[Method of isolating pure cultures of mesophilic, thermotolerant and thermophilic methane-utilizing bacteria]. The paper describes a technique for isolation of pure cultures of various physiological groups (mesophilic, thermotolerant, and thermophilic) of methylotrophs bacteria. The technique is based on the application of solid media containing simultaneously two sources of carbon: elective for the accompanying microflora and elective for the obligate methylotrophs. If the culture to be studied is inoculated into such a medium, the following colonies will be found: (1) the initial culture; (2) pure cultures of the methylotrophs; and (3) the accompanying microflora. The paper presents a scheme for isolation of pure cultures of the methylotrophs, criteria for controlling their purity, recommendations for the composition of growth media which would not inhibit the growth of the obligate methylotrophs by organic substrates. The technique may also be used for the isolation of pure cultures of other bacteria (mycobacteria, lithotrophs, etc.) which are difficult to be separated from the accompanying microflora.


Modification of normal cell surface by smooth membrane preparations from BHK-21 cells infected with Newcastle disease virus. Smooth membrane fractions were prepared from the cytoplasmic extract of BHK-21 cells infected with Newcastle disease virus (NDV). These membranes exhibited high hemagglutinating, neuraminidase, and hemolytic activity but little infectivity, suggesting that they might be precursors for viral envelope. When such membranes were adsorbed to the monolayers of uninfected BHK-21 cells at 4 degrees C and then incubated at elevated temperature for a couple of hours, the cells became highly hemadsorptive even in the presence of cycloheximide. This phenomenon occurred between 15 degrees C and 25 degrees C, and was maximal at 31 degrees C, where approximately 4 times more erythrocytes were adsorbed than to the cells incubated at 4 degrees C. Immunofluorescent staining suggested that diffusion of viral antigens might occurred rapidly over the entire surface of the cells. Cell fractions containing virions induced hemadsorption in uninfected cells, too. However, induction occurred now at 31 degrees C and was maximal at 37 degrees C, and erythrocytes appeared to be adsorbed not to the entire surface of the monolayer but restricted areas of the cells. The diffusion of viral antigens on the cell surface was not so significant under these conditions. On the basis of these findings the possible role of the membranes of the smooth endoplasmic reticulum in virus replication is discussed.


Re-evaluation of the Auxotab (Inolex) Enteric 1 System for identification of enterobacteriaceae. The improved Auxotab Enteric I System was re-evaluated and found to correlate 98% with conventional methods for the identification of Enterobacteriaceae. Possible Reasons for previous poor results with this system are discussed.


Conjugation in Escherichia coli: a study of recombination and the fate of donor DNA at the level of the zygote. We have developed an experimental system for studying concomitantly the fate of the donor DNA and the process of recombination after conjugation in Escherichia coli. We used a set of Hfr and F-strains carrying complementing lacZ mutations. Expression of the lacZ allele on the chromosomal fragment derived from the donor results in the formation of heat sensitive beta-galactosidase by complementation. By intragenic recombination between the two lacZ mutations a lacZ+ gene may be formed, and wild type beta-galactosidase will be synthesized subsequently. So the assay of heat sensitive and wild type beta-galactosidase enabled us to follow respectively the fate of the donor DNA and the recombination process. Using various recombination deficient recipient strains, we found that the donor DNA is progressively inactivated in recA, rec-34 and recH recipients, although the initial rate of expression is equivalent to that in a Rec+ recipient; no significant recombination was observed. In Rec+, recB or recG recipients there was no inactivation and recombination occurred. The kinetics of recombinant formation in the recB strain seems to differ from the wild type; in a recG recipient the recombination activity is significant, but lower than in the wild type recipient.


The regulatory nature of the phoB gene for alkaline phosphatase synthesis in Escherichia coli. Quantitative measurements of alkaline phosphatase activity in various merozygotic combinations and electrophoretic analyses of periplasmic proteins derepressed by phosphate-starvation show that phoB is a positive regulatory gene.


IS1 is involved in deletion formation in the gal region of E. coli K12. The DNA sequence IS1, which is 800 pairs long, has been shown to integrate into various bacterial and phage operons. The presence of this DNA sequence in the gal operon of E. coli K12 leads to an 30-2000 fold increase in deletion formation in the gal region as compared to wildtype. This high frequency of deletion formation is specific for IS1 and is independent of the cellular recA function. While the frequency of reversion of gal::IS1 mutations, which also is independent of recA, is not affected by the growth temperature of the cells, the formation of deletions in the gal::IS1 system is strongly dependent on the temperature of growth. Mapping experiments showed that one endpoint of the deletions in most cases is at the site of the IS1 mutation and the second endpoint seems to be at various but preferred sites. The formation of the different classes of delections observed is affected differently by the growth temperature of the cells. A model to account for these results is presented.


A new gene for ribosomal restriction in Escherichia coli. Two mutations restricting the leakiness of an amber mutant are described. They were selected without the use of streptomycin: one maps in the strA region (at 64 minutes of the current E. coli chromosomal map) but is streptomycin sensitive and the other in the threonine region (at the origin of the map), 23% cotransducible with threonine by P1.


Tetracycline-sensitive mutants of the F-like R factors R100 and R100-1. The majority of tetracycline-sensitive (Tets) mutants of R100 and R100-1 are multisite (deletion) mutants. About 50% of these are also transfer-deficient, indicating that the Tetr locus is closely linked to the transfer genes. Tet(s) mutants with single-site lesions are also described.


Antimutator activity during mitosis by a meiotic mutant of yeast. Diploids homozygous for the mutation spo7-1 do not exhibit net premeiotic DNA synthesis at 34 degrees C and are defective in commitment to recombination following exposure to sporulation medium. The spo7-1 mutation confers antimutator activity during mitosis at 34 degrees C, indicating that the SPO7 gene product is involved in both mitotic and premeiotic DNA metabolism. Strains bearing spo7-1 are slightly more sensitive to killing by ultraviolet light than the wild type but are proficient in UV induced mutation and mitotic intragenic recombination. The mitotic antimutator activity of spo7-1 is directed against a class of forward mutations known to occur more frequently during mitosis than meiosis.


Methionine biosynthesis in Saccharomyces cerevisiae. I. Genetical analysis of auxotrophic mutants. In order to analyse how many structural genes are implicated in the specific steps of the biosynthesis of methionine in Sacch. cerevisiae, a hundred mutants were studied by complementation. 21 groups were defined named MET1 to MET25. Neither recombination between independent mutants of the same complementation group nor linkage between different groups was found. Preliminary to biochemical studies, mutants of each complementation group were tested for their capacity to utilize various precursors of methionine.


A temperature sensitive nonsense mutation affecting the synthesis of a major protein of Escherichia coli K12. A temperature sensitive nonsense (TSN) mutant of E. coli K12 has been isolated in which a major bacterial protein is not synthesized at 42 degrees C. This protein is found in the parental strain at 42 degrees C and in cells rendered temperature resistant due to the insertion of a number of different nonsense suppressors or the normal allele of the mutant locus.


Extensive segments of the Escherichia coli K12 chromosome in Proteus mirabilis diploids. Various Escherichia coli K12 Hfr donors transfer at low frequency portions of the E. coli genome to Proteus mirabilis. By remating such Proteus hybrids with the same or a different E. coli Hfr strain, other genetic characters could be added to yield diploid Proteus hybrids which contained more than 30 percent of the E. coli genome. The extent of the E. coli genetic material in these unstable Proteus diploid hybrids included segments with the following selected markers: gal, lac, ara, mel, mtl, and malA. Unselected markers known to map throughout this region of the chromosome were also detected in these hybrids. Among the markers expressed in Proteus hybrids with the E. coli malA region was the receptor site for coliphage lambda. Although plaques were not seen, lambda was adsorbed by the Proteus hybrids. Examination of DNA from the various Proteus hybrids by CsCl density gradient centrifugation showed a satellite component of E. coli DNA with a size that corresponded to the extent of the E. coli genome present as determined by genetic analysis.


Scintigraphy of the orbit with 67Ga-citrate. The orbits of 50 patients with unilateral exophthalmos have been scanned with 67Ga-citrate. Of the 14 cases of malignant neoplasms in this series, only three cases did not show deposits in a characteristic manner. Some of pseudo-tumours showed patterns characteristic of malignant neoplasmas. 67Ga uptake of cavernous haemangioma was very low compared to the surrounding normal tissues.


Subtotal reconstruction of the orbit after destruction by benign tumour. We present five cases of reconstruction of the orbital walls after destruction by tumours. Treatment is based upon wide exposure through a bicoronal scalp incision and immediate reconstruction with autogenous iliac bone grafts. we do not recommend using foreign materials for reconstructing the orbit.


Subtraction angiography of the orbit.

Subtraction angiography of the orbit. The principles and techniques of subtraction angiography are described. The superimposed confusing shadows are eliminated so that the small opacified arteries and veins as well as the choroidal plexus are clearly seen. The method is useful in the diagnosis of intraocular tumours and in localizing deeply seated intraocular foreign bodies.


Alcoholism: a pharmacogenetic disorder.

Alcoholism: a pharmacogenetic disorder. Alcoholism is an extremely common psychosocial behavioral disorder for which genetic factors may play an important role. Statistical analysis of special kinds of family studies that separate inherited factors from the common family environment point strongly to genetic predisposition. This paper presents data and speculations on the genetically determined differences among population subgroups and individuals in the acute effects of ethanol ingestion, the metabolism of ethanol, the process of tolerance, physical dependence and addictability, premorbid personality features and serious complications of alcoholism in the liver and brain of the alcoholic and in the offspring of alcoholic mothers.


Genetic factors and lithium response in manic-depressive illness. The relationship between success in lithium treatment and the presence of affective illness in the families of manic-depressive patients was investigated in a double-blind study of lithium prophylaxis. Of a total of 89 outpatients who were followed for periods of up to 48 months, 43 were randomly assigned to lithium and 46 to placebo. 56% of the lithium-treated patients remained asymptomatic, as compared to 28% of the placebo patients. Of the 24 successfully treated lithium cases, 16 (66%) had at least one first-degree relative with bipolar illness, while only 4 of the 19 lithium failures (21%) had a first-degree relative with bipolar illness. No relationship was found between response to lithium and the presence of unipolar illness in the patients' families.


Genetics of monoamine oxidase.

Genetics of monoamine oxidase. Evidence for the genetic control of human MAO is now well established. The relationships of MAO activities to neuropsychiatric disorders or response to psychopharmacologic treatments are relatively unstudied. Preliminary findings from our own studies suggest that (1) blood MAO activity is a polygenically controlled trait; (2) there may be a subgroup of depressed patients with high MAO activity who are more severe symptomatically and more resistant to treatment, and (3) that men with atypical and mixed depressions respond more favorably than women to treatment with an MAO inhibitory drug.


Monoamine oxidase. Its inhibition.

Monoamine oxidase. Its inhibition. Some 50 years ago the enzyme MAO was discovered by Hare and in the early 1930s Blaschko suggested that MAO may play an important role in the catabolism of monoamines in the central nervous system. With the discovery of iproniazid as an inhibitor of MAO and its introduction as an anti-depressant, many aspects of MAO activity and biogenic amine metabolism in experimental animals and man were examined. Although many other inhibitors of MAO were discovered and used therapeutically as anti-depressants, these drugs fell into disrepute largely because of their side-effects. Furthermore, their anti-depressant properties were questioned. After some years of relative inactivity there is now a revival of interest in the functional role of MAO in the central nervous system and drugs that inhibit or stimulate its activity "specifically". The basic reason for the upsurge of interest is that the enzyme from many tissues, including the brain of animals as well as man, has been purified and characterised. The evidence that neuronal MAO exist with different substrate and inhibitor specificities has led to the suggestion that they have physiological function and that deamination of non-methylated biogenic monoamines can take place in neurons. These findings have led to the advent of new drugs (clorgyline and depranil) with "selective" inhibition of enzyme forms. Their possible usage in the chemotherapy of depressive illness should be considered seriously. Fluctuation in peripheral organs as well as brain MAO is well documented. Recently they have been associated with changes in naturally occurring steroids. Although a decrease in platelet and brain MAO activity has been reported in a number of affect disorders (schizophrenia and bipolar depression) the results of these findings have recently been questioned (20, 141). Obviously further study in this area of research discussed is badly needed.


Studies on the induction of mitotic gene conversion by ultraviolet irradiation. I. Analysis of dose-frequency relationship. The UV (270-nm) dose-frequency relationship for the induction of intragenic mitotic recombination at trp 5 locus in Saccharomyces cerevisiae was non-linear. Two parameters, alpha and a, in the proposed equation for the non-linear relationship f = (at)alpha were determined so as to fit the experimental data by the method of least squares. The analysis was extended over 5 cell stages during synchronous growth. It was found that (1) parameter alpha changed from 2.02 for unbudded small cells to 1.09 for the stage where the cell had finished the division of the nucleus, and (2) parameter a changed correspondingly from 7.25-10(-4) to 0.180-10(-4) sec-1 during the same period. One interesting outcome in this analysis was the deduction of a dose-dependent nature of relative sensitivity with respect to the stage. The determination of these two parameters enabled us to calculate dose-effect relationships beyond the limits of experimental restrictions. Such an "imaginary" relationship, calculated at an extremely low dose, revealed the existence of maximal sensitivity around the DNA synthesis period. It was further shown that this maximum would easily be masked even in the moderate dose range. Thus, we conclude that the validity of single dose comparisons is diminished unless alpha is constant regardless of the cell stage. Some considerations on the proposed parameters have been made in relation to the mechanisms of the induction of gene conversion by UV.


Studies on the induction of mitotic gene conversion by ultraviolet irradiation. II. Action spectra. Action spectra for the induction of intragenic mitotic recombination (gene conversion) at the trp 5 locus by UV are presented for three cell stages (T0, T9 and T16) taken from synchronously growing cultures of Saccharomyces cerevisiae. The spectra over the range from 230 to 300 nm were taken mostly in 5-nm steps. The peak of action spectra was significantly shifted, regardless of the stage, toward the longer wavelengths as compared with that of the absorption spectrum of DNA (258 nm) or even that of thymine (265 nm). In one extreme case (T16), the peak was shifted 17 nm from the absorption peak of DNA. Further, the spectrum changed its shape as the cell stage advanced from non-dividing (unbudded) (T0) to a dividing phase (T16). Furthermore, the induction cross section decreased by a large factor (about 40), regardless of the wavelength, in going from T0 to T16. From observations of the high photoreversibility of induced conversions, the major primary damage was thought to be pyrimidine dimers in the DNA. One plausible explanation, though not quite satisfactory from the quantitative viewpoint for these findings was that the increasing RNA during growth would screen the incident UV differentially with respect to the stage. If this explanation is correct, thymine dimers may still be considered, in spite of the shifts and deformations in the action spectra, as the major primary damage that triggers the long series of processes leading to gene conversion. Conventional methods for obtaining action spectra are discussed in comparison with the present method, which was based on sensitivity parameter a in the proposed dose (t)-frequency (f) relation, f = (at)alpha (alpha is the multiplicity parameter).


Hepatitis B immune globulin as a prophylactic measure for spouses exposed to acute type B hepatitis. Because the value of usual immune globulin preparations in preventing Type B hepatitis is doubtful, we carried out a double-blind comparison of a control human immune globulin preparation with one--identified as HBIG--that had a high concentration (442 mug per milliliter) of antibodies to surface components of hepatitis B virus. Effectiveness was tested in spouses of patients with acute Type B hepatitis. Within 150 days after injection, nine of 33 spouses in the control group had symptomatic Type B hepatitis, compared with one of 25 spouses receiving HBIG. One non-B case also occurred in the HBIG group. Five control globulin recipients had evidence of subclinical hepatitis B infection, compared with one HBIG recipient.  Thus, HBIG appeared effective in suppressing not only disease, but also infection itself. Prophylactic value has been demonstrated in persons who should now be recognized as being at exceptionally high risk.


Hepatitis B "immune" globulin: effectiveness in prevention of dialysis-associated hepatitis. A randomized, double-blind, multicenter study of hepatitis prevention by immune serum globulin with high anti-HBs titer ("hepatitis B immune globulin") was carried out among 318 new patients and 296 staff members of renal dialysis units. Three milliliters of high titer globulin, repeated at four months, was compared with equal doses of intermediate or normal titer globulin. Among staff members, the cumulative percentages developing hepatitis or HBs Ag, or both, within eight months were 6.9, 11.7, and 11.1 in the high, intermediate, and normal titer groups respectively. The lower incidence associated with high titer globulin was not significant (P greater than 0.05). However, among the patients the respective percentages were 7.9, 21.3, and 23.1 and the lower incidence in the high titer globulin group was significant.


Multiple steps in DNA recognition by restriction endonuclease from E. coli K. The process of DNA recognition by the activated form of the restriction endonuclease from E. coli K involves three enzyme-DNA complexes which can be differentiated experimentally. These are: an initial complex formed at a nonspecific site; a recognition complex involving the host specificity site; and a cleavage complex dependent on the presence of ATP.


Identification of two copies of the gene for the elongation factor EF-Tu in E. coli. Two copies of the structural gene for the elongation factor EF-Tu have been identified in Escherichia coli: one near rif and the other near str. The latter seems to belong to a single transcriptional unit together with the genes for ribosomal protein S7, S12 (str) and the elongation factor EF-G (fus).


Morphine-induced running analgesia in two strains of mice following septal lesions or modification of brain amines. Groups of two inbred strains of mice (C 57 B1/6J and DBA/2J) with septal and control lesions were tested for morphine-induced analgesia and running activity (running fit). As previously observed the effects of morphine on the running fit and analgesia were strain-dependent and a negative strain correlation was evident between the two measures in C 57 and DBA operated control mice which are characterized by different brain levels and turnover of cholinergic and adrenergic mediators. Septal lesions, which cause a reduction in the levels of acetylcholine in the brain areas which receive a cholinergikc input from the septum, anatogonized morphine analgesia in both strains while the running fit syndrome was unaffected. Pharmacological manipulation of brain catecholamines did not interfer with morphine-induced analgesia. The effacts of different pharmacological agents with interfere with noradrenaline synthesis and catecholamine oxidation were assessed in the two strains which are characterized by presence (C 57) or absence (DBA) of increased motor activity following the injection of morphine. The results argue against an exclusive association of morphine-induced motor activity with noradrenergic mechanism.


Relationship between the kidney and parathyroid hormone. This report reviews the interrelationship between the activity of the parathyroid glands and renal function. Among the topics discussed are: effects of parathyroid hormone on various aspects of renal function such as: (1) glomerular filtration rate and renal blood flow; (2) renal handling of phosphorus, calcium, magnesium, sodium and potassium; (3) renal production of 1,25-dihydroxycholecalciferol; (4) renal handling of bicarbonate and acid-base metabolism, and (5) mechanism of action of parathyroid hormone on the renal cell. Further topics include: renal metabolism of parathyroid hormone; the kidney in hyperparathyroidism, and effects of renal failure on structure and function of the parathyroid glands.


Thyroid hormone and the kidney.

Thyroid hormone and the kidney. Thyroid hormones affect both renal morphology and function. They are required for kidney growth and development, and thyroid deficiency results in decreased renal plasma flow and glomerular filtration rate and in impaired urinary concentration and dilution. Thyroid hormones also influence membrane transport and electrolyte metabolism, and alterations in mineral metabolism in hyperthyroidism frequently cause calcium nephropathy which affects renal function adversely. The kidney plays an important role in the peripheral metabolism of iodine and thyroid hormones, and thyroid function is altered in certain kidney diseases, particularly chronic renal failure. The pathogenesis of these alterations is currently under active investigation.


Kidney and adrenocortical hormones.

Kidney and adrenocortical hormones. We have presented a review of the interrelationship between the kidney and the adrenocortical steroids, aldosterone and cortisol primarily in the regulation of water and electrolyte metabolism. The presentation is divided into three parts: (1) the influence of cortisol and aldosterone on renal structure and function; (2) the effect of kidney disease on secretion and metabolism of these steroids, and (3) the role of the kidneys in the plasma clearance of these steroids and their metabolites. There is no evidence that an excess or deficit of these steroids have a direct effect on renal structure, but both are necessary to maintain normal GFR and RPF. Glucocorticoids augment renal hemodynamics in pharmacologic doses. The phenomenon of 'escape' by the kidney from the sodium-retaining effect of adrenocortical steroids is discussed in detail, as well as the ability of glucocorticoid to antagonize the sodium retaining activity of any adrenal steroid of analogue with lesser glucocorticoid noperties. It is included that the impaired water dunesis of glycocorticoid deficiency is due to the absence of the permissive action of these steroids on the kidney, augmented at times by enhanced ADH secretion in response to sustained nonosmotic stimuli. The effect of gluco and mineralocorticoids on the renal excretion of divalentions and uric acid is also discussed. While progressive chronic renal failure (CRF) does not seem to significantly after the secretion or metabolism of cortisol it is possible that CRF causes a state of chronic hyperaldosteronism that is essential to maintain normal excretion (secretion) of potassium per nephron as renal mass progressively decreases. A direct or an indirect effect of potassium ion may be responsible for the hypersecretion or aldosterone rather than the renin-angiotensin system.


Renin and the kidney.

Renin and the kidney. The factors involved in renin release have been extensively evaluated. The primary determinants are the transmural pressure at the afferent arteriole, sodium delivery to the macula densa, and the activity of the adrenergic nervous system. Other possible factors include circulating catecholamines, the serum and cerebrospinal fluid sodium concentration, serum potassium concentration, angiotensin II concentration, and antidiuretic hormone release. There is no convincing evidence that the renin-angiotensin system mediates renal autoregulation. Plasma renin activity is altered in a number of clinical settings. This parameter is elevated in most patients with cirrhosis and the nephrotic syndrome as well as in individuals with severe congestive heart failure. Despite inappropriately large weight gains, plasma renin suppresses normally with increased salt intake in edematous patients who have a normal glomerular filtration rate. The mechanisms of the alteration in the renin-angiotensin system in Bartter's syndrome is still not clear.


Insulin and the kidney.

Insulin and the kidney. Changes in renal function and structure are frequently observed in patients with diabetes mellitus. In the early phases of the disease, alterations in glomerular filtration rate, renal plasma flow, glomerular permeability and tubular capacity for glucose reabsorption occur. In the late stages of juvenile onset diabetes, renal failure is a common cause of death. For this reason, increasing attention is being paid to the possibility of long-term dialysis and renal transplantation in these patients. The kidneys play an important role in regulating insulin metabolism. The renal arteriovenous difference is approximately 30-45% and a linear relationship exists between the arterial insulin level and the renal arteriovenous concentration difference. The renal extraction of insulin is 200 ml/min in man, and it is estimated that 6-8 U are removed and degraded by the kidney in 24 h. The quantity of insulin in urine is small. However, its clearance is relatively constant over a wide range of serum concentrations and is 0.15-0.5 ml/min. The mean basal insulin excretion is 3.6 muU/mg creatinine, and a fourfold rise occurs following a glucose load. The urinary insulin values in neonates, children and patients with diabetes and renal failure are reviewed. In diabetic patients, progressive renal disease is accompanied by decreasing insulin requirements. In contrast, nondiabetic patients who develop renal failure frequently show abnormalities in carbohydrate metabolism, the commonest of which is a pseudodiabetic state.


Erythropoietin and the kidney.

Erythropoietin and the kidney. Erythropoietin is a polypeptide hormone, which is produced in response to a deficit in the delivery of oxygen to the tissues relative to their oxygen needs; although other feedback mechanisms also modulate its production. The kidneys play a major role in the elaboration of this hormone. However, the precise action of the kidney is not yet known. Diseases of the kidneys cause profound alteration in the normal regulation of erythropoiesis. Some of these are reviewed here.


Renal prostaglandins.

Renal prostaglandins. The renal prostaglandins PGS2 and PGE2 possess potent antihypertensive and vasodepressor activity. The mechanism of blood pressure lowering effect is through peripheral arteriolar dilation with a fall in total peripheral resistance. PGA unlike PGE escape degradation by the lung and thus could circulate as antihypertensive hormones. Since plasma PGA levels rise in humans on a low sodium intake, it has been postulated that the beneficial effects of a low sodium diet in some hypertensives may be the result of an increase in peripheral vasodilating PGA. Support that plasma PGA may be a regulator of systemic blood pressure is also derived from the fact a PGA-secreting renal tumor was associated with a fall in blood pressure and a rise in plasma PGA in a previously hypertensive woman. The removal of the tumor resulted in a return of blood pressure to elevated levels and a concomitant fall in PGA. Recently, a number of human patients with essential hypertension have been infused with PGA1 and PGA2. It was observed that there was an initial increase in renal blood flow, sodium and water excretion which was associated with no change in the elevated blood pressure. When blood pressure ultimately fell, there was a return of renal blood flow, sodium and water excretion to preinfusion levels. It would appear that PGA compounds act as 'ideal' antihypertensive agents since they favorably effect renal resistance, sodium and water homeostasis, plasma volume, total peripheral resistance, blood pressure and indirectly cardiac output through baroreceptor stimulation, all factors known to be important in etiology in human hypertension.


Natriuretic hormone.

Natriuretic hormone. The factors that control sodium excretion have been the subject of considerable work in recent years. The natriuresis that follows expansion of the extracellular fluid volume is mediated to a large extent by inhibition of tubular sodium reabsorption. Of the several mechanisms proposed to explain this inhibition, considerable interest has followed the suggestion that a humoral substance is released into the blood stream in response to volume expansion. The present article reviews the evidence for and against the existence of such a humoral substance (natriuretic hormone). It also discusses its proposed chemical nature and its possible site of origin in the organism as well as its mode of action.


Intention myoclonus of multiple sclerosis, its patho-anatomical basis and its stereotactic relief. The typical multiple sclerosis case considered here is especially informative from both the standpoint of its clinical course and on the basis of the autopsy findings. The foci responsible for the severe bilateral intention myoclonus of the trunk and limbs are the nerve cell losses in both red nuclei due to extensive and almost complete demyelination. Thereby the triangle of Mollaret between the red nucleus, inferior olives and dentate nucleus is involved as the patho-physiological circuit responsible for myoclonus. Stereotactic coagulation of dentato-thalamic fibres resulted in complete relief of intention myoclonus. With regard to the triggering of fresh demyelinating foci by stereotactic interventions, our point of view is as follows: Although a stereotactic operation introduces the possibility of triggering new demyelinating foci in less than 10% of the cases, such a possibility does not represent an absolute contra-indication to the stereotactic treatment of action myoclonus in multiple sclerosis, if the patient is informed accordingly.


Separation of brain-RNA by micro-electrophoresis on agarose-acrylamide gels. A simple method is described for RNA fractionation on the microscale (10(-8) to 10(-7) g). The optimal conditions for electrophoretic separation of low molecular weight RNA (4S-16S) on such a scale have been determined running a standard mixture of 4S, 5S and 16S E. coli RNAs on agarose-polyacrylamide gels at three different concentrations of acrylamide. The separations were evaluated for resolution of the different species and for linearity in the relationship between mobility and logarithm of molecular weight. A straight linear relationship and good resolution was obtained on a 3.48 per cent polyacrylamide - 0.7 per cent agarose gel. When a sample of 10(-2) O.D.U.260 of macroextracted cerebral RNA was separated on such a gel, six unusual RNA bands were detected between 5A and 18S. To find out optimal conditions for RNA fractionation in the 16S-28S range a standard mixture of 16S, 18S, 23S and 28S RNA was run on gels of three different acrylamide concentrations. The separations were again evaluated with regard to both the resolution and the linearity of the relationship between the logarithms of the molecular weights and the mobilities of the standard RNA species. A 0.7 per cent agarose - 2.5 per cent polyacrylamide gel appeared to be quite suitable with regard to both. The fractionation of a microsample of RNA macroextracted from whole rat brain is presented. We also present the fractionation of the RNA microextracted from 1 mg of the CA3 region of rat hippocampus.


Comparison of dopa decarboxylase inhibitor (carbidopa) combined with levodopa and levodopa alone in Parkinson's disease. A double-blind study comparing the effects of carbidopa and levodopa combined in a single tablet with levodopa alone was undertaken in 50 patients with Parkinson's disease. After 6 months, there was a statistically significant improvement over baseline in total score, rigidity, and tremor only in the patients randomized to carbidopa/levodopa. In addition, 40 percent of the patients treated with carbidopa/levodopa showed obvious clinical improvement (a greater than 50 percent reduction in their total score) over treatment with levodopa alone. However, after 2 years, only 20 percent continued to show this improvement. Nausea, vomiting, and anorexia developed in 56 percent of patients on levodopa but in only 27 percent of patients on carbidopa/levodopa. However, abnormal involuntary movements, observed in 48 percent of patients on levodopa, were present in 77 percent of patients on carbidopa/levodopa. Despite the increase in abnormal involuntary movements, carbidopa/levodopa is more effective than levodopa.


[T-rosette test in Wilson's disease].

[T-rosette test in Wilson's disease]. Twenty-three patients with Wilson's disease were studied. Using the rosette formation test it was found that the count of T-lymphocytes in the peripheral blood of these patients (29,77% +/- 12,58) was lower than in the control group (61,68% +/- 13,14). Using skin tests for demonstration of delayed hypersensitivity it was noted that in the group of patients the frequency of positive reaction with Candida albicans antigen was lower and these patients showed also less frequently positive reactions after DNCB immunization. The obtained results indicate that in Wilson's disease the functions of T-lymphocytes are distrubed. This may be the cause of previously observed hyperactivity of B-lymphocytes.


[Antiperistaltic esophago-jejuno-duodenostomy after total gastrectomy]. Total gastrectomy forms an essential part of surgical management of gastric carcinoma. The various operations proposed for reconstruction of the alimentary tract are reviewed, reflux oesophagitis, dehiscence of suture. Lastly, the advantages offered by oesophago-jejuno-duodenostomy are illustrated.


[Clinical experiences with the use of a new antibiotic in inflammatory diseases of surgical interest]. Therapeutic and prophylactic management of 23 adults with inflammation of surgical interest using a new antibiotic, cefalexin sodium (Glaxo). 1.5-6 g/day were administered either i.m. (2 cases) or i.v. (21 cases) for 4 to 13 days. Examinations carried out before and after treatment showed that no damage was caused to the liver, kidney or haematopoietic apparatus. The clinical pharmacokinetic data made it clear that high serum levels were reached and renal elimination of the drug was almost complete. Cepoven displayed a high therapeutic capacity in nearly all cases. Both general and local tolerance were excellent.


Antibiotic sensitivity of pathogens from infected skin lesions. One hundred and seven patients attending an accident and emergency department with infected skin lesions were studied. The commonest organisms isolated were Staph aureus and Strep pyrogenes. Routine antimicrobial sensitivity testing of bacterial isolates showed that the antibiotic most likely to be effective against the organisms isolated was a cephalosporin or a tetracycline.


The Gambee intestinal anastomosis in gynecologic surgery. The Gambee single-layer, through-and-through, catgut suture anastomosis of the gastrointestinal tract has been in use from 1969 to 1974. Sixty-four anastomoses have been performed on 56 patients with gastrointestinal involvement or pelvic malignancy. There were no operative deaths, and no patients required reoperation for correction of intestinal anastomotic leaks or rupture of the suture line. This experience suggests that the Gambee intestinal single-layer anastomosis may be useful in the management of gastrointestinal complications of pelvic surgery and malignancy.


Follicle-stimulating hormone response to luteinizing-hormone-releasing hormone in patients with hydatidiform mole. The serum concentration of immunoreactive follicle-stimulating hormone (FSH) and FSH response to synthetic luteinizing-hormone-releasing hormone (LHRH) were investigated in 9 patients with intact hydatidiform moles and 3 patients with aborted moles. The serum concentration of FSH before and after intravenous administration of 200 mug of synthetic LHRH was measured by double antibody radioimmunoassay. Serum FSH was detectable but relatively low compared with the levels seen in the follicular phase of the normal menstrual cycle in all 12 patients. Furthermore, the 12 patients did not respond, or responded subnormally, to exogenously administered LHRH, and there was no significant elevation in serum FSH levels after LHRH injection. The result of the current study is in accord with that of our previous report on the serum concentration of FSH and FSH response to synthetic LHRH during normal pregnancy. Thus, it might be concluded that the follicle-stimulating activity of the anterior pituitary is suppressed by an unknown mechanism during molar pregnancy as well as normal pregnancy.


Upper lid loading with dermis graft and levator weakening. Management of lagophthalmos due to facial palsy. A method to protect the cornea in case of lagophthalmos is presented, consisting in weighting the upper eyelid with dermis graft, combined with a weakening of the levator palpebrae. The technique is described, and the method is discussed versus other methods of upper lid loading.


Diagnostic importance of immunofluorescence in oral bullous diseases and lupus erythematosus. Immunofluorescent tests have proved to be of diagnostic importance for pemphigus, bullous pemphigoid, cicatricial pemphigoid, systemic lupus erythematosus, and discoid lupus erythematosus. Immunofluorescence test procedures, necessary specimens, and test findings have been reviewed as aids to dentists in the utilization and interpretation of these tests for the study of oral lesions.


Continued anticoagulation in oral surgery procedures. Anticoagulants are used in a number of clinical settings for the prevention and treatment of thromboembolic disease. The oral surgeon is seeing an increasing number of these anticoagulated patients with oral and dental disease. A technique is presented which minimizes the nonanticoagulated time for a patient requiring an oral surgical procedure. The technique requires hospitalization and should be used only for patients who are in danger of thromboembolism.


Clinical evaluation of the (+) isomer of mepivacaine. A human clinical study was undertaken to evaluate the effectiveness and safety of dexivacaine 2 per cent, mepivacaine 2 per cent, and mepivacaine 3 per cent. A double-blind technique was used to evaluate time of onset, duration, depth of anesthesia, and side effects. Results indicated no significant differences among the three anesthetics, except that mepivacaine 3 per cent had a significantly longer duration of soft-tissue symptoms in the mandibular block series. The few side effects noted were minimal and of no statistical significance. The evaluation of an anesthetic by the several parameters employed and especially by the over-all opinion of the anesthesia was deemed a valuable research method whem comparing the clinical effectiveness of local anesthetics.


The microbiology of musculoskeletal infection. Of paramount importance in the isolation and identification of bacteria, including mycobacteria, and fungi that cause musculoskeletal infections, are proper selection, collection, and transport of specimens. Material obtained by biopsy, curettage, or aspiration is preferable to that obtained on a swab because too little or unrepresentative material is usually collected on a swab and because swabs cannot be transported readily under conditions favorable to survival of anaerobes. Although actual infections are frequently due to staphylococci, strepococci, Enterobacteriaceae, and Pseudomonadacease, the etiologic agents of chronic lesions may include actinomycetes, brucellae, mycobacteria, and fungi. In chronic lesions, histopathologic examination of biopsy material is an important ancillary procedure. In acute infections, the incidence of gram-negative bacilli, particularly of Enterobacteriaceae and pseudomonads, has increased significantly in recent years.


Septic arthritis in children.

Septic arthritis in children. When septic arthritis involves the hip, the prognosis is much worse than with any other joint. Approximately 50 per cent of the results were unsatisfactory with hip involvement compared to 12 per cent unsatisfactory results with involvement of the other joints. The erythrocyte sedimentation rate is a much more helpful diagnostic test than the leukocyte count or differential cell count. The most important prognostic factors are the duration of symptoms prior to treatment, a penicillinase-producing organism (penicillin-resistant) as the etiologic agent, and evidence of associated metaphyseal osteomyelitis. Early decompression and cleansing of the joint by aspiration or arthrotomy are essential for a good result. Long-term parenteral antibiotic therapy improves the prognosis when osteomyelitis is an assoicated feature. Arthrotomy with continuous irrigation appears to be more effective in decreasing long-term residual effects than arthrotomy alone. Almost all secondary surgical procedures are directed toward correcting the sequelae of septic arthritis of the hip.


Surgery of the nasal tip.

Surgery of the nasal tip. Three techniques of nasal tip cartilage modifications are discussed in detail: the delivery, retroversion, and split (intracartilaginous) techniques. Ancillary procedures of the nasal tip, such as septoplasty without decreasing support, secondary surgery and post-traumatic nasal tip problems, and the rationale for various procedures are discussed.


Augmentation rhinoplasty.

Augmentation rhinoplasty. Augmentation of the depressed nasal dorsum may be accomplished in a variety of ways by utilizing a number of different implant materials. Several techniques are discussed and illustrated. Small areas of depression may be corrected with viable or nonviable cartilage or synthetic implants through an intercartilaginous incision. More extensive saddling is best augmented using either iliac bone placed subperiosteally or irradiated cartilage. When the implant is sizable or a two piece "L shaped" strut is required, placement is done through a gingivolabial sulcus incision.


Surgical stabilisation of the spine.

Surgical stabilisation of the spine. It is important to assess spinal injuries, both in terms of cord damage and column damage, shortly after the trauma has occurred. A decision should then be made concerning the eventual stability of the bony vertebral column. If a lesion is unlikely to heal soundly by bone or if one is unable to obtain a reduction by conservative measures, one should consider surgical stabilisation of the damaged spine in the subacute phase. At the same time as one stabilISES THe spine with metallic fixation, bone grafts should be added for ultimate stability. If an unstable spine is encountered in the later stages of treatment, surgical stabilisation is again indicated. Metallic fixation can greatly aid in stabilising the spine until bone grafts can mature. Osteotomies of the spine through a combined transthoracic and posterior approach can be extremely valuable in correcting deformity. While there is no role for decompressive surgery after spinal cord injury, there is still a definite role for surgery in balancing and stabilising the vertebral column.


Effect of cycloheximide on pregnenolone-16alpha-carbonitrile (PCN)-induced ultrastructural changes in the rat liver. Cycloheximide (10 mg/100 g body weight i.v. twice), an inhibitor of protein synthesis, caused smooth endoplasmic reticulum (SER) accumulation in the hepatocytes of female rats. Pregnenolone-16alpha-carbonitrile (PCN), given p.o., had a similar effect. When cycloheximide was administered to PCN-treated rats, SER proliferation as well as myelin figure formation were noted.


The multiple causes of alpha1-antitrypsin deficiency. Alpha1-antitrypsin deficiency is a genetic model that predisposes to pulmonary emphysema or a form of hepatic cirrhosis in man. The antitrypsin protein protects the tissues from proteolytic digestion by lysosomal proteases from inflammatory cells. The three causes of antitrypsin deficiency demonstrated to date are: 1) A defect in synthesis and release of the Z variant from the liver. 2) Presence of an inactive (null) gene for antitrypsin production, and 3) Increased lability of certain variants associated with the in vivo degradation of antitrypsin.


Further examples confirming the existence of Pi null (Pi-). The existence of the Pi- allele (Pi null) was envisaged by Talamo when he discovered a subject whose serum contained no alpha-1-antitrypsin. We were able to demonstrate that a single dose of this allele exists in three families which we studied. In a fourth family, the propositus carried this allele in duplicate (phenotype Pi- -), which agrees with the results of the quantitative analyses carried out on the parents. The importance of the Pi- allele is envisaged and the necessity of the genetic survey is generally essential to demonstrate its existence.


[Phenotype Pi and alpha 1 antitrypsin deficiency in types A and B chronic obstructive bronchopneumopathies]. The authors studied 79 patients with chronic obstructive lung disease. (COLD) (FEV1/VC less than 70%). Patients with chronic asthma were excluded from the series. These patients with COLD were divided up into 2 groups, depending on radiological and clinical criteria: (1) Type A, primary emphysema, 24 patients; (2) Type B, chronic bronchitis, 49 patients. 6 patients of type X (intermediate type) were excluded. Their respiratory function tests were studied together with clinical and radiological findings and blood gases. Furthermore, were studied in each patient, the antitrypsic activity and the serum concentrations of alpha-1-antitrypsin and phenotype Pi. Group A were, on average, more obstructive than group B. The ratio FEV1/VC was 31% +/- 7% in group A, against 46% +/- 13% in group B. The serum antitrypsin activity and the serum concentration in alpha-1-AT were on average close to normal in both groups. However, group A was divided up into two populations: a small population with a low concentration of alpha-1-AT, and a large population with normal alpha-1-AT. A study of the incidence of various phenotypes in groups A and B showed a significantly higher frequency of phenotype ZZ in group A (12.5%) than in group B (10%). All ZZ subjects were of clinical type A. There was no significant difference in the incidence of other phenotypes encountered. Serum alpha-1-antitrypsin concentration was very low in 3 ZZ patients. One case with phenotype SZ and one MM showed intermediate levels. The authors emphasize the low percentage of cases of pulmonary emphysema which may be explained by an alpha-1-antitrypsin deficiency. Nevertheless, this preliminary report should be completed by a study of a larger sample of patients with COLD with control of the phenotype.


[Study on the relationship between serum alpha 1 antitrypsin level, the phenotype Pi and various bronchopulmonary diseases]. The authors determined in 418 adults, males and females, admitted to hospital on the Respiratory Unit of the Montpellier University Hospital, the serum levels of alpha-1-antitrypsin, phenotype Pi and serum immunoglobulin levels. They compare these data together and with the diagnosis using a mathematical method known as factorial correspondence analysis.


Human blood platelet elastase and proelastase. Platelet elastase has been differenciated from various protein fractions into a trypsin dependent form and a trypsin independent form. Trypsin independent elastase has been purified by affinity chromatography on cellulose elastin column as a pure protein raction of molecular weight: 26,000 ou SDS acrylamide gels. Trypsin dependent elastase has been purified by preparative acrylamide disc gel electrophoresis. This fraction, proteolysed (limited proteolysis) and activated by trypsin into active elastase, has been identified as the precursor (platelet proelastase) of platelet elastase. Its molecular weight is 28,000 before trypsin and 26,000 after trypsin.


[Coupled use of chromatography and acrylamide-agarose gel electrophoresis in the study of polymeric forms of paraproteins]. A study of the physical properties of paraprotein required until now, the use of fairly complicated techniques, such as analytical ultracentrifugation. The use of chromatography on acrylamide agar pearls and electrophoresis on indubiose plates, coupled with the classical techniques of electrophoresis and immunoelectrophoresis, permitted a more simple approach to these problems. The study of IgA paraproteins in several polymerised forms, is an example of the possibilities of this new method of investigation.


[Blood stock management by computers in a transfusion center]. In large blood Transfusion Centers, blood stock management is quite difficult because of the numerous daily movements, the short storage time of blood products, the multiplicity of sample types, and, indeed, of blood antigens, etc. A data processing system has been established in the Blood Transfusion Center ofLille (170 000 bottles a year). From information codified in collection and in distribution departments, the computer is able to give to the authorities essential daily decision elements such as the knowledge of :--the exact profile of each collection (1 119 in 1974),--statistics of blood distributions,--available stock, classified by storage time, volume, blood group, etc. The computer contribution from the security point of view, as well as its utilization in phenotyped blood research is described here.


[Value and duration of the bone localization of gallium in the mouse]. Gallium was administered subcutaneously to mice, and was found to be localized essentially in the skeleton. It was measured in the bones of animals given daily injections of gallium sulfate. There was little or no mortality. The amount of gallium found rose with the number of injections, and was greater when higher doses were injected. Elimination was very low after cessation of treatment. Results were used to study the action of gallium on cutaneous allografts in mice.


[Comparison of blood sugar measured by Hoffman's, glucose oxidase and dextrostix technics during the oral glucose tolerance test]. The venous blood sugar has been measured in 384 adult subjects, between 20 and 60 years if agem during two oral glocose tolerance tests, with three methods: Hoffman's method, Glucose-oxidase method, and assay with reflectance meter (DRM). A good correlation was found with all methods (erg = 0,6 at 60 mn after load); however, the results given by the DRM were lower. So, in spite of its practical and economical advantages, the DRM can neverbe used for the diagnosis of an anomaly in the OGTT results. This method is a good one in emergency situations and in mass screening for diabetes.


[Normal ultrastructure of the small bronchi and bronchioli in man]. Ultrastructural topographic and morphological analysis of the small bronchi and bronchioli was carried out on selected biopsy specimens obtained from 6 operative specimens. The small bronchi had a ciliated cylindrical epithelium identical to that in the large bronchi, apart from a smaller number of goblet cells. Their reticulin layer was thin (1 to 3 microns). The glands in the submucosa were rare whereas there was a rich submucosal vascular network. The lobular bronchioli had a ciliated cylindrical epithelium without goblet cells but possessing rare Clara cells. The epithelium of the terminal bromchioli was characterized by: 1 - The presence of numerous Clara cells, generally grouped in groups of 2 or 3. 2 - The appearance on the opposite side of a satellite artery (this side shows alveoli first) of cells which we interpreted as pre-ciliated cells. These cells possess a range of basal corpuscles under the luminal membrane but do not have cilia. 3 - The appearance of small membranous pneumocytes in islets. The epithelium covering the smooth wall of the respiratory bronchioles still have a gutter of ciliated cells and Clara cells which become thinner towards the periphery. After the secondary respiratory bronchioli, there appears in this gutter a new cell type, the cubical cells. These cells which have poorly differentiated cytoplasmic characteristics, seem to us to be immature bronchial cells, precursors of the Clara cells rather than of the ciliated cells. The remainder of the smooth wall of the respiratory bronchioli is covered with membranous pneumocytes and, in the case of the 3rd order of bronchioli, also by granular pneumocytes. The sub-basal reticulin layer is lacking in the terminal and respiratory bronchioli. The total thickness of the wall becomes considerably thinner, the muscular layer becoming proportionally very thick.


[Histiocytosis X. Histochemical study of intracytoplasmic lipids. Apropos of 3 cases]. Histochemical study combined with differential extractions of lipids from biopsy fragments in three cases of eosinophil granuloma reveals a great amount and variety of lipidic categories existing in histiocytosis X cells : sterids, fatty-acids, triacylglycerols, phosphoglycerids, cholino-phospholipids, sphingomyelins, glycolipids. Comparison of the lipidic content of histiocytosis X cells and that of normal histiocytes, showed a preponderance of cholesterol esters in histiocytosis X contrary to the normal macrophages and alteration in phospholipidic control of cholesterol esterification. This study confirms that the histiocytosis X cells have an active and probably preferential lipid metabolism, explaining the frequent xanthomatous changes of the lesions and the intense production of various cytoplasmic membranous structures.


[Automation of extraction in the determination of blood triglyceride]. A complete automation of the determination of triglycerides is described which replaces the manual extraction and the final determination with an autoanalyzer chain, based on the method of Royer et al. For the automation of triglyceride extraction, we have modified the sampler, by incorporating a magnetic stirrer under the sample table. The sample table has two rows of holes. The sera, which are taken from the inner row and diluted with sulphuric acid, are reacted quantitatively with the extraction reagent in the beakers of the outer row, which contain a magnetic follower. After stirring, the upper phase is quantitatively removed and the determination is started. The problem of phasing the individual steps of the analysis is thus solved.


Peripheral nervous system involvement in experimental tuberculosis. Following intravenous injection of mycobacteria in the mouse the bacilli are regularly found in the peripheral nervous system after the 5th day. The peripheral nerves and autonomic ganglia are involved at the level of the perineural cells and the sheath of Schwann. When the organisms are of low virulence (BCG, Mycobacterium intracellulare) the development of the nodules is limited. In the case of a virulent strain (Ravenel) extensive granulomas are found but epitheloid cells, always found in other organs, are constantly absent. In animals previously immunized, the bacilli seem to implant themselves as in the controls, but multiply more slowly; the nodules are more infrequent and the lymphoid infiltration appears earlier with the multiplication of interstitial cells.


Inhibition of HBsAg immunologic reactivity and intestinal aerobic flora. Cultures of human intestinal aerobic flora did not have any inhibiting action on the immunologic reactivity of hepatitis B antigen even after disruption of bacterial cells by freezing and thawing. This suggests that the inhibitor is elaborated by the human intestinal mucosa.


Cells involved in the immune response. XXIX Establishment of optimal conditions for the primary and secondary immune responses by rabbit lymphoid cells in vitro. Attempts were made to initiate the primary and secondary humoral immune responses to sheep red blood cells (SRBC) in vitro as determined by the hemolytic plaque-forming cell (PFC) response, with cell suspensions prepared from a variety of lymphoid organs of the rabbit- thymus, bone marrow, spleen, appendix, sacculus rotundus, Peyer's patches, popliteal lymph node and circulating leukocytes. A number of different media and gaseous phases were utilized in order to establish the optimal conditions for the immune response in vitro. The induction of a secondary PFC response was consistently obtained with 'memory' spleen cells obtained from rabbits 3-6 months following intravenous immunization with SRBC but not with cells of any of the other lymphoid organs, and this response probably represents the activity of memory cells which reside in the rabbit spleen. A primary response was observed only with 'normal' spleen cells, and the medium which faciliated the response was different from that which facilitated the induction of the secondary response in vitro. It was also observed, using a medium in which normal spleen cells were incapable of generating PFC', that mixed cultures of normal spleen and normal appendix or bone marrow cells could give a marked PFC reponse in vitro. Whether the PFC response to SRBCs obtained with the lymphoid cells of normal, unimmunized rabbits represent a true primary response, a  secondary response, or a response of a different nature as a consequence of continuous subthreshold immunization of the rabbit with enteric microorganisms which cross-react with the antigen, remains to be determined. However, out initial successes with cultures consisting of cells of at least two distinct lymphoid organs in cases where the cells of any one of these organs could not respond, suggest that interaction of at least two functionally distinct cells is required and that the repsonse observed in vitro is probably a primary immune response.


Pathologist and histotechnologist: a marriage in need of counseling. The general level of histotechnology in this country is alarmingly low. Surgical pathology, a difficult field, is made doubly so by poorly prepared sections. The blame for this must rest in part on the pathologist because of his ignorance of histologic procedures, his acceptance of shoddy work, and his lack of interest in seeing that bright young people are enticed into the field and that adequate training facilities and career opportunities are available to them. Today we are asked to perform increasingly complex procedures, and if we are to meet this challenge, as well as perform our duties in pathologic anatomy to the best of our ability, it is essential that we rapidly change our attitude.


Pathogenesis of teratoid tumors of the ovary and testis. Based upon a representative sample of testicular tumors studied at the Armed Forces Institute of Pathology, several testicular and ovarian tumors observed in Denver, pertinent papers in the literature, and the singular thesis of Chevassu on tumors of the testis, the pathogenesis of such neoplasms is elaborated. The findings are philosophical, speculative, and established. Man is a multicellular individual to be regarded as a vehicle for the transmission of unicellular organisms or germ cells from one generation to the next. These cells remain distinct from somatic and trophoblastic cells. The mature human female not only tolerates the normal expression of the fertilized ovum during pregnancy (sex cells, blastoderm, and trophoblast) but also seems capable of greater differentiation of immature somatic cells resulting from parthenogenesis of one or more ova into cells of the three germ layers, as well as the suppression of the growth of neoplastic sex cells and trophoblast cells, with benign cystic teratoma as the most common culmination. The preponderance of malignant teratoid tumors before sexual maturity is a corollary. In contrast, the human male is not equipped with organizers postulated for the human female and thus is unable to differentiate malignant immature somatic cells, the most common cancerous element in testicular tumors. The explanation for such neoplasms must be on the basis of segregation of such cells and abnormal spermatogonia or less often trophoblastic cells in the embryo, with later expression as neoplastic cells, since spermatogonia and progeny are unable to form a new individual. To paraphrase Wilms, the statement may be made that malignant testicular and ovarian tumors of teratoid type are related, despite their different microscopic appearance, to a common form. They differ only in the quality, not in the quantity, of the different tissues comprising them. These tumors contain neoplastic blastodermic cells and differentiated cells of the three germ layers, neoplastic sex cells, and neoplastic trophoblastic cells. The cells of these tumors and the tissues they form resemble very nearly the tissues of the human embryo with nonaxial formation of alimentary and respiratory structures in many instances. The notable frequency of variably differentiated neural elements in the teratoids tumors of the ovary is in sharp contrast to their uncommon occurrence in like tumors of the testis. Dysgenesis of the ovaries and the testes of testicular feminization syndrome should be regarded as likely soil for the development of teratoid tumors.


Idiopathic arterial calcification of infancy: a clinicopathologic study. The clinical and pathologic features of a group of 62 infants dying of idiopathic calcific arterial disease were reviewed. The disease most commonly occurs in infants less than 6 months of age. Pathologically, it is characterized by calcific deposits along the internal elastic membrane of arteries accompanied by fibrous thickening of the intima which causes luminal narrowing. The arterial lesions are widespread but the resultant luminal narrowing invariably promotes myocardial ischemia, causing the infants' deaths. A definite tendency of the disease to occur in siblings has been noted, but additional patterns of inheritance are not yet apparent. Clinical diagnosis is feasible with radiologic study of arteries of the head, neck, and extremities. There is a similarity of idiopathic calcific arterial disease of infancy to the arterial lesions of metastatic calcification in severe renal disease, calcific arterial lesions noted in conjunction with certain cardiovascular anomalies, and hypervitaminosis D. Certain experimental situations and toxic states can also produce calcific and proliferative vascular lesions.


Management problems of mentally retarded children and their families. Pediatricians faced with the difficult task of providing management services to mentally retarded children and their families are confronted with a number of difficult problems. These range all the way from deciding how to inform parents that their child is retarded to dealing with grandparents who are a source of stress. Successful handling of these problems requires a recognition that management is central to the care of the mentally retarded child. The needs of mentally retarded children and their families will not be met by interacting with families only around issues of acute physical illness. Attention must be directed toward psychosocial as well as medical variables and the emphasis must be on the total family system.


Common sexual problems of children and adolescents. The pediatrician is often expected by families to deal with sexual problems of children and adolescents. The physician should be able to identify problems and to guide parents in more meaningful communication and education of their children. Hopefully, he will be able to identify family conflicts and make the appropriate intervention or referral. He should be aware of his own sexual attitudes so as to avoid having his bias interfere with treatment. The childs behavior should not be isolated, but considered in the context of his family, his peers, and his own growth and development. Often, it is more useful to advise the family than to work with a young child. Adolescents present particular problems because of their conflicts over sexual identity, their reluctance to admit to problems, and frequently a mistrust of adults. They often feel a need for a trusting relationship with an adult, however, and are able to relate to a sensitive, non-judgmental professional.


Symposium on behavioral pediatrics. Juvenile delinquency. The pediatrician's first step in responding to delinquent behavior is to make a differential diagnosis between sociological, characterological and neurotic delinquency. Sociological delinquency consists of subculturally sanctioned illegal activity by youngsters who are psychologically well-adjusted members of their peer group, and its treatment depends primarily on prevention through social action programs rather than on the intervention of the clinical practitioner. Characterological delinquency reflects a serious and long-standing personality disorder marked by aggressive and impulsive behavior and a lack of attachment to or consideration for others, and its treatment requires extensive psychotherapy, often in a residential setting. Neurotic delinquency involves uncharacteristic misbehavior of recent origin that represents an attempt to communicate unrecognized needs for attention or help, and it can often be treated effectively with short-term psychotherapy.


Decreased bactericidal activity of leukocytes of stressed newborn infants. Previous studies have established that leukocyte phagocytosis and intracellular killing are normal in term and low-birthweight newborns who are well. To determine the effect of stress or illness on newborn leukocyte function, the phagocytic and bactericidal activity of leukocytes from 40 sick newborns was compared with that of leukocytes from 12 newborns and 23 normal adults. To eliminate abnormal phagocytosis resulting from serum opsonic defects in newborn sera, pooled adult sera were used in all assays. Twenty-five of the 40 stressed newborns (63%) had decreased in vitro activity against either Staphylococcus aureus 502A or Escherichia coli, or both, compared with decreased activity in two of 12 well infants (17%) and in four of 23 adult controls (17%). The mean bactericidal activity (percentage of organisms killed after two hours) of leukocytes from stressed newborns against S. aureus (83% +/- 2 [SEM]) and E. coli. (87% +/- 4 [SEM]) was significantly less than in the combined well infant and adult control group (94% +/- 1 for S. aureus and 97% +/- .5 for E. coli). Although the more severely ill infants had an increased incidence of impaired antibacterial activity, the degree of impairment was not related to the severity of illness. No consistent relationship of decreased activity to birthweight, gestational age, age when studied, or specific diagnosis was seen. The leukocyte abnormality in stressed infants against S. aureus was principally a killing defect, while against E. coli both phagocytosis and killing were abnormal. This study indicates that a wide variety of neonatal disorders may affect one or more of the steps required for normal bacterial killing. The lability of leukocytic antibacterial function under stress is an additional mechanism for the newborn's increased susceptibility to infection.


Human figure drawing characteristics related to juvenile delinquents. Human figure drawings were scored on seven characteristics popularly attributed to juvenile delinquents, i.e., head size, shading, and three indicators of emotional conflict, i.e., transparencies, omissions, and erasures. Ss were adolescents incarcerated at training schools. Delinquency was defined in terms of MMPI profiles associated with delinquency rather than by social-legal or medical-diagnostic classification. The results fail to support popular hypotheses concerning human figure drawings of delinquents. Delinquents drew significantly more transparencies; however, no other emotional indicator was significant. It was concluded that little support exists for hypotheses concerning human figure drawings of delinquents and drawings should be used with caution in the clinical assessment of a delinquent's personality.


Sleep during Transcendental Meditation.

Sleep during Transcendental Meditation. Electroencephalograms (EEGs) and DC electrooculograms (EOGs) were recorded during Transcendental Meditation periods for 8 experienced Ss. The records, scored blind showed that all but 2 Ss spent considerable portions of their meditation periods in unambiguous physiological sleep.


A new method for toilet training developmentally disabled children. 20 profoundly retarded children (4 to 12 yr.) were trained, using a variety of relaxation and tension activities designed to help them differentiate and gain control of the toileting musculature. Operant techniques were used to reinforce appropriate urination. The post-training scores of the experimental and control groups differed significantly for both accidental and appropriate urination.


Prostaglandin induced parturition in swine with some aspects on prevention of the MMA (metritis, mastitis, agalactia) syndrome. The effect of PGF2alpha to induce parturition in sows was studied in two herds. In one herd with a total number of 150 sows and with a good health status 12 sows were injected intramuscularly with 12.5 mg PGF2alpha during late pregnancy (110--114 days). During the same period 12 sows were treated intramuscularly with saline solution at corresponding gestation stage. The results are given in Tables I and II. The mean age calculated as number of litters was 2.6 in the experimental group and 4.3 in the control group. All sows treated with PGF2alpha farrowed within 30 hours after injection at an average time of 25.4 hours. The controls farrowed at an average 80.2 hours after injection. The mean farrowing time was 4.4 hours for the PG-treated sows while the corresponding figure for the controls was 6.6 hours. The litter size at birth, after 3 weeks and at weaning was somewhat higher in the experimental group. The same applies to the litter weight at the age of 3 weeks. The course of parturition was normal in all sows and the health condition during lactation was good. In another herd -- numbering 18 sows -- all sows which hade farrowed during the last 4 months before the present investigation, had developed the Mastitis-Metritis-Agalactia syndrome (MMA). The symptoms were a prolonged gestation length (116--117 days), fever, mastitis and agalactia. During the present study 3 sows were left untreated while 5 sows were given an intramuscular injection with 12.5 mg PGF2alpha during late pregnancy (112--114 days). Four of the five PG-treated sows farrowed within 32 hours, while the fifth sow farrowed 100 hours after injection. The sow not responding to the PG-treatment and the untreated sows all developed MMA while the four sows responding to treatment remained healthy. The gestation length in treated sows responding to treatment was 113--115 days. In the sows developing MMA the gestation length was 116--117 days. The potential effect for prevention of MMA of shortening the gestation length in this herd is discussed.


[Immunofluorescence study of bacteriuria. A new technic for the localization of urinary infection]. The detection by immunofluorescence of immunoglobulins fixed to the wall of urinary bacteria makes it possible to localise the site of the urinary infection. The presence of immunoglobulins was noted in 18 out of 19 patients with a high urinary tract infection involving the renal parenchyma. They were absent in 25 out of 28 subjects with a lower urinary tract infection. The three apparently discordant positive reaction involved 1 case of prostatitis and two cases in which the diagnosis of pyelonephritis was made later. In the case of renal involvement, these immunoglobulins, essentially IgG, are seen with greater frequency than humoral antibodies. Whilst the biological significance of these immunoglobulins remains uncertain, their existence probably being a reflection of parenchymatous inflammation, this nevertheless is a new and, apparently, reliable, method for the determination of the site of an infective process.


[Surgical treatment of the non suppurated sacrococcygeal cyst. Technical improvements]. Some justified technical improvements have been made to the method of treatment for non-infected and sacro-coccygienally located "pilo-nidal". The absence of tension due to the use of a rotational autoplasty and the drying of the residual cavity by an efficient aspirative drainage are the means essentially employed.


[Treatment of arteriovenous fistulas and of aneurysms using an inflatable and releasable balloon. Experimental principles. Application to man]. The authors have perfected a technique making possible the percutaneous introduction of a balloon filled with hydrosoluble iodine and releasable, either in an arteriovenous fistula or in an aneurysm. Experimental jugulo-carotid fistulae and experimental aneurysms in the dog were treated in this way. The technique has been used in two human patients - one with a traumatic caverno-carotid fistula and the other with a complicated vertebral fistula.


[Current problems of data processing in clinical nuclear medicine. Symposium of Rhine-Westphalian Society for Nuclear Medicine in Bonn, Dezember 7, 1974]. Practical aspects of the use of computer systems in Nuclear Medicine were discussed in a symposium sponsored by the "Rheinisch-Westfälische Gesellschaft für Nuklearmedizin" which was held at Bonn in December '74. In the opening session the president of the Society, Prof. Winkler (Bonn), gave a brief survey upon the development of data processing procedures for radionuclide diagnostics. He pointed out that at present computer application is not only of essential significance for camera scintigraphy but also for most of the other test methods as well as for the solution of organizing problems when running departments of Nuclear Medicine. For the performance of all these tasks and also for scientific purposes a special process control computer system has been developed in the Institute of Nuclear Medicine at the University of Bonn. A detailed description of this system was given by R. Knopp (Bonn). He emphasized in his paper that the rather bulky Bonn System, which consists of a dual computer (Siemens 305/306) and an extensive operating system, can not be regarded as a standard device for routine use in hospitals. However, on the basis of experiences which have been gathered on hand of the research system in Bonn efforts are in full activity for developing a compact Nuclear Medicine Computer system (CNMCS) suitable for the application within departments of any size. The CNMCS (which will be commercially available in the near future) is based on a 64 K, 16 bit central unit with a highly flexible operating system which permits a simultaneous multi user application of the computer. For CNMCS a comprehensive user software package will be at the clinician's disposal which can be easily handled.


A chemical approach to studies of the three-dimensional structure of tRNA - alkylation with a reagent covalently bound to a "peculiar site'. Yeast valine tRNA1 was chemically modified with chlorambucil N-hydroxysuccinimide ester. tthe reagent was attached covalently to the valine residue of valyl-tRNA1Val under the conditions which prevented tRNA from alkylation. Chlorambucilyl-valyl-tRNA1Val thus obtained was separated from excess reagent and incubated in an aqueous solution at neutral pH in the presence of Mg++ions. Highly efficient intramolecular self-alkylation of chlorambucilyl-valyl-tRNA1Val took place. The chlorambucil residue bound covalently to the amino group of the valine residue of tRNA1Val alkylates the 5'-terminal phosphate group of the molecule, and its 3'-terminal sequence -A-C-C-A.


A model for chromatin structure.

A model for chromatin structure. A model for chromatin structure is presented. (a) Each of four histone species, H2A (IIbl or f2a2), H2B (IIb2 or f2b), H3 (III or f3) and H4 (IV or f2al) can form a parallel dimer. (b) These dimers can form two tetramers, (H2A)2(H2b)2 and (H3)2(H4)2. (C) These two tetramers bind a segment of DNA and condense it into a "C" segments. (d) The adjacent segments, termed extended or "E" segments, are bound by histone H1 (I or fl) for the major fraction of chromatin; the other "E" regions can be either bound by non-histone proteins or free of protein binding. (e) The binding of histones causes a structural distortion of the DNA which, depending upon the external conditions, may generate the formation of either an  open structure with a heterogeneous and non-uniform supercoil or a compact structure with a string of beads. The model is supported by experimental data on histone-histone interaction, histone-DNA interaction and histone subunit-DNA interaction.


Specificity of deoxyribonucleic acid transmethylase induced by bacteriophage T2. I. Nucleotide sequences isolated from tmicrococcus luteus DNA methylated in vitro. (Deoxyribonucleic acid from Micrococcus luteus was methylated in vitro in the presence of S-adenosyl-(14C methyl)methionine with a DNA methyltransferase purified from extracts of te. coli infected with bacteriophage T2. The labelled DNA was degraded by enzymatic and specific chemical methods and the resulting short oligonucleotides were separated and characterized. tthe analytical data permit the conclusion that the tdna transmethylase reacts specifically with N-G-A-T-C-N sequences in which it converts adenine to a 6-methyl-aminopurine residue.


tRNA tertiary structure in solution as probed by the photochemically induced 8-13 cross-link. The conformation of ten purified tRNAs from Escherichia Coli has been investigated by means of the photo-induced cross-linking of 4Srd8 and Cyd13, which is sensitive to the juxtaposition of the two bases. Three tRNAs photo-react abnormally slowly; tRNAPhe, tRNAMet/m a and tRNAVal/2; a comparison with normally reacting species suggests that base 47 (Urd or modified Urd) is involved in a tertiary interaction in Class I tRNAs with the triplet 8, 14, 28. The UGA suppressor tRNATrp photoreacts significantly slower than the wild type. Thus the single base change Gua 24 to Ade induces a conformational change that alters the rate constant for the cross-linking reaction.


Utilization of an Escherichia coli mutant for carbon-13 enrichment of tRNA for NMR studies. The enrichment of tRNA at specific sites with carbon-13 has been accomplished in vivo using a mutant of Escherichia coli. A relaxed strain of E. coli auxotrophic for methionine was grown in a specifically defined medium supplemented with either [14C] or [13C]-methyl labeled methionine. Cells were collected at the end of the log-phase of growth and tRNA was extracted. Analysis of the radioactivity of the [14C]-labeled tRNA established an incorporation ratio of three labeled carbons per tRNA molecule. Incorporation of the [14C]-label in vivo was confined to the methylation of nucleotides as determined by thin layer chromatography of nucleotides resulting from a ribonuclease digestion of [14C]-labeled tRNA. The carbon-13 NMR spectrum of [13C]-enriched tRNA indicated a similar degree of incorporation into the methylated nucleotides by the substantial enhancement of [13C]-methyl NMR signals only. Assignment of signals has been made for the methyl groups of ribothymidine and N7-methylguanosine in E. coli tRNA.


Misincorporation of (TP during transcription of poly dAT-dAT and poly dABU-dABU. The synthetic DNA alternating copolymers poly dAT-dAT and dABU-dABU have been transcribed with E. coli RNA polymerase to measure the level of BrdU-induced misincorporation of guanine during transcription. GTP is found to be misincorporated into both copolymers at a frequency of 1 per 1000-2000 nucleotides polymerized. Using alpha-32P-GTP, the nearest neighbors to GMP are found to be UMP (approximately 63%), GMP (approximately 25%) and AMP (approximately 17%), with no apparent difference between the two templates. These results suggest that BrdU-substitution in DNA does not necessarily increase the potential for base mispairing during transcription, and hence, promote the production of faulty RNA molecules.


Analysis by isopycnic centrifugation of isolated nucleoids of Escherichia coli. The isolated, formaldehyde-fixed nucleoid of E. coli has been analyzed by isopycnic centrifugation in CsCl density gradients. The membrane-free nucleoid bands at a density of 1.69 +/- 0.02 g/cm3. The membrane-associated nucleoid bands at a density of 1.46 +/- 0.02 g/cm3. Both species sediment to equilibrium as nearly monodisperse bands in CsCl, suggesting that the nucleoid components of DNA, RNA and protein are present in relatively constant ratios. These ratios are constant regardless of the position of the nucleoids in the heterogeneous sedimentation profile of a preparative sucrose gradient. The fixed nucleoids remain condensed during isopycnic centrifugation and there is no detectable loss of RNA from the nucleoid.


RNA nicking activity associated with DNA ligase of T4 infected E. coli: properties and influence on in vitro reactions of ligase. Highly purified DNA ligase from T4 infected E. coli displays an RNA nicking activity which cleaves endonucleolytically the RNA of ribo-desoxy-and ribo-ribo type doublestranded structures to oligonucleotides with 5'phosphoryl-and 3'hydroxy termini. In the presence of ATP the generated nicks are repaired by the ligase except at the ends of the doublestranded regions where some short oligonucleotides are released before ligation can occur. As judged from its behaviour during the various purification steps and from some of its properties, the nicking activity seems to be different from known nicking enzymes.


Atomic co-ordinates for yeast phenylalanine tRNA. Atomic coordinates are presented for yeast tRNA(Phe) derived from a wire skeletal model fitted to an electron density map at 2.5 A resolution obtained by isomorphous replacement.


[Goblet cells in spontaneous colibacteriosis in pigs]. This work is a part of the studies on the intestinal barrier undertaken to cast some more light on the pathogenesis of colibacteriosis in pigs. The objective of the work was to investigate the goblet cells in the intestines of pigs ill with spontaneous colibacteriosis in the form of oedema disease and gastrointestinal form. The investigations were carried out on 26 pigs segregated into 3 groups: I group -- typical oedema disease (12 pigs), II group -- colibacteriosis in the gastrointestinal form (8 pigs), III group -- healthy controls (6 pigs). The segregation into the first two groups was based on the clinical, pathological and bacteriological criteria. In all the animals, the number of the goblet cells was counted in the duodenum, jejunum, ileum, cecum and colon. The results, analysed statistically, showed that in spontaneous colibacteriosis (oedema disease as well as the gastrointestinal form) a slight decrease of the number of the goblet cells was observed. In oedema disease, this decrease is significant only in the epithelium of the jejunal villi and in that of the colon, in the gastrointestinal form -- in the duodenal and jejunal villi. It results from the present investigations that the goblet cells, as one of the factors of the intestinal barrier, are not liable to such changes in spontaneous colibacteriosis as to explain or cast light on the pathogenesis of this disease.


[The nucleus cervicalis lateralis in sheep]. The objective of the work was to determine: a) the presence of the nucleus cervicalis lateralis in the sheep, b) the extent of this nucleus in the spinal cord and medulla oblongata, and c)the number and size of its cells. The histological method of staining the nerve tissue with methylene blue according to Nissl was employed. The nucleus cervicalis lateralis of the sheep is situated in the lateral funiculus, in the caudal part of the medulla oblongata and in the first three cervical segments of the spinal cord. The total number of cells making up the studied nucleus was 1629 in sheep I, 678 in sheep II, and 732 in sheep III. The average size of the cells ranged between 18.0 and 28.0 mu. In comparison with the same nucleus examined in other animals, that of the sheep shows a number of cell-free areas. It is composed of a very small number of cells, whose average diameter is small. These characteristics make it possible to regard the nucleus cervicalis lateralis in the sheep as a rudimentary structure.


Pediatric surgical patients' and parents' stress responses and adjustment as a function of psychologic preparation and stress-point nursing care. The purpose of this study was to test the hypotheses that children who receive systematic psychologic preparation and continued supportive care, in contrast to those who do not, would show less upset behavior and more cooperation in the hospital and fewer post-hospital adjustment problems and that their parents would be less anxious and more satisfied with information and care received. Eighty children scheduled for minor surgery and their parents were randomly assigned to experimental and control conditions. The experimental intervention consisted of accurate information about sequences of events, sensory experiences, role expectations and appropriate responses, previews of procedures through play techniques, and supportive care given at critical points pre- and postoperatively. Significant differences between experimental and control children and parents on ratings of upset behavior, cooperation with procedures, pulse before and after painful procedures, resistance to induction, time to first voiding, posthospital adjustment, and parental anxiety and satisfaction with information and care consistently supported the hypotheses. Results were also analyzed in relation to the age and sex of the children and whether parents roomed with the children.


Analysis of nurse-doctorates; data collected for the International Directory of Nurses with Doctoral Degrees. In an American Nurses' Foundation survey of the 1973 population of nurses with doctoral degrees (N = 1,020) general trends in doctoral education of nurses were elicited. Specific unique characteristics were highlighted, including: a continuing trend for nurses to earn the Ph.D. rather than the Ed.D., a divergence between field of doctoral study and the current field of research interest, and a slight number of these qualified nurses actually participating in research of any kind. The majority of subjects were single; most were employed in a university or college where they held either full or associate professorships; most considered themselves still to be in the field of nursing, although their doctoral studies frequently took them out of the discipline; their work responsibilities were heavily loaded with administrative duties. As compared with the holders of doctoral degrees in other fields, nurses earned their degrees later, but took no longer to complete them. While universities in the Mid-Atlantic states were the largest producers of nurse-doctorates, universities in the Midwest were found to be the most frequent employers. Questions regarding the future direction of nurse-doctorates were raised.


Reduction of airborne microorganisms by filtering recycled air in a chick hatcher. An experimental chick hatcher designed to filter recycled ventilation air was tested for its effectiveness in reducing the number of viable airborne microorganisms. Chicks in a filtered hatcher and a control hatcher (no filter) were artificially contaminated with Serratia marcescens as ventilation air was recycled in the hatchers for twelve hours. The number of viable S. marcescens particles in the filtered air of the conditioning chamber was less than detectable. The number of viable airborne S. marcescens particles in the hatching chamber of the filtered hatcher indicated a reduction of greater than 90 percent over the number in the unfiltered hatcher. The filter was effective in reducing the number of airborne particles carrying viable S. marcescens organisms in the hatcher.


Effect of filtering recycled air in a chick hatcher on airborne pathogenic microorganisms. Two experimental chick hatchers in which ventilation air within the hatcher was partially recirculated in a positive pressure system, one with an air filter in the system and the other without a filter, were simultaneously tested to determine effect of the filter on quantitative reduction of viable airborne microorganisms. Chicks were artificially contaminated with either Escherichia coli or Staphylococcus aureus (coagulase-positive). Air was sampled for total test bacteria per cubic foot of hatcher air. The filter effectively reduced the number of viable airborne particles contaminated with E. coli and S. aureus contributed by chicks in the hatcher.


Release of a prostaglandin E-like substance into mixed venous blood during endotoxin hypotension in cats. An iv injection of E. coli endotoxin (10--15 mg/kg) produced biphasic hypotensive reaction in cats. The second phase of hypotension developed 5--10 min after the administration of endotoxin and was paralleled by an appearance of a substance contracting the chick rectum and rat colon which were bathed in mixed venous blood. On the basis of differential sensitivity of the assay organs to prostaglandins it was concluded that a prostaglandin E-like substance (PGEs) was released. Its peak concentration in blood was 1--3-5 ng/ml in terms of PGE2-like activity. Indomethacin (10 mg/kg) interrupted the liberation of PGEs into blood and at the same time a slow but steady increase in arterial blood pressure occured. The amelioration of endotoxin hypotension by indomethacin was abolished by an infusion of PGE2 at a rate of 20--100 ng/kg/min. It is suggested that the second phase of endotoxin hypotension in cats is mediated by a release of PGEs.


Idoxuridine in the treatment of herpes zoster. An uncontrolled, double-blind, random-selection study of fifty consecutive patients with attacks of herpes zoster treated with one of two concentrations (5 per cent or 40 per cent) of idoxuridine (IDU) in dimethyl sulphoxide (DMSO) has shown that, over all, the patients fared better than would have been expected had they been treated only symptomatically. There was no apparent difference between the two concentrations of idoxuridine in regard to either side-effects or benefits. In 17 of the fifty patients the skin lesions healed more rapidly than would have been expected without treatment, and pain was relieved more rapidly than expected in 26 of the 47 patients in whom it was a feature of the attack. Side-effects, which included a transient stinging or burning sensation in 29 patients and acute sensitivity to idoxuridine (confirmed by patch-testing) in one, did not lead to withdrawal of any patient from the trial. Three patients complained of an unpleasant, garlicky taste during treatment. No significant abnormalities were noted in liver-function tests and in white-cell or platelet counts in patients in either treatment group. The solutions of idoxuridine in dimethyl sulphoxide were provided by W.B. Pharmaceutical Ltd.


Granulation in chronic leg ulcers. A trial with a new material. Twenty-two patients with chronic ulcers of the lower limb were treated with 'Varihesive', a modified form of 'Stomahesive'. The results showed that granulation was stimulated by the dressing, and no side-effects were encountered. The treatment is considered to be a useful adjunct to routine supportive measures. I should like to thank E.R. Squibb & Sons for providing the material for this study.


Isolation of DNA from yeast by chromatography on hydroxyapatite. A simple procedure is described for isolation of purified non degraded total DNA from yeast cells. The procedure involves conversion of the cells into spheroplasts by enzymatic treatment, lysis of the spheroplasts in 8 M urea - 0.24 M sodium phosphate buffer - 0.01 M EDTA (ethylendiamintetraacetic acid, sodium salt) - 1% SDS (sodium dodecyl sulphate), deproteinization of the lysate with chloroform-phenol and separation of the DNA from proteins, RNA and other contaminants by hydroxyapatite chromatography. The yield is about 90% of the DNA in the starting material (spheroplasts).


Fragments of beta-galactosidase from Escherichia coli. Fragmentation, purification, characterization and in vitro complementation. Thermal fragmentation of the beta-galactosidase was studied in different buffer solutions and at different temperatures. Fragmentation of the subunits in small size polypeptides could be observed directly. The fragmentation proceeded in buffer solution, pH 7.0, at either 75 degrees C or 100 degrees C in the presence of sodium dodecyl sulfate. The elevated temperature appeared to accelerate this process. At 100 degrees C, pH 7.2, the fragmentation proceeded in the absence of sodium dodecyl sulfate, but in the presence of 8 M urea. Molecular weights, determined by sodium dodecyl sulfate disc gel electrophoresis were from 130,000 to about 20,000. Multiple bands were observed. After dissociation was complete at 37 degrees C, the fragments were purified by ion-exchange column chromatography. Of the five fragments thus obtained, four were homogeneous by disc-gel electrophoresis. Molecular weight of the homogeneous fragments were found to be near 25,000. The fifth comprised a mixture of four fragments having molecular weights from 29,000 to 72,000. Two of the fragments were active as the alpha-donor in in vitro complementation with mutant M15, which contains a deletion in the alpha-region of the z gene.


In vivo and in vitro phosphorylation of DNA-dependent RNA polymerase of Escherichia coli by bacteriophage-T7-induced protein kinase. After infection with bacteriophage T7 the beta' and to a lesser extent the beta subunits of E. coli DNA-dependent RNA polymerase (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) are phosphorylated by a phage-gene-encoded protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37). The phosphorylation occurs on threonine residues and appears site-specific. It is probably the molecular basis of the early transcriptional control.


Proton nuclear magnetic resonance of spin-labeled Escherichia coli tRNAf1MET. Thiouridine at position 8 (s4U8) of tRNAf1Met was spin-labeled with the nitroxide free radical, N-(1-oxyl-2,2,5,5-Tetramethyl-3-pyrrolidinyl) bromacetamide, for proton nuclear magnetic resonance spectroscopic studies. The well-resolved methyl peak of ribothymidine is unperturbed, but the peak tentatively assigned to the C-5 methylene group of dihydrouridine is considerably broadened in spin-labeled tRNAf1Met. Of the approximately 27 slowly exchanging protons observed in the region between 11 and 15 ppm downfield from 4,4-dimethyl-4-silapentane-1-sulfonic acid, the equivalent of about five protons apparently disappeared in spin-labeled tRNAf1Met. The well-resolved single proton at 14.8 ppm was missing not only in the paramagnetic species, but also in the diamagnetic reduced form of spin-labeled tRNAf1Met, and was unequivocally identified as a hydrogen bond involving s4U8 by comparison of several forms of tRNAf1Met specifically modified at s4U. Evidence that the perturbation of a second single proton resonance at 14.6 ppm (shift and broadening) is coupled to the loss of a tertiary hydrogen bond involving residue 8, arises from the same modified forms. The resolved resonances in the methyl and N-H regions, particularly the resonance at 14.6 ppm as well as the four N-bonded proton resonances at higher field which are broadened solely due to their proximity to the unpaired electron of the spin label, provide specific indicators of the geometry of tRNAf1Met structure in solution. Their observability by nuclear magnetic resonance spectroscopy opens up the possibility of monitoring distance changes among the base residues of spin-labeled tRNAf1Met upon its interaction with aminoacyl-tRNA synthetase and other enzymes.