Electromyographic studies in calves with spastic paresis.

As part of the investigation into the cause of spastic paresis in cattle, electromyographic studies were done in a number of calves with spastic paresis of one limb and in a number of normal calves. The calves with spastic paresis were also studied at various intervals after total neurectomy of the tibial nerve or tenotomy of the Achilles tendon structure. A marked increase in activity was perceptible in a number of muscles but characteristic changes in the EMG were not observed.


[Dermatophyte infections in animals (author's transl)].

Dermatophytes are more or less species-specific in animals. The diagnosis may be based on the microscopic specimen and is verified by cultural studies. This is subject to the restriction that fungus spores are only microscopically and culturally detectable during a particular period in which clinical symptoms are present. When the animal has had a primary infection, immunity will occur. This immunity is believed to play a role as early as spontaneous recovery from the primary infection. The stage of the disease should be taken into account in treating dermatophyte infections. The economic significance and risk of infection in human subjects are briefly discussed.


Histocompatibility (HL-A) antigens and primary open-angle glaucoma.

To assess the association between open-angle glaucoma and HL-A antigens, the frequencies of 25 HL-A antigens were determined in 49 patients with OAG, and 22 patients with increased intraocular pressure, due to causes other than OAG, using the microcytotoxicity method. The results were compared to 250 individuals from the general population who were tested in the same laboratory at the same period of time. Using rigid statistical analysis, the incidence of the Bw35 antigen was found to be significantly (less than 0.012) higher among OAG patients. In a group of 27 first relatives of OAG patients who were tested at the same time, the frequency of Bw35 antigen was increased compared to the general population. The biological importance of the association between Bw35 and OAG, which may still be a chance deviation, is not yet fully understood. It may indicate that the Bw35 antigen or the HLA loci are among the genetic factors which produce susceptibility to open-angle glaucoma.


HLA antibodies and period of gestation: decline in frequency of positive sera during last trimester.

The incidence of cytotoxic antibodies in relation to the number of pregnancies and the different periods of gestation was analysed in sera from 2,686 pregnant women. In all groups, except among women pregnant more than five times, a significant decline in the incidence of active sera occurred during the last trimester of gestation.


HLA CW3 in thyrotoxicosis patients with and without endocrine ophthalmopathy.

Fifty-four thyrotoxic patients (23 with and 31 without endocrine ophthalmopathy EOP) were HLA typed for A, B, and C locus antigens. The frequency of this third locus antigen CW3 was found to be significantly increased in patients with EOP compared with those thyrotoxic patients without EOP. These findings point to a possible genetic heterogeneity in thyrotoxic patients with or without EOP. HLA B8 was observed in only 10 of the 54 patients studied, which is not in accordance with the previously reported statistically significant increased frequency of this B locus antigen in thyrotoxic patients.


An unusual type of secretory cell in the ventral pedal gland of the gastropod mollusc Buccinum undatum L.

The ventral pedal gland in the foot of the mature female whelk Buccinum undatum L. consists of a shallow pouch containing a layer of elongated cells which partially penetrate a basement membrane overlying layers of smooth muscle. This glandular epithelium contains acid mucopolysaccharide cells, ciliated and interstitial cells as well as the upper part of a new type of subepidermal gland cell. These gland cells consist of an elongated extracellular tubular duct formed by an invagination of the cell membrane and lined by numerous microvilli. Into this duct are discharged packets of a densely staining secretion. The secretion packets are produced in Golgi regions around the nuclei of the cells and are passed up through the cell to the base of the duct through or along an extensive assemblage of microtubules. The secretion packets show organized internal structure and may contain aromatic aldehydes and protein associated with the sclerotization of the egg capsules, which pass through the gland after leaving the genital tract.


An unusual receptor in the octopus.

The epithelium of the rim of the octopus sucker in the site of several different types of primary receptors. One is a non-ciliated cell with unusual characteristics. (1) The surface of the cell is extremely irregular with finger-like extension of cytoplasm, especially far reaching in the basal region. (2) The slender neck contains a canal whose apical opening is in contact with the environment. This canal is lined with microvilli and contains granular material in an electron-dense matrix. (3) Patches of presumed glycogen granules occur throughout the cell, being especially abundant in the outer reaches of the cytoplasmic extensions. Their presence, together with numerous mitochondria and free ribosomes, indicate a high intrinsic metabolism. (4) Small fascicles of microtubules are randomly situated throughout the perikaryon. They gather into a coherent system of larger and larger bundles which ultimately enter the axon leading from the cell. This axon extends some distance in the basal region of the epithelium before crossing the subepithelial space to enter the infundibular muscle. Possible functions of this cell are discussed. On the basis of its specific position on the sucker and its intrinsic morphology we suggest that it is a mechanoreceptor involved in shape and/or negative pressure discrimination.


The sarcolemma of Aplysia smooth muscle in freeze-fracture preparations.

Smooth muscle cells in the sheath covering the visceral ganglion of Aplysia californica were examined with the techniques of freeze-fracture and conventional electron microscopy. The sarcolemma of these muscle cell invaginates to form myriad caveolae that have an intrinsic marker within their membrane. This intrinsic structure of the caveolar membrane is revealed by freeze-fracture and consists of rows of large particles in the outer half and matching grooves on the complementary inner half of the membrane. In thin plastic sections, parallel striations or shelves within the caveolar membrane appear to be the equivalent of the particles and grooves of the fractured membrane. Physical fixation of some specimens by rapid freezing in super-cooled liquid nitrogen or in liquid helium suggests that in their natural state, the caveolar ostia are not uniform in size and that at any given moment a number of caveolae are flattened. When segments of the connective nerves which link the visceral ganglion to the cephalic ganglia are stretched in vitro two to three times their in situ length, the caveolae lose their invaginated shape and are fully exposed to the extracellular space. The caveolar membrane, so stretched, is pulled into the line of fracture with the result that the large particles rather than the ostia appear on the cleaved surface. This flattening of the caveolae is reversible and suggests that they might serve as miniature stretch-receptors within the membrane of the smooth muscle cells. The caveolae are accessible to extracellular horseradish peroxidase but do not appear to pinocytose the protein.


Analysis of fiber types in the pigeon's metapatagialis muscle. II. Effects of denervation.

The pigeon's metapatagialis muscle consists of three slips, two twitch and one tonic, and these slips are distinguishable at the gross anatomical level. Comparative studies of denervation are facilitated because the two fiber types are under the same mechanical forces, can be denervated as one muscle, and can be distinguished after denervation. Both fiber types atrophied after denervation, with the twitch fibers having a more variable response. Pathological alterations observed by light microscopy suggested that the twitch fibers were more affected by denervation than the tonus fibers. Ultrastructurally, both fiber types showed the same changes, with the twitch fibers again being more consistently altered. Proliferation of the transverse tubular system and sarcoplasmic reticulum were more marked in the tonus than twitch fibers, and the sarcoplasmic reticulum proliferated prior to the transverse tubules. Filament and fibril degeneration, peripheral and central degeneration, lysosomes and their derivatives, and satellite cell proliferation were common to both fiber types. Contracture knots were common to the denervated fibers, and were suggested to be characteristic of degenerating fibers. Degenerating motor end plates were observed, and most neurons in the fibers were naked, lacking myelin sheaths. The results are discussed in relation to the function of the neuron in maintaining the muscle, and the possibility of denervation inducing a transformation of tonic to twitch fibers.


Cellular composition of erythropoietic cell populations and aggregate cell cultures derived from early chick blastodiscs.

Light and electron microscopy of suspensions of cells prepared by dispersing chick blastodiscs at primitive-streak and head-fold stages showed the presence of numerous yolk granules, yolk-rich endodermal cells and occasional presumed ecto- and mesodermal cells. Several cell fractions prepared from this suspension by sedimentation through discontinuous Ficoll gradients were of similar composition. No enrichment of any particular cell type which might account for either differential sedimentation or erythropoietic potential of the fractions could be recognized. Two fractions, EP 1, and EP 2, were cultured as cell aggregates on vitelline membranes. EP 1 produced highly organized blood islands containing developing erythrocyte cells, organized endothelium, fibroblasts, thrombocytes and occasional granulocytes. Blood islands derived from EP 2, on the other hand, contained essentially only aggregates of erythroblasts embedded in endoderm. It is tentatively suggested that EP1 contains young multipotential hematopoietic precursors while EP 2 has only older blood-cell precursors committed to erythrocyte development. No cellular basis for the resolution of EP 1 into two complementary subfractions could be recognized.


Fine structure of postgonopodial glands of a myriapod Glomeris marginata (Villers).

The postgonopodial gland of the myriapod Glomeris marginata (Villers), which produces a pheromone, is an integumentary gland comprising numerous functional secretory units. Each secretory unit consists of two proximal secretory cells, an intermediary cells lacking secretory characteristics and a canal cell surrounding the canal, which is secretory in nature. Secretory proximal cells exhibit a zone of small channels originating from invaginations of the plasma membrane and through which secreted material is released. Apposing each invagination of these cells is a corresponding invagination of the intermediary cell: the two units in the centre of the intermediary cell join another which communicates with the canal. Secretion produced by the latter passes through the canal wall and bends with secretion of the two proximal cells. The most striking feature of all these cells is the abundance of tubules and fibrils in the small canal zone in the proximal cells, which also exhibits a centriole; in the intermediary cell around cytoplasmic membrane invaginations where a diplosome is present, and in almost the entire canal cell.


Autolysis in axon terminals of a new neurohaemal organ in the cockroach Periplaneta americana.

An ultrastructural investigation showed that there was a neurohaemal organ in the wall of the ampulla of the antennal pulsatile organ. The neurosecretory axon terminals occurred singly or in small groups, rather than closely packed together as in other neurohaemal organs. All axons contained the same type of neurosecretory granule. The granules had varying electron density and a diameter in the range 1000-2500 A. Some terminals contained small, elliptical electron-transparent vesicles and the axolemma was apposed to the stroma. Other terminals were large and enveloped by glial tissue and the contents of the terminals exhibited varying degrees of autolytic degeneration. Autolysis was characterized by the occurrence of dense bodies and multilaminate bodies which enclosed mitochondria and neurosecretory granules. It was suggested that the neurosecretory material affects antennal function.


The fine structure of some carabid beetle eyes, with particular reference to ciliary structures in the retinula cells.

Paired centrioles and associated ciliary root material occur in all eight retinula cells in the nine species investigated. In the diurnal Notiophilus, Elaphrus and Bembidion where the distal rhabdomere of cell 7 is fused with the proximal rhabdom formed by cells 1 to 6, the roots in cells 1 to 6 extend for the entire length of the retinula. In Notiophilus their arrangement around the rhabdom suggests a complementary mechanical relationship between the six large roots and the four Semper cell processes. In five relatively nocturnal species a retinula cell column separates the distal rhabdomere from the proximal rhabdom. In cells 1 to 6 root material is associated with the distally located centrioles as follows. In Leistus roots extend into the proximal rhabdom layer. In Loricera and Agonum roots at the level of the proximal rhabdom are not continuous with the rootlets or short roots associated with the centrioles. In Pseudophonus and Feronia, and in the diurnal Cicindela, short rootlets link the centrioles. Cell movements on dark-adaptation of notiophilus and Cicindela include shortening of the crystalline tract. In Notiophilus the entire rhabdom is apparently displaced, whereas in Cicindela the narrow distal rhabdomere becomes dissociated from the proximal rhabdom.


Fine structure of the rectum in cockroaches (Dictyoptera): general organization and intercellular junctions.

The organization of the rectal pads is described in cockroaches belonging to the Groups Blattoidea (Periplaneta americana, Blatta orientalis) and Blaberoidea (Supella supellectillu, Blaberus craniifer). In the Blattoidea, each pad is composed of two layers (principal and basal cells) and is surrounded by very narrow junctional cells supporting the sclerotized cuticle of the pad frame; basally, the junctional cells abut on to the basal cells. In the Blaberoidea, the basal cell layer is discontinuous, the basal cells being interspersed between extensions of the junctional cells beneath the pad. The ultrastructural features of each cell type is described, with special reference to the intercellular junctions, which exhibit unusual complexity. Four types of junction are recognized: desmosomes (belt and spot desmosomes), gap junctions, septate junctions and scalariform (ladder-like) junctions. The last are usually closely associated with mitochondria, forming mitochondrial-scalariform junction complexes (MS). The distribution of these junctions is examined in relation to the partitioning of extracellular spaces, and to the problem of fluid transport.


Tridimensional ultrastructure of freeze-fractured rat kidney cortex (studied in stereo).

The tridimensional ultrastructure of the inner cortex of rat kidney has been studied by observing freeze-fractured tissue in stereo. The complex structure of the tubules, fenestrated capillaries and glomeruli is more readily observed through the irregular fracturing of the tissue that occurs in this technique. The ultrastructure of the brush border and interdigitating membranes of the proximal tubules, the structure of the fenestrated endothelial membranes of the capillaries and the ribbon-like appearance of the filtration space between the foot processes of the glomeruli were especially well depicted in stereo images of freeze-fractured renal tissue.


Vinyl chloride-induced depression of hepatic non-protein sulfhydryl content and effects on bromosulphalein (BSP) clearance in rats.

Rats were exposed to atmospheres of 2000, 1000, 250, 150, 50 and 10 ppm vinyl chloride (VC) for 1-7 h to determine the effect of VC on the hepatic non-protein sulhydryl content, Exposure to 2000, 1000, 250 and 150 ppm VC caused a progressive depression of the hepatic non-protein sulfhydryl content. Following exposure to 50 ppm VC for 7 h the depression was inconsistent, and no depression was observed after 10 ppm VC for 7 h. Also, exposure to 1000 ppm VC did not alter the serum clearance of bromosulphalein (BSP).


Toxicity of methylmercury chloride in rats. III. Long-term toxicity study.

Four groups, each of 25 male and 25 female weanling rats, were given dietary levels of 0, 0.1, 0.5 and 2.5 ppm MeHgCl for 2 years. Observations were made on behaviour, growth, food intake, haematology, serum enzymes, urinalysis, microsomal liver enzymes, organ weights and histology with special reference to the nervous system, histochemistry of the kidneys and cerebellum and on tissue Hg concentrations. Significant findings included a slight growth reduction in females at 2.5 ppm, increased relative kidney weight at 2.5 ppm and histochemical changes in kidney enzymes at 2.5 ppm. No effect was seen on the nature or incidence of pathological lesions or tumours at any level. From the results obtained in the short-term, reproduction and long-term studies, the no-toxic effect level for rats appears to be between 0.1 and 0.5 ppm MeHgCl in the diet. Exposure of the Dutch population does not appear to present a health hazard at the moment because the mean intake of total Hg is still far below the intake deemed to be safe.


[Nicotine metabolism in the pig (author's transl)].

After i.v. injection of 0.33 mg nicotine/kg the elimination of unchanged nicotine as well as nicotine-N-oxide, cotinine, nornicotine and norcotinine was determined in the urine of pigs dependent on time. In female pigs 16.3% and in male pigs 25.9% of the applied nicotine were recovered in form of the mentioned compounds within 31h. Nicotine elimination essentially stopped in the collecting period 3-8 h. The main decomposition products nicotine-N-oxide and cotinine were eliminated to a significant extent also 8-23 h after application.


Action of lead on early divisions of the mouse embryo.

The number of cells in mouse embryos 48 h after mating was studied in normal and lead-treated females (0.125, 0.25, 0.5, 1% of lead in the diet). The percentage of embryos in the 4-cell stage compared to those in the 8-cell stage increased after 0.125, 0.25 and 0.5% of dietary lead. After the highest dose an increase in nondivided eggs was also seen which occurred at the expense of 4-cell embryos. The different possibilities, delay of all divisions, delay of only the first division and action of lead on only a part of the embryonic population, are discussed.


Effect of lead on some parameters of the heme biosynthetic pathway in rat tissues in vivo.

Lead was administered to male and female rats in drinking water for 3 and 6 weeks at the following doses: 0, 10, 100, 1000, 5000 ppm and for 6 months at 10 ppm only. Various parameters of blood - lead concentration (Pb-B), hematocrit (Htc), hemoglobin (Hb), free erythrocyte porphyrins (FEB), delta-aminolevulinate dehydratase (ALAD), reticulocytes - and tissue - ALAD, free tissue porphyrins (FTP), lead concentration (Pb-T) - were determined. Pb-B increases with dose but reaches rapidly a plateau despite continuous Pb administration. Concentration of Pb in kidney, liver and brain correlates with Pb-B. Pb does not accumulate in heart. Kidney is the main site of Pb deposition and kidney ALAD is the parameter most susceptible to lead, since reduction is observed in all treated groups after 3 weeks of exposure. However, kidney ALAD inhibition is transitory since after 6 weeks it is only observed in the 5000 ppm group. At 10 ppm lead prevents also the increase in blood ALAD activity normally associated with the reticulocytosis of repetitive bleeding. The next parameters affected by lead are: ALAD in blood which is inhibited after 6 weeks of treatment with 100 ppm lead, and FEP, delta-aminolevulinic acid plus other pyrrole-forming substances in urine (ALA-U), and FTP in kidney which are increased after 3 or 6 weeks of treatment with 1000 and 5000 ppm lead.


Teratogenic and toxicological examination of 2,4,5-trichlorphenoxyacetic acid in developing chick embryos.

Practical grade 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), dissolved in dimethylsulfoxide (DMSO), was injected into the air space of fertilized chicken eggs prior to incubation. Doses of 2,4,5-T administered were 12.5, 25, 50, 75, 100, and 125 mg/kg to determine herbicide toxicity on the first day of incubation. A similar group was studied on day 5 of incubation with doses of 2,4,5-T at 50, 75, 100 and 250 mg/kg. LD50 was estimated to be 62 mg/kg on day zero and 68 mg/kg on day 5. Additionally, embryos were exposed to 2,4,5-T at 50 mg/kg on day zero of gestation and sacrificed after 48 h of incubation. Serial sections were examined for teratological and developmental anomalies. None were found.


Long-term and multigeneration toxicity studies with cyclohexylamine hydrochloride.

Cyclohexylamine (CHA), the metabolite of cyclamate produced in varying degree by gastrointestinal microorganisms, was subjected to a 2-year multi-generation feeding study in rats, at dosages of 15, 50, 100, and 150 mg/kg/d. Observations included growth, feed efficiency, clinical and hematological tests, reproduction, teratology, mortality and gross and microscopic pathology. Rats from the first litters of each generation from F0 through F4 were mated to produce the next succeeding generation. Those from the second litters of F1 through F4 were also mated, half the dams being delivered by hysterotomy for teratological examination, while litters from the other half were raised to maturity. Except for some non-progressive growth retardation in the higher dosage groups, due to lower food consumption, the physical and clinical observations in the test groups fell substantially within normal limits and were not significantly different from the untreated controls. Reproduction rates were normal in all groups but at the higher dosages the size of the litters and their weaning weights were slightly reduced. At the 150 mg/kg level, histopathological examination revealed mucosal thickening of the bladder walls and evidence of renal calcification; however, no bladder tumors were seen, such as occurred in the chronic feeding study in which rats received 2500 mg/kg of a cyclamate: saccharin (10 : 1) mixture. A significantly higher incidence of testicular atrophy, characteristic of aged rats, was observed in the F0 group at the highest dosage level; however, these males continued to be fertile, in two cases up to 6 consecutive matings.


Percutaneous absorption of triclocarban in rat and man.

The route and rate of excretion by rats of the germicide (1 4 C) Triclocarban formerly called trichlorocarbanilide, given by parenteral injection has been investigated. Blood levels based on radioactivity and by chemical determination after parenteral injection have been compared with those obtained after topical application of (1 4 C) Triclocarban in soaps and in dimethylformamide (DMF) through occluded rat skin has been studied. Other soaps and a hand cleanser containing (1 4 C) Triclocarban have been applied to rat skin without occlusion and the effects of duration of contact, concentration and the use of a solubilizer have been investigated. In humans, absorption of Triclocarban through skin after bathing daily for 28 days has been investigated by chemical analysis of blood and urine. The data show that elimination by the rat is rapid and complete principally via the faeces. Blood levels after parenteral injection are low and comparison of the radioactivity and chemical determinations suggest rapid metabolism of the Triclocarban. After application to the skin, blood levels based on 1 4 C are very low. Absorption of (1 4 C) Triclocarban through occluded rat skin was greater from DMF than from soaps. With non-occluded rat skin, absorption from soaps was less and was dependent on concentration but independent of duration of contact. The use of a solubilizer did not increase absorption through skin. No measurable Triclocarban (less than 25 ppb) was present in blood and urine samples of volunteers during or shortly after a 28-day intensive bathing regimen.


Comparative toxicity of two-dexamethasone derivatives following topical ocular instillation to rabbits. II. Systemic histopathological changes.

Dexamethasone-21-tertiary butyl acetate (dexamethasone TBA) and dexamethasone alcohol at concentrations of 0.2, 0.1, 0.01, and 0.001% were topically instilled into the right eyes of groups of 10 rabbits for 21 consecutive days. Vehicle control and untreated control groups were used for comparative evaluation. The dose-dependent changes for each compound were (1) lipid and glyocogen infiltration of liver, (2) hydropic changes of liver, (3) vacuolation and multifocal hepatic necrosis of liver, (4) atrophy of Peyer's patches of intestines, (5) white pulp atrophy of the spleen and (6) atrophy of the adrenal cortex. No pathological changes were noted for other tissues including the eye. In conclusion, the results indicate that systemic histopathologic changes for both steroids were comparable and typical for steroids.


Toxicity of methylmercury chloride in rats I. Short-term study.

In the range-finding test, 6 groups of 4 male and 4 female weanling rats were given dietary levels of 0, 0.1,0.5, 2.5, 12.5 and 250 ppm methylmercury chloride (MeHgCl) for 2 weeks. Signs of central nervous system toxicity, weight loss and high mortality appeared at 250 ppm but not at lower levels. No haematological changes were observed at 0.1-12.5 ppm. The relative weights of the liver in females on 2.5 and 12.5 ppm and of the kidneys in females on 12.5 ppm were significantly increased; the effects in males were less marked. Total mercury concentration in the kidneys increased proportionally with increasing dietary levels of MeHgCl. In the short-term test, 5 groups of 15 male and 10 female weanling rats were given dietary levels of 0, 0.1, 0.5, 2.5 and 25 ppm MeHgCl for 12 weeks. Toxic signs, weight loss and restricted food intake were observed at 25 ppm starting from week 9 onwards. Haematological, serum enzyme and urinalysis changes were seen at 25 ppm. Liver microsomal enzyme activity was increased non-significantly and liver glycogen was depressed at 25 ppm. Organ weight changes were evident at 25 ppm and histological changes seen in the spleen, kidneys, brain, spinal cord and peripheral nerves were confined to the 25 ppm level. Histochemical changes in kidney enzymes occured at 2.5 and 25 ppm. Hg concentrations in blood, hair, kidneys, liver and brain were higher at 12 weeks than 6 weeks and generally increased with increasing MeHgCl level in the diet.


Serum enzyme activities and hepatic triglyceride levels in acute and subacute acetaminophen-treated rats.

The dose- and time-related hepatotoxic effects of acetaminophen were investigated in rats using biochemical parameters as indices of hepatotoxicity supplemented by the histopathological examination of the livers. The acute or subacute (twice daily for 7 days) administration of 0.25 g/kg acetaminophen did not produce any noticeable hepatocellular damage. On the other hand, dose-dependent elevations in serum enzyme glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and sorbitol dehydrogenase (SDH) activities and hepatic triglyceride (TG) levels were observed following the administration of single doses of 0.5 and lg/kg acetaminophen. Maximal hepatic damage occurred 12-18 h after acute dosing, while the hepatic function returned to control levels by 48-72 h. In contrast with the acutely treated rats, the serum enzyme activities and the hepatic TG levels remained unchanged following 7-day treatment with 0.5 or 1 g/kg acetaminophen. Also, histopathologically the degree of acetaminophen-induced hepatic necrosis was found to be far less extensive in rats given 0.5 and 1 g/kg acetaminophen twice daily for up to one week, as compared with the animals sacrificed 18 h after administering single equivalent doses of this drug. The results suggest that the liver function is reversibly impaired following acetaminophen overdosage, and that the intensity of acetaminophen-induced hepatotoxicity becomes less severe after repeated exposure to this hepatotoxin.


Toxicity of methylmercury chloride in rats. II. Reproduction study.

A reproduction study over 3 generations of rats was carried out in which groups of 20 female and 10 male rats received in the diet 0, 0.1, 0.5 and 2.5 ppm MeHgCl. The parameters studied included growth, food intake, haematology, serum and urinalysis, organ weights and reproductive performance, No effect was exerted on fertility index, lactation index or on the 21-day body weights of pups but the viability index was impaired at 2.5 ppm in the F1 and F2 generations. Weight gain reductions observed at 12 weeks for the 2.5 ppm level were not accompanied by reductions in food intake. At 6 months, Fla females on 2.5 ppm showed a reduced leucocyte count whilst P males on 0.5 and 2.5 ppm showed an increase in neutrophils and a decrease in lymphocytes. The relative weights of the kidneys, heart, spleen brain and thyroid were increased at 2.5 ppm and in some cases the increases of kidney weights were inconsistently seen at the 0.1 and 0.5 ppm levels. No significant histological changes were seen at any level. In a special 7-week study involving the F3a generation, weanling rats obtained from the four different F2a groups, each comprising 20 females and 10 males, were all transferred to diets containing 25 ppm MeHgCl. Toxicity signs were evident at 7 weeks. No evidence was obtained of increased susceptibility to the toxicity of MeHgCl in successive generations.


The successful induction of molting in the adult male lobster (Homarus americanus) with a slow-release form of ecdysterone.

In an initial, and then a confirmatory experiment, adult, male lobsters were injected with solvent, ecdysterone (E, 2.0 mug/g live weight) or ecdysterone acetate (EAc, 2.5 or 5.0 mug/g live weight) emulsions in Freund's incomplete adjuvant (FIA). Control lobsters underwent no molts and only one death in the two cases. The E treated animals all died (average: exp. 1, 19.2 +/-2.1 days; exp. 2, 25.3 +/- 8 days). After the lobsters were treated twice with 2.5 mug EAc/g live weight, in the first experiment, four out of five molted and one died; in the second experiment six out of eight molted, one died and one remained refractory. The high EAc dose resulted in five deaths, one molt and two pseudomolts after one treatment. It is concluded that the use of the oil emulsion and EAc sufficiently slowed the release of free ecdysterone to allow complete premolt development in the lobster.


Metabolism of 17 beta-hydroxy-2alpha, 3alpha-cyclopropano-5alpha-androstane in the rabbit.

The neutral urinary excretion products of 17beta-hydroxy-2alpha, 3alpha-cyclopropano-5alpha-androstane from the rabbit, dosed orally, were investigated. Column chromatography yielded five crystalline metabolites which were identified by GLC and spectroscopic measurements. Three of these substances were hydroxylated in the 4alpha-position and one in the 6alpha-position with the cyclopropane ring intact. The fifth substance, 17beta-hydroxy-3beta-methyl-5alpha-androstan-2-one, can be derived from initial hydroxylation of the cyclopropane ring at C-2 followed by ring opening. The dosed substance and triol material was shown to be present by GLC and m.s. measurements. GLC determinations show that hydroxylation has occurred at C-4-C-6-C-2.


Biliary metabolites of estriol in the rat.

Following the subcutaneous administration of estriol-6,7-3H to rats, biliary metabolites were identified and quantitated. Approximately 70% of the metabolites were excreted in the form of "glucosiduronate" conjugates. 3,17beta-Dihydroxy-2-methoxy-1,3,5(10)-estratrien-16-one was the major metabolite in this conjugate fraction. Significant amounts of 3,17beta-dihydroxy-1,3,5(10)-estratrien-16-one and 2,3,17beta-trihydroxy-1,3,5(10)-estratrien-16-one, as well as smaller quantities of 1,3,5(10)-estratriene-2,316alpha,17beta, tetrol and 2-methoxy-1,3,5(10)-estratriene-3, 16alpha, 17beta-triol, were also found. In 17alpha-ethinylestradiol-treated animals, the rate of excretion of radioactivity and the proportion of 16-oxo-17beta-ol metabolites found in the "glucosiduronate" fraction were reduced.


A synthesis of 7alpha-hydroxyandrost-4-ene-3,17-dione.

The first convenient chemical synthesis of 7alpha-hydroxyandrost-4-ene-3,17-dione is reported. Androsta-4,6-diene3, 17-dione was converted into its 6alpha, 7alpha-epoxy-derivative; reduction of the epoxide with aluminum amalgam gave 7alpha-hydroxyandrost-4-ene-3,17-dione. This reducing agent is more efficient than chromous acetate for the purpose.


The synthesis of some cholest-7-en-6-one derivatives related to ecdysones.

Cholest-7-en-6-one, 14alpha-hydroxycholest-7-en-6-one, 2beta, 3beta, 5alpha-trihydroxycholest-7-en-6-one and ten other related compounds have been synthesized by efficient routes from cholesterol. The named compounds possess some of the characteristics of the insect moulting hormones, ecdysones.


Androgen metabolism by rat epididymis. 4. The formation of conjugates.

The ability to form androgen conjugates and the hormone dependency of the conjugating enzymes have been studied in the rat epididymis. Following the in vitro incubation of 3H-testosterone with epididymal slices from intact and castrated rats, the radioactivity recovered was partitioned between water and ether. Examination of the water soluble radioactivity demonstrated the presence of glucuronides and sulfates. The total radioactivity in the conjugate fraction was the same for both intact and castrated animals. However, castrated rats showed a 3-fold increase in the glucuronide fraction with a corresponding decrease in the formation of sulfates. Characterization of the ether soluble radioactivity after solvolysis of the conjugate fraction from castrated animals, showed DHT (17beta-hydroxy-5alpha-androstan-3-one) and 3alpha-diol (5alpha-andro-stane-3alpha, 17beta-diol) to be the main metabolites. After beta-glucuronidase hydrolysis of the same, only 3alpha-diol could be demonstrated at a significant level, although traces of DHT and delta16 compounds were present. Corresponding hydrolysis of the water phase from incubation of epididymis from intact rats, demonstrated a marked quantitative difference. Here approximately 40% of the conjugated aglycones consisted of delta16 compounds, whilst only about 12% was comprised of 3alpha-diol. The preferential conjugation of DHT and 3alpha-diol to a sulfate radical was demonstrated in both intact and castrated rats. Since the conjugated delta16 compounds were detected only in the epididymis from intact animals, it is possible that these are formed by the spermatozoa.


Kinetic analysis of cholesterol turnover in rat tissues.

A number of studies have been conducted on serum cholesterol disappearance following a single injection of tracer. They have shown 2 or 3 component curves depending on the length of time of observation. They have been interpreted to indicate pools of cholesterol in fast or slow equilibrium with serum and generally depicted as representing groups of tissues. A cholesterol kinetic study was conducted using rats so that each tissue could be analyzed for appearance-disappearance of cholesterol from 30 minutes to 75 days. Serum and liver appeared to die-away for 30 days in a 2 component configuration, then exhibited a repetition of the same curve in the next 30 days. Skeletal muscle and kidney had a slow buildup for 2 weeks, then a plateau for 2 weeks then a 2 component die-away. Adipose showed a high plateau from 30 minutes to 30 days then a 2 component die-away, with specific activity higher than serum at all times. The data are interpreted to indicate that adipose tissue sequestered part of the tracer dose and all tissues reached equilibrium at about 30 days. After that time all tissues had a statistically significant 2 component die-away curve. The mathematical models tested suggest that in the steady state, cholesterol enters and exits the slow pool of serum, kidney, muscle and adipose and in liver enters both pools. Interpretation of the complete die-away is that the tracer dose first equilibrates with membrane free cholesterol, then with the intracellular cholesterol, and finally dies-away at the rate of release by the slow intercellular pool.


Identification of (23S)-5beta-cholestane-3alpha, 7alpha, 12alpha, 23, 25-pentol in cerebrotendinous xanthomatosis.

The synthesis of (23R)- and (23S)-5beta-cholestane-3alpha, 7alpha, 12alpha, 23, 25-pentols is described. Norcholyl aldehyde was converted into the cholestanepentols by a Reformatsky reaction with ethyl bromoacetate followed by a Grignard reaction with methylmagnesium iodide. One of the synthetic pentols, the 23S epimer was identical with a bile alcohol isolated from patients with cerebrotendinous xanthomatosis.


High-resolution gas chromatography/mass spectrometric analysis of tobacco and marijuana sterols.

Components of the sterol fraction of tobacco and marijauna were resolved as trimethylsilyl derivatives by gas chromatography with glass capillary columns. Ten phytosterols in tobacco and five in marijuana were identified by comparisons of their retention with authentic compounds on three different stationary phases and through mass-spectral data.


Exclusion of 20(22)-dehydrocholesterol as an intermediate in the biosynthesis of pregnenolone in bovine adrenocortical mitochondrial acetone-dried powder preparations.

Incubation of (22R)-(22-180)20-hydroxycholesterol with a bovine adrenocortical mitochondrial acetone-dried powder preparation in air yielded (20R, 22R)-20, (22-18O)22-dihydroxy-cholesterol. Incubation of (20S)-(20-18O)22-hydroxycholesterol yielded (20R, 22R)-(20-18O)20,22-dihydroxycholesterol. The formed glycols and the substrates reisolated at the end of the incubations had the same 18O abundance as the starting materials. No significant (20R, 22R)-20,22-dihydroxycholesterol was formed following incubation with either (E)-or (Z)-20, (22)-dehydrocholesterol. (20R,22S)-20, 22-Epoxycholesterol yielded approximately 1/5 of the amount of pregnenolone obtained in a similar incubation with cholesterol. No significant pregnenolone formation was observed with (20R, 22R)-20,22-epoxycholesterol. These results exclude a mechanism for the biosynthesis of (20R, 22R)-20,22-dihydroxycholesterol from the monohydroxylated cholesterol derivatives by way of dehydration followed by epoxidation and hydration. Similarly, the participation of an olefin and an epoxide as intermediates in the transformation of cholesterol to pregnenolone in acetone-dried powder preparations of adrenal cortex mitochondria is unlikely.


Progesterone in the uterus. VI. On the question of the in vitro progesterone metabolism in human endometrium and myometrium.

Human endometrial and myometrial tissue pieces were incubated with radioactively labeled progesterone in nutrient medium for 20 min., 1 hr and 2 hrs. The only compound extracted from the tissue pieces and the nutrient fluids was identified to be progesterone by TLC, chemical reactions and crystallization experiments. Radiometabolites could not be detected in the tissue pieces and in the nutrient fluids under the experimental conditions applied (10(-7) M 1,2-3H-progesterone in the incubation medium). This result is comparable with recent findings on the in vitro progesterone metabolism by rat uterine tissue.


Steroids and related products. XLII. (1) The synthesis of 11-oxa steroids. IV. (2) The synthesis of 17,21-dihydroxy-11-oxa-4-pregene-3,20-dione, an 11-oxa analogue of the 17-hydroxylated glucocorticoids.

The synthesis, from 11-oxa-5alpha-pregnane-3,20-dione, available from hecogenin, of 17,21-dihydroxy-11-oxa-4-pregnene-3,20-dione, the first 11-oxa analogue of corticoid hormones, is described. The acetate of its 1-dehydro derivative, 17-hydroxy-21-acetoxy-1,4-pregnadiene-3,20-dione, analogous in structure to the acetates of prednisone and prednisolone, is an intermediate in the synthesis.


Radioimmunoassay of androsterone and androsterone-3-sulfate in plasma.

Details of a sensitive and specific radioimmunoassay for androsterone (1) and androsterone sulfate in plasma have been presented. Benzene extracts of plasma were chromatographed on alumina to isolate the androsterone fraction either (a) directly after extraction (A) or (b) after solvolysis (AS). Following treatment with rabbit anti-A-17-BSA, antibody bound steriod was precipitated by ammonium sulfate. Androsterone concentrations in normal male plasma averaged 57 +/- 24 (S.D.) ng/dl, range 35-135 ng/dl and for normal women, 44 +/- 21 (S.D.) ng/dl, range 18-98 ng/dl. Androsterone sulfate concentrations were: males 55 +/- 28 mug/dl (range 10-114 mug/dl); premenopausal females 52+/- 31 mug/dl (range 16-318 mug/dl).


The inhibition of the conversion of testosterone into 5alpha-dihydrotestosterone in the reproductive organs of the male rat.

The inhibition of testosterone 5alpha-reductase activity by 3-oxo-4-androstene-17beta-carboxylic acid in the male reproductive organs of the rat was demonstrated in vitro. The medium for incubation of caput epididymis showed the highest concentration of 5alpha-dihydrotestosterone (5alpha-DHT) whereas the highest concentration of testosterone (T) was recorded in medium for incubation of decapsulated testis after two hours of incubation. The 3-oxo-4-androstene-17beta-carboxylic acid (1.58 X 10(-5)M) inhibited the conversion of T to 5alpha-DHT in all the organs tested (testis, caput and cauda epididymis and ventral prostate) under identical incubation conditions.


Antiprogestational agents. The synthesis of 7-alkyl steroidal ketones with anti-implantational and antidecidual activity.

A series of 7alpha- and 7beta- alkyl derivatives of steroidal 4-en- and 5-en-3-ones were prepared by 1,6-conjugate addition of organocopper reagents to various steroidal 4,6-dien-3-ones of the androstane, estrane and gonane series. Biological study of these and related compounds revealed that 17beta-hydroxy-7alpha-methyl-5-androsten-3-one (2), 17beta-hydroxy-7alpha-methyl-5-estren-3-one acetate and 17beta-hydroxy-7alpha-methyl-4-estren-3-one acetate had significant anti-implantational and antidecidual activities. The contragestative effects were associated with the latter anti-hormonal properties, and not with the androgenicity of these compounds.


Effects of prednisolone metasulfabenzoate on the induction of DNase II in comparison to alkaline phosphatase and acid phosphatase activities in cultures of HeLa S3 cells.

Cultures of HeLa S3 cells were treated with prednisolone metasulfobenzoate (Na), a derivative of prednisolone which is readily soluble in water. The steroid induced an increase in DNase II, a lysosomal enzyme which was not used previously in enzyme induction by steroids. Alkaline phosphatase, a known inducible enzyme by other steroids and acid phosphatase, a known uninducible enzyme by other steroids, were included for comparative reasons.


Preparation of 3beta, 16beta-dihydroxyandrost-5-en-17-one: stabilization of its alpha-ketolic group toward alkali by formation of a semicarbazone.

Alkaline hydrolysis of a 16beta-acetoxy-17-oxo steroid is accompanied by almost complete rearrangement of the product to a 16-oxo-17beta-hydroxy steroid. Hydrolysis can be achieved without rearrangement by 1) formation of a C-17 semicarbazone, 2) alkaline removal of the acetate group, and 3) removal of the semicarbazone group in the presence of pyruvic acid-acetic acid. By employing this technique, the title compound was obtained from its diacetate in a yield of 65%.


Radioimmunoassay of 15alpha-hydroxyestriol (estetrol) in pregnancy serum.

A more specific antisera against 15alpha-hydroxyestriol (estetrol) was produced in rabbits by immunization with 6-oxoestetrol-6-carboxy-methyloximino-bovine serum albumin. The synthesis of estetrol tetraacetate was greatly improved. Characterization of estetrol antisera revealed that it is more specific than those formerly obtained. A simple method of extraction of estetrol with alcohol from serum with high recovery is described. A radioimmunoassay method for pregnancy serum is characterized in regard to its specificity, accuracy, sensitivity and precision. The method is able to measure as little as 50 pg/tube or 167 pg/ml of serum. The intraassay coefficient of variation is 7.8% and that for interassay including personnel variation is 14.2%. Accuracy of the method, as determined by the recovery of non-radioactive estetrol (1 ng/ml) added to non-pregnancy serum, is found to be 89 +/- 8 (SD)%, CV = 8.7%, without correction for experimental losses. One hundred twelve pregnancy sera were analysed; the values obtained from normal subjects in the third trimester ranged from 240-950 pg/ml. The values obtained by this method are somewhat lower than those reported previously, presumably due to the higher specificity of the antibody.


Human urinary and liver conjugates of 17alpha-ethnylestradiol.

Chromatographic profiles of the conjugates of 17alpha-ethynylestradiol (EE2) were obtained from the urine of castrate and normal women given tritium labeled EE2 orally. Five distinct radioactive peaks were observed, with considerable quantitative variation between individuals. Glucosiduronate fractions comprised the dominant excreted radioactivity. In vitro incubation of normal human liver also produced five conjugate types. Simultaneous intravenous/oral (14C/3H) administration of EE2 demonstrated conversion to identical urinary conjugate and free steroid products, with a greater excretion of the intravenous material. Authentic 3-glucuronide of EE2 was synthesized and its position in the chromatographic system relative to the urinary conjugate peaks demonstrated.


Production of cortisol from cortisone by the isolated, perfused fetal rabbit lung.

Perfusion of the isolated 26 day fetal rabbit lung with 3H-cortisone resulted in its conversion to 3H-cortisol and release into the perfusate. Little conversion of 14C-cortisol to 14C-cortisone occurred. Quantitative study of homogenized fetal rabbit lung revealed the development of both the cofactor and the enzyme for 11beta-hydroxy steroid dehydrogenase activity between 21 and 29 days gestation. These results suggest increasing production of cortisol from cortisone by the fetal rabbit lung as a function of gestational age. This conversion may be of significance with respect to both lung development and parturition, both events being accelerated by cortisol treatment.


Survey of the use of crisis intervention centers by the black population.

In an attempt to determine the extent to which crisis centers meet the needs of black communities, questionnaires were sent to 12 centers. Responses were received from six. Only two centers, in Nashville and Washington, D.C., had statistics of callers identified by race. The findings from these two centers indicate that there are differences between the white and black callers with regard to age, marital status, and type of problem. As an example, the typical black male caller was older and more concerned about his job and financial problems than were white males. This kind of information suggests a need for expanded services within the crisis center framework, possibly for a more preventive approach. More data gathering concerned the black community using crisis centers is urged in order better to identify the needs of this population and the methods to be used for meeting those needs.


Current status of program evaluation efforts.

This article represents an overview of the various types of evaluation research conducted in the fields of crisis intervention, suicide prevention, and mental health in general. An attempt is made to classify it according to its content and purpose, and to assess the relative merit of each. Emphasis is on goal attainment and outcome type of evaluation.


Rescue fantasies in homicide-suicide.

Thirteen homicide-suicides, events in which an individual murders one or more persons and kills himself immediately afterward, were studied. Findings were presented in terms of the setting in which these events occurred, the relationship between perpetrator and victim, and the rationalizations produced by the perpetrators to explain their behavior. The results are interpreted to suggest that persons who commit homicide-suicide are acting out a three-party rescue fantasy in an attempt to resolve unbearable stress.


An assessment of the utility of suicide prediction.

Efforts to predict a future event assume varying levels of confidence depending on its base rate and the error rate of the prediction instrument. Most researchers working with suicide prediction instruments seem tacitly to assume they will be able to predict a future suicide most of the time. Applying basic decision theory on a neuropsychiatric hospital population indicates that researchers using a prediction schedule will be unlikely to predict a future suicide beyond a 20% level of efficiency. Contrary to the general clinical view, eliminating false negatives was shown to be more practical than eliminating false positives in increasing the efficiency of a predictive schedule.


Frequency of suicidal thought and self-destructive behavior among females.

The focus of the present investigation was to examine the importance of a control group in suicide research and to develop an instrument to distinguish between levels of suicidal thought among subjects who had a history of attempted suicide and among a comparison group of nonsuicidal individuals. The sample was comprised of female university students ranging in age from 18 to 25 years. A 31-item questionnaire designed by the investigator was given to 199 students, 20 of whom were found to have histories of one or more previous suicide attempts. The remaining 179 nonsuicidal subjects were divided into two categories based on the frequency of expressed suicidal thought. Fifty individuals were randomly selected from each of these two groups. The three groups (individuals who had attempted suicide, individuals who had not attempted suicide but who thought about suicide on a frequent basis, and individuals who had not attempted suicide and who thought about suicide on an infrequent basis) were compared on the variables of motivation for suicidal thoughts, history of self-destructive behaviors, probability of a future suicide attempt, and age of first suicidal considerations. A chi-square analysis was performed on each of these items in order to assess the extent to which the items discriminated among the three comparison groups. The differences among the three groups on each of the items were found to be statistically significant at less than the .01 level. The results of the study have provided support for the necessity of a distinction between groups within a nonsuicidal comparison population and for the suggestion that there may be a quantitative relationship between the frequency of suicidal thought and the likelihood of attempted suicide.


Serum-derived immunosuppressive substances. I. Partial purification and range of action.

Two alpha-globulin fractions which had in vivo and in vitro immunosuppressive activity were prepared from human serum. The larger fraction eluted from a molecular sieving gel in the albumin fraction and was heat labile whereas the smaller one was present in the elute fraction containing materials of 8,000-25,000 daltons and was heat stable. It is believed that the smaller of the two fractions is the immunoregulatory alpha-globulin described by several other investigators. The comparative activities of various starting materials and of partially purified derivatives in several systems (in vivo and in vitro) were examined. The possibility that these substances are lymphocytic chalones is considered.


Histocompatibility-2 system in wild mice. II. H-2 haplotypes of t-bearing mice.

As a first step in the study of the possible relationship between the T/t and H-2 complexes, the H-2 antigenic composition of the strains carrying factors t12, tw32, tw2, tw8, t1, t0, t6, tw1, tw71, tw73, tw12, tw5, tw75, and t38 was studied by using a battery of antisera containing antibodies against inbred-derived H-2 antigens. In addition, five t strains (t12, t6, tw5, tw1, and tw2) were selected for the production of antisera against the H-2 complexes carried by t chromosomes. Spleen, lymph node, and thymus cells from H-2b/t heterozygotes and tw2/tw2 homozygotes were injected into appropriate F1 hybrids between two inbred strains that carried the inbred-derived H-2 antigens of the donor. Four new H-2 antigens and one Ia antigen were uncovered and were assigned the symbols H-2.106 through H-2.109, and Ia.101, respectively. Three new H-2 haplotypes were also described, based upon the H-2 antigenic pattern of three t factors, t12, tw1, and tw5. These new haplotypes were given the symbols H-2t12, H-2tw1, and H-2tw5. When the t factors were grouped according to their H-2 haplotypes, their distribution, with certain exceptions, corresponded to the complementation groups. Thus, t chromosomes in the same complementation group carried similar, if not identical, H-2 haplotypes, despite the fact that these chromosomes were derived from widely separated geographic areas. Such an association between the t and H-2 complexes is most unusual in light of what is known of the polymorphism of H-2 haplotypes in wild mice populations. It suggests more than a casual relationship, at least at the population level, between the t and H-2 loci.


Destruction of allogeneic tumour cells by peritoneal macrophages.

The population of peritoneal macrophages from mice immunised with allogeneic tumor cells contains two types of cytotoxic cell. One lyses the specific target cell, the other initiates activation of macrophages and hence leads to inhibition of growth of the specific target cell. The yield of lytic effector macrophages was found to depend on the route and the nature of the cell used for immunisation and the condition of the mice. The yield correlated with the yield of complement-dependent cytotoxic antibodies. In contrast, production of specific "activator" macrophages did not depend critically on these factors. The results underline the difference between the two types of cell and suggest that they are produced independently of one another.


Antirat erythrocyte agglutinins.

Antirat hemagglutinins may be found in the sera of both normal and sick persons. High titers of these antibodies are influenced by the major blood groups, the antigen B tending to suppress these antibodies, and by age where juveniles have higher titers than adults. Elevated titers may be stimulated by immunization, injection of pooled gamma-globulin, infection, and transplantation.


Quantitation of the immune rejection of allotransplanted AKR leukemic cells.

AKR leukemic cells were transferred into both CD2F1 and C3H/He mice and the growth and rejection of the cells followed by a quantitative cellular assay. While the leukemic cells initially grew at the same rate in both strains of mice, the CD2F1 mice eventually rejected the cells. The time to rejection was found to be dependent upon the initial inoculum size.


Radiological studies on the upper digestive tract in Tanzanians at Mwanza.

Among 462 barium meals performed in rural Tanzanians in 1973-1974 121 pathological lesions were diagnosed. The principal were peptic ulcer in 59 patients, duodenitis in 20, serious gastritis in 10, carcinoma of the stomach in nine and of the oesophagus in seven. Peptic ulcer was most prevalent in young adults. The frequency of duodenitis was associated with invasion by parasitic worms. The social factors in the prevalence of peptic ulcer are discussed. Gastroptosis was a very common finding in patients with stomach complaints.


Histiocytic medullary reticulosis: a report of four cases from India.

Four cases of histiocytic medullary reticulosis encountered between 1968 and 1972 at the All-India Institute of Medical Sciences Hospital, New Delhi, are reported. One of the cases was diagnosed during life and the other three postmortem. A complete remission was achieved in the former following prednisolone and cyclophosphamide therapy. The histological changes consisted of malignant histiocytosis with erythrophagocytosis in the organs of the reticuloendothelial system. The lymph nodes and the bone marrow were involved in all the cases. The importance of biopsy examination of these organs in making an early diagnosis is emphasised.


Maternal and foetal vitamin B12 concentration at parturition among Nigerians.

Serum vitamin B12 concentrations were determined immediately after delivery among fifty healthy mothers and in cord blood of their newly delivered babies. The serum vitamin B12 concentrations of the infants were higher than those of their mothers and the ratio was approximately 2:1. The maternal serum vitamin B12 concentration was significantly higher than other maternal serum vitamin B12 concentration reported previously and the infant serum vitamin B12 level was also significantly higher than other infants studied in similar projects. These results suggest that the high serum vitamin B12 concentration reported among Nigerians is most probably due to both genetical and environmental factors coupled with some microbial synthesis in the gastro-intestinal tract after resuming a full adult diet.


Biological features of Anopheles fluviatilis and its role in the transmission of malaria in Iran.

Anopheles fluviatilis is a vector of malaria in the southern regions of Iran. Its biological features and its significance are described.


Human brucellosis in Kenya.

The serology, epidemiologic features and clinical presentation of 39 patients suffering from Brucellosis in Kenya are described. The prevalent species was Brucella melitensis. There was a striking preference in the localisation of the infection for the spine and the hip joint. The disease runs a protracted course. Phenomena due to hypersensitivity and neuropsychiatric disorders are discussed. Advice regarding specific treatment is given.


Congenital toxoplasmosis in Indonesia.

An 18-month-old male Indonesian with blindness, microphthalmia and bilateral cataracts was found to have antibody titers against Toxoplasma gondii of 1:512, 1:1024 and 1:1024 respectively by the indirect hemagglutination, indirect fluorescent antibody and Sabin-Feldman dye test. Serum from the child's mother by the same test also demonstrated antibody titers of 1:1024, 1:512 and 1:512 respectively. The clinical manifestations in the child and the presence of anti-toxoplasma antibodies in both mother and child suggest that the disease was congenitally acquired.


Infective endocarditis-experience in Nigeria.

Ninety cases of infective endocarditis seen over a 10-year-period at University College Hospital, Ibadan, are reviewed. The peak incidence was in the third decade and rheumatic heart disease was the commonest pre-existing lesion in 59 cases with subacute endocarditis. In most cases the source of infection was not known. In 41 of the 90 cases (44%) the diagnosis was made only at autopsy. The bacterial isolation rate was low, the commonest organisms being staphylococci, streptococci, micrococci and gramnegative bacilli. The overall mortality was 70%. A plea is made for increasing awareness of the disease and prompt institution of effective treatment.


Microfilariae in the cerebrospinal fluid, and neurological complications, during treatment of onchocerciasis with diethylcarbamazine.

Microfilariae of Onchocerca volvulus were found in the cerebrospinal fluid (CSF) of 5/8 heavily infected onchocerciasis patients. During treatment with diethylcarbamazine citrate 10/11 patients showed increased numbers of 0. volvulus microfilariae in the CSF. Patients with concentrations of 8-31 mf/ml CSF developed severe vertigo, and some other neurological manifestations, during treatment. A hypothesis is put forward to account for this clinical piciture, and its importance in relation to the treatment of onchocerciasis is discussed.


The populatin dynamics of Onchocerca volvulus microfilariae during treatment with suramin and diethylcarbamazine.

During treatment with suramin the numbers of O. volvulus microfilariae in the blood, urine, sputum, and anterior chambers of the eye fell before those in the skin. When diethylcarbamazine (DEC) was given after suramin, increased numbers of microfilariae appeared in the blood, urine, cerebrospinal fluid (CSF) and sputum, but the increase in the blood was less marked, and of shorter duration, than in similar patients receiving DEC without previous suramin. Microfilariae are thought to enter the urine, sputum and CSF directly from the blood by penetrating the capillary walls in the glomeruli, pulmonary alveoli, and choroid plexuses. Those in the aqueous humour do not appear to come directly from the bloodstream. The total numbers of microfilariae in the skin of some heavily infected onchocerciasis patients are estimated, as are the total numbers moving into the blood-stream under the influence of DEC and the proportion which escape into the urine, sputum and CSF. It is concluded that the majority of the microfilariae which appear in the blood during DEC therapy must be destroyed in the body, probably in the liver.


Studies on quantitative aspects of the transmission of Wuchereria bancrofti.

Feeding experiments with Anopheles gambiae and Culex fatigans infected with Wuchereria bancrofti showed that the mosquito females were losing about 20% of their worm burden when they were feeding on a blood chamber as well as on the guinea pig. 6.6% of all mature larvae found in the mosquitoes succeeded in entering the final host. A striking high infection rate was observed in those mosquitoes which refused to feed on a guinea pig. These mosquitoes have also to be considered when the loss of filarial larvae is calculated. Furthermore the experiments showed, that only very few larvae of Wuchereria bancrofti get lost when the mosquitoes are feeding only on sugar water solution.


Surface properties of bloodstream Trypanosomes (Trypanosoma brucei).

The African trypanosome (Trypanosoma brucei brucei) in its bloodstream phase has been found to possess rather unique surface properties. Results of lectin and iron colloid binding studies have indicated that the parasite's surface coat is devoid of many types of exposed carbohydrate residues which commonly are expressed on a variety of mammalian cell types. These include: glucose, mannose, galactose, n-acetylglucosamine, n-acetylgalactosamine, and neuraminic acid. A number of these carbohydrates (E.G., glucose, mannose, galactose and n-acetylgalactosamine) are, however, buried within the surface coat as evidenced by lectin binding to trypsinized parasites. The surface of well preserved parasites also lack exposed sialic acid and phospholipid moieties. Moribund parasites (or trypsinzed organisms) with altered surface coats were found to possess well defined phospholipid regions, but not negatively charged sialyl residues. Results presented tend to suggest that carbohydrates and phospholipids are not present in the outermost portion of the glycocalyx, thus exerting little or no influence on surface-mediated biological activities. However, the presence of such components on the plasmalemma is presumed to be structurally significant; especially during those developmental phases where the glycocalyx is absent, i.e., fly midgut phase.


An outbreak of Oropouche virus diease in the vicinity of santarem, para, barzil.

An epidemic of human febrile illness caused by Oropouche virus was studied in the village of Mojui dos Campos, Pará State, in February 1975. The major clinical symptoms, fever, chills, headache, myalgia, arthralgia and dizziness persisted for 2 to 7 days. Leukopenia was commonly observed. Some patients were severely ill but no deaths were attributed to the disease. Recurrence of symptoms was reported in several people. 55 cases of recent infection were diagnosed in Mojuí dos Campos between February and April. In the same period 26 cases were recorded from the Palhal area, near to Mojuí. Two additional cases were observed, one in the small settlement of Terra Preta and the other in the town of Santarém, which are 12 and 20 km from Mojuí, respectively. Of the 83 infections, 65 were proven by virus isolation from the blood of patients and 18 by the demonstration of an increasing antibody level to the agent. Both sexes of the population were infected in equal proportions. Most patients were below 20 years of age. In the village of Mojuí dos Campos with a population of about 2,900, 45 (40,1%) out of 112 students aged 4 to 18, had HI antibodies to the virus when examined late in February. The epidemic, however, only declined after the middle of March. Two isolations of Oropouche virus were obtained from some 15,000 Culicoides inoculated into mice. About 4,000 Culicoides and all the 9,420 mosquitoes captured during the outbreak remain to be inoculated. Over 95% of the Culicoides were C. paraensis. Only 1 rodent of the genus Proechimys had HI antibodies to Oropouche virus out of the 602 wild and domestic mammals captured in the area. All 5 reptiles examined were negative. 34 (4.9%) out of the 681 wild birds and 12 (5.8%) out of the 206 domestic birds examined were positive for the presence of HI antibodies to the agent.


[Investigations on the Filariidae of the Cervidae in Southern Germany. 4. Onchocerca garmsi Bain and Schulz-Key, 1976, a subcutaneous Filaria of red deer (Cervus elaphus)].

O. garmsi is a filaria living free in the subcutaneous tissues on the chest of red deer. The microfilarial distribution pattern in the skin of the host is studied. The convergent distribution of microfilariae of O. garmsi, O. tubingensis and O. cervicalis on the one hand and of O. tarsicola and W. rugosicauda on the other hand is discussed.


[The relationship between the conception of the role of histones in the mutagenic process and the combined effect of trichloracetic acid and dimethylsulfate on Arabidopsis].

Separate and combined effect of TChAA and DMS was studied as applied to Arabidopsis of Estland race. When the Arabidopsis seeds were treated with TChAA in M1 separately, stimulation was observed as to certain features. A combined treatment with TChAA + DMS reduces significantly the yield of chlorophyll mutations both as compared to variants of separate treatment and to those of control. On the basis of the data obtained an important role of histones in mutation process is suggested.


[Differential reactions of heterochromatin and euchromatin to beta-mercaptoethanol].

The responses of interphase and mitotic chromatins to beta-mercaptoethanol were studied. The reaction of X-chromatin of interphase nuclei was expressed in the increase of the percentage of cells with X-chromatin. beta-Merceptoethanol removed a condensing effect induced by spermine on the diffused chromatin of interphase cultured fibroblasts. beta-Mercaptoethanol caused a differential staining of metaphase chromosome when added to the cultured cells 0.5 hours prior to fixation. The treatment of chromosome preparations with different concentrations of beta-merceptoethanol and for different times led to different staining of chromosomes with asur--eosin. Low concentrations and/or short treatment induced G-banding, most typical with moderate concentrations. Higher concentrations and longer treatment prevented G-staining due to the loosening of G-segments.


[Use of a mixed cell suspension obtained from the livers of different rats for cytological studies].

The possibility of employing a mixed suspension of isolated liver cells from several rats for estimation of some quantitative characters commonly used in cytological investigations was studied. It is demonstrated that the disaggregation rate of liver in different animals varies slightly, and the mean values of the parametres studied (the proportion of dividing and binucleated cell) obtained from individual animals coincides well with those of the mixed suspension.


[The effect of extracts from Fallopian tube tissues, uterine fibromas and uterine adenocarcinomas on the growth and capacity for cell division of a human cell line].

Effects of the extracts prepared from tissues of fallopian tubes, uterine fibroid and uterine adenocarcinoma on mitotic activity and amitotic division in culture Tg33 were studied. Extracts with two protein concentrations, 25 and 100 mkg/ml, resp., were used. Differences were found between effects of extracts from malignant tissue and those of histologically unchanged fallopian tube extracts, and also the extract from tissues of uterine fibroid. The extracts from fallopian tubes removed during operation of the ovarian cyst and uterine fibroid (protein concentration 25 and 100 mkg/ml), and the extract of uterine fibroid (100 mkg/ml) caused the increase in mitotic activity. The extract from malignant tissues of adenocarcinoma (protein concentration 25 mkg/ml) and fallopian tubes (25 and 100 mkg/ml) caused no increase in the number of mitoses. The extract from tissues of uterine adenocarcinoma (protein concentration 100 mkg/ml) inhibited the number of mitoses in the culture. The above extracts effecting Tg33 cells caused the increase in the number of amitoses. The number of pathological mitoses did not increase under the influence of all the tested extracts.


[Development of pollen tubes in self-fertile and self-sterile lines of sugar beets in isolation].

Studies in pollen germination on stigmas of isolated plants showed a great difference in this process in different forms. A rapid and steady growth of pollen tubes, their accumulation near the micropyle and penetration in it are observed in self-fertile plants. Pollen tubes grow slowly, often forming thickenings and swellings in self-sterile forms. Some of them penetrate deeper, reaching sometimes the seedbud but turn back without penetrating into it.


[The relationship between genetic and stochastic damage during the process of cell and bodily aging].

The paper deals with the conception formulated by the author concerning the dual nature of the ageing process determined by genetic and random factors which manifest their action at the molecular, cellular and organism level. The review is given of the author's own studies in the ratio of programmed and stochastic mechanisms of ageing in different organisms and cells in the tissue culture. A conclusion is made that genetic factors are the leading ones in determining the main mechanisms of ageing.


[The effect of hydrocortisone on the proliferative activity ureteral epithelial cells].

Autoradiography has demonstrated that a single injection of hydrocortisone (10mg/100 gm b.w.) reduced statistically significant the number of DNA synthesizing cells and the intensity of 3H-thymidine incorporation in these cells, as well as reduced the number of mitotically dividing epithelial cells in the rat ureter. 16 hours after hydrocortisone administration, the amount of proliferating cells increases statistically, but in 48 hours it reaches the control level.


[Alteration of the phospholipid composition and functional state of skeletal muscle fiber mitochondria during muscular activity and rest].

An intensive or prolonged muscular activity causes a decrease in mitochondrial phospholipid content (at the expence of phosphatidylcholine and phosphatidylethanolamine fractions) an augmented turnover of phosphate groups, a decrease of the optical density in mitochondria and the P/O ratio (at the expence of lowering of deltaP). During the recovery period, the content of phospholipids gradually restores: first phosphatidylethanolamine, and then phosphatidylcholine, a temporary increase in the amounts of polyglycerolphosphatide and acid phospholipids proceding. The augmentation of optical density of mitochondria and of P/O ratio over the inintial level coincides in time with the increase in acid phospholipid content. The enrichment of the animals diet with linoleic acid and methionine diminsihes biochemical changes caused by muscular activity in mitochondria to accelerate the normalization.


[An interferometric study of the reaction of neurons in the motor area of the cerebral cortex to early visual deprivation].

Interferometrically is was shown that the absence of visual impulsation from the very birth of the animal caused alterations in protein substances not only in the neurons of visual area of the brain cortex but also in those of the motory one. However, unlike the visual area with the alteration of the deficience type (lowered protein contents, reduced dimensions of neurons), the alterations observed in the motory area are of the compensation order (increased protein contents, enlarged neurons). The influence of visual deprivation as an exterior factor on the plastical properties of neurons and the compensation of function is discussed.


[The "anomalous" relationship between the concentration of potassium in the medium and the membrane potential of muscle fibers with a decreased intracellular potassium concentration. I. Movement of potassium, accompanying ions and water].

A study was made of the electrogenesis on (Na+C1)-free muscles in potassiumsulfate media, with the membrane potential not corresponding to Ek. It was found that the potassium content in these muscles may change: at 2.5 mM external potassium, the internal potassium content decreases, whereas at 75 mM it increases. Undoubtedly, some other ions (phosphates?) apart from K+ do penetrate the muscle membrane. The evidence obtained disprove a previous idea that under the condition described it is potassium alone which is involved in potential genesis.


[The "anomalous" relationship between the concentration of potassium in the medium and the membrane potential of muscle fibers with a decreased intracellular potassium concentration. II. Rate of forward and reverse K42 transport through muscle fiber membranes in saccharose-sulfate solutions with potassium concentrations of 2.5 and 75 mM].

The measurements were made of the unidirectional potassium fluxes, the rate constants and the permeability coefficient. At external potassium 2.5 mM, the outflux and influx are 10--15, and 22-29 micromol/h g d. wt, respectively, and the net flux is comparable with the unidirectional fluxes. At external potassium 75 mM, the unidirectional fluxes increase up to 70--80 micromol/h, g d. wt. and the net flux does not exceed 0.1 of the unidirectional one. The outflux rate constant/influx rate constant ratio for both the potassium concentrations is about 1.5 times below the Ussing's ratio. This effect cannot be accounted for the single file phenomenon since it is independent of the direction and value of the net potassium flux. The discrepancy between the measured membrane potential and EK may, to some extent, be due to peculiarities of potassium movement.


[Abscence of the tetrodotoxin effect on sodium permeability under conditions of prolonged depolarization].

Using frog muscle fibres, it is shown that 10(-6) tetrodotoxin does not practically affect the membrane permeability to lithium ions during a continious depolarization, with the membrane potential being near zero, but causes half a decreased lithium permeability under conditions of normal membrane potential. The absolute value of the lithium permeability for these two states are very close. A 10 mM tetraethylammonium chloride does not influence the lithium permeability of muscle membrane with the normal membrane potential and during a continious depolarization. It is proposed that intact and inactivated sodium channals may have almost equal ion passing capacities, but differ in their gate systems, especially as concerns its interaction with tetrodotoxin.


[Relationship between erythrocyte membrane permeability and the concentration in it of total cholesterol and its fractions and possible seasonal influences on these indices].

A correlation between the content of labilly connected cholesterol fraction in erythrocytes and their penetration for urea was demonstrated. The dependence of erythrocyte membrane penetration on general cholesterol content and cholesterol fractions in the membrane was found to be season-influenced. A biochemical mechanism responsible for the changes in the labilly connected cholesterol fraction in erythrocyte membrane is discussed.


[Adhesive properties of the upper surface of fibroblasts and epithelium in cultures].

Adhesive properties of the upper surface of cultured normal and neoplastic epithelial cells and of fibroblasts were studied. It was shown that the attachment of prelabeled homo- and heterologous cells introduced into epithelial sheets were very low as compared with the free substratum and dense cultures of fibroblasts. The upper surface of cells of cultured anaplastic hepatoma 22a was adhesive for prelabeled cells. Morphological characteristics of the studied cultures were compared. It was found that low adhesiveness of the upper surface of epithelial sheets correlated with the formation of firm intercellular contacts which remained unbroken during migration into the wound. It is suggested that when epithelial cells make contacts with each other, their surface is subdivided into two types of regions: areas of low adhesiveness (the upper surface), and those of firm intercellular contacts. This may cause the formation of monolayer epithelial sheet.


[Cyotchemical indices of the protein-synthesizing apparatus of hyperchromic nerve cells].

Cytophotometric, interferometric and autoradiographic methods were applied to evaluate hyperchromic motoneurons (HM) from spinal cord of mice which were allowed to swim for 4 hours. The HM in comparison with the normochromic motor nerve cells are characterized by a higher RNA content and a lower dry weight of perikaria. The autoradiographic data with H3-uridane make it possible to suggest that RNA exchange between the nucleus and cytoplasm of HM is accelerated. The mode of distribution of labelled proteins along the sciatic nerve 6 days after the local injection of H3-leucine in the ventral horn of L3--L4 spinal cord segments allows to conclude that the amount of protein transported with the slow component of axonal flow in the cases connected with the increase of the number of HM in corresponding nuclei is changed.


[A quantitative cytochemical study of mouse hepatocyte chromatin in the early periods following hepatectomy].

Mouse hepatocytes of different ploidy react to the partial hepatectomy by changes in cytochemical properties of the chromatin, leading to an increased binding to DNA of a basic dye acridine orange and an antibiotic actinomycin D, and to decreased DNP stability to acid hydrolysis. These alterations reach their maximum 1.5 and 2.5 hours after the operation in di-and tetraploid, and octaploid cells, resp. and decrease markedly by 5 hours after the operation. The differences in the chromatin reaction of cells with different ploidy to the activation stimulus reflects presumably the particular roles played by these cells in liver regeneration. The difference in chromatin cytochemical properties of activated and non-activated hepatocytes is interpreted as a result of changes in DNA interaction with chromatin proteins.


[Scanning intergrating cytospectophotometry of tightly apposed micro-objects (as an example, a study of the circadian rhythm of RNA and protein concentrations in different neuron--neuroglia systems)].

A scheme of electron aperture is described which permits a scanning intergrating cytospectrophotometry of adjacent microobjects. Results are presented of such cytophotometry to determine RNA and protein content in various neuron--neuroglia units of the rats studied every 4 hours during 24 hours period. Contraphase character of circadian fluctuations has been shown for RNA level in cerebllum Purkinje cells, hypothalamus supraoptic neurons and spinal cord motoneurons as compared with the fluctuations in corresponding glial satellite cells. Protein content fluctuations were of contraphase character only in the spinal motoneurons and in their perineuronal glia, whereas in all the other neuron-neuroglia units the period of fluctuations was rather similar in the neurons and in the glial cells. A great value of quantitative cytochemical methods is outlined to carry out a functional biochemical analysis of nervous tissue cells.


[Cytophotometric determination of the relationship between the chief isoenzyme forms of lactate dehydrogenase in the neuron--neuroglia system in different fuctional states of the nervous system].

In white mice, unlike the Wistar rats, the ratio of activities of H- and M-forms of lactate dehydrogenase (LDH) is lower in the cerebral cortex neurons but higher in the spinal cord motoneurons within the limits of sensitivity and correctness of the cytospectro-photometric method. No statistically significant species differences in the activity ratios of H- to M-forms of LDH were found in the Purkinje cells of the cerebellum, as well as in the perineuronal glia of all the areas studied. Rats of the Krushinsky--Molodkina strain with a hereditary high sensitivity to audiogenic convulsions differed from the Wistar rats only with a higher H- to M-form activity ratio in the Purkinje cells and in their glial satellite cells. The ratio of H-forms to M-forms of LDH did not differ significantly in the majority of the neuron types studied as well as in the neurons as compared with their glial satellite cells. Histotoxic hypoxia in mice due to KCN injection gave rise to activation of M-forms of LDH in spinal cord motoneurons and spinal ganglia neurons, of H-forms in cerebral and cerebellar cortex neurons and of both forms in the neuroglial cells adjacent to the cerebellum Purkinje neurons. Audiogenic convulsions in the Krushinsky--Molodkina rats induced an increase of the H-form activity of LDH in perineuronal glia of spinal cord anterior horns, and of the M-form activity in the cerebellum Purkinje cells with a decrease in the M-forms of the cerebellum neuroglia. An importance of multiple forms of enzymes for the functional regulation of the cell biochemical pattern is discussed.


[Cytophotometric correlation of changes in the RNA and protein concentrations of perineuronal oligodendrogliocytes and ependymal cells of the spinal cord under different experimental conditions].

By means of ultraviolet and visible cytospectrophotometry, RNA and total protein content per cell was determined in perineuronal oligodendrogliocytes of spinal cord anterior horns and in ependyma cells of spinal cord central canal in Wistar rats under various experimental conditions. It was only in one experimental series that the cell kinds compared were characterized by a similar metabolic response: daily adrenaline injections for two weeks resulted in RNA accumulation both in the oligodendroglia and in the ependyma: besides, in both the kinds of spinal cord cells, no changes in RNA amount was found due to acute hypoxic hypoxia and to 6-mercaptopurine administration. In all the other experimental series (aurantin adminstraion: adrenalectomy and hydrocortison treatment; posthypoxic reparation), changes in RNA content markedly differed in the oligodendroglia and in the ependyma. The data are presented concerning the changes in protein content in the cytoplasm of spinal cord ependyma cells under the experimental conditions applied. Importance of topochemical analysis of nervous tissue structures by means of quantitative cytochemical methods is outlined.


[A microfluorimetric study of glycogen fractions in rat liver under different conditions of liver perfusion and animal nutrition].

A study was made of the amount of a labile and a stable glycogen fractions in the rat liver cells under various feeding regimes and different durations of liver perfusion. The amount of the glycogen fraction revealed after a 40 minutes' treatment in a Schiff type  reagent--Auramine--SO2 was found most chaneable at hunger, at feeding with carbohydrate rich food and at liver perfusion. This fraction is removed from the cells after the treatment with cold trichloroacetic acid (TCA-fraction). The amount of the glycogen fraction revealed after a more prolonged treatment of cells (90 minutes) in Auramine--SO2 and extracted only with hot KOH (KOH fraction), is relatively stable. According to the cytochemical evidence, the TCA and KOH fraction contents in the rat liver cells reach 80--85 and 15--20%, resp. The cytochemical evidence provided obtained with the fluorescence PAS-reaction permits to consider as identic the glycogen fractions revealed with biochemical methods.


[Prezygotic selection of male gametes in laboratory mice].

Frequency of aneuploid male gametes was related to the number of early embryos with numeral chromosomal aberrations in progeny of male mice, heterozygous for the Robertsonian translocations T1 (15.6) AID, and T1 (17.8) IEM. In mice heterozygous for translocation T1 (15.6) AID, the number of spermatocytes II with NF=21 was very low and corresponded to the number of trisomic embryos at stages of major organogenesis. In mice heterozygous for T1 (17.8) IEM translocation, the number of aneuploid gametes was 26.2%, but neither embryo of their progeny, on the 8 12th days of gestation, was found to be trisomic. The involvement of chromosomes 8 and 17 in the control of postmeiotic stages of spermatogenesis in mice is suggested.


[The role of cations and surface membrane proteins in the adhesion of rat liver parenchymal cells. II. The influence of calcium ions on the structure of cell contacts].

The structural interrelations of hepatocytes, under the rat liver perfusion with calciumless solutions, were studied with the electron microscopy. Lantanum chloride, alcian blue and ruthenium red were used for revealing the intercellular space, specialized junctions and cell coats. Significant alterations in the interelations of the hepatocytes after a long liver perfusion (1.5h) were discovered. The structure of the specialized cell junctions and the space intercellular width under a 15-20 min. liver perfusion remained unchanged. The results obtained suggest the important role of Ca2+-ions and supramembranic material in the cellular adhesion.


[The peroxidase activity of rat cerebral hemisphere neurons during hypoxia training].

Peroxidase activity (PA) was studied in the rat's brain cortex during a 2 months training to hypoxia according to the Barbashova method. PA was investigated histochemically by an ammonium--molibdate--benzidine method on blocks of surviving brain tissue, thereafter they were studied by the contact microscopy. PA was also determined biochemically in water-salt extracts of the brain tissue. A progressive increase of PA in the course of training was shown by both the techniques. The increase of activity is accounted for by the growing quantity of neurons developing the reaction as well as by the growing intensity of reaction in each neuron. The nature of PA of neurons and its adaptive significance in hypoxic conditions is discussed.


[The prereplicative period in hepatic regeneration].

Using H3-thymidine autoradiography and biochemical methods, it was revealed that the inhibition of thymidine incorporation in the nuclei of hepatocytes and duodenal crypt epithelial cells occurs in the middle of the preperlicative period (between the liver resection and the increase of DNA synthesis) in the rat regenerating liver. The transition of cells from G1 to phase S was also blocked. No decrease in the uptake of H3-thymidine by liver cells was seen after hepatectomy.


[Adrenergic receptors in murine epidermis].

The availability of alpha- and beta-adrenergic receptors in murine epidermal cells was revealed by means of adrenomimetic and adrenolitic drugs, these receptors having direct influence on the cell division in epidermis. The simultaneous as well as independent stimulation of alpha- and beta-receptors by mesation (phenylephrine) and isadrin (isoproterenol), respectively, markedly inhibits the transition of epidermal cells from interphase into mitosis. The effect is observable in 2 hours. Thus, the interaction of adrenaline with adrenergic receptors in epidermis may be considered as a way by which this hormone may control the mitotic activity.


[Factors of coagulation and fibrinolysis in somatic and autonomic nerve fibers and their role in the process of excitation].

Somatic and vegetative nerve fibres contatin a very active thromboplastin, antiheparin factor, proactivator, activator, plasminogen and plasmin. Fibrinolytic agents are more numerous in the nuerolemma than in nerve fibres. Plasmin and its activator are firmly bound with the tissue structure, unlike plasminogen and proactivator. It is supposed that these factors may be significant in the structural modification of protoplasm at excitation of cell elements.


[A quantitative assessment of enzyme activity by cytophotometry using a standard].

The usage of the standard has been offered in cytospectrophotometrical measurements of enzymatic activities that are revealed histochemically. A tetrazolium method was used to demonstrate lactate dehydrogenase activity in sections of the rat brain. As a standard, a mixture of the enzyme (a crystalline forme of LDG) and gelatine was taken. The method of standardization permits fulfilling a quantitative comparison of heterogenic biological materials.


[Monochromators for cytophotometers and cytofluorimeters].

Two monochromators for microspectrophotometers are described. The attachments have been designed so that the peculiarities of the optical system of microscope have been taken into consideration. Simple, small sized monochromator is executed as a part of biological microscope and will be used mainly in cytophotometry. Another attachment is a commercially available single monochromator which has been easily adapted as a double one for using in cytophluorimetry by means of autoreflector set behing the exit split.


An assessment of the carcinogenicity of isoniazid in patients with pulmonary tuberculosis.

In an assessment of the carcinogenicity of isoniazid, 3,842 adult tuberculous patients admitted to 2 sanatoria in the period 1950 to 1957 (that is, in the years immediately before and after the introduction of isoniazid) have been followed up for a mean period of over 19 years. Their mortality has been compared with that expected during the same calendar period in a general population group in England and Wales with the same age and sex distribution. The relative risk of death (the observed divided by the expected number of deaths) from all malignant neoplasms in patients first starting chemotherapy in 1950 to 1952, before the general introduction of isoniazid, was 0.8 for those who received isoniazid at some time, compared with 0.5 for those who never received it; for those first starting chemotherapy in 1953 to 1957, after the general introduction of the drug, the respective risks were 1.4 and 1.8. The relative risk of death from malignant neoplasms was 2.1 in the first 4 years after starting the treatment with isoniazid; this high relative risk is unlikely to be attributable to isoniazid and largely disappears subsequently, for in successive 4-year periods it was 1.3, 0.9, 1.2 and 1.4. The relative risks of death from all malignant neoplasms for patients receiving a total dosage of less than 50, 50-99, 100-199 and 200 g or more were 1.5, 1.5, 1.0 and 1.3, respectively. For patients receiving a maximum daily dose of less than 250 g the relative risk was 1.3, and for those receiving 250 g or more it was 1.2. There was a curious and unexplained difference in the mortality from malignant neoplasms in patients first starting chemotherapy in 1950 to 1952 (relative risk 0.6) and those first starting in 1953 to 1957 (relative risk 1.5). This is being studied further. This study has provided no evidence of a carcinogenic effect of isoniazid in a period of follow-up averaging nearly 20 years. The follow-up is being continued.


The pathogenicity of Mycobacterium fortuitum and Mycobacterium chelonei in man: a report of seven cases.

The clinical records of 7 patients referred to the National Jewish Hospital and Research Center over a 6-year period for evaluation of an abnormal chest x-ray and repeated sputum isolates of rapidly growing mycobacteria (Runyon's Group IV) were reviewed to determine the potential pathogenicity of these organisms. Mycobacterium fortuitum was isolated from 5 patients and Mycobacterium chelonei from 2. Haemoptysis, cough and weight loss were prominent in 6. Three had rheumatoid arthritis. Although two demonstrated cutaneous anergy, lymphocyte responsiveness to PHA was normal. PPD-F was not useful in skin testing or in the in vitro evaluation of lymphocyte function. Histologic examination of the lungs of 2 patients demonstrated caseating granulomata. One patient died of massive pulmonary haemorrhage soon after intiation of therapy. Multi-drug treatment regimens generally resulted in progressive sterilization of the sutum and improvement in the appearance of the chest x-ray. We conclude that some rapidly growing mycobacteria can cause potentially fatal cavitary lung disease and that intensive anti-tuberculosis therapy may successfully alter its course.


[Isolation of the fragment D dimer from stabilized fibrin and a study of its antipolymerization action].

The dimer of fragment D is isolated preparatively by CM-cellulose chromatography (in neutral medium) from dialyzed tryptic hydrolyzate of stabilized fibrin. Contrary to the fragment D monomer obtained from fibrinogen under the same conditions, the dimer itself cannot inhibit polymerization of monomeric fibrin. However with the presence of monomer D in the amount sufficient for essential inhibition of the fibrin polymerization the addition of dimer D produces the further delay in polymerization. Under these conditions dimer D is highly effective inhibitor if its amount is not too little, as its small doses are not effective.


[Localization of Ca2+ in the smooth muscle and glandular cells of the rabbit uterus].

The pyroantimonate and radiometric procedures were used to establish the presence of three foci of selective accumulation of ions Ca2+ in the myometrium smooth-muscular cells: in nuclei, mitochondria and endoplasmatic reticulum. In the epithelium of the womb glands, besides the same foci a considerable amount of ions Ca2+ is contained in the cytoplasm matrix. Under the effect of serotonin the myometrium nuclei lose 45Ca most actively in the epithelium cells of the womb glands the content of Ca2+ changes, that gives reason to suppose that these structure participate in the calcium redistribution with a change in the functional activity of myometrium.


[Acetylcholinesterase in the rabbit hippocampal formation after destruction of the septohippocampal connections].

After deafferentation of the septofimbriate introitus to the rabbit hippocamp acetylcholinesterase activity lowers in homogenates and usbcellular fractions within different areas of the hippocampal formation and subiculum. The greatest decrease is observed in homogenates of the denticulate fascia (up to 25% of the norm). In the subcellular fractions the greatest decrease is observed in the activity of the coarse mitochondrial and MHN-20 fractions as compared to the nuclear and microsomal ones. When separating the coarse mitochondrial fraction within the linear gradient of sucrose density (0.7--1.6 M), the greatest decrease in acetylcholinesterase activity is observed in the upper layers of the gradient. Distruction of septohippocampal relations produces a strong drop in the activity of butyryl cholinesterase and lactate dehydrogenase in the fimbria homogenates.


[Changes in monoamine oxidase activity and catecholamine content in the tissues of guinea pigs saturated with ascorbic acid under the influence of actinomycin D, tetracycline and cycloheximide].

A short-time saturation of guinea pigs with ascorbic acid (100 mg per 1 kg of weight every hour for 5 h) causes its accumulation in the adrenals and blood, an increase in the monoaminooxidase activity in the liver and in the content of adrenaline in the adrenals. The content of noradrenaline in the liver and brain does not change. Inhibitors of protein synthesis, actinomycin D, tetracycline and cycloheximide, have a different effect on the increase in the monoaminooxidase activity evoked by introduction of ascorbic acid: tetracycline blocks the increase in the enzyme activity, actinomycin D has no effect on it. Cycloheximide introduced against a background of chronic saturation of guinea pigs with ascorbic acid also blocks the increase in the monoaminooxidase activity in the liver mitochondria.


[Carbohydrate content and glycolysis enzymatic activity in the liver of young purebred and hybrid cattle of both sexes].

It is established that the content of glycogen, glucose, fructose and the activity of phosphoglucomutase and phosphogexoisomerase is considerably higher in the heifer liver and the content of pentoses of adenylic system and the activity of aldolase is essentially lower than in the liver of bulls of the same breed. In the liver of growing hybrid young cattle (except of the Hereford heifers) as compared to the purebred ones the value of the total pentoses: glycogen and pentoses of adenylic system: glycogen ratios are significantly higher. These values in the bull liver of all the breed groups are essentially higher than in the heifer liver. The data obtained evidence for possibility of applying the values of ratio of total pentoses and especially of pentoses of adenylic system to glycogen as well as the activity of aldolase in the liver tissue as biochemical test for estimating the high rate of growth and prognosing the meat productivity of young cattle of different sex.