Production of epidermal acantholysis in normal human skin in vitro by the IgG fraction from pemphigus serum. Normal human skin was maintained in organ cultures for several days in Ham's F-10 medium with good preservation of the epidermal cells. When the partially purified IgG fraction from the pooled sera of patients with pemphigus vulgaris or pemphigus foliaceous was added to this culture system, after 24 hr some evidence of epidermal acantholysis was seen. By 72 hr, extensive suprabasilar epidermal acantholysis had occurred in which the acantholytic cells were indistinguishable histologically from the acantholytic cells in biopsies from skin lesions of patients with pemphigus vulgaris. In the control cultures (i.e., F-10 medium or F-10 medium + normal human serum IgG), none of these changes was seen. Direct immunofluorescent staining of these explants using fluorescein-labeled goat antihuman IgG showed that by 6 hr binding of the pemphigus IgG had occurred in the intercellular cement substance of the epidermis. The staining intensity was maximal by 18 to 20 hr. When the pemphigus serum was fractionated by DEAE-cellulose column chromatography, three major IgG-containing peaks (presumably IgG) were eluted which bound to the epidermoid intercellular substance and caused acantholysis in culture. The complement system did not play a role in the antibody-induced acantholysis since complement was not included in this system and heating the reconstituted F-10 + pemphigus IgG for 1 hr at 58 degrees C did not destroy the acantholytic activity. Autoradiographic experiments showed that after about 2 days in culture the rates of incorporation of RNA and protein precursors in the suprabasilar cells in the presence of pemphigus IgG were reduced to less than 10% of the normal IgG controls, whereas these synthetic activities of the basal cells were only slightly affected. These observations lead to the proposal that it is the interaction of the pemphigus autoantibody(s) with the suprabasilar epidermal cell which initiates and possibly substains the process(es) of acantholysis.


Effect of pigment on photomediated production of thymine dimers in cultured melanoma cells. It was the aim of these studies to determine whether the presence of intracellular melanin quantitatively alters the rate of production of thymine dimers in DNA of irradiated cells in culture. Pigmented and nonpigmented Cloudman mouse melanoma cells were selected assuming that the two cell lines differ primarily in their content of melanin pigment. Cells were cultivated in tritiated thymine in order to label their DNA and were then exposed to ultraviolet (UV) irradiation (260 nm, 500-2000 ergs/mm2). Neither cell line survived these doses of irradiation. DNA was extracted immediately following irradiation and was subjected to acid hydrolysis. The presence of thymine dimers was determined by two-dimensional paper chromatography. The percent of labeled thymine recovered as thymine dimer was calculated and was found to be a linear function of UV dose for both cell lines. The rate of formation of dimers in the nonpigmented cells was nearly twice that in the pigmented cells. These data demonstrate the photoprotective property of intracellular melanin in shielding isolated cells from one type of photomediated injury to DNA.


Skin flora maps: a tool in the study of cutaneous ecology. We sampled 162 and 175 skin sites, respectively, of a patient with severe atopic dermatitis and of a healthy subject, and constructed maps of the two individuals depicting the density and distribution of aerobic cutaneous flora over the entire body. All isolates of Micrococcaceae were biotyped. Neither the density nor the kinds of microorganisms were homogeneously arrayed. Instead, the separate types of flora were skewed in distribution, tended to segregate on large anatomical regions, and inhabited overlapping territories. No two sites were exactly alike in their carriage of microorganisms. Many of the apparently normal skin sites of the eczema patient carried high numbers of Staphylococcus aureus, which often was the dominant organism. Skin flora maps are seen as a potentially useful tool, especially in studying the dynamics of cutaneous microbial populations.


Trans-unsaturated fatty acids in human skin surface lipids. Methyl esters of the fatty acids obtained by saponification of human skin surface lipids were subjected to thin-layer chromatography on silica gel-silver nitrate revealing the presence of trans-monounsaturated components constituting approximately 0.3% of the total fatty acids. The positions of unsaturation in the 18-carbon trans-unsaturated acids in 2 subjects resembled those present in the corresponding acids from margarine, although this was not a component of the diet of one of the subjects. Dietary origin is possible for these components, which could also arise from bacterial action in the pilosebaceous follicle.


Calcium and sulfur location in human nail. Analytical electron microscopy was performed in order to elucidate the importance of calcium and sulfur to the hardness of nails. The free surfaces adsorb a considerable quantity of calcium from the environment. It is suggested that such adsorption occurs due to ion exchange. This concept is supported by the fact that the distribution of sulfur does not vary over the nail cross-section. Analytical electron microscopy offers unique possibilities of elemental distribution analysis in tissue fragments or sections from keratinized tissues.


Characterization of bile acid methyl ester acetate derivatives using gas-liquid chromatography, electron impact, and chemical ionization mass spectrometry. The gas-liquid chromatographic retention times on 0.5% SP-525 for 48 bile acids and related compounds as their methyl ester acetate derivatives are given. Ion tables for electron impact spectra have been compiled that permit direct access to ion structures for any given ion mass. Chemical ionization yields highly simplified mass spectra with two or three ions predominating for each compound. When the relative retention times of bile acids as their methyl ester acetates are combined with selective ion monitoring techniques in chemical ionization mass spectrometry, the retention time and ion mass number form a coordinate system which can be a powerful tool in the characterization of bile acid mixtures.


Effects of insulin, glucagon, and epinephrine on the plasma membrane of the white adipose cell: a freeze-fracture study. A quantitative study of the adipocyte plasma membrane under the influence of lipipolytic or lipogenic hormones has been carried out by freeze-fracture. The number of plasma membrane invaginations (so-called pinocytosis) and of intramembranous particles was evaluated. Under the influence of either insulin, glucogon, or epinephrine, the membrane invaginations were significantly increased with respect to control adipocytes. Insulin was shown to increase the number of intramembranous particles of the plasma membrane whereas glucagon or epinephrine had an opposite effect. These data point to a hormonal modulation of the fine-structural organization of the adipocyte plasma membrane.


The use of [7alpha-3H]- and [7alpha, 7beta-3H]cholesterol in the enzymic assay of cholesterol 7alpha-hydroxylase. A tritium release method is described for following the enzymic conversion of cholesterol to 7alpha-hydroxycholesterol. Incubations of rat liver subcellular preparations (containing microsomes) with [7alpha-3H]cholesterol or [7alpha,7beta-3H]cholesterol release the labeled hydrogen in the 7alpha position as 3H2O which, after counting, allows for the determination of the fraction of exogenous cholesterol converted to 7alpha-hydroxycholesterol. These findings document those recently reported by Van Cantfort, Renson, and Gielen (1975. Eur J. Biochem. 55:23). Analysis of incubation mixtures containing both [4-14C]cholesterol and either [7alpha-3H] or [7alpha,7beta-3H]cholesterol demonstrate that one atom of hydrogen (from the 7alpha position) is incorporated into H2O for every molecule of exogenous cholesterol that is converted to 7alpha-hydroxycholesterol. In the case of [7alpha-3H]cholesterol no label is retained by the product. With [7alpha,7beta-3H]cholesterol, one atom is released as 3H2O and one is retained by the product in the 7beta position. Microsomal incubations with [7alpha,7beta-3H]cholesterol were performed, followed by the acetylation of the steroid fractions with [14C]acetic anhydride. If intermixing of exogenous with endogenous cholesterol were complete during the enzymic reaction, one would expect the 3H: 14C ratio of the isolated cholesterol acetate to be four times that observed in the 7alpha-acetoxycholesterol acetate. Average values of 4.23 in one series and 4.03 in a second series indicate that intermixing was sufficiently complete to use the tritium release method as an indicator of mass conversion.


Hepatic 7alpha-hydroxylation of cholesterol in ascorbate-deficient and ascorbate-supplemented guinea pigs. Cholesterol 7alpha-hydroxylase activity was assayed in liver microsomes from guinea pigs supplemented with ascorbate and from guinea pigs in a state of ascorbate deficiency. A mass fragmentographic method was used by which the 7alpha-hydroxylation of endogenous cholesterol could be measured. The 7alpha-hydroxylation was markedly reduced in the ascorbate-deficient animals as compared to animals treated with ascorbate. Addition of ascorbate to the incubations did not increase this activity. 11- and 12-Hydroxylation of laurate as well as 25- and 26-hydroxylation of 5beta-cholestane-3alpha, 7alpha-diol were not significantly affected by the ascorbate status of animals. In the presence of excess NADPH-cytochrome P-450 reductase and a phospholipid, partially purified cytochrome P-450 from the microsomal fraction of liver of an ascorbate-deficient guinea pig had a much lower capacity to 7alpha-hydroxylate [4-14C]cholesterol than a corresponding system containing cytochrome P-450 from liver of an ascorbate-supplemented guinea pig. It is suggested that ascorbate affects the synthesis or breakdown of the 7alpha-hydroxylating system, in particular the cytochrome P-450 component.


On the heterogeneity of the mitochondrial C27-steroid 26-hydroxylase system. Mitochondrial 26-hydroxylation of exogenous cholesterol, endogenous cholesterol, and 5beta-cholestane-3alpha,7alpha,12alpha-triol was studied. 26-Hydroxylation of endogenous cholesterol was measured by mass fragmentography. NADPH and isocitrate stimulated 26-hydroxylation of endogenous as well as exogenous cholesterol. 26-Hydroxylation of endogenous cholesterol was linear with time for 15 min, whereas that of exogenous cholesterol was linear with time for at least 40 min. This finding indicates that the fractions of exogenous and endogenous cholesterol that were 26-hydroxylated did not equilibrate. Mg2+ stimulated isocitrate- and NADPH-dependent 26-hydroxylation of exogenous cholesterol but inhibited in the case of endogenous cholesterol. Ca2+ stimulated NADPH-dependent and inhibited isocitrate-dependent 26-hydroxylation of both exogenous and endogenous cholesterol. It is suggested that the differing effect of Mg2+ on the 26-hydroxylation of exogenous and endogenous cholesterol is related to transfer of the steroid to the enzyme. Isocitrate- and NADPH-dependent 26-hydroxylation of exogenous 5beta-cholestane-3alpha,7alpha,12alpha-triol differed from that of exogenous cholesterol in response to Mg2+ and Ca2+. 26-Hydrocylation of 5beta-cholestane-3alpha,7alpha,12alpha-triol was stimulated by Mg2+ in low concentrations but inhibited by Mg2+ and Ca2+ in high concentrations. Mg2+ had the same influence on the 26-hydroxylation of three dioxygenated C27-steroids known to be intermediates in bile acid biosynthesis. The results are not only compatible with heterogeneity of the mitochondrial 26-hydroxylase system but also with differences in the transport of cholesterol and 5beta-cholestane-3alpha,7alpha,12alpha-triol to the enzyme. The finding of a differing effect of Mg2+ on 26-hydroxylation of exogenous and endogenous cholesterol seems to favor differences in transport rather than heterogeneity of the 26-hydroxylase as an explanation of the results.


Composition of the neutral lipids of bovine meilbomian secretions. Lipids secreted form the bovine meibomian glands were assigned to following classes: cholesteryl esters (A) (fatty acyl chain lengths from 15 to 27 carbon atoms), 41%; wax esters, 29%; triacylglycerols, 10%; and cholesteryl ester (B) (fatty acyl chain lengths from 14 to 18 carbons), 15%. The remaining 5% consisted of cholesterol, fatty acids, and highly polar material. Analysis of the lipids showed that only the cholesteryl esters (A) contained fatty acyl chains greater than or equal to C20:0. One third of the fatty acyl chains of the wax esters and the cholesteryl esters (B) was iC15:0. The fatty alcohol moieties of the wax esters were found to be branched chain, C23:0-C27:0. A computer-based programmable gas-liquid chromatographic procedure using 10% apolar 10C on Gas Chrom Q could be used to distinguish both iso and anteiso fatty alcohols and esters of fatty acids.


Bile acids. LI. Formation of 12alpha-hydroxyl derivatives and companions from 5 alpha-sterols by rabbit liver microsomes. A comparison of the activity of rabbit liver microsomes fortified with 0.1 mM NADPH to promote 12alpha-hydroxylation over 60 minutes with appropriate sterols provided the following relative order of activities: kalpha-cholestane-3alpha, 7alpha-diol, 100; 7alpha-hydroxy-5alpha-cholestane-3one, 76; 7alpha-hydroxycholest-4-en-3-one, 64; 5alpha-cholestane-3-3beta, 7alpha-diol, 26; allochendoexycholate, 22. If the more polar products formation. Investigation by gas-liquid chromatography-mass spectrometry of the nature of these more polar products derived form 5alpha-cholestane-3alpha, 7alpha-diol showed that a series of tetrols was dormed; i.e., 5alpha-cholestane-3alpha, 7alpha, 12alpha, 25-tetrol as the major product and lesser amounts of 5alpha-cholestane-3alpha, 7alpha, 12alpha, 24- and 3alpha, 7alpha, 12alpha, 23tetrols. No significant amount of 26-hydroxylated product was formed.


The effect of high sugar intake on the esterification of dihydroxyacetone phosphate by rat liver microsomes. Rat liver microsomes were used as an enzyme source to study dietary-induced changes in the rate of dihydroxyacetone phosphate esterification. Rats were fed (1) 75% glucose or fructose diets for various time intervals, or (2) fed a fractose diet for six days and then a chow diet. Both the glucose and fructose diets produced a 2--3-fold increase in total and neutral glycerolipid formation from dihydroxyacetone phosphate measured in the presence of ATP, palmitate, CoA, and NADH. The increased rate of dihydroxyacetone phosphate esterification and a simultaneous rise in serum triglyceride level in rats fed fructose was rapidly reversed when chow was substituted for the fructose. The results indicate that an increased rate of dihyroxyacetone phosphate esterification may contribute to the acceleration of endogenous glycerolipid biosynthesis noted under these dietary conditions.


Chylomicron protein content and the rate of lipoprotein lipase activity. Chylomicrons isolated form rat intestinal lymph were incubated with plasma. Protein transfer to chylomicrons, reaction rate with purified lipoprotein lipase, and content of lipase cofactor were determined. While the overall protein content of chylomicrons was increased 3--4-fold, and the content of lipase cofactor increase 4-fold, reaction velocity of the activated particles with lipoprotein lipase was increased only 1.3-fold. Maximal rate of hydrolysis was achieved in the presence of much smaller quantities of activator than the lipoprotein particles were capable of binding, and chylomicrons were fully activated for triclyceride hydrolysis in the presence of only 10% plasma for triglyceride concentrations of up to 3 mg/ml. Cofactor protein was not rate-limiting for hydrolysis of triglyceride from chylomicrons. These results are discussed in the light of recent concepts of the regulation of lipoprotein lipase activity.


Studies on the substrate specificity and inhibition of prostaglandin biosynthesis with methyl branched isomers of eicosa-8, 11, 14-trienoic acid. Seven radioactive methyl branched isomers of eicosa-8, 11, 14-trienoic acid, in which a methyl branch was located at carbon 2, 5, 10, 13, 17, 18, or 19, were used as substrates to study their enzymatic conversion into homologues of prostaglandin E1 by microsomes from bovine vesicular glands. The products of this reaction were partially characterized. When the methyl branch was moved towards position 13, the site of sterospecific hydrogen removal by prostaglandin synthetase, the rate of prostaglandin formation decline rapidly. When a methyl branch was a position 10, 13, 17, 18, or 19, the rates of prostaglandin formation were less than 25% of that from eicosa-8, 11, 14-etienoic acid. However, when a methyl branch was at positions 2 or 5, these isomers were converted to prostaglandins at least 50% as rapidly as eicosa-8, 11, 14-trienoic was converted to prostaglandins. The apparent Km and Vmax values for eicosa-8, 11, 14-trienoic acid were respectively 224 muM and 4.62 nmoles/min/mg protein. Kinetic data suggest that the enzyme converted eicosa-8, 11, 14-trienoic acid to prostaglandins 3.6 times faster than the 5-methyl branched isomer, although the enzyme bound the branched isomer twice as firmly as eicosa-8, 11, 14-trienoic acid. The concentration-dependent inhibition of prostaglandin formation from eicosa-8, 11, 14-trienoic acid by the 13-methyl branched isomer was also demonstrated.


Gas-liquid chromatography of ethyl ester artifacts formed during the preparation of fatty acid methyl esters. Ethanol is typically used as a stabilizer in chloroform. Failure to remove this ethanol from the chloroform used in the extraction of lipids leads subsequently to the formation of ethyl ester artifacts during the preparation of methyl esters by a commonly employed transesterification procedure. Depending on the conditions and phases used during gas-liquid chromatography, the ethyl esters may be resolved from the corresponding methyl esters. The resulting chromatograms contain extraneous peaks and may be incorrectly identified.


Effect of ionic environment on the release of human placental lactogen in vitro. Short-term incubation of human placental tissue in Krebs-Ringer bicarbonate buffered media with various concentrations of K+ and Ca2+ showed a graded response in human placental lactogen (HPL) release at different Ca2+ concentrations, but no effect at increased K+ concentration. Media with high Ca2+ caused an inhibition of release, while Ca2+-free media caused a stimulation in HPL release. High concentrations of Mg2+ inhibited release minimally, while Ba2+ had no effect. There was no change in HPL release of HPL but the significance of this effect is unknown. These results suggest that Ca2+ is not required for HPL secretion from placental tissue. It seems that HPL secretion in vitro does not follow the usual pattern where a physiological stimulus or high K+ concentration causes inward movement of calcium which couples stimulation to secretion.


Pituitary and plasma levels of gonadotrophins in foetal and newborn male and female rats. Levels of LH and FSH were measured by radioimmunoassay in serum, pituitary and placental tissues of male and female foetal and newborn rats. No gonadotrophins were detected in placental tissues or amniotic fluid. In the male, pituitary FSH and LH were first detected on day 17 of gestation. Gonadotrophins could not be detected in any female tissues until birth. In male foetuses the highest levels of both LH and FSH in the circulation were found on day 16 of foetal life; subsequently the levels decreased dramatically.


Inhibitory effect of prostaglandin F2 alpha on oxytocin release and on milk ejection in lactating rats. The effect of prostaglandin F2 alpha (PGF2alpha) on milk ejection and on oxytocin release during suckling for one or two periods of 30 min was studied in lactating rats. Doses of PGF2 alpha (20 or 40 phi g) were injected i.p. 15 min before the suckling period. Control rats were injected with physiological saline. An inhibition of milk ejection proportional to the dose of drug administered was obtained. A normal milk ejection response was induced with a small dose of oxytocin injected immediately before nursing to mothers treated with PGF2 alpha, indicating that the blocking effect was not due to a lack of mammary gland response. Two groups of mothers were injected with 40 phi g PGF2 alpha 2 and 4 h respectively before suckling. In both groups milk ejection was partially but significantly inhibited. In rats pre-treated with sodium pentobarbitone (3-5 mg/100 g body wt) to prevent the release of oxytocin induced by suckling, PGF2 alpha (10 or 20 phi g) did not modify the inhibition of milk ejection indicating that PGF2 alpha does not have milk-ejecting activity. The administration of oxytocin to anaesthetized rats, immediately before a second suckling period, induced a normal milk-ejection response while in the rats treated with PGF2 alpha, oxytocin was less effective. The results indicate that PGF2 alpha inhibited milk ejection by a central block on oxytocin release and that the lipid is not able to mimic peripherally the milk-ejecting activity of oxytocin.


Distribution of prostaglandins E2 and F2 alpha within the foetoplacental unit throughout human pregnancy. The concentrations of prostaglandin E2 and F2 alpha have been measured by radioimmunoassay in portions of cord, placenta, amnion, chorion, decidua and myometrium. The samples were obtained at defined periods of pregnancy, and the results have been compared with those obtained from the analyses of endometrial and myometrial tissue removed from women during the secretory phase of a menstrual cycle. The results showed that during pregnancy the mean concentration of prostaglandin E2 was higher (27-518%) than the corresponding value for prostaglandin F2 alpha in all tissues. At term the concentration of prostaglandin E2 (ng/100 mg wet weight of tissue, mean +/- S.D.) was higher in the umbilical cord (5-54 +/- 0-88), decidua (4-02 +/- 1-78) and myometrium (4-19 +/- 1-06), than in the amnion (2-25 +/- 1-27), chorion (1-64 "/- 0-63) or placenta (1-04 +/- 0-25). During labour there was a significant rise (P less than 0.0005, Student's 't' test) in the concentration in decidua (10-76 +/- 4-45), and to a lesser extent (P less than 0-05) in the myometrium (5-84 +/- 2-65) and amnion (4-77 +/- 2-51). The overall concentration in decidua during the first trimester (3-09 +/- 1-02) was significantly lower (P less than 0-005) than in endometrial tissue(16-82 +/- 10-13). The concentration was lower in myometrial tissue from non-pregnant subjects (2-90 +/- 2-21), than in the corresponding tissue removed at term (4-19 +/- 1-06) or during labour 5-84 +/- 2-65). The results for prostaglandin F2 alpha showed a similar pattern, but the values were significantly lower in the umbilical cord, and the percentage changes in concentration in the decidua and myometrium were of a higher magnitude.


Role of the thyroid gland in regulation of metabolic rate in an air-breathing siluroid fish, Heteropneustes fossilis (Bloch). Studies on cyclic activity of the thyroid and seasonal variations in oxygen consumption (VO2) under experimental conditions in which surfacing was either allowed or prevented were made in H. fossilis to try to establish a relationship between these measures and to ascertain the possible role of the thyroid in the regulation of metabolic rate. A good correlation was found between the activity of the thyroid and VO2 in this species. This finding was further confirmed by the administration of L-thyroxine or thiouracil to this fish. The thyroxine-and thiouracil-treated animals showed significantly higher (P less than 0-05) and lower (P less than 0-01) rates of VO2 respectively, thus indicating the probable role of the thyroid in the regulation of metabolic rate.


Changes in the weight of the adrenal glands and in the concentration of plasma corticosterone in perinatal rats after prenatal treatment with oestadiol benzoate. On day 20 of gestation, foetal rats received a subcutaneous injection of 0-01 mg oestradiol benzoate dissolved in 0-05 ml sesame oil; foetuses in other litters were given sesame oil alone. Autopsy was performed on day 22 of gestation, at delivery or at various times after birth. Gravimetric and histological observations of the adrenals from oestradiol-treated, oil-treated and intact litter-mate control foetal and neonatal rats were performed together with determination of plasma corticosterone concentrations. Activity of 3 phi-ol dehydrogenase was also examined histochemically in the adrenals from these animals. The results indicated that oestradiol benzoate when given prenatally prevented the neonatal decline of adrenal weight and adrenocortical cell size. In normal or oil-treated rats, plasma corticosterone concentration was greatly increased during delivery and 2 h after birth, declining up to 12 h after birth. Oestradiol benzoate prevented this perinatal increase and suppressed the activity of 3 phi-ol dehydrogenase in the perinatal adrenal cortices.


Bilateral adrenalectomy of lambs in utero: effects on maternal hormone levels at induced parturition. Progesterone, 17 alpha, 20 alpha-dihydroxypregn-4-en-3-one, androstenedione, total unconjugated oestrogen and oestrone sulphate have been measured by radioimmunoassays in maternal utero-ovarian venous, maternal peripheral venous and/or foetal posterior vena caval plasma from six sheep bearing bilaterally adrenalectomized lambs, in which premature parturition was induced by administration of glucocorticoid. Three of the ewes were overiectomized, and in one of these three animals the foetal testes were also excised, at the time of foetal adrenalectomy. Adrenalectomy was judged to be complete on the basis of plasma cortisol levels in the neonatal lambs, and by examination of the site of ablation at necropsy. In all cases foetal administration of glucocorticoid led to the onset of labour, and lambing, and in all animals the hormonal changes preceding parturition were indistinguishable (either qualitatively or quantitatively) from the changes observed in animals carrying intact lambs. Since therapy with glucocorticoid alone successfully compensates for ablation of the foetal adrenal cortex, it is suggested that glucocorticoid is the only adrenal product required to cause parturition, and that foetal adrenal secretion of androgens may be unnecessary.


Deoxyribonucleic acid reassociation in the classification of the 'rhodochrous' complex and allied taxa. The degree of binding was determined between DNA preparations from gordonae and rhodochrous strains and uracil-labelled DNA from five reference strains, Nocardia asteroides NK20, N. pellegrino PII, Gordona bronchialis TI, G. terrae T5 and rhodochrous strain R90. Most of the rhodochrous and pellegrino strains fell into one of two genetically homogeneous taxa. The nucleotide sequence homology data also suggested that G. bronchialis, G. rubra, and more equivocally G. terrae, formed distinct species. However, the values for DNA relatedness between these species, and between then and the rhodochrous homology groups, were comparatively low. Only a small degree of nucleotide sequence homology was found between the N. asteroides reference system and the rest of the taxa studied. The nucleotide composition of the DNA preparations from 29 of the 30 test strains fell between 63 and 69 mol% guanine plus cytosine.


Defined bacterial populations in the rumens of gnotobiotic lambs. Five gnotobiotic lambs were fed on sterile diets until they were killed at 13 to 21 weeks of age. They were dosed orally with different combinations of 11 species of rumen bacteria. The biochemical reactions of each of the bacteria inoculated had been determined in pure culture in vitro, and they were chosen to perform the main reactions known to be associated with digestion in the normal mature rumen. Two of the bacteria could not be reisolated, but the remainder had established readily in the rumen, forming stable, mixed, defined populations. The total numbers of bacteria in the rumen, and the viable counts of most of the individual species were comparable to those of normal sheep. The concentration of volatile fatty acids was lower, however, and in four of the lambs there was a higher proportion of butyric acid and a lower proportion of propionic acid than in normal sheep. Cellulolytic, ureolytic, and methanogenic activities appeared to be taking place and lactate-utilizing bacteria appeared to reverse the accumulation of lactate which resulted from the activity of lactate-producing bacteria. Some of the bacteria also established at high levels in the caecum.


Sensitivity of Staphylococcus aureus to unsaturated fatty acids. Some unsaturated fatty acids were found to inhibit the growth of Staphylococcus aureus. Their effectiveness was related both to the degree of unsaturation and to the configuration of the molecule about the double bonds. Both linoleic acid and linolenic acid increased the proportion of plasmid-negative bacteria in a growing culture of bacteria containing a penicillinase plasmid. This was not due to a 'curing' effect of the fatty acids but was the result of greater sensitivity of the growth of bacteria containing penicillinase plasmid to inhibition by the unsaturated fatty acids. The presence of a plasmid conferring resistance to tetracycline, however, did not make the bacterium more sensitive to inhibition by linoleic or linolenic acids.


Metabolism of methanol by Rhodopseudomonas acidophila. Rhodopseudomonas acidophila strain 10050, grown anaerobically in the light on methanol, contained a methanol and formaldehyde dehydrogenase which could be coupled to phenazine methosulphate; an NAD-linked formaldehyde dehydrogenase which required GSH for activity; and an NAD-linked formate dehydrogenase. The specific activities of these enzymes varied in a non-coordinate manner when the organism was grown on different alcohols, formate or succinate. The affinity of the phenazine methosulphate linked methanol dehydrogenase for methanol was increased 10-fold if the cell-free extract was prepared and assayed in the absence of oxygen. Pulse-labelling experiments with [14C5methanol and [14C]bicarbonate indicated that fixation of carbon dioxide occurred via the ribulose diphosphate cycle and C3 + CO 2 fixation reaction(s). No evidence was obtained for operation of a reduced C1 fixation sequence. This conclusion was borne out by the enzyme content of cell-free extracts of the organism.


Influence of dilution rate on enzymes of intermediary metabolism in two freshwater bacteria grown in continuous culture. Two freshwater bacteria, a Pseudomonas sp. and a Spirillum sp., were grown in continuous culture under steady-state conditions in L-lactate-, succinate-, ammonium- or phosphate-limited media. In Pseudomonas sp., NAD-independent and NAD-dependent L-lactate dehydrogenases, aconitase, isocitrate dehydrogenase and glucose 6-phosphate dehydrogenase activities increased up to 10-fold as the dilution rate (D) was decreased from 0.5 to 0.02 h-1, regardless of whether the growth-limiting nutrient was carbon, ammonium or phosphate. In contrast, 2-oxoglutarate dehydrogenase and succinate dehydrogenase activities were not influenced by D, and NADH oxidase activity increased with D. Spirillum sp. gave different results in some respects, but it also exhibited an increase in the activity of several enzymes at low D values. Such increases may emanate from release of catabolite repression, and catabolite repressors for the five enzymes in Pseudomonas sp. showing such increases are probably compounds of carbon, nitrogen and phosphorus. It is likely that increased enzyme syntheses in low D cultures represent the normal physiological state for bacteria in aquatic environments where growth occurs slowly under nutrient limitations. Such increases probably permit a more effective utilization of nutrients present at sub-saturating concentrations.


Divalent cations in the envelope of a psychrophilic Achromobacter. The function of Ca2+ in a psychrophilic Achromobacter, previously found to bind large amounts of these ions to its envelope, has been studied. Bacteria suspended in media of low ionic content showed decreases in wet weight, dry weight and growth capacity, and increases in light scattering and in the release of u.v.-absorbing substances into the medium. The permeability barrier to Ca2+ was also damaged, and there was a release of radioactivity from bacteria labelled with 45Ca2+. These events occurred at the optimum growth temperature, and took place at increased rates at higher temperatures. Damage was prevented to about the same extent by 0.1 mM-CaC12, BaC12 or MgC12 and by 10 mM-NaC1, KC1 or LiC1. Ion competition experiments showed that Ca2+ was preferentially taken up and retained in comparison with Ba2+, Mg2+ and Na+, in that order. Isolated envelopes gave similar results. The dry weight of envelopes was reduced by 35% when they were suspended in water at 40 degrees C. It is clear that the function of certain envelope components in Achromobacter is highly dependent on divalent cations; and that both the integrity of the permeability barrier and the stability of the envelope are affected at low ion concentrations.


Effect of growth temperature and culture age on the lipid composition of Vibrio cholerae 569B (Inaba). The relative amounts of the major phospholipids (phosphatidylethanolamine, phosphatidylglycerol and lyso-phosphatidylethanolamine) and fatty acids in Vibrio cholerae 569B (Inaba) varied with growth temperature and between exponential and stationary phases of growth.


Effect of growth temperature on the cryopreservation of prototheca. The temperature at which Prototheca spp. were grown determined their response to freezing to -196 degrees C and subsequent thawing. Cells cultured at 35 degrees C were the most sensitive to freezing injury; at lower growth temperatures, resistance to freezing damage was seen. At all culture temperatures examined, the freezing tolerance varied with the age of the culture.


The induction of interferon by temperature-sensitive mutants of Sindbis virus: its relationship to double-stranded RNA synthesis and cytopathic effect. Sindbis virus strain AR339 induces interferon by 3 h after infection at 39 degrees C and by 8 h after infection at 30 degrees C. The time course of interferon induction between 4 and 9 h after infection at the restrictive temperature (39 degrees C) was measured for 24 temperature-sensitive (ts) mutants, all of which induced interferon by 16 h after infection. Mutants showing total RNA synthesis at 39 degrees C greater than 10% of the wild-type level induced interferon with kinetics similar to the wild-type. Of those mutants showing 1 to 10% of the wild-type level of RNA synthesis at 39 degrees C, four induced interferon with kinetics similar to the wild type, whereas six showed a lag in induction. Nine mutants, showing 0 to 5% of the wild-type level of RNA synthesis at 39 degrees C, and the wild type, were examined for single and double-stranded RNA synthesis at 30 and 39 degrees C, using a combination of lithium chloride precipitation and CF11 cellulose chromatography. Six of these mutants showed a lag in interferon induction at 30 degrees C, while three showed no lag. For all nine mutants, double-stranded RNA synthesis at 39 degrees C was undetectable, although easily detectable for the wild type. Both the wild type and the mutants synthesized double-stranded RNA at 30 degrees C. For all mutants, time of interferon induction at 39 degrees C was correlated with c.p.e. as measured by trypan blue uptake 30 h after infection. The mutant F104, showing undetectable RNA synthesis and a long lag in interferon induction at 39 degrees C, was examined for interferon induction in a temperature shift system. Only 1/2 h at 30 degrees C, before a shift to 39 degrees C, was required for interferon to be induced with wil-type kinetics, and this was correlated with an increased c.p.e. 30 h after infection. Increased RNA synthesis and infectious virus production were detectable at 30 degrees C after an initial hour at 30 degrees C. It is concluded that, for interferon to be induced with normal kinetics, early virus functions are required, but that normal levels of double-stranded RNA synthesis are not necessary. The events which lead to interferon induction also lead to visible c.p.e.


Adenovirus protein maturation at 42 degrees C. Incubation of adenovirus type 2 infected cells at 42 degrees C resulted in an inhibition of assembly of virus particles although all the major viral structural polypeptides and virus-induced cellular polypeptides so far identified were detected by electrophoretic analysis. Selective high salt-acid-urea extraction of low mol. wt. polypeptides revealed the absence of protein VII at 42 degrees C whereas precursor polypeptide P-VII and core protein V were found. Pulse-chase and temperature shift experiments indicated that cleavage of P-VII into VII was a reversible thermosensitive process, requiring de novo protein synthesis after shift-down to 37 degrees C. Virus particles assembled at 37 degrees C after transfer from 42 to 37 degrees C contained both viral DNA and polypeptides pre-labelled during the eclipse phase at 42 degrees C, including core protein VII.


Malignant melanoma and the central nervous system. A guide for classification based on the clinical findings. Twenty-seven cases diagnosed as having malignant melanoma affecting the central nervous system have been studied. In 20 patients the tumours represented secondary spread from elsewhere, but there were six who had a primary melanoma either of the spinal cord, leptomeninges, or brain. Confusion exists in the literature about how to differentiate primary from secondary tumours but this suggests several clinical factors which may indicate that the lesion is probably a primary one. This method of categorizing the cases is supported by the differences in duration of symptoms and survival times for each group and a simple classification can therefore be proposed.


Primary intracranial rhabdomyosarcoma producing proptosis. A case is reported of a primary rhabdomyosarcoma occurring in the right subfrontal region of a 16 year old girl. The patient suffered from dull frontal headache and proptosis for three months before hospitalization. The circumscribed and demarcated neoplasm involved the dura mater, and invaded the frontal sinus and roof of the orbit on the same side. The pathogenesis of the tumour is thought to be related to aberrant differentiation of unstable mesenchyme. A suggestion is made that the "medullomyoblastoma" should be classified as a type of neoplasm of mixed mesenchymal and neuroepithelial origin.


A damping factor in human voluntary contraction. Experiments on patients with Parkinsonism showed that the damping factor was lowered, so that, a tension stimulus being without supraspinal effect, oscillation occurred.


Conduction velocity in the proximal segments of a motor nerve in the Guillain-Barré syndrome. Conduction velocity from spinal cord to axilla (estimated using the F wave) has been compared with conduction velocity from axilla to wrist (measured in the conventional manner) in the motor fibres of the ulnar nerve in 17 controls subjects and in 11 patients with the Guillain-Barré syndrome (GBS). In the patients with GBS the conduction velocity was, in general reduced to a similar extent in both the proximal and the distal portions of the motor fibres, suggesting that the disease process is usually diffuse. In two patients, however, the conduction velocity in the proximal segment was disproportionally reduced and in one of these the conduction velocity in the distal segment was normal. It is concluded that the estimation of conduction velocity in the proximal segments of motor nerves may be of value in the assessment of patients with GBS.


Functional relationships between myotatic reflex arcs of the lower limb in man: investigation by excitability curves. In 30 normal subjects, the influence of the reflex activation of one myotatic reflex arc on the excitability of other myotatic reflex arcs of the lower limb has been investigated using excitability curves. Soleus, quadriceps, and short biceps tendon reflexes as well as H reflex at two different intensities (liminal and H max/2) were used either as conditioning or as conditioned responses. The reflex activation of the soleus muscle has opposite effects on antagonistic muscle groups of the thigh: facilitation of the quadriceps myotatic arc and inhibition of the short biceps myotatic reflex arc. Conversely, activation of both quadriceps and short biceps muscles leads to a marked and long lasting (+/- 5000 ms) inhibition of the soleus myotatic reflex arc. The differences of functional organization between proximal and distal myotatic reflex arcs are emphasized and the role of the afferent impulses secondary to the conditioning muscular contraction is discussed.


Longitudinal sliding of the median nerve during movements of the upper limb. An incidental finding during recordings from the median nerve was that the nerve trunk slides longitudinally in its bed when the limb is moved. The amount of movement has been measured in 19 subjects. The observations are discussed with reference to the pathology of entrapment neuropathies and it is suggested that, where longitudinal movement of a peripheral nerve is restricted, continual trauma results from normal movements of the limb.


Neurological associations of chronic heart block. A large group of patients with chronic heart block was studied for evidence of neurological disorder. Six out of 892 patients were found who had neuromuscular disease related to the conduction disturbance. In four patients, cardiac involvement appeared selectively to affect the conducting tissues. Three of these patients had a scapuloperoneal syndrome, the fourth, the oculocraniosomatic syndrome. In the remaining two patients, one with limb girdle dystrophy and the other with dystrophia myotonica, cardiomyopathy was present in addition to the conduction disturbance.


Neurological aspects of sinoatrial heart block. The symptoms of 100 patients with chronic cardiac sinoatrial disorder were analysed. The most common presenting features were syncope in 34 cases and dizziness in 22 cases. Over three-quarters of the patients had cerebral ischaemic symptoms at some stage of the disease. Diagnostic difficulties are often encountered and are illustrated by two case histories. Although sinoatrial disorder has been described in association with neuromuscular diseases, only one such example was found in this series. The patient had a limb girdle dystrophy with cardiomyopathy and diffuse disease of the cardiac conducting system. Muscle biopsy samples taken from 11 patients with idiopathic sinoatrial disorder were normal showing no evidence of subclinical muscular disease.


Neurological applications of surface-recorded electrocochleography. A new outpatient technique, involving the recording of auditory-evoked responses from scalp electrodes, is described. Responses are obtained from the cochlea, cochlear nerve, and auditory brain stem nuclei. The effects of various disorders on these responses are illustrated and the procedure is assessed as a diagnostic technique.


Wechsler Memory Scale performance and its relationship to brain damage after severe closed head injury. Eighty-two patients with severe head injury were tested on the Wechsler Memory Scale and compared with 34 normal subjects. Head injured patients had severe memory difficulties, particularly on Logical Memory and Associate Learning. Severity of head injury (post-traumatic amnesia duration) was related to poor memory, as was increasing age, but both persisting neurological signs, including dysphasia, and skull fracture were not.


Plasma lactate in anterior horn cell disease. This communication reports biochemical findings in 7 patients with anterior horn cell disease. The diagnosis was confirmed by evidence of denervation in the EMG and mukle biopsy with normal motor conduction velocities. In 4 of these patients, upper extremities were involved in a symmetrical fashion. In 1, the upper and lower extremities were involved in a symmetrical fashion. In the other 2, one upper or lower extremity were respectively involved in isolation. Pyramidal tract signs were evident in 2 patients of this group. Seventh cranial nerve and 12th cranial nerve involvement were seen in 2 patients. None of the patients manifested 8th cranial nerve dysfunction. All of these 7 patients showed elevation of raised fasting plasma lactate, with normal plasma citrate and plasma pyruvate values. This is in contrast to the altered citrate and pyruvate levels described by other workers in other cases of anterior horn cell disease. The significant biochemical relationship are discussed.


Effect of an inapparent viral encephalitis on the levels of lysosomal glycosidases in mouse brain. The changes in the activity of several lysosomal glycosidases of mouse brain which occured during an inapparent infection with the A774 strain (avirulent) of Semliki Forest Virus (SFV) have been related to the histopathological and viral changes caused by the disease. N-acetyl-beta-D-glucosaminidase, N-acetyl-beta-D-galactosaminidase and beta-glucuronidase were significantly elevated between post-inoculation day 7 and 28. Lesions characteristic of encephalitis were also observed between these times. Histochemical and biochemical of encephalitis were also observed between these times. Histochemical and biochemical observations showed that not all areas of brain were affected equally; the cerebellum, parts of the mid-brain and the spinal cord showed the most sevre biochemical and histochemical changes, whilst histopathological lesions were more evenly distributed. The biochemical results have been related to the histological, histochemical and virological findings and the production of glycosidases from 2 or more cellcular types has been postulated.


The epidemiology of amyotrophic lateral sclerosis in Finland. A study based on the death certificates of 421 patients. The mortality and prevalence of ALS in the various countries of Finland was studied. The work was based on death certificates derived from a 10-year period from 1963 to 1972, and altogether 421 cases were found. The mean duration of the disease was 2.7 years, and the mean age at death was 61.2 years. The average annual mortality rate was 0.91 per 100,000. The male to female ratio was 0.87 to 1, males outnumbered females only in age groups under 65. Some clustering of the cases seems to be taking place in the south-eastern part of the country. The rural to urban distribution of the patients' places of birth and domiciles did not differ markedly from that of thw whole population. After ALS itself pneumonia was the most common direct cause of death. Of other significant conditions coded in the death certificates schizophrenia and cancer did not occur more often than could be expected by chance. No evidence of inheritance of the disease was found.


Central pontine myelinolysis. An ultrastructural and elemental study. Central pontine myelinolysis (CPM) has been classified as a unique disease of myelin with a peculiar localization in the central pons. Although its etiology and pathogenesis are unknown, some have compared its histopathology to that of multiple sclerosis. Ultrastructural studies of suitably preserved tissue have been lacking. We have recently studied 3 cases of CPM, selectively immunostaining 2 cases and examining the fine structure and elemental composition of the third case obtained shortly after death. IgG could not be demonstrated within or around the lesions. The findings of an increased Na/K ratio and of intramyelinic vocuoles at the periphery of the lesion sjggest that the pathogenesis of CPM might include a phase of intramyelinic edema with subsequent rupture of the distended myelin sheaths. An increase in the permeability of the blood-brain barrier might represent a complicating factor. The spheroids in our case are primarily reactive in type and do not support pior light-microscopic interpretations of concomitant neuroaxonal dystrophy. The unexplained presence of tin within the lesion indicates a need for further study of this element in CPM.


International collaborative study of the spinal muscular atrophies. Part 1. Analysis of clinical and laboratory data. There is considerable variation in age of onset, though in over three-quarters of cases onset is before 4 years of age. A febrile episode, often of viral origin, may be present at the time of onset and might possibly be of aetiological significance, perhaps by precipitating the disease in a genetically predisposed individual. Reduced fetal movements and floopiness at birth are present in about one third of those cases where the onset is in early childhood. It would seem that when the onset is before 4 years of age, and particularly if the child has never been able to sit without support, the prognosis is much worse than in cases where the onset is after the age of 4 years. The proximal limb muscles are predominantly affected and muscle tone is usually reduced but pseudohypertrophy is uncommon. Rarely are the cranial nerves affected. Muscle fasiculations are present in about half the cases. Almost 10% of cases appear to be mentally retarded. With regard to the EMG findings, spontaneous activity, reduced full effort pattern increased potential amplitude and duration and increased motor unit territory appear to be the most reliable diagnostic criteria. Routine histological evidence of neurogenic atrophy seems to be a more reliable diagnostic criterion than muscle histochemistry. However, this may be only reflect the way in which the data were selected, that is, from cases where a muscle biopsy showed evidence of neurogenic atrophy on routine histology. Finally the serum level of creatine kinase is rarely very high and in more than half the cases it is normal. The CSF chemistry is always normal.


Vascular leakage in the dorsal root ganglia of the rat, studied with horseradish peroxidase. Horseradish peroxidase (HRP) was found to pass from ganglionic blood vessels into the extracellular space of dorsal root and Vth nerve ganglia within 2 min of intravenous injection in the rat. By 5 min, the tracer had penetrated into perineuronal and periaxonal spaces. A brisk macrophage response occured, and these cells rapidly engulfed the tracer so that it has almost completely disappeared from the extracellular space 2-3 hr. Fenestrated blood vessels, with and without diaphragms were seen within ganglia. On the basis of the pattern of tracer distribution following post-fixation perfusion of HRP, it was concluded that the fenestrations and endothelial intercellular clefts were probably the most important route of tracer leakage. Because of the foreign and possibly toxic nature of the tracer, its movements and fate may not parallel that of normally extravasated proteins.


Kinetics of active sodium transport in rat proximal tubules and its variation by cardiac glycosides at zero net volume and ion fluxes. Evidence for a multisite sodium transport system. 1. Transepithelial Na concentration difference, deltaCNa, across proximal tubules of rat kidney was measured at varying intraluminal Na concentrations (CNainfinity) under conditions of zero net volume and Na flux. Simultaneous stopped-flow intratubular and artificial peritubular capillary perfusion techniques were used together with intratubular raffinose to achieve zero net fluxes. Under these conditions in rat proximal tubules, deltaCNa represents active transport, JactNa, factored by permeability, PNa, plus an electrical factor depending on transepithelial potential difference. 2. The relationship between CNainfinity and deltaCNa appeared sigmoidal with saturation being reached when intratubular Na was above 80 m-mole/kg. In the presence of ouabain (10(-2)M) and scilliroside (10(-3)M) the relationship remained the same. The maximum deltaCNa was reduced by approximately 50% by cardiac glycoside inhibition whereas the half-saturation constant was essentially unchanged. These changes from the control represent simple non-competitive inhibition by the cardiac glycosides. 3. Absence  of potential difference (p.d.) measurements precludes exact description of the relation between true active transport and substrate concentration but much evidence indicates that the apparently sigmoid relation in the presence and absence of cardiac glycoside inhibition, would be retained if correction of deltaCNa values were possible. Such results could then be explained if there are at least three or more sites for Na on the pump system, of which at least two are not cardiac glycoside sensitive. They would also unequivocally exclude the presence of a single-site single-pump system or the simple algebraic addition of two such units since the kinetic curves for both would be hyperbolic rather than sigmoidal.


Extravascular albumin in bone tissue.

Extravascular albumin in bone tissue. 1. The amount of albumin in extravascular tissue fluid in bone, kidney, intestine, skin and muscle and in plasma of young rabbits has been measured by radial immunodiffusion. 2. The majority of extravascular albumin in kidney, intestine, skin and muscle is exchangeable with plasma albumin, whereas in bone, only the proportion which is in tissue fluid is readily exchangeable; the remaining fraction in calcified matrix is more permanently fixed. 3. About 27% of the albumin in young bone is in tissue fluid, about 57% in calcified matrix and about 16% is intravascular. The total amount of extravascular albumin per unit mass of bone is similar to that found in soft tissues. 4. The volume of intravascular plasma in tissues was determined in two ways: from 51Cr-erythrocyte radioactivity and the venous haematocrit and from the '5 min 125I-fibrinogen space'. 5. The rate of egress of albumin from blood vessels has been estimated from the initial slope of the ratio of extravascular radioactivity in the tissue to plasma radioactivity plotted against time after injection of 125I-albumin. 6. The rate of clearance of the albumin in extravascular tissue fluid in bone is approximately once every hour. This is more rapid than in skin and muscle, comparable with intestine and less rapid than in kidney. 7. The amount of albumin incorporated into calcified matrix of bone per day is calculated to be less than 0-5% of the total albumin passing through the tissue fluid of bone per day.


Stimulus-secretion coupling in pancreatic acinar cells: inhibitory effects of calcium removal and manganese addition on pancreozymin-induced amylase release. The role of Ca ions in stimulus-secretion coupling has been analysed in the isolated and perfused rat pancreas. 2. The omission of [Ca2+]O diminished but did not abolish the release of amylase in response to continuous stimulation with 5 m-u. pancreozymin (Pz)/ml. The addition of Mn2+ (1-0 mM) to this Ca-deficient environment abolished the residual release of amylase. This was followed by a complete recovery of amylase output when the control [Ca2+]O was reestablished. 3. The addition of Mn2+ (1-0 mM) to the extracellular environment containing 2-5 mM-Ca2+ reversibly inhibited the Pz-induced release of amylase. 4. A kinetic scheme based on competition of Ca and Mn at a carrier in the acinar cell membrane could quantitatively explain the effects of Ca and Mn upon the Pz-induced amylase release. 5. These results support the view that the Ca2+ influx into the acinar cells is the major contributor to the rise in [Ca2+]i which, in turn, mediates the processes in the stimulus-secretion coupling in the exocrine pancreas, and suggest that the mode of Ca influx is a facilitated diffusion.


Excitation of phasically firing hypothalamic supraoptic neurones by carotid occlusion in rats. 1. The activity of supraoptic neurones has been recorded extracellularly during bilateral occlusion of the common carotid arteries in anaesthetized rats. 2. Experiments in lactating rats showed that occlusion liberated sufficient amounts of neurohypophysial hormones to cause a rise in intramammary pressure 15-25 s after the onset of occlusion. 3. Ninety-one percent of the phasic neurones (defined as those showing bursts of activity alternating with periods of silence) were activated by carotid occlusion less than 10 s after the onset of occlusion. Most randomly firing neurones were inhibited or were unaffected. 4. The activation of phasic neurones is unlikely to be just a nonspecific effect, because in the same animals, phasic neurones were excited whilst random neurones were not. 5. Moreover, in phasic neurones, statistical analysis shows (a) that the intervals during which an occlusion was performed were significantly shorter than the intervals between spontaneously occurring bursts, and (b) that this activation was followed by a period of reduced firing probability. 6. The results are discussed with reference to the correlation of supraoptic neuronal activity with hormone release. The possibility is considered of relating the tendency of some supraoptic neurones to fire in bursts with the secretion of vasopressin.


Dual role for potassium in Balanus photoreceptor: antagonist of calcium and suppression of light-induced current. 1. The mechanism of reduction and final abolition of the depolarizing receptor potential of Balanus eburneus photoreceptors in K+-free saline was examined with electro-physiological techniques including voltage-clamp and ion specific electrodes. 2. An extended exposure to K+-free saline reduces the transient peak and the steady phases of the depolarizing receptor potential by approximately equal amounts. The process can be reversed in normal saline although the wave form of the response is often more rectangular upon recovery. Restoration of K+ induces a transient hyperpolarization of the resting membrane for several minutes. 3. The depolarizing receptor potential can also be restored in K+-free solution by reducing the Ca2+ concentration. This saline depolarizes the resting membrane, and the wave form of the depolarizing receptor potential assumes a rectangular configuration. 4. Voltage-clamp experiments revealed that an extended exposure to K+-free saline produced an extreme reduction of the inward light-induced current (LIC), but no detectable change in the membrane potential at which the current reverses sign. Membrane conductance in darkness showed little change. Reduction of the Ca2+ concentration from 20 to 0-2 mM in K+-free restored the current and produced a negative 8-10 mV shift in the zero current potential. There was also a significant decrease in membrane conductance in darkness. 5. Current-voltage relations of the membrane in K+-free, low Ca2+, or K+-free low Ca2+ salines were somewhat dependent upon the order the salines were presented. 6. Low Ca2+ saline (0-2 mM) by itself produced a -5 mV shift in the zero-current potential. Removing K+ in low Ca2+ produced an additional shift (-5 mV) in the zero-current potential.


Electrical properties of the rod syncytium in the retina of the turtle. 1. Intracellular responses were recorded from rods in isolated eye-cups of the snapping turtle. Chelydra serpentina. Responses to flashes of small (less than 100 mum diameter) and large (1000 mum diameter) spots of 500 nm light were studied. 2. Responses produced by small and large diameter spots which delivered less than 0-3 photons mum-2 had the same shape. The responses produced by large spots were, however, nearly ten times greater in amplitude. The difference in amplitude is termed enhancement. 3. Perfusing an eye-cup with a Co2+-containing medium blocked synaptic transmission from receptors to horizontal cells but did not affect the responses of rods. 4. The membrane conductance of a single rod, estimated by three independent methods, was approximately 1-2 X 10(-9) MHo. 5. Enhancement can be predicted by a mathematical model which treats rods as an electrical syncytium. The space coefficient describing the spread of current is approximately 65 mum indicating that the coupling conductance between rods was relatively high. 6. When the intensity of a small spot was increased from 0-3 photons mum-2 up to 6 photons mum-2, the shape of the response was unchanged. When the intensity of a large spot was increased to more than 0-3 photons mum-2, the voltage during the recovery phase was decreased. This decrease is termed disenhancement. 7. The voltages produced by bright, large and small diameter spots which delivered the same quantity of light to the impaled rod were compared. The voltage produced by a large diameter spot became for a short period during the recovery phase less than the voltage produced by a small diameter spot. This observation indicates that the response to a large spot included during recovery an active process which is not apparent in the response to a small spot.


A study of the vascular and acid-secretory responses of the rat gastric mucosa to histamine. 1. The effects of histamine on gastric mucosal blood flow in the presence and absence of gastric acid secretion were studied in the rat. 2. Histamine, in doses greater than those required to stimulate maximal acid secretion, caused a small increase in mucosal blood flow per unit acid output. 3. When acid secretion was inhibited by methyl analogues of prostaglandin E2, histamine reduced arterial blood pressure and gave a dose dependent rise in mucosal blood flow. 4. When acid secretion was inhibited by the histamine H2-receptor antagonists, burimamide and metiamide, histamine still increased mucosal blood flow. 5. The use of H1-receptor antagonists to inhibit the histamine-induced hyperaemia was made difficult by their vasodilator actions. 6. The selective histamine H2-receptor agonist, 4-methyl histamine, had no effect on arterial blood pressure in doses which stimulated acid secretion. The increase in mucosal blood flow which accompanied the stimulation of acid secretion was inhibited by the anti-secretory prostaglandins and H2-receptor antagonists. 7. The selective histamine H1-receptor agonist, 2-pyridyl ethylamine, had no effect on acid output but increased resting mucosal blood flow. 8. These results suggest that histamine H2-receptors, primarily concerned with acid secretion, and H1-receptors concerned with vasodilatation are both present in the rat gastric mucosa.


Histamine metabolism of the guinea-pig gastric mucosa. 1. The mobilization of gastric mucosal histamine as reflected by changes in formation and content has been studied in guinea-pigs on feeding and after injections of pentagastrin or 2-deoxy-D-glucose. 2. Re-feeding fasting guinea-pigs as well as injections of pentagastrin or 2-deoxy-D-glucose raised the rate of mucosal histamine formation; pentagastrin induced a fourfold rise. 3. Some properties of the enzyme catalysing the formation of histamine were examined. The results indicated that this enzyme is histidine decarboxylase, L-histidine carboxy-lyase, E.C. 4.1.1. 22. 4. The enzyme imidazole-N-methyl transferase, E.C. 2.1.1.8, which carries out methylation of the imidazole ring to yield 1-methyl-4-(beta-aminoethyl)imidazole (methylhistamine), was found in high amounts in the mucosa. The enzyme did not change upon stimulation of the mucosa. 5. The metabolism of histamine within the gastric mucosa is discussed in relationship to a suggested role of the amine in exciting acid secretion.


Subcellular localization of the heparin-neutralizing factor in blood platelets. 1. The distribution of the heparin-neutralizing factor (platelet factor 4, PF4) in subcellular organelles of blood platelets of rabbits and man was investigated. 2. In both species the organelles storing 5-hydroxytryptamine (5-HT storage organelles) contained only trivial amounts of PF4. 3. In contrast, the content of PF4 was highest in the subcellular fractions rich in alpha-granules. 4. In conclusion, PF4 is probably localized in the alpha-granules and therefore the platelets contain at least two types of organelles (5-HT organelles and alpha-granules) capable of releasing their contents in response to the same stimuli, such as exposure to collagen, thrombin, etc.


Mechanisms underlying recurrent inhibition in the sacral parasympathetic outflow to the urinary bladder. 1. In cats with the sacral dorsal roots cut on one side electrical stimulation (15-40 c/s) of the central end of the transected ipsilateral pelvic nerve depressed spontaneous bladder contractions. The depression was abolished by transecting the ipsilateral sacral ventral roots. 2. Electrical stimulation of acutely or chronically transected ('deafferented') sacral ventral roots depressed spontaneous bladder contractions and the firing of sacral parasympathetic preganglionic neurones innervating the bladder. The depression of neuronal firing occurred ipsilateral and contralateral to the point of stimulation, but only occurred with stimulation of sacral roots containing preganglionic axons and only with stimulation of sacral roots containing preganglionic axons and only at intensities of stimulation (0-7-4V) above the threshold for activation of these axons. 3. The inhibitory responses were not abolished by strychnine administered by micro-electrophoresis to preganglionic neurones, but were blocked by the intravenous administration of strychnine. 4. The firing of preganglionic neurones elicited by micro-electrophoretic administration of an excitant amino acid (DL-homocysteic acid) was not depressed by stimulation of the ventral roots. 5. It is concluded that the inhibition of the sacral outflow to the bladder by stimulation of sacral ventral roots is related to antidromic activation of vesical preganglionic axons. Collaterals of these axons must excite inhibitory interneurones which in turn depress transmission at a site on the micturition reflex pathway prior to the preganglionic neurones.


Activation of the contractile mechanism in the anterior byssal retractor muscle of Mytilus edulis. 1. The electrical and mechanical responses of the anterior byssal retractor muscle (ABRM) of Mytilus edulis to acetylcholine (ACh), high [K]O or the removal of external Ca were examined under a variety of conditions. 2. ACh (10(-6)--10(-3)M) produced contracture tensions larger than those produced by high [K]O (30-300 mM) for a given amount of depolarization. In Ca-free solution, the rate of decline of ACh-contractures was much smaller than that of K contractures, though both ACh- and K-contractures eventually disappeared. 3. 5-HT (10(-4)M) of procaine (1 mM) markedly reduced the height of ACh-contractures, but had little or no effect on K-contractures. The height of K contractures was markedly decreased by Mn ions (20 mM) or low pH (4-5), while ACh-contractures remained unaffected. 4. Partial replacement of [Na]o by choline (30-100 mM) reduced both ACh-induced depolarization and contracture tension, whereas K-contractures remained unchanged even after total replacement of [Na]o by choline. 5. ACh could produce little or no tension when applied during the relaxation phase of K-contractures, while high [K]o produced the maximal contracture tension when applied during the relaxation phase of ACh-contractures. 6. Following the removal of external Ca from solutions containing less than 10 mM-Mg, the ABRM showed a marked tension development associated with repetitive electrical activity superimposed on a gradual decline of membrane potential. 7. These results suggest that ACh-contractures are mainly due to the release of intracellularly stored Ca, while K-contractures are mainly associated with the inward movement of external Ca.


Localization of calcium-accumulating structures in the anterior byssal retractor muscle of Mytilus edulis and their role in the regulation of active and catch contractions. 1. The localization of Ca-accumulating structures in the anterior byssal retractor muscle (ABRM) of Mytilus edulis and their role in the contraction-relaxation cycle were studied by fixing the ABRM at rest or during various phases of mechanical activity with a 1% osmium tetroxide solution containing 2% potassium pyroantimonate. 2. In the resting ABRM, electron-opaque pyroantimonate precipitate was observed at the inner surface of the plasma membrane, the vesicles and the mitochondria. 3. Electron X-ray microanalysis showed the presence of Ca in the precipitate, indicating that the precipitate provides a valid measure for Ca localization. 4. In the ABRM fixed at the peak of mechanical response to the Ca-removal or to acetylcholine, the precipitate was found to be diffusely distributed in the myoplasm in the form of a number of particles. At the completion of spontaneous relaxation, the precipitate was again seen at the inner surface of the plasma membrane. 5. During the catch state, the precipitate was found to be re-accumulated in the peripheral structures with a corresponding decrease of the precipitate in the myoplasm. 6. These results not only provide evidence for the involvement of the Ca-accumulating structures in the contraction-relaxation cycle in the ABRM, but also suggest that the transition from active to catch contractions is related to a decrease in myoplasmic free Ca ion concentration.


Antagonism by antipyretics of the hyperthermic effect of a prostaglandin precursor, sodium arachidonate, in the cat. 1. Injection of sodium arachidonate (100-400 mug) into lateral cerebral ventricles of unanaesthetized cats caused shivering and rapid development of dose-related hyperthermic responses. Unless arachidonate is hyperthermogenic per se, this indicates that in vivo formation of prostaglandins, or perhaps an endoperoxide intermediate, can cause hyperthermia. 2. Tolerance gradually developed when arachidonate was administered repeatedly at intervals of 1-7 days. Examination of the brains of several tolerant animals revealed in each case marked enlargement of the lateral ventricles which apparently accounted for the diminished response to arachidonate. 3. Sodium salicylate (40, 160 mg/kg, i.v.) antagonized arachidonate but only after a 3-4 hr latent period. 4. Paracetamol (10, 40 mg/kg, i.v.) reduced the hyperthermic effect of arachidonate but a dose of 40 mg/kg antagonized centrally administered bacterial endotoxin more effectively than it did arachidonate. 5. Indomethacin (40 mug/kg, i.v.) significantly reduced arachidonate-induced hyperthermia in only one of two studies. This reduction was comparable to the hypothermic effect of indomethacin in afebrile animals and was attributed to a non-specific action on thermoregulatory function rather than to inhibition of prostaglandin synthesis. Indomethacin antagonized endotoxin and leucocytic pyrogen to a greater degree than it did arachidonate. 6. Comparison of the relative effectiveness of the antipyretics in blocking hyperthermic responses to pyrogens and to sodium arachidonate indicates that, if prostaglandins do mediate pyrogen-induced fever, these antipyretics exert their primary at a step before prostaglandin synthesis.


Progress of topographic regulation of the visual projection in the halved optic tectum of adult goldfish. 1. The patterns of re-established visual projections on to the rostral half-tectum are studied following excision of the caudal tectum at various intervals after section of either the contralateral optic nerve or the ipsilateral optic tract in adult goldfish. 2. The pattern of a newly restored retinotectal projection depends on the duration of the post-operative period given to the halved tectum before it is re-innervated by regenrating optic fibres from the retina. 3. When the duration is such that regenerating optic fibres invade the denervated rostral half-tectum at about 40 days or longer after excision of the caudal tectum, the remaining half-tectum is able to accommodate incoming optic fibres not only from the appropriate temporal hemi-retina but also from the foreign nasal hemiretina in an orderly compressed topographic pattern. 4. If the surgical operations are timed so that the halved tectum receive regenerating optic fibres earlier than 33 days after excision of the caudal tectum, the halved tectum initially accommodates only those optic fibres originating from the temporal half of the retina at this early stage. 5. This normal (uncompressed) pattern of the newly regenerated visual projection, however, eventually changes into an orderly compressed pattern at a later period. Post-operative dark-deprivation of the operated fish has no significant effect on the temporal transition. 6. The temporal transition from an initially normal pattern into an orderly compressed pattern may reflect the time course of progressive and systematic changes involved in topographic regulation of the halved tectum into a whole.


Effect of bombesin and related peptides on the release and action of intestinal hormones on pancreatic secretion. 1. Pancreatic volume flow as well as bicarbonate and protein secretion from pancreatic fistulas have been measured in response to i.v. infusion of graded doses of bombesin and related peptides containing the COOH-terminal fragment of the bombesin molecule in conscious dogs with intact antrum and in anaesthetized animals with antrectomy, or antrectomy and enterectomy. 2. Bombesin and related peptides given to conscious dogs produced a potent and dose-dependent increase in pancreatic protein output reaching a maximum equal to that induced by the octapeptide of cholecystokinin (OP-CCK) as well as a small rise in bicarbonate output attaining a peak amounting to about 10% of that evoked by secretin. The serum gastrin level rose progressively during the infusion of bombesin to reach a peak with the highest dose of peptide. 3. Bombesin infused i.v. in anaesthetized animals with resected antrum also evoked a marked increase in pancreatic protein secretion without significant changes in the serum gastrin level. Following the removal of the antrum and small intestine, bombesin failed to show any stimulation of the pancreatic secretion or any change in the serum gastrin level. It is concluded that the strong stimulatory action of bombesin and related peptides on pancreatic secretion cannot be entirely ascribed to the release of gastrin but might be attributed at least in part to the release of intestinal hormones, particularly CCK. 4. Atropine and the growth hormone-release inhibiting hormone (GH-RIH), which were shown to inhibit the release of CCK induced by duodenal perfusion of an amino acid mixture, also caused the inhibition of pancreatic protein secretion by bombesin but failed to affect the pancreatic response to OP-CCK. The results indicate that bombesin releases, in addition to gastrin, CCK from the gut by a mechanism largely dependent upon cholingeric innervation.


Effects of various ambient temperatures and of heating and cooling the hypothalamus and cervical spinal cord on antidiuretic hormone secretion and urinary osmolality in pigs. 1. Plasma ADH concentration, urinary and plasma osmolality and haematocrit were measured in young pigs placed in cold, thermoneutral, warm and hot ambient temperatures. In some experiments a thermode placed in the hypothalamus or over the cervical spinal cord was heated or cooled at various ambient temperatures. 2. Plasma ADH concentration remained at a low level (0-5--5 muu. ml.-1) over 2 hr or 3 hr periods when the pigs were in cold, thermoneutral or warm ambient temperatures. A hot environment, which caused a marked rise in the pigs' rectal temperature, was associated with a large rise in plasma ADH level. 3. The rise in plasma ADH level which occurred during an increase in body temperature was consistently and completely suppressed by simultaneous cooling of the thermode in the pre-optic region to 5 to 10 degrees C. When the thermode was in the region of the supraoptic nucleus the rise in ADH was only partly suppressed, and when it was over the cervical cord it was only sometimes suppressed. 4. Cooling the thermodes in any position at a cold or thermoneutral ambient temperature, or heating them at a thermoneutral or warm ambient temperature, caused no consistent change in ADH. 5. A diuresis, with a urinary flow-rate of at most 1 ml. min-1 and minimal urinary osmolality of 53 m-osmole kg-1, was observed on only three occasions, twice during cooling of a thermode in the hypothalamus and once after the end of a period when the thermode was heated. In each case, the plasma ADH was less than 2 muu. ml.-1. 6. A slight rise of haematocrit in cold ambient conditions and a slight fall in the warm were observed. Otherwise changes in haematocrit were trivial, and a shift of water between vascular system and interstitium could not be invoked to account for changes in ADH levels. Observed variation of plasma osmolality was also slight.


Action of sympathetic nerves of inner and outer muscle of sheep carotid artery, and effect of pressure on nerve distribution. 1. The direction of torsion produced during active shortening of helical strips of sheep carotid arteries was measured to assess whether inner or outer muscle was contracting. 2. Noradrenaline contracted inner (non-innervated) muscle in lower concentrations than were needed to contract outer (innervated) muscle, even with desipramine present to prevent uptake of noradrenaline by the nerves and with enough cyanide present to rise the normally low O2 tension of inner muscle to that of outer muscle. 3. Activation of sympathetic nerves in the outer part of the artery by nicotine caused almost evenly balanced contraction of both parts of the wall, with slight bias to outer contraction. 4. Moderate external constriction of the artery in vivo for 10-17 days, in order to raise pressure throughout the wall to intraluminal pressure, made the entire wall nerve-free. 5. The results provide evidence that the nerves can induce substantial activation of inner muscle, which is highly sensitive to noradrenaline, and that the absence of nerves from inner muscle can be explained by the high pressure there.


The nature of the pi1 colour mechanism of W.S. Stiles. The ppi1 colour mechanism was isolated by means of Stile's auxiliary field technique: that it is pi1 which is isolated is proven by both test and field action spectra. 2. The fundamental mechanisms of human trichromatic colour vision must satisfy Grassman's law of additivity. The hypothesis that pi1 is one of the three fundamentals is tested by experiments in which pairs (u1, u2) of monochromatic adapting fields are mixed 3. When two fields with wave-lengths in the neighbourhood of its primary mode (mu1, mu2 less than or equal to 500 nm) are combined, pi1 is field-additive, consistent with the hypothesis that this portion of the pi1 action spectrum is that of the short-wave-length-sensitive photoreceptors. 4. When a short-wave-length adaptation field (mu1 less than or equal to 500 nm) is mixed with a longer wave-length field (mu2 greater than or equal 550 nm) i1 is strongly non-additive. This result proves that the long-wave-length portion of the pi1 field spectrum is generated at least in part by a signal originating in the long- or middle-wave-length sensitive cones. 5. Analysis of the additivity failures supports a model of pi1 in which the signal to be detected is generated in the short-wave-length cones, and must pass serially through two gain stages: the gain in the first stage is controlled by the short-wave-length cones alone; the gain in the second stage is controlled by a signal originating in the middle, or long-wave-length cones, or both.


Thermoregulation in rabbits during fever. 1. We have studied the effect of fever on the efficacy of the thermoregulatory control system in conscious rabbits. 2. The control system was challenged by a series of systemic thermal loads produced by the intravenous infusion of hot or cold isotonic solutions. The time integral of the consequent upward or downward displacement of brain temperature was used as an index of the response of the control system. Steady-state fever was induced by intravenous infusion of plasma containing leucocyte pyrogen. 3. With cold loads there was a linear relation between load and response. The regression coefficients were not significantly changed by fever in any of the six rabbits. Wth hot loads given to afebrile rabbits the regression of response on load was generally not statistically significant, but the responses were not demonstrably greater in the febrile state. 4. We were not able to demonstrate impairment in the capacity of the febrile animal to compensate for systemic thermal loads.


Desensitization to gamma-aminobutyric acid in crustacean muscle fibres. 1. Desensitization to gamma-aminobutyric acid (GABA) was demonstrated in crab muscle fibres by measurements to conductance changes induced by the drug. 2. In standard solutions (containing 34 mM-Ca2+), complete desensitization occurred in the presence of 5 X 10(-4) M-GABA. In Ca2+-free solutions, however, only partial (70-80%) desensitization was observed after the application of the same concentration of GABA. 3. Complete recovery of the membrane sensitivity to GABA was achieved after less than 60 min of continuous washout with standard solution. Only partial (10%) recovery was observed after 1 hr of washout with Ca2+-free solution. 4. The results support the 'receptor hypothesis' of desensitization which assumes transformation of the receptor from an effective to refractory state, as opposed to the 'ionophore hypothesis' which assumes direct inactivation of the synaptic current. 5. The possible mechanism by which Ca ions effect desensitization is discussed in terms of the 'cyclic model' of Katz & Thesleff (1957).


[Cineangiography in adult mitral valve disease. 41 cases of comparison of anatomical with radiological findings (author's transl)]. During the course of their preoperative assessment, 41 patients with severe mitral valve disease underwent left ventricular cineangiography, AP and lateral at rapid speed (100 images per second). This gave a particularly precise anatomical and physiopathological inventory of the lesions, as was confirmed by preoperative findings. The presence of mitral stenosis was confirmed in all cases and an indication of its degree in the majority.


[Sub-adventitial traumatic rupture of the left renal artery (author's transl)]. On the basis of two cases of sub-adventitial traumatic rupture of the left renal artery, as well as data from the literature, the authors indicate the relative poverty of clinical signs of traumatic rupture of the renal arteries. They stress the value of early intravenous pyelography in lumbar trauma, with immediate arteriography in the presence of a non-functioning kidney, making conservative surgery possible.


[The contribution of nephro-urotomography in the diagnosis of unilateral non-functioning kidney in the adult (author's transl)]. The aetiological diagnosis of a unilateral nonfunctioning kidney is achieved by angiographic or retrograde techniques. Pyelography indicates only that organ is non-functioning. 71 patients were explored by nephro-urotomography carried out using high doses of contrast medium (2 cm3/kg) with rapid injection (10cm3/sec.) and repeated tomographic sections taken during the first minute after injection. These tomographic sections, three in number, made it possible to study the three phases of the nephrogram: cortical nephrography, cortico-medullary nephrography and tubular nephrography. The aim of this study was to assess the contribution of this technique in the aetiological diagnosis of a unilateral non-functioning kidney. In the majority of cases it is possible to suspect the vascular or neoplasic origin of the non-functioning kidney. Obstructive non-functioning kidneys have two distinct nephrographic appearances. Pelvic and retroperitoneal obstructions are visualised chiefly during the phase of cortical nephrography, which shows marked parenchymatous atrophy with the presence of rounded intrarenal lacunae. By contrast, obstruction secondary to pyelo-ureteral junction syndrome results in total destruction of the parenchyma. The phenomenon of total corporeal opacification plays a major role in the visualisation of the fibrous speta which form the limits of the pseudocystic pockets. In these patients, the contribution of study of early nephrograms is less evident. Bacillary non-functioning kidneys have an analogous appearance characterised by the particular frequency of abnormal opacities, calcified ormastic. Thus the aetiological diagnosis of a unilateral nonfunctioning kidney may be obtained in the majority of cases. This permits more judicious selection of those cases requiring angiography or retrograde exploration necessary to pre-operative assessment.


[Hepatic echo-angiostructure: echo-anatomical study of the intraparenchymatous canal structures (author's transl)]. Hepatic echo-angiostructure: echo-anatomical study of the intraparenchymatous canal With a suitable technique (real time, grey scale) hepatic ultrasonography is able to display intraglandular ductal elements: portal veinous network, supra-hepatic veinous network, and, if enlarged intrahepatic biliary tree. A careful echoanatomic study is necessary to identify the enlarged biliary network in case of obstructive jaundice; such a study is also necessary not to confuse normal ductal structures, insufficiently displayed, with pathological reflections - a rather frequent hazard with conventionnal techniques.


[Radio-electrogastro-enterographic correlations (author's transl)]. Recording of the electro-gastro-enterogram (E.G.E.G.) and the simultaneous taking of a 70 mm ampliphotography series shows the high degree of correlation between E.G.E.G. and peristaltis, with characteristic waves for each part of the digestive tract, both in the normal condition as well as in certain pathological states. The future and role of the E.G.E.G. appear very promising, on the one hand by virtue of its simplicity and secondly because of the information it is capable of providing from a functional viewpoint. In no case, however, can it replace the precise nature of radiological images.


[Critical analysis of the arteriography of primary malignant tumors of the bones, on the occasion of 19 unedited cases]. From the analysis of a series of 62 unedited cases of arteriography of osseous tumors including 19 primary malignant tumors, it was confirmed that the majority of angiographic signs described as being characteristic of malignant tumors of the bones are not significant. They are found in benign tumors and in ordinary inflammatory phenomena: several cases of osteoid osteoma, myeloplax tumor or simply of osseous reconstruction permit one to make criticisms. On the other hand, one must endeavour to demonstrate, by means of a technique whose main elements are recalled, vascular abnormalities which are the only typical ones and which furthermore are found in "silent" tumors such as chondrosarcomas or fibrosarcomas. These vascular abnormalities are given in detail, and several examples of them are given.


[Irradiation in radiodiagnosis: recent possibilities of decreasing the doses (author's transl)]. Depending on the film used, the new super-fast re-enforcing screens enable a four to six fold reduction in diagnosis cutaneous irradiation. This diagnosis irradiation which remains rather considerable under classical techniques, is frequently injustly neglected: the distribution of this new type of material seems desireable. On the contrary, the use of xeroradiography leads to an irradiation which is three times greater than in conventional techniques and fifteen times greater than in these new techniques: xeroradiography must therefore be reserved for very specific problems.


[A rare tumour of the right hypochondrium in the child (author's transl)]. Pancreatic pathology in the child is rare and usually limited to necrotic or traumatic pseudo-cysts. The authors report a case of multicystic dysplasis localised in the pancreas in a one-year old infant. The preoperative diagnosis of a traumatic cyst was made in error as the result of the discovery of a fracture of the skull. At operation, the "tumour" was seen to be a multicystic mass within the duodenal loop but pediculated under the inferior surface of the pancreas. Histological examination confirmed its dysplasic nature. The presence, as a result of vascular compression, together with the post-operative resolution of hypertension lend further originality to this case.


[Simultaneous discovery of osteopetrosis in a mother and fetus on the occasion of radiopelvimetry (author's transl)]. On the occasion of radiopelvimetry, requested for suspected narrowed pelvis, osteopetrosis was discovered simultaneously in the mother and fetus. At birth, the child was perfectly normal and subsequently showed no clinical or laboratory disorder apart from diffuse osseous condensation. The genetic enquiry proved difficult owing to the family situation and up to this day it is not complete and definitively stopped. Although the beginning of the osseous disorders starts in the fetus on an average at the 4th to 5th month of pregnancy, Albers-Schonberg disease is exceptionally diagnosed during the parenatal period. In fact, the incidence of osteopetrosis in the population remains low and on the other hand prenatal radiological examinations are sparingly requested for specific clinical indications. It is the simultaneous discovery of the condition in the mother and the fetus which makes this case a novel one. The discovery of the fetal involvement does not permit prediction concerning progress towards a benign or malignant form.


Neutrophil and rheumatoid factor-Immunoglobulin G insoluble complex interactions: phagocytosis and sequelae. Studies utilizing 51CrCl3 labelled human immunoglobulin G have demonstrated a quantitative, time-related increase in the uptake of insoluble rheumatoid factor-immunoglobulin G complexes by human neutrophils. A burst of hexose monophosphate shunt activity occurs when these complexes are phagocytized by neutrophils as evidenced by the increased oxidation of glucose-l-14C to 14CO2. Metabolic and electron micrographic studies suggest that a heat stable serum factor is needed for maximum complex uptake and shunt activity. Phagocytosis of complexes did not affect the adherence of neutrophils to nylon fiber columns, but did not produce selective release of lysosomal enzymes. This study has delineated in an in vitro system, functional and metabolic sequelae of neutrophil phagocytosis of insoluble rheumatoid factor-immunoglobulin G complexes, which may be important components of the inflammation occurring in the joints of patients with rheumatoid arthritis.


Impaired blastogenic response of lymphocytes from synovial fluid and peripheral blood of patients with rheumatoid arthritis. Synovial fluid lymphocytes from patients with rheumatoid arthritis demonstrated a markedly diminished blastogenic response to both phytohemagglutinin and pokeweed mitogens, when compared to normal peripheral blood lymphocytes. The blastogenic response to rheumatoid peripheral blood lymphocytes to both mitogens was also depressed, when compared to the response of normal lymphocytes, but the difference was less marked and was within limits which could be accounted for by recent salicylate therapy. Lymphocytes of both peripheral blood and synovial fluid of rheumatoid patients showed a delayed response to PHA (five days to achieve maximum thymidine incorporation vs four days for normals).


Septic arthritis in patients with rheumatoid disease: a still underdiagnosed complication. Eight cases of septic arthritis occurring in patients with rheumatoid arthritis are reviewed. The difficulty in diagnosis of this condition is due in part to a failure of these patients to respond normally to infection. Consequently patients often present late in the course of their septic episode and treatment is often delayed. The importance of early diagnosis and treatment of the infection is stressed by the high mortality rate in this group of patients. Many factors operate to encourage infection in rheumatoid arthritis and the current concepts of the problem are reviewed.


Demonstration of articular effusions and popliteal cysts with ultrasound. Echography has been employed in 10 patients with knee effusions and in two patients with Baker's cysts. In all instances, echography clearly identified the effusions. In four patients, the presence of connective tissue septa were also shown. This technique appears to be preferred to arthrography or the intra-articular injection of isotopes. Nevertheless, echography provides only "morphologic" information which complements other methods of investigation.


Azathioprine in the treatment of chronic polyarthritis: longterm results and adverse effects in 25 patients. Azathioprine was administered to 25 patients with severe, progressive polyarthritis in a mean dose of 1.4 mg/kg daily. Synovitis improved in 12 patients. Psoriasis and vasculitis were also ameliorated. The therapeutic response did not correlate with dose, concomitant steroid therapy or leukopenia, the latter occurring in nine patients. Carcinoma developed in two patients, after four and nine months of treatment respectively. Low dose azathioprine therapy may be useful in the management of some patients with refractory polyarthritis, but the unsettled issue of oncogenesis requires further investigation.


Immunopathology of penicillamine-induced glomerular disease. Four patients with rheumatoid arthritis developed heavy proteinuria after five to 12 months of treatment with D-penicillamine. Light microscopy of renal biopsy samples showed minimal glomerular capillary wall thickening and mesangial matrix increase, or no departure from normal. Electron microscopy, however, revealed subepithelial electron-dense deposits, fusion of epithelial cell foot processes, and evidence of mesangial cell hyperactivity. Immunofluorescence microscopy demonstrated granular capillary wall deposits of IgG and C3. The findings were similar to those in early membranous glomerulonephritis, differences being observed however in the results of staining for the early-acting complement components C1q and C4. It is tentatively concluded that complement was activated by the classical pathway.


Evaluation of a clinic education program for patients with rheumatoid arthritis. A group education program was developed for clinic patients with rheumatoid arthritis. Teaching methods used included the Arthritis Foundation's handbook, Rheumatoid Arthritis, and a lecture by a rheumatologist. The 20 patients in the study were given a multiple choice test before and after the teaching program to determine their knowledge of arthritis. Results showed group education to be an effective teaching device. It was demonstrated that patients learned from reading the handbook alone, but the combination of reading and lecture was found to be a more effective method. Correlation studies showed that prior to group education, patients had a significant knowledge of their disease which was related to native intelligence, formal education, and socio-economic status, but not to duration of disease or length of clinic attendance. This suggests that future patient education experiments should include a pre-instruction test to document prior knowledge.


The effect of levamisole on adjuvant arthritis in the rat. Levamisole (LEV), an immunostimulatory agent, was studied for its effect on adjuvant disease of the rat. The drug was administered continuously according to three schedules: (a) seven days prior to immunization with complete Freund's adjuvant (CFA); (b) simultaneously with CFA; or (c) 14 days after CFA. Control animals received CFA alone, LEV alone, or were sham treated with saline. Three weekly evaluations were made, recording the general condition, weight curves, joint scores, and volume of hind paws. Whole body radiographs were made at the end of six weeks. In all experimental groups, LEV accentuated the severity of the disease as compared to animals receiving CFA alone. Within the experimental groups, an increased severity was observed with earlier administration of LEV, although the day of disease onset was not altered. Spinal involvement was less severe with each consecutive administration of LEV. These findings suggest that LEV is effective not only in restoring an impaired cellular immune response, but also in enhancing an already activated system. It seems however, that for this stimulation the timetable of LEV administration is crucial, and that continuous therapy may result in a loss of efficiency.


The incidence of systemic lupus erythematosus in North American Indians. The annual incidence (AI) of systemic lupus erythematosus (SLE) was determined in 75 highly inbred North American Indian tribes, a total of approximately 800,000 people, during the fiscal years 1971-1975. Seventy-two of the Indian tribes had an AI of SLE which was of similar magnitude to previously published studies from Sweden, Rochester (Minn.), Alabama, New York City, and San Francisco. However, Three tribes, the Crow, Arapahoe, and Sioux Indians, had a markedly elevated AI of SLE. These three tribes share common historical, geographic, and cultural characteristics. Further, they all reside in the northern half of the United States, in states that do not receive intense sun exposure, thereby eliminating photosensitivity as a major determinant of this increased prevalence. Finally, the AI of SLE in the Sioux Indians was highest for "full-blooded" members and lowest for genetic admixtures.


Symptomatic Sjögren's syndrome in mixed connective tissue disease. Twelve of 25 patients with mixed connective tissue disease complained of xerostomia and/or ocular symptoms of keratoconjunctivitis sicca. In addition to the clinical features of mixed connective tissue disease, all 12 patients had high titers of antibody to the ribonuclease-sensitive component of the extractable nuclear antigen. Eight patients had both clinical xerostomia and keratoconjunctivitis sicca, one had keratoconjunctivitis sicca and salivary gland enlargement, while there had xerostomia but no ocular complaints. Sjörgren's syndrome was confirmed in all 12 patients by means of Schirmer's tests, Rose Bengal staining tests, salivary gland scintiscans, radionuclide excretion studies in saliva, parotid sialographies, and lip biopsies. At least three of these tests were abnormal in all patients.