions. Explicit rationing, in contrast, depends more on administrative decisions that limit physician discretion. A better understanding of the effects of different rationing technics on patient and physician behavior and the quality of care, as well as on cost, is required.


Sensitivity to 5-fluorocytosine and virulence for mice of some human isolates of Aspergillus.

The sensitivity of 5-Fluorocytosine (5-FC) and the virulence for mice was assessed for 16 human isolates of Aspergillus: A. fumigatus 2, A. niger 7, A. flavus 4, A. terreus 2 and A. conicus (A. restrictus group) 1. Fourteen strains were recovered from ear exsudates, 1 from sputum and 1 from the pus of mastoid cells of an autopsy case with meningeal and cerebral involvement. Nine of them, which included strains of A. fumigatus and A. niger were sensitive to 5-FC (M.I.C. less than or equal to 6.4 microgram/ml) whereas strains of A. flavus and A. terreus were resistant (M.I.C. greater than 51.2 microgram/ml). Cultures of A. fumigatus, A. flavus and A. conicus proved to be the most virulent for mice and A. terreus strains the less virulent. Results observed with the strain of A. conicus deserves further investigations.


Bacteriological contamination of dialyzers. Clinical, bacteriological and scanning electron-microscopic evaluation of different dialysate mixing systems.

Membranes from Gambro Lundia Nova dialyzers were investigated for presence of bacteria after hemodialysis with centrally and peripherally mixed dialysate. Centrally mixed dialysate was found contaminated with Pseudomonas aeruginosa, and bacterial cultures as well as electron scanning micrographs showed the presence of these bacteria on the dialysate side as well as on the blood side of membranes from dialyzers perfused with this dialysate during hemodialysis. No bacteria were found on membranes used with peripherally mixed dialysate, in which very few bacteria were found. Despite this the frequency of febrile episodes in patients submitted to hemodialysis with the two different dialysate mixing systems showed no significant difference in our material.


Quantitative histochemical studies of the hypothalamus: dehydrogenase enzymes following androgen sterilization.

Four enzymes, selected as representative of major metabolic pathways (malic dehydrogenase, of the citric acid cycle, lactic dehydrogenase, of glycolysis, glucose-6-phosphate dehydrogenase, of the pentose pathway and glutamic dehydrogenase, of glutamate metabolism), were measured by quantitative histochemical methods in individual hypothalamic nuclei of adult neonatally androgenized female rats. Malic dehydrogenase (MDH) was significantly reduced in nuclei of the anterior hypothalamus: the suprachiasmatic, supraoptic and anterior. Lactic dehydrogenase (LDH) increased significantly in the lateral preoptic area. Glucose-6-phosphate dehydrogenase G-6-PDH was also significantly elevated in anterior hypothalamic nuclei: medial preoptic, lateral preoptic, supraoptic and paraventricular. Glutamic dehydrogenase (GDH) was generally elevated throughout the hypothalamus with significant increases of activity occurring in the paraventricular, lateral ventromedial, arcuate, medial mamillary and posterior nuclei.


[Comparative balance study of the value of amino acids for humans after oral and parenteral input].

The biological value (BV) of an amino acid mixture, according to the potato-egg principle (KE), was determined in the case of oral and parenteral input with three healthy adult volunteers in a long-term complete test of metabolic balance: KE-amino acid pattern with oral input, BV=134.4; KE-amino acid pattern with parenteral input, BV= 131.4; egg protein (reference) with oral input, BV=100. The long-term metabolic balance experiment with human subjects under criteria of compensated nitrogen balances was used to test nitrogen substances like whole egg protein and amino acids (under parenteral and oral input); the BV of a nitrogen substance is defined as the reciprocal value of the minimum nitrogen requirements compared with the reference protein whole egg, which is set at 100. The results confirm in principle (1) the almost identical utilization and value of identical nitrogen substances (amino acids), even with different ways of input with oral and parenteral nutrition of the human being, and (2) the ability of reproduction of the BV of the optimal potato-egg protein mixture (65% potato nitrogen + 35% egg nitrogen with oral input: BV = 137.6) by means of simulation through corresponding L-amino acids, considering the modification necessary for technical as well as physiological reasons, which concern the non-essential part of the pattern.


Bacteriolytic activity of amniotic fluid.

Bacteriolytic activity and lecithin concentration were measured in amniotic fluid samples from both normal and pathologic pregnancies, including conditions such as severe Rh isoimmunization, placental dysfunction, preeclampsia, and diabetes. The bacteriolytic activity increased threefold from the 25th gestational week to term, after which a slight reduction was found. No difference was found between pathologic and normal pregnancies. No correlation was found between lecithin content and bacteriolytic activity. Samples from pregnancies in which the infant developed respiratory distress syndrome had low lecithin concentrations but showed normal bacteriolytic activities.


The effect of zinc phosphate and carboxylate cements on the healing of experimentally induced pulpitis.

The effects of zinc phosphate and carboxylate cements on the healing of experimentally induced pulpitis have been studied. The results demonstrate that both cements allow healing of pulp imflammation when used as base materials.


Denture stabilization with peralveolar tubing.

Mock dentures were stabilized in six monkeys by means of polyethylene tubings passed through surgically created buccolingual peralveolar channels. Macroscopic, radiographic, and microscopic examinations demonstrated that the dentures were stabilized and the tubings well tolerated throughout the 120-day study period.


Eosinophilia in Kenyan baboons (Papio anubis) induced by Trichinella spiralis and Schistosoma mansoni.

High primary doses of Trichinella spiralis administered orally to Kenyan baboons (Papio anubis) induced a marked but unpredictable eosinophilia which started 2--3 weeks after infection and persisted as erratic waves for at least 6 months. Low primary oral doses induced no eosinophilia but a later, high challenge gave an accelerated eosinophilic response, although the peak was lower than in high primary infection. Intravenous injection of infective T. spiralis larvae resulted in a predictable, rapid eosinophilic response which persisted for several weeks. Intravenous injection of a particulate material, Sepharose, gave no oesinophilic response. Percutaneous Schistosoma mansoni infection of baboons resulted in a two-stage eosinophilic response: an initial rise occurred about 2/3 of the way through the pre-patent period and was followed by a second rise at the onset of patency. After peaking, the eosinophilia waned erratically over the next 3 or 4 weeks. A strong antibody response, measured by countercurrent immunoelectrophoresis, was given in oral infections with T. spiralis, but intravenous injections elicited little or no antibody formation. Parasitological evidence indicated no cross-resistance to S. mansoni in baboons injected with T. spiralis 9 days previously. Thus, the intravenous injection of infective T. spiralis larvae appears to be a suitable method of inducing experimentally a non-specific eosinophilia to investigate possible immune mechanisms to S. mansoni in the baboon.


[N-Acetyl-beta-hexosaminidases. Present knowledge regarding chemical characterization and genetic relationships (author's transl)].

In recent years considerable attempts have been directed towards the chemical characterization of lysosomal hexosaminidases. Hexosaminidase A had been shown to be a heterotetramer: alpha2 beta2 and hexosaminidase B a homotetramer: beta4. Studies of GM2 gangliosidosis supported this theory, in fact alpha and beta chains require genes on different chromosomes.


[Monoclonal gammapathies. (Critical review of 219 cases collected over 3 years)].

219 monoclonal gammapathies have been studied since 1rst January 1973 up to 31st December 1975, regarding 121 males and 98 females, 121 myeloma (mean age: 66 years), 38 Waldenstrom's macroglobulinemia (mean age: 7u years) and 60 various monoclonal gammapathies, among which 19 benign monoclonal gammapathies (mean age: 73 years). 214 immunoelectrophoresis have been performed: 110 IgG, 46 IgA, 49 IgM, 8 light chain myelomas and 1 without M-component myeloma. Bence-Jones proteinuria was detected only in 51,1% of cases.


Deficiency of dihydrolipoyl dehydrogenase (a component of the pyruvate and alpha-ketoglutarate dehydrogenase complexes): a cause of congenital chronic lactic acidosis in infancy.

A male child died at 7 months of age with progressive neurologic deterioration and persistent metabolic acidosis. Investigations during life showed this child to have elevated blood pyruvate, lactate, and alpha-ketoglutarate as well as elevation of branched chain amino acids and occasional hypoglycemia. Cofactor therapy using either thiamine-HCl (2 g/kg/24 hr) or thiamine tetrahydrofurfuryl disulfide had no measurable effect on the clinical or biochemical status of the patient. Tissue taken postmortem showed normal levels of key gluconeogenic enzymes but a deficiency in the activity of pyruvate dehydrogenase in all tissues tested (liver, brain, kidney, skeletal muscle, and heart). Examination of the individual activities of pyruvate dehydrogenase complex showed pyruvate decarboxylase (E1) to be normal in liver and other tissues. Dihydrolipoyl dehydrogenase (E3), on the other hand, was deficient in all tissues tested. alpha-Ketoglutarate dehydrogenase complex, which depends of E3 for its total activity, was also deficient in all tissues tested. The absence of this enzyme id discussed in relation to the clinical and biochemical status of the patient.


Partially restricted antitoxins of tetanus and diphtheria in man.

Antibodies of restricted specificity have been identified in the human in response to certain antigens. The present study analyzed tetanus and diphtheria antitoxins isolated from selected human sera and suggested a restricted response in antibody production to each of these antigens. Purified antibodies from eight serum specimens with elevated hemagglutination titers to tetanus and four to diphtheria yielded only IgG proteins in concentrations of 160-500 microgram/ml. Although some of the tetanus specimens were derived from cord sera and tetanus immunoglobulin, none of the total group had antibodies of the IgA and IgM classes. Utilizing immunoelectrophoresis against heavy chain subclasses, genetic markers, and kappa and lambda quantitations, a predeliction for the kappa IgG1 subclass was established for both tetanus and diphtheria antibodies. The lambda light chains were present in diminished quantities, IgG2 heavy chains were absent, and the IgG3 and IgG4 chains were variably identified.


A note on ECG changes observed during Pavlovian conditioning in a rhesus monkey following coronary arterial occlusion.

Changes in the ECG of a rhesus monkey during a classical aversive conditioning trial conducted 10 minutes after occlusion of the marginal branch of the left circumflex coronary artery have been observed. This appears to reflect an instance where myocardial ischemia following coronary occlusion was exacerbated by presentation of a conditional stimulus.


Cardiac Purkinje fibres: [Ca2+]i controls steady state potassium conductance.

The influence of intracellular calcium concentration [Ca2+]i on the steady state membrane currents i infinity was studied in a range of clamp potentials between -20 and -100 mV. Injection of CaCl2 or Ca-EGTA (pCa less than or equal to 6) increased i infinity whereas injection of K-EGTA diminished it. The changes delta i infinity were attributed to a change in steady state potassium conductance, gK infinity, by four arguments: delta i infinity was restricted to potentials negative to -20 mV and depended on clamp potential in an inward rectifying manner. delta i infinity displayed a reversal potential, Erev' which followed log [K+]o with 60 mV for a tenfold change. Since Erev obtained during Ca injection agreed with Erev observed during EGTA injection the potassium driving force had to be constant. When gK was blocked by superfusion with 20 mM Cesium neither CaCl2 nor K-EGTA injection modified i infinity.


Cardiac Purkinje fibres: [Ca2+]i controls the potassium permeability via the conductance components gK1 and gK2.

The pacemaker tail current of sheep Purkinje fibres became larger when CaCl2 was injected intracellularly by pressure, whereas it was reduced or even abolished by injection of K-EGTA. The analysis of the [Ca2+]k-induced changes in the steady state activation (s infinity) curve suggested that the effect could not be explained on the basis of internal screening of surface charges. The position of the s infinity-curve on the potential axis remained almost unchanged after the injection of CaCl2 or K-EGTA. On the other hand, the vertical amplitude of the s infinity-curve on the current axis, proportional to gK2, was enlarged during CaCl2 injections and strongly diminished by K-EGTA injections. Ca injection displaced the fully deactivated part of the s infinity-curve to larger outward current which corresponds to an increase in gK1. EGTA injection reduced gI1. The results correspond to a [Ca2+]i-sensitive potassium permeability. A possible interpretation is that [Ca2+]i controls Ca-binding near the inner mouth of a potassium channel and that the binding is followed by a change in the channel's configuration from a closed to an open state.


A doubtful relationship between tyrosine tRNA and suppression of the vermilion mutant in Drosophila.

The conditions under which Drosophila melanogaster are grown markedly influence the amount of the hypermodified nucleoside Q found in certain tRNAs. This effect on Q biosynthesis was found in both the wild-type and the suppressor of sable [su(s)2] mutant. Suppressed vermilion flies [su(s)2v; bw] with 78% of the tyrosine tRNA in the Q-lacking (gamma) form had brown eyes indistinguishible from su(s)2v; bw flies with only 6% of the tyrosine tRNA in the gamma form. The proposal that this tRNA is a specific inhibitor or tryptophan pyrrolase in vermilion flies, and that its absence in su(s)2 flies is the mechanism of suppression is not consistent with these results. In addition, the su(s)2 locus does not seem to be primarily responsible for controlling Q biosynthesis as previously suggested.


Severe pulmonary disease and hyperviscosity in macroglobulinaemia.

A case of Waldenstrom's macroglobulinaemia with various clinical manifestations of the condition is presented. Hyperviscosity and respiratory complications are discussed with a brief review of the literature.


Antiinflammatory activity of Tylopilus felleus (Bull. ex Fr.) P. Karst.

Tylopilus felleus lyophylised preparation (Tf) tested in the carrageenin induced oedema test in rats, exhibit a significant inhibition of inflammation at all doses above 50 mg/kg sc while oral administration produced no significant results.


Second-order schedules of intravenous drug self-administration in rhesus monkeys.

Lever-pressing behavior was generated and maintained in 3 rhesus monkeys by intravenous infusions of morphine or cocaine under a second-order schedule of reinforcement. Under this schedule, every tenth lever-press response (FR 10) during a fixed interval of time produced a 2 sec stimulus light. The first FR 10 completed after a 60 min interval had elapsed produced the stimulus light and an intravenous infusion of morphine or cocaine. The stimulus light remained on for the duration of the drug infusion (50-60 sec). Sessions of morphine or cocaine presentation, each with distinct stimulus light conditions, alternated on a daily basis. Under this schedule, single doses of morphine from 0.125 to 1.0 mg/kg maintained high overall response rates (maximum of 40 Rs/min) in the pattern characteristic of fixed interval (FI) schedules of reinforcement. There was no functional relationship between the response-rates and the doses of morphine tested. The simultaneous infusion of naloxone (0.125 mg/kg/) with morphine (0.25 mg/kg) markedly decreased response rates. However, the infusion of the same dose of naloxone five min after the presentation of morphine failed to suppress self-administration behavior. Naloxone had no effects on cocaine-reinforced responding.


Effects of d-amphetamine, chlordiazepoxide and promazine on responding of squirrel monkeys maintained under fixed-interval schedules of food presentation and stimulus-shock termination.

Responding of two squirrel monkeys was maintained under a multiple 5-min fixed-interval schedule of food presentation and termination of a stimulus in the presence of which shocks occurred. Under the stimulus-shock termination schedule, shocks occurred independently of responding, on the average of every three minutes; a response after 5 min terminated the prevailing stimulus and shock-presentation schedule. Response rates and patterns of responding under both schedules were comparable although they differed slightly between monkeys. d-Amphetamine increased and promazine decreased responding under both fixed-interval schedules. Chlordiazepoxide increased responding maintained by food presentation but decreased responding maintained by termination of the stimulus-shock complex. Under certain conditions and with certain drugs, the event that maintains responding can determine the effects a drug will have on behavior.


The binding of aurothiomalate to plasma proteins in vitro.

The physicochemical factors responsible for the aurothiomalate-albumin interaction were studied by a thermodynamic analysis of the binding of the anion to bovine albumin. The binding process was entropically driven and it was concluded that electrostatic bonding formed the basis of the aurothiomalate-albumin interaction. The binding of aurothiomalate to human plasma proteins at 37 degrees C and pH 7.45 and the modification of its binding by indomethacin and phenylbutazone was studied by ultrafiltration. Aurothiomalate was bound to human plasma albumin at a single site with an affinity constant of 6.1 X 10(3) M-1 and also at several sites of lower affinity. The plasma protein binding of the anion was increased in the presence of indomethacin and phenylbutazone. At therapeutic concentrations in vitro phenylbutazone significantly increased the plasma protein binding of aurothiomalate.


Energy and muscular contraction.

In this paper, a model of the chemical energy conversion into mechanical energy is presented. According to this model, for each stage, the transfer of the energy is produced in the framework of a polymolecular system composed by a donor molecule, an enzyme and an acceptor molecular couple. The energy is released in the form of two quanta of electronic excitation. The transfer of the energy determines the change of the orbital directions, as well as the ionic constellations previously fixed at the level of the donor molecule and at the level of the acceptor molecular couple. Subsequently, an allosteric modification of the enzyme which connects the donor with the acceptor molecular couple is produced. The conversion of the chemical energy into mechanical energy is explained by means of the ions movement and by the conformational changes of the enzymes involved in the processes of the energy transfer.


Lithium therapy and alkaline earth metal metabolism: a biochemical screening study.

A study is described of 90 patients receiving lithium prophylactically for recurrent affective disorder. A total of 90 biochemical variables was analysed by correlation matrices. No abnormality in calcium or magnesium metabolism was detected though this may merely be a reflection of the insensitivity of the screening technique used.


Cost-benefit analysis and the evaluation of psychiatric services.

The paper sets out a method for evaluating changes in psychiatric services in a cost-benefit framework. The first section of the paper analyses some of the problems which arise with those elements which can be measured in monetary terms--the 'hard' costs and benefits. The second section looks at a method of presenting the less tangible effects--the 'soft' costs and benefits. Finally, it is suggested how these can be brought together to aid rational decision-making.


Analgesia induced by vaginal stimulation in rats is apparently independent of a morphine-sensitive process.

Previous studies have suggested that in rats probing against the vaginal cervix with a glass of is analgesic, for this stimulus elevates the threshold for eliciting vocalization in response to tail shock. In the present studies pretreatment with naloxone HCl (1 or 10 mg/kg), a potent narcotic antagonist did not antagonize this vaginal stimulation-induced analgesia. Furthermore, vaginal stimulation was found to exert its analgesic effect even in rats made tolerant to, and dependent upon, morphine sulfate. These results suggest that the analgesic effect of vaginal stimulation is not necessarily mediated by an opiate-sensitive neural system. However, we hypothesize that even though vaginal stimulation and other analgesic manipulations may act via different neural substrates, they may nevertheless converge onto a final common mechanism for pain suppression.


Interaction between morphine and reinforcing lateral hypothalamic stimulation.

The interaction between morphine and lateral hypothalamic self-stimulation in rats was investigated in three experiments. In nonaddicted animals injections of moderate doses of morphine (8 mg/kg) resulted in a short-lasting increase in the self-stimulation threshold. Injections of low doses (2 mg/kg) did not alter the self-stimulation threshold significantly. In addicted animals self-stimulation thresholds were significantly lower 2 h compared to 22 h after injection of 200 mg/kg morphine hydrochloride (calculated as the salt). A 16 mg/kg injection of morphine in non-addicted rats suppressed self-stimulation. However, when the animals were administered noncontingent priming stimulation and were hand-shaped toward the lever whenever they left it, they continued to lever-press throughout the entire 90-min postinjection testing period. The animals that were neither primed nor shaped (and therefore remained unstimulated), however, showed a significantly better recovery when tested 90 min after the injection; i.e., their response rate was higher than that of the primed and shaped animals, which were engaged in bar-pressing throughout the entire testing procedure.


Stereotypy and hyperactivity in rats receiving ethanol and a monoamine oxidase inhibitor.

The combined administration of tranylcypromine (TCP) and ethanol to rats produced both a marked increase in general locomotion such as walking and running and the appearance of repetitive stereotyped head and trunk weaving, forepaw padding, and circling movements. Pretreatment with p-chlorophenylalanine (pCPA) abolished the stereotyped behaviors. In contrast, animals pretreated with alpha-methyl-p-tyrosine (AMPT) were virtually indistinguishable from those receiving only TCP + ethanol, except for a decrease in running behaviors. The above results are consistent with a serotonergic mediation of these specific stereotypes. The mechanisms by which TCP + ethanol might produce these effects are discussed.


Passive avoidance learning in the rat as functions of d-amphetamine dosage and shock intensity.

The effects of d-amphetamine dosage (0, 1, 3, and 5 mg/kg) and shock intensity (0.2, 0.5, and 0.8 ma) on the learning of a passive avoidance response were assessed in rats. A curvilinear dose-response relationship was found at all shock levels, showing slower learning under moderate doses of d-amphetamine. The lowest shock level produced slower learning, especially in conjunction with the lowest dose of d-amphetamine. Results are discussed in terms of freezing behavior.


Locomotor stimulation by L-dopa: relative importance of noradrenaline receptor activation.

The importance of brain noradrenaline synthesis and receptor activation for the hyperkinesia induced by carbidopa plus L-Dopa in reserpine-treated or normal mice was analyzed in four different models. After pretreatment with reserpine and the monoamine oxidase inhibitor nialamide, the hyperkinesia induced by L-Dopa (25 mg/kg i.p.) was partly mediated via stimulation of noradrenaline receptors since it was significantly antagonized by the noradrenaline receptor-blocking agent phenoxybenzamine. Treatment with reserpine plus L-Dopa (125 mg/kg i.p.) produced an increase in motor activity probably due to stimulation of dopamine receptors since it was not accompanied by an accumulation of noradrenaline and it was not inhibited by phenoxybenzamine. The hyperkinesia following treatment with reserpine and a higher dose of L-Dopa (250 mg/kg i.p.) was probably due to stimulation of both dopamine and noradrenaline receptors since the dopamine-beta-hydroxylase inhibitor FLA-63 partly reduced the effect of L-Dopa. Phenoxybenzamine potentiated the motor stimulation by L-Dopa (125 mg/kg i.p.) in mice not pretreated with reserpine, perhaps depending on a slight enhancement of the net accumulation of brain dopamine. Thus, noradrenaline receptor activation is of importance for the L-Dopa-induced hyperkinesia, at least after high doses or after monoamine oxidase inhibition.


EEG, blood level, and behavioral effects of the antidepressant mianserin (ORG GB-94).

A pharmacokinetic analysis of a new antidepressant drug, mianserin (ORG GB-94), was undertaken in 4 male volunteers, each of whom received 15 mg mianserin on two occasions. Plasma levels peak at 2 h with a median level of 11.0 ng/ml, a median beta-phase half-life of 10.0 h, and a median apparent volume of distribution of 3.3 X 10(3) 1. EEG profile analysis shows mianserin to increase frequencies below 6 Hz, decrease those from 7.5 to 15 Hz, and increase frequencies above 18 Hz, a pattern similar to amitriptyline. Peak EEG effects range from 2 to 5 h with a pattern of measured changes that parallels plasma levels with varying latency. Decreases in vigilance measures and in critical flicker-fusion frequency show a similar time course. Mianserin is a putative thymoleptic on EEG profile analysis with high cerebral penetrance.


d-Amphetamine and adjunctive drinking in rats.

In the first experiment four food-deprived rats developed high levels of adjunctive water drinking during daily sessions of intermittent food pellet delivery. When the water was removed and a solution of d-amphetamine sulfate (0.01 mg/ml) put in its place, adjunctive drinking was disrupted towards the end of each session although the rats ingested doses of approximately 0.5 mg/kg daily for over 40 sessions. Consumption of the d-amphetamine solution was increased by injections of several doses of alpha-methyl-p-tyrosine (AMPT). In a second experiment injections of d-amphetamine (0.25, 0.5, 1.0, 2.0 mg/kg) were found to reduce adjunctive water consumption in six rats. It was also found that the actions of the two highest doses of d-amphetamine were reduced by pretreatment with a dose of AMPT (100 mg/kg), which itself slightly reduced levels of drinking. These results suggest that, although adjunctive drinking may be a useful technique for inducing rats to self-administer d-amphetamine, the amount of drug consumed is limited by a direct action of the drug on drinking.


Factors influencing blood concentrations of chlordiazepoxide: a use of multiple regression analysis.

Three groups of male and female subjects aged 24-74 years received 25, 100, or 200 mg of chlordiazepoxide hydrochloride by mouth as a single dose or as two divided doses. The relation of plasma or whole blood concentrations for chlordiazepoxide (CDX) and its metabolite, desmethylchlordiazepoxide (DMCDX), to time since the last dose, weight, age, and sex were determined by simple and multiple regression analyses. Both CDX and DMCDX levels were negatively correlated with weight. Concentrations of CDX decreased, while those of DMCDX increased, with the time since the last dose. Lower levels of both drugs were associated with female sex, and lower levels of DMCDX were noted with increasing age. In the largest sample group, age and weight were more important variables than sex in accounting for CDX and DMCDX. Sex was of significance, and more important than time or age in explaining the variance of CDX in one series of observations. Multiple regression analysis is a useful approach to assessing interrelated factors influencing blood levels of drugs, especially when combined with a consideration of the interactive components of variance. Age and sex, in addition to weight and time, may be important factors that deserve further attention.


Pentazocine, cyclazocine, and nalorphine as discriminative stimuli.

Pentazocine, cyclazocine, and nalorphine are narcotic antagonists that also have analgesic activity of their own. The present investigation compared the stimulus properties of these three drugs in rats. Each drug was used as a discriminative stimulus for a separate group of rats. Depression of one lever resulted in food reinforcement following the administration of drug, and the opposite lever was reinforced after saline. Each drug readily acquired control of discriminated responding. The specific narcotic antagonist, naloxone, which antagonizes many of the effects of pentazocine, cyclazocine, and nalorphine, also antagonized the discrimination of these drugs. Stimulus generalization tests to each other narcotic antagonist, d-amphetamine, morphine, and LSD, showed that each narcotic antagonist has highly specific stimulus properties. Clear generalization occurred only to pentazocine and cyclazocine in the nalorphine-saline group, but neither cyclazocine nor pentazocine generalized to nalorphine.


Effects of withdrawal from chronic amphetamine intoxication on exploratory and stereotyped behaviors in the rat.

Rats were administered 3, 6, and 12 mg/kg of d-amphetamine s.c. twice daily on a weekly increasing staircase schedule. On days 1, 7, 14, and 28 after the last injection of amphetamine the animals were challenged with 1 and 3 mg/kg of d-amphetamine and their behavior was observed. The 7-, 14-, and 28-day withdrawn animals required less amphetamine than controls to induce stereotyped behaviors. However, it was found that withdrawn animals and control animals were equally sensitive to the effects of apomorphine. Reserpine pretreatment eliminated the differences between control and withdrawn animals. alpha-Methyl tyrosine pretreatment blocked the effects of 1 but not 3 mg/kg of d-amphetamine in the withdrawn animals. Possible chemical mechanisms underlying the change in amphetamine sensitivity in the withdrawn animals are discussed.


Adrenergic modulation of a cholinergic emotional reaction in the cat's thalamus.

Direct carbachol stimulation of the intralaminar nuclei of the thalamus evokes an affective defense reaction in the cat. Pretreatment of the region with noradrenaline inhibited the reaction in a dose-related manner. Phenylephrine was ineffective in this respect while isoprenaline exhibited roughly the same inhibitory action as noradrenaline. The alpha-receptor blocking dihydroergotamine left the inhibitory effect of noradrenaline unaffected while the beta-receptor blocking propranolol abolished it. These findings suggest that the inhibitory effect of noradrenaline on the carbachol-induced thalamic emotional reaction is caused by its influence on beta-type adrenergic receptors. Since a similar adrenergic-cholinergic interaction was previously demonstrated also for the hypothalamus and red nucleus, it can be concluded that adrenergic modulation of cholinergic reactions in the central nervous sytem seems to be a principle of more general validity than has been assumed thus far.


Morphine and shuttle-box self-stimulation in the rat: a model for euphoria.

In a shuttle-box self-stimulation paradigm, analgesic doses of morphine increase the amount of time a rat leaves rewarding brain stimulation on, without altering average OFF times. This paradigm may serve as a model for the euphoria induced by narcotic drugs and as a useful tool for evaluating the reinforcing effects of drugs.


Interaction between narcotic antagonist (naloxone) and lysergic acid diethylamide (LSD) in the rat.

LSD administration in rats elicited a diphasic reaction consisting of a brief excitable period ( up to 8 min) followed by a prolonged catalepsy (8 min-1 h). While the cataleptic response was antagonized by a single injection of naloxone (given 30 min after LSD administration), pretreatment with naloxone shortened the excitable phase and potentiated the catalepsy.


[Statistico-mathematical correlation of the B and C isoenzyme ratio of carbonic anhydrase and fetal hemoglobin, and its probable biological significance in the metabolism of zinc].

The AA. performed a study on the Bravais-Galton's correlation  coefficient. They applied this coefficient to the HCAB/HCAC ratio and to the fetal haemoglobin often groups of twenty children (one month four years old) values. The result support the assumption that there is a strong biochemical relationship between zinc-carbonic anhydrase and haemoglobin in erithrocytes.


Social interaction and serum insulin values in the monkey (Macaca mulatta).

Social interaction studies were conducted with two groups of rhesus monkeys with abnormally elevated serum insulin values. In both studies, the animals that were lowest on the dominance-submissiveness scale showed a fall in insulin levels to within the normal range for the monkey. Upon removal from the group, insulin values in these animals returned to their previous elevated level. In neither instance was the fall in insulin level accompanied by fasting hyperglycemia.


Dose to the metaphyseal growth complexes in children undergoing 99mTc-EHDP bone scans.

The spatial temporal distribution of radionuclides in children may differ greatly from that accepted for adults. Following injection of a bone-seeking agent (99mTc-EHDP), radioactivity in the metaphyseal growth complexes of the distal femur and proximal tibia was quantitated in a series of children 4 to 16 years of age, using a gamma camera/computer system. The dose to the growth plate was fount to range from 0.8 to 4.7 rads when adjusted to an administered activity of 200 muCi/kg, compared to approximately 0.6 rad to the adult skeleton for a corresponding study.


Demonstration of prostaglandin synthesis in collecting duct cells and other cell types of the rabbit renal medulla.

The renal medulla has a high capacity for prostaglandin production and the interstitial cells, which contain abundant lipid inclusions have been suggested to be the site of synthesis. However, histochemical studies have indicated that the collecting ducts are the main site of production. The object of the present study was to study the distribution of prostaglandin synthetase in the rabbit renal medulla by direct, quantitative determination of the enzyme activity in different cellular fractions. Slices were cut from rabbit renal papilla and immersed in a hypertonic saline solution. 92% of the collecting duct cells were then removed from the slices by suction through a micropipette. The remaining dissected slices thus contained mainly three cell types, cells of Henle's loop, endothelial cells, and interstitial cells. The isolated collecting duct fraction, the corresponding dissected slices, from which the colelcting duct cells were removed, as well as intact slices were assayed for prostaglandin synthetase activity using a quantitative assay with [14C] arachidonate as substrate. Of the prostaglandin in synthetase activity 39% was found in the collecting ducts, 53% in the dissected slices, and 7% in the dissection medium. It is thus concluded that significant prostaglandin synthetase activity is present in collecting duct cells as well as in at least one other cell type of the medulla.


Biosynthesis and metabolism of prostaglandins in chick epiphyseal cartilage.

Microsomal fractions of cells isolated from chick epiphyseal cartilage catalyzed the synthesis of prostaglandins from radiolabeled delta8,11,14-eicosatrienoic and from arachidonic acids. In addition, the microsomal supernatants contained both 15-hydroxyprostaglandin dehydrogenase and prostaglandin 15-keto delta13,14-reductase activities. Two major classes of prostaglandins (E and F) were synthesized; however, a major product which chromatographically behaves as PGA was also isolated. Synthetase activities were analyzed for pH optima and response to known stimulators and inhibitors of prostaglandin systhesis. The different activators had varying stimulatory effects on prostaglandin synthesis; the anti-inflammatory drugs were all strongly inhibitory. Synthetase activity in the growth plate was highest in the zone of hypertrophy, declining substantially in the more heavily calcified regions. Degradative enzyme activities were highest in the zone of maturation and significantly lower in the adjacent hypertrophic zone. The net effect of these opposing activities would be to elevate prostaglandin levels at the zone of hypertrophy, a finding which suggests that prostaglandins may play a role in the modulation of epiphyseal cartilage metabolism.


Stimulatory effect of prostaglandins on the production of hexosamine-containing substances by cultured fibroblasts (3) induction of hyaluronic acid synthetase by prostaglandin F2alpha.

The mechanism of the stimulatory effect of prostaglandin(PG)F2alpha on the production of hexosamine-containing substances by cultured fibroblasts was studied. Treatment of the cells with 1 microgram/ml of PGF2alpha resulted in a doubled net synthesis of acidic glycosaminoglycans during 20 hrs measured with uronic acid as index, and also resulted in 300 per cent increase of 3H-glucosamine incorporation into hexosamine-containing substances during the first 6 hrs. Fractionation of the PGF2alpha-stimulated hexosamine-containing substances with double isotope technique revealed that hyaluronic acid was the most stimulated component. Prior to the increase of hyaluronic acid, hyaluronic acid synthetase activity was found to be augmented by PGF2alpha as high as 4 times over the control. The augmentation of hyaluronic acid synthetase activity by PGF2alpha did not take place if actinomycin D was simultaneously present in the culture medium, suggesting that PGF2alpha induced the enzyme.


[Dosimetry problems in irradiation of mediastinal tumours (author's transl)].

Various physical parameters are described for evaluation of the quality of the irradiation plane. Of these, the integral dose and the dose gradient index are regarded as particularly significant and their calculation is included in a computerised dosimetry programme. Examples are drawn from the comparison of various mediastinum irradiation techniques: 60Co, high energy X-rays, fast electrons.


[Study of various constituents of a strain of Pseudomonas aeruginosa].

Using a strain of Ps. aeruginosa (A.T.C.C. 10.145), several preparations were obtained: cytoplasm, cellular wall, extract with veronal buffer and carbohydrates. A morphologic and biochemical study of the bacterium was performed and the soluble fractions were analysed by electrophoresis in poliacrilamide gel with strains for proteins, carbohydrates and lipids. The results led the following conclusions: 1. -Electrophoresis of cytoplasm in poliacrilamide gel made it possible to recognize 17 proteic, 9 carbohydrate and 3 lipid fractions. 2. -Eight of the protein fractions were combined with carbohydrates and 9 were proteins. 3. -The extract obtained with veronal buffer showed 12 protein, 7 carbohydrate and 4 lipid fractions. 4. -The seven carbohydrate fractions were combined with proteins. 5. -Five of the cytoplasm proteins fractions were not extracted with veronal buffer; two protein fractions extracted by veronal buffer were not from cytoplasm. 6. -Heating the extract obtained with veronal buffer determined the loss of most of the fractions extracted probably due to denaturalizations of the proteins. 7. -The heated extract obtained with veronal buffer showed diffuse bands coloured with protein, carbohydrate and lipid strains.


[Tele-E.E.G. recordings of three epileptic attacks classified as episodes of PM status (author's transl)].

The authors present the tele-E.E.G. resording of three episodes of PM status, occurring in three known epileptics (ages: 16, 20 and 22 years). One episode was induced by an injection of bemegride and the other two by overbreathing. Their duration was 27, 31 and 44 minutes respectively. The development of abnormalities was progressive in all three cases, whilst they disappeared suddenly in two cases. Study of these three episodes was made in two ways: an electrical study and a clinical study. In addition, a brief retrospective study of the psychological experience of the episodes was carried out. The main finding was that the three episodes recorded and observed represented prolonged attacks and not a succession of attacks. The authors concluded that episodes classified under the name of PM Status may be studied in two ways: either considering them as prolonged attacks which are not status epilepticus, or considering them as repeated attacks, their repetition resulting in the appearance of unusual additional signs and which are status epilepticus.


Precision of single injection (51Cr)EDTA plasma clearance and endogenous creatinine clearance determinations in children.

The precision of two different clearance methods as used for routine assessment of the glomerular filtration rate (GFR) was investigated in thirty-one children aged 0.6-14 years: total [51Cr]EDTA plasma clearance (E) determined by a simplified single injection method; and 24 h endogenous creatinine clearance (C). Determination of C twice only succeeded in twenty children because of problems in collecting 24 h urine accurately. The precision (determined from the total day-to-day variation) for single determinations in patients with E greater than or equal to 80 ml/min/1.73 m2 was 5.5% for E and 13.8% for C. The corresponding figures for E less than 80 ml/min/1.73 m2 was 7.8% for E and 20.8% for C. Data in the literature on the inaccuracies of C and E versus GFR suggest that the degree of inaccuracy in predicting GFR from C is much higher than that from E, a feature which together with the present findings on precision indicates that E is much more reliable than C for routine determination of GFR in children.


Single injection (51Cr)EDTA plasma clearance determination in children using capillary blood samples.

The reliability of a determination of the total [51Cr]EDTA plasma clearance (E) (and with it the glomerular filtration rate), by a simplified single injection method (injected dose: 4.5 muCi per kg b.w.) using capillary blood samples (0.2 ml), was investigated in twenty children. Clearance values determined from capillary blood samples did not differ significantly from those measured simultaneously from venous blood samples, the mean ratio +/-SD being 1.02 +/- 0.06 (n = 10). The reproducibility (total day-to-day variation) of E determined from capillary blood samples was 6.7% in children with decreased renal function (n = 3) and 6.9% in children with normal renal function (n = 7). The present data indicate that the use of capillary blood samples is an accurate and very precise approach for determination of E in children.


Experimental pulpitis in immunized monkeys.

Bovine serum albumin (BSA) was topically applied to exposed dentin to assess whether inflammatory reactions can be induced in the pulp of monkeys immunized against BSA. Four cynomolgus monkeys received repeated injections of BSA emulsified with Freund's incomplete adjuvant. Pulp challenge was performed by applying BSA in freshly cut dentin cavities prepared on the buccal surface in 34 teeth. In 29 control teeth ovalbumin (OVA) was applied. Control applications of BSA were also performed in 15 teeth prepared in three nonimmunized monkeys. Forty-eight hours after the initiation of the pulp challenge the monkeys were sacrificed and the pulp tissue examined in the light microscope. Topical application of BSA to freshly exosed dentin in immunized monkeys resulted in severe inflammatory lesions in the pulp, characterized by bleeding and extravascular infiltration of large numbers of leukocytes. Extensive tissue damage was an important feature in several pulps. Identical applications of OVA in control teeth and BSA applications in nonimmunized monkeys produced no such reactions. The results indicate that interactions between antigens and antibodies can occur within the dentin-pulp area and following the formation of immune-complexes, severe injury to the pulp can be induced.


Identification and characterization of different amyloid fibril proteins in tissue sections.

Antisera specific for 4 different classes of amyloid fibril proteins, amyloid protein AA and the immunoglobulin light-chain amyloid proteins AlambdaI, AlambdaIV, and AlambdaV, were used to identify these proteins directly in tissue sections from 25 patients with amyloidosis. The specificity of these reactions was established by blocking experiments with purified amyloid fibril proteins and Bence Jones proteins of known variable subgroups. Protein AA was detected in 17 patients, including all 13 with secondary amyloidosis, 2 with primary amyloidosis and 2 with Waldenström's macroglobulinemia. Immunoglobulin light-chain proteins AlambdaI, AlambdaIV, and AlambdaV were in 3, 1, and 2 patients, respectively, all of whom had primary or myeloma/macroglobulinemia-associated amyloidosis. Antiserum specific for the amyloid-related serum protein SAA reacted with the same tissues as anti-AA and had the same pattern of staining in tissue sections.


Enhanced cytotoxicity of human lymphocytes against rabies-infected cells by rabies-specific antibodies.

Human anti-rabies immune sera enhanced the in vitro cytotoxicity of human lymphocytes against rabies virus-infected green-monkey kidney cells. The immune sera were collected from patients immunized with rabies vaccine produced either in human diploid cells or in nervous tissue. Significant cytotoxicity was observed even with high serum dilutions, indicating that the K-cell assay might be a sensitive tool for detection of anti-rabies antibodies.


Endocarditis on a Björk-Shiley mitral prosthesis due to Neisseria meningitidis.

To our knowledge, there has been reported only one previous case of prosthetic valve endocarditis due to Neisseria meningitidis. In describing a second fatal case, we emphasize the difficulty of clinical diagnosis due to lack of characteristic high fever, murmur, skin rash, or splenomegaly. This lack of findings plus the chronic, intermittent course suggest a rare occurrence of endocarditis complicating chronic meningococcemia with an acute exacerbation, leading to rapid decompensation and death.


[Allergic reaction to meningococcal antigen. Clinical aspects, pathogenesis and diagnosis related to a case history].

A case report illustrates a complication of meningococcal meningitis which often causes differential-diagnostic problems: allergic reaction to the meningococcal antigen. The pathogenesis and diagnostic principles are discussed in the light of the literature.


[Stress hemodynamics in fresh myocardial infarct].

Hemodynamic measurements before and during graded leg-up tilt were performed in 20 patients on the 1st and 3rd day following myocardial infarction. In those with an elevated pulmonary capillary pressure (greater than 11 mm Hg), independent of the cardiac index, the tilt-test (i.e. an additional increase in preload) unmasked heart failure. When applied to test drug responses, furosemide (n = 7) reduced the tilt-stimulated cardiac index with an attendant fall in pulmonary capillary pressure; nitroglycerine (n = 7) did not change cardiac index but reduced the pulmonary capillary pressure.


[Familial oculo-cutaneous hypopigmentation of dominant transmission due to a disorder in melanocyte formation. Association of Prader-Willi syndrome with a chromosome abnormality in one of the subjects involved].

Four members of a Swiss family were affected with oculo-cutaneous hypopigmentation of dominant transmission which differed from the previously described cases of dominant oculo-cutaneous albinism by its ultrastructure. The hypopigmentation described here is characterized by the formation of numerous, but very small, melanosomes. Melanocytic tyrosinase activity was normal in light microscopy. However, on electron microscopy, tyrosinase activity was strong in premelanosomes of stage I only, and decreased rapidly in the later stages. One of the affected members also presented a Prader-Willi syndrome and a chromosomal anomaly, both being probably unrelated to the pigmentary disorder.


Environmental hydrocarbons produce degeneration in cat hypothalamus and optic tract.

2,5-Hexanedione, the principal neurotoxic metabolite of the industrial solvents n-hexane and methyl n-butyl ketone causes axonal degeneration in the mammillary body and visual nuclei of cats. Prolonged, low-level exposure to hydrocarbons in the environment may cause premature deterioration in areas of the human brain vital for perception and behavior.


Control of sequential compartment formation in Drosophila.

During development of Drosophila melanogaster, sequential commitment to alternative development programs occurs in neighboring groups of cells. These commitments appear to be reflected by lines of clonal restriction, called compartmental boundaries, which progressively subdivide the early embryo, and later the imaginal discs, which give rise to different adult appendages. We propose that a reaction-diffusion system acts throughout development and generates a sequence of differently shaped chemical patterns. These patterns account for the sequence and geometries of compartmental boundaries, and predict that each terminal compartment is specifiied by a unique combination of binary choices made during its formation. This binary "code" interprets coherently the patterned metaplasia seen in transdetermination and homeotic mutations.


Phthalate ester plasticizers: a new class of marine pollutant.

Phthalate ester plasticizers have been detected in the open-ocean environment. Samples consisting of water, sediment, air, and biota from the Gulf of Mexico and of water and air from the North Atlantic were analyzed and found to contain two phthalate esters, di-(2-ethylhexyl) phthalate (DEHP) and di-n-dibutyl phthalate (DBP): the concentrations of polychlorinated biphenyls (PCB's) and DDT's (p,p'-DDT and p,p'-DDE) were also determined. Like the ubiquitous PCB's and DDT's, the phthalate plasticizers were found in almost all samples analyzed; DEHP was present at higher concentrations than the PCB's or DDT's in water and sediment. The environmental impact of the concentrations found in these studies, coupled with the continued high production and wise use of these plasticizers, requires assessment.


Acceleration of plasma bicarbonate conversion to carbon dioxide by pulmonary carbonic anhydrase.

In isolated rabbit lungs perfused with solutions containing little or no carbonic anhydrase activity, nearly complete equilibration between H14CO3- and 14CO2 occurs during a single circulation. This equilibration can be inhibited by blocking pulmonary carbonic anhydrase with acetazolamide.


Total parenteral nutrition.

Total parenteral nutrition has evolved as a distinct therapeutic reality within the past decade. Starvation or malnutrition need no longer be accepted as a necessary component of prolonged illness. Though current TPN techniques can be both safe and effective, the prevention of potential complications must always have a high priority. Changes in technique are to be anticipated as further knowledge and improved materials allow the pursuit of more basic clinical problems. The recent experience with the use of high caloric TPN solutions for prolonged gastrointestinal failure in 73 patients at the Loyola University Medical Center has been summarized. The need for the involvement of an experienced TPN team in the care of these patients cannot be overemphasized if the numerous and diverse potential complications of the TPN system are to be minimized.


Adoption of Thayer-Martin culture medium by physicians in office-based practice.

In the summer of 1972, 26.4% of 900 physicians surveyed in the United States reported that they had performed one or more endocervical cultures for gonorrhea during a week of study. Obstetrician-gynecologists (62.8%) were considerably more likely than others to employ this diagnostic technique. The use of Thayer-Martin cultures was associated with the number of women examined and type of laboratory used (public, private or hospital), but not region of practice (East, Midwest, South, of West), area of practice (urban, suburban, or rural), or month of interview (July, August, or September). Results of this survey are consistent with the diffusion of innovation model proposed by Rogers.


Congenital cerebral and ocular malformations induced in rhesus monkeys by Venezuelan equine encephalitis virus.

Rhesus monkey fetuses were inoculated with Venezuelan Equine Encephalitis (VEE) vaccine virus by the direct intracerebral route at approximately 100 days gestation to determine possible teratogenicity of the virus. Congenital micrencephaly, hydrocephalus and cataracts were found in all animals and porencephaly in 67 percent of the cases. The virus replicated in the brain and other organs of the fetus. VEE vaccine virus is teratogenic for non-human primates and must be considered a potential teratogen of man.


Lack of correlation between killing of gonococci by serum and antibodies directed against pili from strain 2686 of Neisseria gonorrhoeae.

In patients experiencing initial or repeated gonococcal infections there appeared to be little correlation between elevated levels of serum antibody to pili from Neisseria gonorrhoeae strain 2686 and the presence or absence of serum bactericidal activity against the patients' infecting isolates. Of eight patients who experienced their first gonococcal infection, four had elevated antipili antibody levels; all eight sera from patients who had repeated gonococcal infections had high antipili antibody levels. All the patients' sera were bactericidal for strain 2686 of N. gonorrhoeae.


Methylmercury teratogenesis in the killifish, Fundulus heteroclitus.

Exposure of developing eggs of the killifish, Fundulus heteroclitus, to 0.03 or 0.04 mg/l of methylmercuric chloride resulted in a variety of abnormalities. Percentage of axis formation was reduced somewhat, and many embryos developed cyclopia or intermediate conditions leading to cyclopia, reflecting interference with induction of the forebrain. Defects in the cardiovascular system also appeared in the form of failure of the heart to differentiate properly into chambers. The heart was a thin, feebly beating tube, incapable of causing the blood to circulate. Other tissues, however, continued developing fairly normally, and embryos showed spontaneous movement comparable to controls. Embryos with severe cardiovascular or optic defects did not hatch. Upon hatching, some embryos which had previously appeared normal were found to have skeletal malformations in the form of vertebral bends or the inability to uncurl from the position which they had while still inside the chorion. Exposure to the toxicant for shorter periods of time (6, 12, or 24 hours) reduced the incidence of abnormalities. The second day of development was found to be the most sensitive period.


Experience with a tuberculosis antigen test in Rhodesia.

Experience with a new serological method for the diagnosis of tuberculosis is reported in a predominantly black population. We have found that in only 69% of 167 patients was there agreement between serology and the presence or absence of tuberculosis. Both false positive and false negative results were common. Of 47 healthy controls, 80% were positive. These results are less satisfactory than previous studies but differences in the reading of the results seems an unlikely explanation. Differences in the populations studied may be an important factor.


Hormonal regulation of intraocular pressure.

A detailed review of the hormonal effects on intraocular pressure is presented. There is evidence that corticotropin, vasopressin, thyroxin, insulin, glucocorticoids and mineralocorticoids may play a role in the physiologic regulation of intraocular pressure. Growth hormone, melanocyte stimulating hormone, progesterone, estrogen, chorionic gonadotropin and relaxin may influence intraocular pressure when administered in pharmacologic doses. Whether the key to understanding primary open-angle glaucoma lies in recognizing abnormal endocrine mechanisms, especially involving glucocorticoids, remains unclear at the present time.


Isolation and identification of 15-beta-hydroxy cyproterone acetate as a new metabolite of cyproterone acetate in dog, monkey and man.

15-beta-hydroxy cyproterone acetate could be identified by thin layer chromatography, mass spectrum, NMR and IR spectrum as a major unconjugated metabolite of cyproterone acetate in plasma and urine of dog, monkey and man. This metabolite has been found to interferein the Mattingly method for the determination of 11-hydroxy-corticosteroids which suggests, that this method is inadequate in controling the adrenal function of subjects treated with cyproterone acetate.


A review of metozoite vaccination against Plasmodium knowlesi malaria.

Techniques for the isolation of merozoites of Plasmodium knowlesi malaria have allowed their use in experimental vaccines. Rhesus monkeys were protected to a very great extent from otherwise lethal challenge with this malaria when Freund's Complete Adjuvant was a vaccine component.


Mechanisms of malarial immunity.

Immunity to malaria in many species, including man, is acquired only after long exposure to infection and is associated with chronic low-grade parasitaemia. Vaccination of Rhesus monkeys with P. knowlesi merozoites in FCA induces sterilizing immunity which is species specific. Merozoite-blocking (inhibitory) antibody usually correlates with clinical immunity and protection can be passively transferred with immune sera. However, vaccination using adjuvants other than FCA may induce inhibitory antibody without clinical protection. In addition, vaccinated animals usually become susceptible to challenge 4 to 5 weeks after splenectomy, although inhibitory antibody levels are not reduced. These observations indicate that immunity induced by merozoite vaccination involves merozoite blocking (inhibitory) antibody and also specific antibody or immune complexes acting synergistically with cytotoxic splenic cells stimulated by FCA. During natural infection on the other hand soluble circulating antigens, partly derived from the merozoite coat during red cell penetration, are produced and these may block immune effector mechanisms and promote parasite survival.


A yellow fever epizootic in Zika Forest, Uganda, during 1972: Part 2: Monkey serology.

During the 1972 yellow fever epizootic in Zika Forest, Uganda, sera from 21 monkeys shot in a number of forests around the Entebbe area were tested for the presence of a number of arbovirus antibodies. All sera were tested for antibodies against Chikungunya (CHIK), O'nyong-nyong (ONN), Zika, yellow fever (YF) West Nile (WN) and Wesselsbron (WESS) by the haemagglutination-inhibition (HI) test. Because of the crossreaction within the flaviviruses (group B arboviruses) mouse protection test (PT) was also carried out on the sera against YF, WESS and Zika viruses. Serological studies carried out on monkey sera from different parts of Uganda, including the Entebbe area, during 1968 gave results which reflected a surprisingly low rate of YF immune monkeys (3%) throughout the country compared with the rate of over 40% immune monkeys obtained by Haddow et al. in 1951. 40% of the monkey sera collected during 1972 were immune to YF by the PT. Since no YF virus had been isolated between 1968 and 1972 the results indicate strongly that the monkeys in the Entebbe area were involved in the epizootic of 1972. No sick or dead monkeys were found in all the forests checked around Entebbe area during the epizootic. This indicates that the animal-to-animal cycle of the equatorial African forests involved the mild endemic infection characteristic of a virus in its natural habitat and infecting its natural host.


Epidemiological and serological study of scrub typhus among Chinese military in the Pescadores islands of Taiwan.

An outbreak of 69 cases of scrub typhus occurred among Chinese military personnel stationed in the Pescadores Islands, Taiwan Province, Republic of China between May and November 1975. A retrospective epidemiological study of this outbreak indicated that military personnel over 40 were more likely to have scrub typhus than those under 40. High risk groups included the Garrison Force (home guard), anti-aircraft gunners and infantry and armoured units stationed at Hsing-jen. The onset of symptoms in 69% occurred within one year of residence in the Pescadores. The clinical course of scrub typhus and the serological response to infection were also studied. Eschar formation, fever, headache chills and lymph node enlargement were the predominant clinical manifestations noted. The indirect immunofluorescent antibody test (IFAT) demonstrated diagnostic (four-fold) rises in antibody titres to Rickettsia tsutsugamushi reference strains in 36 of 41 paired sera tested. 11 of 19 patients from whom only single sera were obtained had IFA titres presumptive of scrub typhus (greater than or equal to 1:160). Of 19 patients experiencing possible primary infections, 13 (68%) responded with antibodies directed against more than one reference strain of R. tsutsugamushi. These results suggest that several antigenically diverse strains of R. tsutsugamushi may be active in the Pescadores.


A comparison of isotopic and enzyme-immunoassays for tropical parasitic diseases.

A comparison is made of enzyme-immunoassay and radio-immunoassay for the detection of antibody in Chagas's disease, sleeping sickness, malaria, schistosomiasis ans invasive amoebiasis. Both assays were sensitive and reproductible and gave comparable results.


Autoantibodies mimicking alloantibodies.

A patient with myelofibrosis, who has produced many red blood cell autoantibodies, is described. Although the patient is phenotypically R1R1 (CDe/CDe), eluates made from his red blood cells have consistently contained what appeared to be anti-E, and more recently another antibody that appeared to be anti-c. In in vitro experiments we have shown that the "anti-E" and "anti-c" can be totally adsorbed by E-negative and c-negative red blood cells, respectively. We conclude that the two antibodies have quite different specificities from those indicated by simple antibody identification studies, and that both are more closely related to the anti-Hr series of antibodies than to anti-E or anti-c.


A "normal" individual with a positive direct antiglobulin test: case complicated by pregnancy and unusual autoantibody specificity.

A "normal" individual with a positive, direct antiglobulin test is described. In common with many other "normal" persons in whom a similar finding has been made, there was no evidence of an increased rate of in vivo red blood cell destruction in this patient. The patient successfully completed a pregnancy during the time that detailed serologic studies on her autoantibodies were being performed. Although the maternal autoantibodies were demonstrable in both an eluate made from the red blood cells of her newborn infant, and in the cord serum, there was no reason to believe that the antibodies caused red blood cell destruction in the infant. The case was of further interest because of the specificities of some of the autoantibodies. Although the mother and child were both C-negative, eluates from their red blood cells contained what ostensibly appeared to be anti-C. Studies that showed that the antibody could be totally adsorbed with C-negative, as well as C-positive red blood cells, proved that this was another example of an autoantibody mimicking an alloantibody. Although this autoantibody appeared initially to have anti-C specificity it was eventually shown to be more closely related to anti-Hr or anti-Rh34, than to anti-C.


Partial plasma exchange, and adjunct in therapy to complex clinical problems.

The use of therapeutic partial plasma exchange (PPE) is reviewed as an adjunct in the treatment of certain complex clinical problems. The procedure is performed with a Model 30 Haemonetics Blood Cell Separator in which the patient's plasma is partially exchanged with fresh frozen plasma, fresh frozen plasma with cryoprecipitate removed or with plasma protein fraction. The present study describes the use of PPE on 12 patients within the last 15 months as a means of altering the plasma proteins to achieve certain therapeutic goals. The study consists of six procoagulant deficient patients (five congentital and one acquired) in which five of the six patients responded by reflecting a satisfactory rise in the plasma procoagulant level following the procedure, resulting in cessation of bleeding. The sixth patient was thought to have had a procoagulant inhibitor, thus the procoagulant level was changed only minimally. The remaining six patients (five with hyperviscosity syndrome and one with platelet antibody) responded only to the degree of the intensiveness of the PPE procedure. More aggressvie, repeated PPE and/or plasmapheresis are needed if the clinical objective is to decrease the plasma viscosity or to lower a humoral antibody within the patient's plasma.


Cost effectiveness of use of frozen blood to alleviate blood shortages.

Human blood shortages are a perennial problem because of the relatively short life span (21 days) of stored blood and the traditional shortage periods during summer vacation months and other vacation periods. This study evaluates the use of frozen blood during these traditional shortage periods. An empirically-based simulation model is used. During periods of excess supply surplus blood is frozen and during shortage periods frozen blood is thawed and used as a substitute for stored blood. The results of the study indicate that the use of frozen blood during shortage periods alleviates shortages but at a high cost. Improved blood collection scheduling management and promotion will attain the same results at a lower cost.


Methods and medium for the culture of tubercle bacilli.

A brief account is given of methods recommended for the culture of tubercle bacilli and improved media are described appropriate for each. The chief changes suggested are reductions in the phosphate and dye content of media previously devised for alkaline inocula.


The zonal anatomy of the prostate in man and in the rhesus monkey (Macaca mulatta).

Study of whole sections of human prostate has confirmed McNeal's (4) concept of a dual morphology of the external glands (2) in the terms of a central zone cranially and a peripheral zone caudal to this. A study of the non-human primate, Macaca Mulatta, has shown cranial and caudal prostatic entities in this animal whose anatomical relationships and histological characteristics suggest homology with the central and peripheral zones of the human.


Androgen receptors in the prostate of the Rhesus monkey.

The presence of an androgen receptor protein in the supernatant preparation of the prostate from Rhesus monkey (macaca mulatta) is described. The molecular weight of this receptor protein was found to be 2.8 - 2.9 X 10(5) daltons. The levels of free and bound androgen receptors were measured in the caudal and cranial lobes of the prostate by an exchange assay using methyltrienolone (R1881). The concentration of the free binding sites in the caudal lobe ranged between 3.7 - 23.7 fmol/mg proteial binding sites in the caudal lobe ranged between 36.0 - 112.7 and in the cranial between 21.2 - 55.0 fmol/mg. The bound receptor ranged between 43.3 - 109.0 and 19.1 - 47.3 fmol/mg protein for caudal and cranial lobes respectively. The level of both bound and free receptors was found to be significantly higher in the caudal lobe. This data suggests that the two lobes of the prostate in the Rhesus monkey can be equated with the two zones of the human prostate in respect of androgen responsiveness.


The ultrastructure of Rhesus monkey prostate.

An ultrastructural study of immature and mature rhesus monkey prostate is described and a comparison is made with human tissue. The immature gland consists of largely undifferentiated epithelium showing little or no secretory activity. The mature gland exhibits the general characteristics of prostates of the other species studied. Columnar epithelial cells and undifferentiated basal cells are observed. The two lobes of the gland show several differences, the caudal lobe being rich in secretory granules, with the cranial lobe consisting of taller vacuolated cells. The description provides a basis for comparison with ultrastructural changes produced during in vivo and in vitro experimentation and with characteristics of normal and diseased human prostate.


[Effect of different systems of colostral nutrition on the level of immunoglobulins in the blood of calves].

New-born calves, artificially fed colostrum or native colostral whey, either dried or preserved by another method, had good health and good weight gains (between 0.05 and 0.60 kg). No greater differences were observed between the groups of calves given three times the colostrum of their mothers, calves given mixed colostrum, and calves fed colostral whey powder. In all groups only individual differences in IgG content in the blood serum were observed after 48 hours from birth. Hypogammaglobulinaemia occurred in individual cases both in calves given small amounts of colostrum or colostral whey and in calves given sufficient quantities. The time that had elapsed from birth to the first drinking did not exert any greater influence upon the IgG level in the blood; the decisive factor was the amount of colostrum taken in by the calf in the first dose. The rate of the absorption of IgG1, IgG2, IgA, and IgM from colostrum and the concentration of the immunoglobulins in the serum depended on the quantity of colostrum in the first dose and were not influenced to any greater degree by the amount of colostrum given to the calves in further doses. The amount of IgG in the blood serum of calves corresponded approximately to the level of colostral antibodies to the virus PI-3. The antibodies to the virus PI-3 and small quantities of IgG were observed also in the serum to new-born calves before drinking colostrum.