[Computer tomography for rare soft tissue tumours of the extremities (author's transl)].

Five patients with undiagnosed soft tissue masses in the extremities were examined and in two a pathological diagnosis could be made. One was an extensive, invasive fibroma (desmoid) 22 cm long which could be followed from the thigh almost into the pelvis. It was sharply demarkated form the surrounding muscles and of higher density. The second case was a 12 cm long cavernous haemangioma in the semi-membranosus muscle. This was originally hypo-dense, but showed marked increase in its density after the administration of contrast.


[Therapeutic embolisation of visceral arteries. Animal experiments, early clinical experience, introduction of a new embolising material (author's transl)].

Silicone elastomer was found to be suitable embolsing material in animal experiments and has been used in 16 patients. It produces permanent vascular occlusion, is easy to use, well tolerated and can be steam sterilised. The disadvantage of the method is the time taken to prepare it in the laboratory. Embolisation of tumours was successful in all cases; angiography nine months later showed that the vessels had remained occluded and that the tumours had ceased to grow or become smaller. The development of collateral vessels shows that this is only a palliative procedure and that surgery remains the main form of treatment. In ten of the 16 patients, the course of the disease was influenced beneficially.


[Indications and value of treatment by catheter occlusion (author's transl)].

The value of the catheter occlusion therapy is analyzed in 92 cases retrospectively, and the indication, and complication risk of these procedures are considered. In the following vessel areas occlusion with different methods have been performed with decreasing frequency; kidneys, pelvis, legs, gastrointestinal tract, external carotid and internal carotid artery. Serious complications have been observed in therapeutic investigations at the head, especially in occlusions of the external carotid artery. In this group embolisation therapy should be performed with strict indication only.


[Percutaneous nephropyelostomy: indications and technique (author's transl)].

Percutaneous nephropyelostomy has been performed on 24 patients. The method is simple, has few complications and can be performed rapidly; it can be recommended for both temporary and permanent supravesical urinary drainage. It represents an improvement in urologic techniques.


[Ultrasonography of the adrenals--limits of a real time scanner (author's transl)].

Sonography is an efficient, non invasive diagnostic tool in evaluating pathological enlargement of the adrenals. In 11 out of 27 patients, who had adrenal sonography, a tumor diagnosis was established. In 7 patients the sonographic findings and diagnosis were proved by scintigraphy, surgery and histology. With conventional ultrasound technique one cannot see the normal and nodular hyperplastic adrenal. At the same time we believe, tumors smaller than 2.5 cm cannot be diagnosed accurately in general. Some problems of adrenal sonography could be eliminated with most recent ultrasound technology. (Grayscale processing, scan converter system, electronically focused transducers with higher frequencies). In future patients with pathologies in the adrenals can be evaluated non-invasive and definitely by ultrasound and computerized tomography.


[Studies on the reliability of the 99mTc-uptake as a measure of thyroidal stimulation (author's transl)].

In 44 patients with stimulated goitre the trapping kinetics of 131I-iodide and 99mTc-pertechnetate are analyzed having corrected for different size of the thyroid and different physical properties of the tracers under use. Unidirectional iodide clearance (UDCL) is chosen as reliable estimator of thyroidal stimulation. UDCL shows strong correlation to iodide uptake tests and the correlation to pertechnetate uptake tests is sufficiently strong for semiquantitative evaluation of thyroidal stimulation. Under the conditions of clinical routine work the reproducibility of pertechnetate uptake tests exceeds that of iodide, thus, pertechnetate uptakes are more suitable for evaluation of regulation tests, i.e. suppression test and stimulation test with TSH. 99mTc-thyroid-uptake (TcTU) 20 min after injection is a useful parameter of thyroidal stimulation for clinical routine work as it combines excellent reproducibility with strong correlation to unidirectional iodide clearance as the relevant parameter of thyroidal stimulation.


["Cold lesions" in bone scintigraphy (author's transl)].

Frequency and location of "cold lesions" has been analysed in 1000 consecutive bone scans. Among the 554 abnormal cases there were 18 (1,8% of the total) with localized diminished activity due to metastatic lesions and 5 (0,5%) secondary to radiation osteitis. 10 of the 18 patients with metastatic disease had pure defects while 8 showed a reactive margin. It is pointed out that the quality of the examination is crucial for the demonstration of such defects and that single scans of the different regions of the skeleton are superior to a whole body scan. The survey of the literature shows that "cold lesions" are predominant in malignant bone diseases, however no relation exists to a definite histology.


[Estimation of 131I hippuran clearance during pregnancy (author's transl)].

Changes in 131I hippuran clearance were estimated by a non-catheter method, as well as total clearance and clearance of each kidney, in 43 women at various stages of pregnancy and in 13 non-pregnant women who were not using hormonal contraceptives. The results are demonstrated in graph form. The methods used are described in detail. The procedure for determining clearance in separate kidneys is indicated. It was found that clearance values increased up to the 35th and 36th weeks of pregnancy. The difference between the sides that were found corresponds with the previously known difference in the function of the right and left kidneys and ureters.


Influence of age on the sensitivity of the rat to streptozotocin.

The relationship between age and sensitivity to the diabetogenic effect of streptozotocin was investigated. Changes in the serum levels of several parameters (glucose, immunoreactive insulin, lipids), as well as changes of the pancreatic insulin content were monitored at 2, 4, 8, 24 and 48 h after the intravenous administration of different doses of streptozotocin in rats of various weights. Different concentrations of blood glucose and lipid and different amounts of pancreatic immunoreactive insulin could be found in rats of different ages 24 and 48 h after injection of the same dose of the drug (in mg/kg body weight). Also, age-dependent changes of serum immunoreactive insulin could be observed as early as 4 h after streptozotocin administration. All these changes indicate that the sensitivity of the rat to the diabetogenic effect of streptozotocin is inversely related to the age of the animals. Most likely, age-dependent pancreatic factors have an important role. In fact, the changes of the minimum dose of streptozotocin required to cause diabetes in rats of different weights closely parallel the age-related changes of the total immunoreactive insulin content of the pancreas of the intact rats. The role of other age-related factors which may influence the effectiveness of streptozotocin action is briefly discussed.


Peritoneal exudate T lymphocytes with specificity to sheep red blood cells. III. High dose of antigen induces suppressor T cells which influence the appearance in exudates of effector T cells for delayed-type hypersensitivity and helper T cells for humoral immune responses.

Antisera produced in rabbits against adherent cells of rat alveolar or peritoneal lavage fluid (anti-rat alveolar macrophage sera, ARAMS, or anti-rat peritoneal macrophage sera, ARPMS) were used to detect antigenic differences between alveolar (AM) and peritoneal (PM) macrophages in an indirect membrane immunofluorescence (IMF) test. Of all sera tested, the IMF titres were higher with cells of that population which was used for immunization. These differences were found before and after exhaustive absorptions with insolubilized rat plasma, rat erythrocytes, and non-adherant rat kidney, spleen, thymus and bone marrow cells. The differences were not due to antigens specific for one of the macrophage populations, as demonstrated by cross-adsorption studies with macrophages of different localization. It is assumed that two or more macrophage specific antigenic determinants are present in different density in the two macrophage populations.


Dengue virus-induced thymus-derived suppressor cells in the spleen of mice.

Adoptive transfer of spleen cells obtained from mice given three weekly i.p. doses of dengue type 2 virus (DV) suppressed DV antigen-specific antibody secretion as detected by the Jerne plaque technique. This suppression was produced by non-glass-adherent cells but not by glass-adherent cells. Immune spleen cells depleted of macrophages by carbonyl iron treatment had higher suppressor activity. Immune spleen cell homogenate could transfer the activity equally well. The immune spleen cells were separated into T and B lymphocytes by a nylon wool column. B lymphocytes had no suppressor activity; almost all the suppressor activity was present in T lymphocytes. Thus, macrophages and B lymphocytes had no suppressor activity; it was mediated by T lymphocytes through soluble factors.


Staphylococcal lung abscess and acute glomerulonephritis.

A patient with a staphylococcal lung abscess developed acute glomerulonephritis with clinical and pathological features typical of postinfectious glomerulonephritis. There was no evidence of streptococcal infection and the nephritis resolved following treatment of the abscess.


[Contact urticaria].

Report of a 42 year old woman who had given up her profession as a hairdresser because of urticarial skin eruptions following contact with substances used during working. An open patch test showed after 30 min positive urticarial reactions against permanent wave solution, fixation solution, p-aminodiphenylamin, lanolin-alcohol and clioquinol.


[Lupus miliaris disseminatus faciei].

Three typical cases of lupus miliaris disseminatus faciei are presented with emphasis on clinical and histological data. Pathogenesis, differential diagnosis and therapy are shortly discussed.


Purification and chemical characterization of the rodlet layer of Neurospora crassa conidia.

The rodlet layer of Neurospora crassa macroconidia has been purified and chemically characterized. Sheets of rodlets were released from the conidial surface by vigorously shaking conidia in water. Conidia were removed by filtration and low-speed centrifugation, and the rodlets were recovered from the supernatant by high-speed centrifugation. The rodlet pellet comprised 1.9% of the initial dry weight. Chemical analysis was hampered by the insolubility of the rodlets. They were not solubilized by heating in various protein-denaturing buffers and were only partially dissolved by heating in 1 M NaOH at 100 degrees C for 5 min. Nevertheless, they were found to be largely composed of protein (91%, based on total nitrogen). The major amino acids in acid hydrolysates were aspartic acid, glycine, serine, alanine, half-cystine, and valine. Glucosamine was not detected in acid hydrolysates. The sulfur content was 2.5%, and this could be accounted for in half-cystine and methionine. Carbohydrate comprised just over 2%. The phosphorus content was 0.21%, of which less than one-third was accounted for in phospholipid. The total fatty acid content was 1.0%, most of which could be accounted for by the fatty acids of the phospholipids.


In vitro tests of cellular immunity in man.

There has been a recent rapid increase in the number of assays for cellular immunity in man and in information related to the mechanisms underlying the observed reactions. These tests have been applied clinically for three main purposes: (a) Evaluation of cell-mediated immune competence of patients with primary immune deficiencies and of possible immunological depression associated with cancer or other diseases. (b) Determination of major differences in histocompatibility antigens which might be important in rejection of organ transplants. Some cellular immune assays have become part of the routine battery of assays used for immunological evaluation of potential donors and recipients. (c) Measurement of specific immune reactivity against antigens associated with a variety of diseases, including infectious diseases, autoimmune diseases and cancer.


Chemiosmotic coupling in Methanobacterium thermoautotrophicum: hydrogen-dependent adenosine 5'-triphosphate synthesis by subcellular particles.

Hydrogenase and the adenosine 5'-triphosphate (ATP) synthetase complex, two enzymes essential in ATP generation in Methanobacterium thermoautotrophicum, were localized in internal membrane systems as shown by cytochemical techniques. Membrane vesicles from this organism possessed hydrogenase and adenosine triphosphatase (ATPase) activity and synthesized ATP driven by hydrogen oxidation or a potassium gradient. ATP synthesis depended on anaerobic conditions and could be inhibited in membrane vesicles by uncouplers, nigericin, or the ATPase inhibitor N,N'-dicyclohexylcarbodiimide. The presence of an adenosine 5'-diphosphate-ATP translocase was postulated. With fluorescent dyes, a membrane potential and pH gradient were demonstrated.


Siderophore synthesis in Klebsiella pneumoniae and Shigella sonnei during iron deficiency.

Klebsiella pneumoniae 298/53 and Shigella sonnei 43-GG9 exhibited restricted growth and enterochelin synthesis only under iron-deficient conditions. S. sonnei also produced an unidentified secondary hydroxamate siderophore.


Isolation of Neurospora crassa bradytrophs.

A method was developed for the isolation of Neurospora bradytrophs. The bradytrophs (representing lesions in a number of pathways) were resistant to DL-p-fluorophenylalanine when growing in a leaky fashion but were sensitive when grown in the presence of their stimulating supplement.


Response to a metal ion-citrate complex in bacterial sensing.

Salmonella typhimurium responds chemotactically to gradients of divalent cations in the presence of citrate ions. The actual chemoeffector is the citrate-metal ion complex, which acts as an attractant. Citrate (which is also a chemoeffector for Salmonella) and the citrate-metal ion complex are recognized by different receptors. The response of Salmonells,  which can transport citrate through its membrane, is quite different than that of Escherichia coli, which cannot.


Cloning and physical mapping of the dnaA region of the Escherichia coli chromosome.

The dnaA gene of Escherichia coli K-12, supposedly present in the deoxyribonucleic acid (DNA) of specialized transducing phase lambda i21 dnaA-2, was cloned onto plasmid pBR322. The new plasmid was named pMCR501. Physical analyses of DNAs of lambda i21 dnaA-2 and pMCR501 revealed the following. The lambda i21 dnaA-2 DNA retained the delta sr I lambda 1-2 and ninR5 deletions and imm21 substitution which were originally present in the parental phage. The size reduction was compensated for by the insertion-substitution segment (tna-dnaA region) in lambda  i21 dnaA-2 DNA. The fractional size of this segment was approximately 7 megadaltons (Md), or 10 kilobases, which was found to be the sum of the tna insertion subsegment of ca. 3.5 Md and the dnaA substitution subsegment of ca. 3.5 Md. Phage P1-mediated transductional mapping between the dnaA46 and tna mutations gave a cotransduction frequency of 84%, corresponding to approximately 5 kilobases. Thus, it is strongly suggested that the dnaA gene resides in the lambda i21 dnaA-2 DNA. Cleavage mapping with the restriction endonuclease of pMCR501 DNA confirmed that it was constructed by excising a BamHI fragment of 4.29 Md, containing the 3.5-Md dnaA substitution segment, from the lambda i21 dnaA-2 DNA, inserting it into the sole BamHI cleavage site on pBR322.


Conditionally lethal amber mutations in the dnaA region of the Escherichia coli chromosome that affect chromosome replication.

Three amber mutations, dna-801, dna-803, and dna-806, were isolated by localized mutagenesis of the dnaA-oriC region of the chromosome from an Escherichia coli strain carrying temperature-sensitive amber suppressors. When the mutations were not suppressed at 42 degrees C, the cells did not grow and DNA synthesis was arrested. They were very closely linked to each other and to the dnaA46 mutation. The mutant phenotype of each strain was converted to the wild type by infecting the mutants with specialized transducing phase lambda i21 dnaA-2 but not with lambda i21 tna. Derivatives of lambda i21 dnaA-2, each of which carried the amber mutation dna-801 dna-803, or dna-806, converted the dnaA mutant phenotype to Dna+ but did not convert rhe amber mutants to the wild-type phenotype. E. coli uvrB cells were irradiated with ultraviolet light and infected with each of these phage strains. An analysis of proteins synthesized in the cells revealed that two proteins with molecular weights of 50,000 and 43,000 were specified by lambda i21 dnaA-2 but not by lambda i21 tna. When the ultraviolet-irradiated cells did not carry an amber suppressor, the derivative phage with the amber mutation invariably failed to produce the 43,000-dalton protein, but when the host cell carried supF (tyrT), the protein was produced. The 50,000-dalton protein was unaffected.


Inactivation of prophage in ultraviolet-irradiated Escherichia coli: dependence on recA gene activity.

The fate of the prophage part of the lysogenic chromosome was followed in the course of post-ultraviolet incubation. For this purpose, lambda cI857 ind prophage, which can be induced by heat but not by ultraviolet light, was used. The prophage, intially more resistant than its repair-proficient host cell, was rapidly inactivated. This inactivation was not caused by the impaired capacity of irradiated cells to support growth of the phage. Over the entire dose range tested, little, if any, sensitivity difference between the host and the prophage was found at the end of cell division delay. Rapid inactivation of the prophage was also observed in uvr cells after small doses of ultraviolet light. The same small doses did not cause inactivation in lysogens carrying a mutation in the gene recA. This suggests that the functional gene recA is required for inactivation of the prophage part of the lysogenic chromosome.


Immunochemical analysis of triton X-100-insoluble residues from Micrococcus lysodeikticus membranes.

Triton X-100-insoluble residues from Micrococcus lysodeikticus membranes were analyzed by crossed immunoelectrophoresis after dispersal of the residues in sodium dodecyl sulfate (SDS). Conditions which produce no obvious distortion of the immunoprecipitate profile and which allow qualitative and quantitative analyses of the antigens present in the extracts are described. Two main antigens were detected; these were identified as succinate dehydrogenase (EC 1.3.99.1) and adenosine triphosphatase (EC 3.6.1.3). As determined by peak area estimations, the maximal release of succinate dehydrogenase and of adenosine triphosphatase from Triton X-100-insoluble membrane residues occurred at protein/SDS ratios of about 4.3:1 (0.2% SDS) and 6.8:1 (0.13% SDS), respectively. A comparison of enzyme activities of SDS extracts with those of untreated, control Triton X-100-insoluble membrane residues indicated that both the succinate dehydrogenase and the adenosine triphosphatase antigens were released with a full (or enhanced) catalytic potential at or below concentrations of SDS required to effect maximal solubilization of the enzyme in question. Evidence is also presented to suggest that the more acidic of the two components detected by crossed immunoelectrophoresis for the heterogeneous adenosine triphosphatase antigen is more sensitive to SDS than is the other. Both succinate dehydrogenase and adenosine triphosphatase lost catalytic activity and were denatured at protein/SDS ratios lower than 3.4:1.


Analysis of the allosteric properties of rabbit muscle phosphofructokinase by means of affinity labeling with a reactive ATP analog.

A reactive ATP analog, N6-(6-bromoacetamidohexyl)-AMP-PCP, reacted specifically with the ATP inhibitory site of rabbit skeletal muscle phosphofructokinase without affecting the active site. Modification resulted in the incorporation of 1.01 mol of the reagent per mol of enzyme subunit. The modified enzyme was insensitive to allosteric inhibition by ATP and to activation by AMP at pH 7.2, where the native enzyme exhibits allosteric kinetic behavior. These observations demonstrate that we had succeeded in obtaining PFK fixed in the T state. Using the kinetic parameters of this modified enzyme, the kinetic properties of native enzyme can be quantitatively accounted for by the allosteric model of Monod-Wyman-Changeux. Further, the reagent was shown to have reacted with a specific cysteine residue near or at the ATP inhibitory site, and the sequence around the cysteine was determined as Cys-Lys-Asp-Phe-Arg.


The effect of sarcomere length and stretching on the rate of ATP splitting in glycerinated rabbit psoas muscle fibers.

The effect of sarcomere length and stretching on the tension and the rate of ATP splitting was studied using small fiber bundles from glycerinated rabbit psoas muscle. The rate of ATP slitting was determined by measuring ADP production, while the tension development in response to a contracting solution (at pCa 5.3) was recorded in the same preparation. The isometric tension developed by the preparation decreased when the sarcomere length was increased. The decrease of tension development was accompanied by a decrease in the rate of ATP splitting. If a preparation exerting steady isometric tension was stretched by 5--10% at a velocity of 0.1 mm/s, the rate of ATP splitting was increased after stretching, while the steady isometric tension attained after stretching was also higher than the initial value. The extent of the excess ATP splitting caused by stretching decreased with increasing sarcomere length. These results suggest that the rate of the interaction cycle between actin and myosin molecules may increase as a result of stretching.


X-linked ichthyosis: a metabolic disease.

Sex-linked ichthyosis, a rather common genodermatosis, has recently been linked with deficiency of the enzyme steroid sulfatase. Data supporting this association and suggesting that alterations in lipid metabolism may cause abnormal keratinization are herein reviewed.


Rat strain differences in copulatory behavior after para-chlorophenylalanine and hormone treatment.

The potentiation of masculine copulatory behavior in castrated male rats following systemic para-chlorophenylalanine (PCPA) treatment was found to be dependent upon the strain of rat and the recency of castration. Wistar (W) and Sprague-Dawley (SD) males displayed a decline in behavioral responsiveness to PCPA treatment following castration, the W males retaining their behavioral responsiveness longer than SD males. Castrated W males were also behaviorally more responsive to androgen replacement than were SD males. Ovariectomized W and SD females receiving estrogen replacement displayed a strain difference in hormonal sensitivity. In tests for feminine copulatory behavior, ovariectomized W females were behaviorally more sensitive to estrogen treatment than SD females. Ovariectomized and estrogen-primed females of both strains displayed potentiated lordotic behavior following chronic PCPA treatment. Concomitant treatment with dexamethasone to reduce adrenal steroid output abolished the potentiation of lordotic behavior found with PCPA treatment.


Seborrheic keratoses and trichostasis spinulosa.

In 54 of 325 seborrheic keratoses, trichostasis spinulosa was found within the keratinous cysts and between papillomatous surface keratin, in addition to being present in contiguous hair follicles. Trichostasis in seborrheic keratoses and trichostasis spinulosa are both more frequent in older age groups. Trichostasis spinulosa represents a marker of vellus hair follicles and indicates that some seborrheic keratoses incorporate and may be partially derived from the cells of the infundibular portion of the follicle.


Ultrastructural cytochemical studies of plasma membrane phosphatase activities during the HeLa S3 cell cycle.

Alkaline phosphatase (AP), 5'-nucleotidase (5'N), Mg2+-activated ATPase (Mg-ATPase) and Ca2+-activated ATPase (Ca-ATPase) were studied in sychronized HeLa S3 cells with cytochemical methods and electron microscopy. It was found that AP activity, as determined by the deposition of lead phosphate reaction product (r.p.) was most active in mitotic (M), early and middle G1 cells, less active in late G1 and almost undetectable in S phase cells. Most AP enzyme activity was found to be associated with undulations (mainly microvilli) of the plasma membrane. Fluctuations and the redistribution of 5'N were also observed; the reaction for 5'N was positive in all phases of the cell cycle studied, it was strongest in M cells and in the majority of middle G1 cells. Mg-ATPase activity was present in the plasma membranes of cells throughout the cell cycle, but did not show noticeable fluctuations in activity and distribution. Ca-ATPase activity appeared in plasma membranes and in limited areas of cell nuclei but was evident only in S phase cells. The results of the present study confirm and extend previous biochemical observations and indicate that changes in membrane phosphate activities are associated with enzyme activity redistributions within the plasma membrane during the HeLa S3 cell cycle.


Inhibition of MLC stimulator function by antibodies directed to non-HLA antigens.

The properties of five human alloantisera which inhibit the stimulating capacity of cells in an MLC reactions are described. All of the sera showed patterns of inhibition in families which did not correlate with HLA haplotypes. In a large proportion of the families investigated the sera did not react with parental cells but inhibited the cells from one or more of the children. Absorptions were performed with one of these sera using such non-reactive parental cells. Paternal cells absorbed out the inhibiting activity while maternal cells did not. This indicates that expression of the antigen with which the inhibiting antiserum reacts is insufficient for inhibition and other factors, either environmental or inherited from the mother, influence the capacity of the antiserum to cause inhibition. This antigen was most likely a non-HLA antigen.


The effect of 5-bromodeoxyuridine on interferon production in human cells.

5-Bromodeoxyuridine (BrdUrd) increased interferon production by the Namalwa line of human lymphoblastoid cells treated with Sendai virus, but inhibited their growth. Thymidine, which also inhibited cell growth had no effect on interferon production, so that growth inhibition per se was not the cause of the stimulation. BrdUrd was incorporated into cellular DNA; 5-chlorodeoxyuridine and 5-iododeoxyuridine (which are also incorporated) increased the interferon yield, but 5-fluorodeoxyuridine (which is not incorporated) did not. Thymidine reduced both the incorporation of BrdUrd and its stimulatory effect on interferon production. Deoxycytidine (which prevents the cytotoxic effects of BrdUrd) had no effect on the stimulation. BrdUrd also stimulated interferon production in response to poly(rI) . poly(rC) in growing human diploid fibroblasts but not in SV40 virus-transformed human cells. Since BrdUrd was incorporated into the DNA of all these cells, we concluded that incorporation is necessary, but not sufficient for the stimulation of interferon formation.


Transient global amnesia after clioquinol: five personal observations from outside Japan.

Five personal observations of an acute amnestic episode in younger individuals after intake of clioquinol are described together with three observations from the medical literature. In five of these cases the episode began after an unusually large dose, in three after a therapeutic one with a latency of about 24 hours. The clinical aspect closely resembled classical transient global amnesia but the episode after clioquinol lasted longer (24 hours to three days) and a more or less extensive retrograde amnesia persisted permanently. In one patient after three tablets of Mexase a clioquinol concentration of 12 microgram/ml in plasma was found 24 hours after the specified dose, which is an unexpectedly high concentration compared to those reported as late as 24 hours after a single equal dose of Mexase or any other clioquinol-containing preparation. Another patient had a brief relapse two years after the first episode, after a single therapeutic dose of another clioquinol preparation.


Primary writing tremor.

We describe a patient who complained of jerking of the right forearm on writing. Active pronation of his arm produced several beats of pronation/supination tremor. A burst of tremor also could be elicited by tendon taps to the volar surface of the wrist, to the finger extensors, and to pectoralis major, and by forcible supination of the wrist delivered by a torque motor. The subject's writing difficulty and tremor were temporarily abolished by partial motor point anaesthesia of pronator teres. We conclude that the tremor was caused by an abnormal response to muscle spindle input from pronator teres.


Interactions between central monoaminergic systems: dopamine-serotonin.

Concentration of dopamine and serotonin metabolites (HVA and 5-HIAA) in the CSF was evaluated before and after pharmacological treatment in 19 patients with different neuropsychiatric diseases. In every case a reciprocal modification of the two metabolites occurred after treatment. The result supports the hypothesis of a functional balance between the monoaminergic systems in the central nervous system.


An evaluation of some carrier detection techniques in Duchenne muscular dystrophy.

Some recently described abnormalities in the serum and red cell membranes in Duchenne dystrophy have been examined as methods of carrier detection in a single-blind controlled study. Twelve carriers (4 definite, 3 probable and 5 possible carriers previously found to have raised creatine kinase levels) and 12 normal female controls of the same age, were examined on 3 separate occasions at approximately two-weekly intervals. Analysis of age-dependent red cell shape changes, serum haemopexin levels, red cell K+ efflux rate, sensitivity of red cell ghost membrane ATPase to ouabain, membrane protein phosphorylation studies and lactate dehydrogenase isoenzyme profiles on agarose gel electrohoresis all failed to distinquish carriers from controls. The carriers suffered muscle cramps more frequently than the controls and all but one carrier and two control subjects were correctly identified by manual muscle strength testing, certain proximal muscles in paricular being consistently weaker in carriers than in the control group subjects. Scalar electrocardiography revealed higher values for the R/S ratio in Leads V1 and V2 and the sum (R-S) in V2.


Association of myocardial cell necrosis with experimental cardiac hypertrophy.

Cardiac hypertrophy was induced in rabbits by injecting thyroxine or isoprenaline, or by surgically constricting the abdominal aorta. An increase in heart weight was associated with a change in the ratios of bound to free forms of five lysosomal enzymes, a change in serum creatine phosphokinase and lactate dehydrogenase, and a change in the morphology of the myocardial cells. Isoprenaline treatment for 5 days induced a maximal change in heart weight, in the ratio of lysosomal enzymes, and in the serum enzymes. Thyroxine treatment was required for 15 days before maximal changes in heart weight, ratio, and serum enzymes were observed. In contrast, coarctation of the aorta caused a progressive change in heart weight, in the ratio of lysosomal enzymes, and in serum enzymes. These results suggest that necrosis of the myocardial cells does indeed accompany cardiac hypertrophy. It was further observed that autophagosomes, degenerating mitochondria in the myocardial cells during the induction of cardiac hypertrophy, and myofibril lysis were found, all of which confirms the suggestion of myocardial cell necrosis in the experimentally enlarged heart.


[Pericardial effusions (85 cases): radiological aspects (author's transl)].

A radiological study of 85 patients with acute pericarditis and effusion included a group of 35 cases observed before the introduction of ultrasonography and a second group of 50 patients in whom the presence of pericarditis had been confirmed by this investigation. The most important conclusions established were the following: --Absence of radiological signs in 55% of cases (group 1 : 46%, group 2 : 60%); normal heart size in 54% (group 1) and 78% (group 2), and increased size in 34% (group 1) and 20% (group 2). --Hilar manifestations (overlapping and obscuring of the left hilar region) in 26% of cases with a clear predominence of the left forms (14 out of 22). The cardiomegaly was not significant in 28% (group 1) and 14% (group 2). --The high frequency of pericarditis with a normal heart size has to be emphasized. The diagnostic value of hilar manifestations is also mentioned; the sign of left hilar overlapping is described in greater detail. --An overall comparison between the two groups shows, more particularly, the equal importance of left hilar manifestations for the radiological diagnosis of pericarditis. In a general way, it would appear that these hilar signs are the only elements which enable objective diagnosis of pericardial effusions on standard films.


Historical predictability of abnormal laparoscopic findings in the infertile woman.

The conventional approach to laparoscopy in an infertility workup has been to perform the procedure in the latter stages. Alternative ways have been suggested. Our investigation attempted to assess the suitabilities of an alternative approach. The laparoscopic findings in a group of 231 patients examined as part of an infertility workup have been analyzed. The predictability of abnormal findings has been demonstrated with accuracy in those patients with certain symptomatic or historical associations. The ability to predict abnormalities would suggest that laparoscopy should be performed early in the workup in this group. This holds true regardless of the discovery of any other abnormality which might be thought to be related to the patient's infertility.


Ketamine--HCl--diazepam anesthesia for laparoscopy.

Laparoscopy was performed on 150 patients under ketamine-HCl-diazepam anesthesia via intravenous drip infusion. No psychomotor disturbances were noted during the emergence phase. No complications occurred during the procedures, neither from the surgical nor from the anesthesiologic point of view. No alarming stimulation of the cardiovascular system was noted. The patients became responsive within a short time, but a state of strong sleepiness remained for several hours. Therefore, ketamine-HCl-diazepam anesthesia does not appear suitable for outpatient laparoscopies but is a valuable alternative to other methods of anesthesia for laparoscopy.


HLA B27 in patients with seronegative spondarthritides.

We investigated the pattern of genetic susceptibility to rheumatic diseases in Indians by means of HLA analysis. HLA B27 was present in more than 90% of cases included under the broad category or seronegative spondarthritides. In this respect our data resembled results reported for Caucasian populations. In our population, however, the phenotypic frequency of HLA B27 was low as reported from Japan.


Tomographic examinations of sacroiliac joints in adult patients with rheumatoid arthritis.

Tomography of the sacroiliac joints (SIJ) was performed in 72 patients with rheumatoid arthritis (RA) and in 50 controls. Twenty-seven rheumatoid patients (38%) showed typical sacroilitis with predominantly severe intraarticular ankylosis and subchondral erosions. Fourteen patients (19%) had a probable sacroilitis with mild erosions and intraarticular ankylosis and concomitant degenerative changes. Fifteen patients (21%) showed predominantly degenerative changes and 16 RA patients (22%) had no radiological manifestation of the SIJ. There was no relation between typical sacroilitis and age of patients, duration of disease, rheumatoid factor, Steinbrocker's stage and frequency of HLA B27.


Usnic acid derivatives as potential antineoplastic agents.

Usnic acid, a lichen antibiotic, showed low-level activity in the Lewis lung carcinoma test system. In an effort to produce new agents of potential use in the treatment of lung cancer, derivatives of the natural product were synthesized and evaluated with a cytotoxicity assay. Structure--activity analysis of the cytotoxicity data indicated the importance of the lipophilicity and the beta-triketone moiety of usnic acid on cytotoxicity. No significant increases in survival of test animals over controls were shown by any of the synthetic compounds in the P388 leukemia or the Lewis lung carcinoma test systems.


Restoration of diminished splenic responses to phytohemagglutinin and concanavalin A in adjuvant-induced disease by corticosteroids: further evidence for the presence and pathogenetic role of two populations of splenic suppressor cells.

This study confirms observations that active adjuvant-induced disease is accompanied by diminished spleen cell responses to phytohemagglutinin and concanavalin A; and that these diminished responses are due to suppressor cells, some adherent only to glass, and others adherent to plastic or glass. Corticosteroid inhibition of adjuvant disease is accompanied by a diminution or absence of these splenic suppressor cells. Some of these suppressor cells are inhibited in vitro by corticosteroids, in preference to the mitogen-responsive cells. This suggests that suppressor cells may play a role in the pathogenesis of AID.


Synthesis and antitumor properties of 7-deoxy-7-[(cis- and trans-3-aminocyclohexane)thio]carminomycinone.

The synthesis of analogues of carminomycin in which the daunosamine group has been replaced by (cis- and trans-3-aminocyclohexane)thio moieties is described. The new compounds were found to exhibit none of the antitumor or antibiotic activity associated with carminomycin.


Restoration of diminished splenic responses to phytohemagglutinin and concanavalin A in adjuvant-induced disease by virazole: possible pathogenetic role of a virus and suppressor cells.

Adjuvant arthritis is inhibited by the interferon-inducing anti-viral agents statolon, pyran copolymer and tilorone, and by the passive transfer of interferon. The present experiments demonstrate that Virazole, a non-interferon-inducing, anti-viral agent also inhibits adjuvant arthritis. The responses of splenic lymphocytes to phytohemagglutinin and concanavalin A are diminished in active adjuvant disease, due to suppressor cells. Suppressor cells are absent during spontaneous, methodrexate or corticosteroid-induced remissions. Suppressor cells are also absent during Virazole-induced inhibition of adjuvant disease. Methotrexate and corticosteroids inhibit suppressor cells in preference to mitogen-responsive cells in vitro. The preferential inhibition with Virazole is superior to that noted with methotrexate or corticosteroids.


Noninvasive Doppler ultrasound evaluation of aortocoronary bypass.

Using ultrasound method, aortocoronary bypass patency was determined by means of bidirectional Doppler's flowmeter. In 8 (3%) of 302 subjects without aortocoronary bypass was recorded diastolic signal which might distort the results of postoperative evaluation of graft patency. Two-hundred and ninety-seven patients with 330 aortocoronary bypasses were studied at the mean time of 8 months after operation. The graft patency was 84.5%. Comparison of 89 ultrasound findings with angiographic results established considerable specificity (90%) and sufficient sensitivity (77%). Reproducibility of this method was also good. The method is inexpensive and not time consuming. The advantages are also its safety and convenience for the patient. In the present level of development it can be used mainly as screening test at long-term follow-up of aortocoronary graft patency.


Effects of 2-nicotinamidoethyl nitrate on the cardiovascular system.

Using the dog as experimental animal, effects on the cardiovascular system of a new vasodilator, 2-nicotinamidoethyl nitrate (SG-75), were studied. In the heart-lung preparation, the compound produced a dose-dependent increase in the coronary blood flow, which was associated with only a minimal increase in the myocardial oxygen consumption. There was essentially no change in the myocardial function. The myocardial redox potential was shifted to more positive values. In the isolated perfused heart preparation (Langendorff's preparation), SG-75 produced a dilatation of only the small resistive arterioles. However, it produced a dilatation of the large conductive artery in underperfused myocardium. SG-75 produced a significant increase in the cerebral venous outflow, associated with an increase in the cerebro-spinal fluid pressure. It produced a reducation of the venous return, which was especially prominent in the lower half of the body. In the isolated smooth muscle preparation of the coronary artery, high-doses of SG-75 induced calcium antagonistic effects and produced a relaxation of the lanthanum contracture.


[Some experiments on the allergic reaction among workers in a pharmaceutical factory (author's transl)].

A survey was made on workers handling powdered drugs in a pharmaceutical factory. In this factory, two kinds of anti-inflammatory enzyme (bromelain and trypsin), one anti-inflammatory agent (flufenamic acid), one antispasmodic (flopropion) and two kinds of antibiotics (ampicillin and cephalexin) are mainly produced. Twenty four workers were examined by interviews and checked by Cornell Medical Index, and 18 of them complained of respiratory symptoms. These 18 workers were physically examined by skin scratch tests, pulmonary function tests and serum immunological tests. Among 24 workers, 9 handled powdered drugs (A group), 5 handled the same in the past and had already been transferred to other sections for their symptoms (B group), 3 engaged in the process of capsul-filling (C group) and 7 handled several times occasionally during one year (D group). Their average months spent in handling powdered drugs were, in the case of anti-inflammatory enzyme, A group 53.2, B group 66.2, and in the case of antibiotics, 5 workers in A group 24.0, 2 workers in B group 7.0, 3 workers in C group 25.7. Twenty workers complained of symptoms which were mainly irritation of mucosa including the respiratory system and itching of the skin while they were working, and accelerated nasal discharge, urticaria and asthma after working. Group A and group B were higher than group D in the rate of respiratory complaints in C.M.I. (p less than 0.001). Fourteen workers pointed out anti-inflammatory enzyme as a cause of main symptoms, 7 workers flufenamic acid, 3 workers flopropion, 4 workers antibiotics. Three workers who had past history of asthma or articular rheumatism had been transferred to other sections. Of 18 workers who were physically examined, 11 workers showed positive reactions to skin scratch tests with handling drugs. On 8 workers of them, some kinds of drugs which were pointed out as drugs causing main symptoms reacted positively. Numbers of workers with increased immunoglobin values were, IgE 3, IgM 2, IgA 4, IgM 2. Two workers showed decreased FVC and FEV (1.0 sec.) values in pulmonary function tests. The causes of the occupational allergic reaction in this factory are guessed as follows: 1) control of powdered materials was incomplete in the process of production, 2) various kinds of sensitizing drugs were handled by the same workers.


[Peritoneoscopy in infancy and childhood, indications, technique and diagnostic value (author's transl)].

Indications, technique and diagnostic value of peritoneoscopy in infancy and childhood are reviewed from the literature; own results are discussed as well. Peritoneoscopy is an important procedure in the diagnosis of chronic inflammatory liver disease and gonadal dysgenesis in this age group. If other diseases are suspected, non-invasive examination techniques may give sufficient diagnostic information.


[Alpha 1-antitrypsin deficiency, liver cirrhosis and pulmonary emphysema (author's transl)].

It is well known that incidence of chronic obstructive lung disease in adult patients with alpha 1-antitrypsin deficiency (ATD) is high. Adult carriers of this genetic trait with cirrhosis of the liver, and also with fibrosis of the liver and hepatoma, have been reported. A causal relationship between ATD and liver lesions has been suspected. In most cases liver disease has been recognized at post morten, - in a few cases, however, intra vitam, when severe symptoms of the liver disease had become apparent. The case of a 59 year-old patient is reported with PIZZ-homozygous ATD, moderate pulmonary emphysema and with marked portal fibrosis and focal transition in cirrhosis of the liver without any sequelae. The clinical course has been rather benign so far.


Effect of endurance training on myocardial myosin adenosine triphosphatase activity of the dog.

Endurance exercise training has been found to enhance the functional capacity of the myocardium in several animal models. The sub-cellular phenomena accompanying the augmented function are yet to be explained. The present study sought to determine if the myosin ATPase activity of cardiac muscle increased as a result of endurance conditioning. Five beagles trained by running on a motor driven treadmill (T) and five control (NT) animals were studied. Follwoing 10 weeks of training the T group had a significantly (P less than .05) lower heart rate than the NT while performing the same submaximal exercise and the gastrocnemius cytochrome oxidase activity was significantly greater (P less than .005) in the T than in the NT. These two measurements established that the exercised animals were physically trained. Myosin was isolated from the left ventricular myocardium and activated in a medium containing K-EDTA. No significant (P less than .05) difference in maximum myosin ATPase activity was observed between the NT and T groups in cardiac muscle. It was concluded that cardiac muscle myosin ATPase activity was not affected by 10 weeks of endurance conditioning induced by treadmill running in dogs.


Loss of rac locus DNA in merozygotes of Escherichia coli K12.

DNA-DNA hybridization was used to demonstrate that the substituted DNA in the bacteriophage lambda recE (formerly called lambda reverse) is homologous to DNA at the rac locus in Escherichia coli. Strains that are rac- do not contain appreciable amounts of this DNA, and it is lost from a rac+ episome (F' 123) after transmission to a rac- recipient. This is consistent with the proposal that the rac locus contains a cryptic prophage (Low, 1973).


Lambda transducing phages derived from a FinO- R100::lambda cointegrate plasmid: proteins encoded by the R100 replication/incompatibility region and the antibiotic resistance determinant.

Three lambda transducing phages have been isolated from pEDR20, an R100::lambda cointegrate plasmid in which the lambda insertion inactivated the R100 finO gene. Physical analysis of the three phages showed that the lambda is inserted at kilobase coordinate 81.3 of R100. All three phages carry different amounts of R100 DNA in the left arm of lambda. Each pahge contains ISlb, the mer genes and the region between coordinate 81.3 and 88.6; thus, all contain the genes necessary for R100 replication. One phage, VA lambda 73, contains the entire r-determination of R100 in addition to the above DNA. Five proteins coded by the region between 81.3 and 88.6 were detected. These had subunit molecular weights of 10,400; 12,200; 16,200; 19,600; and 38,300. The first was made constitutively and the other four only from a lambda promoter. Other constitutive proteins were one from the cml fus region with a molecular weight of 22,400 (cml) and two from the str sul region with molecular weights of 31,500 (str?) and 30,100 (sul?). Mercuric ion induced synthesis of at least 10 proteins. Six of these were known from earlier work. The total size of the proteins which appear to derive from the mer genes exceeds by a factor of 1.5, the coding capacity of this region without overlapping genes. Some, or all of these extra proteins may be chromosomal in origin, possibly derepressed in response to mercury gene products.


Cloning the trpR gene.

In Escherichia coli, the structural gene for purine nucleoside phosphorylase, deoD, is subject to insertional inactivation by prophage lambda. From one such secondary site lambda lysogen, strain SP265, one may isolate deletions that remove all or part of the trpR gene and other genes in the deo-thr sector of the E. coli chromosome. Specialized transducing phages harboring serB+ and trpR+ were liberated following induction of SP265. All such phages were N-defective, bio-type pseudolysogens whose DNA persisted in the form of plasmids. A collection of transducing phages, differing in their complement of bacterial DNA, was used to locate cleavage sites for BamHI, SalI, and PvuI within the deoD-trpR region of the E. coli genome. The trpR gene lies within a specific 950 base pair BamHI-PvuI segment. A 1250 base pair BamHI fragment carrying a functional trpR gene was cloned into the amplifiable plasmid pBR322. A single SalI site in this fragment was shown to lie within the TrpR gene. In two situations where increased gene dosage might generate elevated amounts of Trp repressor (N-defective trpR+ pseudolysogens and strains harboring pBR322 trpR+ plasmids) neither tryptophan auxotrophy, enhanced sensitivity to DL-5-methyl-tryptophan, nor super repression of the tryptophan biosynthetic enzymes was observed.


Transcription and membrane attachment of bacteriophage lambda DNA in the absence of N function in the E. coli suA 1 mutant.

In the polarity suppressor strain psuA 1, we observe a partial N independence of both transcription and DNA-membrane attachment for a lambda NN mutant. These results, in agreement with the genetical data reported by Dambly et al. (1976), suggest that the N product and rho factor are involved in the same process but may not interact directly.


[Endomyocardiopathy and eosinophilia (author's transl)].

Clinical, laboratory, and necropsy findings in a male patient with marked eosinophilia and fatal cardiac failure are reported. Necropsy revealed an obliteration of the left ventricle caused by endomyocardial fibrosis, left ventricle hypertrophy, and white thrombus. There was also found endomyocardial fibrosis and hypertrophy of the right ventricle. Pathogenesis and treatment of endomyocardiopathies are discussed.


The implantable infusion pump: a new concept in drug delivery.

Several of our most useful drugs cannot be administered orally. This paper is a summary of our work with a new drug delivery system: a totally implantable, continuous infusion pump, with a self-contained inexhaustible power source. Currently, after bench tests and animal experimentation, we have initiated clinical series utilizing this device to treat individuals with refractory thromboembolic conditions by intravenous heparin, and patients with localized solid tumors by intra-arterial chemotherapy. The use of this device for the infusion of insulin in the management of diabetes mellitus is yet in the laboratory stage of development. In addition to improving dy-today diabetic control and obviating the need for daily insulin injections, this pump offers an ideal opportunity to test whether optimal blood glucose control can significantly prevent or delay the onset of the crippling vascular complications of diabetes. The potential uses of this device, in many fields, are myriad.


Partial characterization of a phosphoryl group transferring enzyme in the membrane of catecholamine storage vesicles.

Phosphoryl group transfer from ATP to ADP occurred in the isolated membrane of catecholamine storage vesicles. The reaction was accelerated by extraction of the membranes with 50% (v/v) acetone and by treatment with 1% (v/v) Triton X-100. The phosphoryl group transfer reaction was activated by Mg2+ and by Mn2+. The activation profile differed from that obtained for the ATPase activity. The Michaelis-Menten kinetics of the phosphoryl transfer reaction were not entirely linear. From the linear parts of the double reciprocal plots KmATP approximately equal to 1 mM and KmADP approximately equal to 0.4 mM was obtained. All lines of the double reciprocal plots intersected indicating a sequential reaction mechanism. The reaction exhibited a narrow specificity for nucleoside diphospate and a broader one for nucleoside triphosphate indicating that ADP was the true substrate. The transfer reaction was slightly inhibited by AMP, orthophosphate and P1, P5-di(adenosine-5')pentaphosphate. The thiol reagents, N-ethylmaleimide and para-chloromercuribenzoate (PCMB), affected the ATPase activity and the phosphoryl transfer activity differently: with the blockade of 2.4 essential thiol equivalents by N-ethylmaleimide the ATPase was inhibited 50% and net uptake of catecholamine ceased, while the phosphoryl transfer remained unimpaired. PCMB affected both, the ATPase activity and phosphoryl transfer reaction. Treatment of the membranes with dithioerythritol prevented the PCMB-induced inhibition of the phosphoryl transfer, but was ineffective in protecting the ATPase activity, indicating that different thiol groups must be involved in the both enzymatic activities.


Evidence for a receptor supersensitivity following impairment of central serotoninergic activity in the rabbit.

In order to investigate whether a chronic impairment of neuronal serotoninergic transmission in the CNS could result in a receptor supersensitivity, rabbits were pretreated either with 5,6-dihydroxytryptamine (5,6-DHT) or p-chlorophenylalanine (PCPA) and then tested for their hyperthermic response to serotoninergic agonists. A previous (10 days before) intracerebroventricular injection of 5,6-DHT (75 microgram into each cerebral ventricle) significantly potentiated the increase in body temperature induced either by quipazine (1 mg/kg i.v.) or by 5-hydroxytryptophan (5-HTP 2 mg/kg i.v.) in combination with a MAO inhibitor (phenylethylhydrazine 10 mg/kg i.v. 16 h before). Pretreatment with PCPA (100 mg/kg s.c. four times on alternate days, the last dose 48 h before the experiment) also enhanced the hyperthermic effect of quipazine, whereas it inhibited the hyperthermic response to 5-HTP plus MAO inhibitor. These results suggest the existence of a receptor supersensitivity following prolonged blockade of serotoninergic neuronal transmission in the CNS.


Inhibition of cell-mediated cytotoxicity against tumor-associated antigens by suppressor lymph node cells from mice bearing methylcholanthrene-induced sarcomas.

Suppression of cell-mediated cytotoxicity directed against tumor-associated membrane antigens of methylcholanthrene (MC)-induced sarcomas by lymph node cells (LNC) from tumor-bearing mice was examined by inhibition of the 3H-thymidine incorporation assay. Normal LNC from B10 mice had been sensitized in vitro by 6-day cultivation on layers of irradiated syngeneic sarcoma cells and the effect of the generated cytotoxic lymphocytes was then inhibited by the admixture of suppressor cells present in lymph nodes of tumor-bearing mice. Suppressor cells were detected in lymph nodes from 7 of 16 (44 per cent) individually examined tumor bearers when LNC were added to cytotoxic lymphocytes which had been presensitized in vitro. When the experimental schedule was reverted and the tumor bearers' LNC were admixed to the normal LNC prior to the in vitro sensitization so that they were present in the population of the effector cells throughout the period of sensitization, the suppressor effect was detected in only 1 of 9 (11 per cent) tumor-bearers. The suppressive effect of tumor bearers' LNC was found to be nonspecific, being elicited not only by LNC derived from bearers of the sensitizing tumor, but also by LNC from bearers of an unrelated, immunologically noncross-reacting MC-induced sarcoma.


Extrusion of peritoneal catheter through abdominal incision: report of a rare complication of ventriculoperitoneal shunt.

A rare complication of a ventriculoperitoneal shunt is reported. The peritoneal catheter extruded through the well-healed abdominal incision. This is the first report of such an occurrence in an adult patient.


Evaluation of electrode array material for neural prostheses.

Matrix support materials for brain surface electrodes used in neuroprosthetic applications were evaluated after chronic subdural implantation over the parietal cortex of the cat. Four types of array fabricated with Silastic, Dacron mesh, or platinum wire annuli were implanted for periods ranging from 5 weeks to 1 year. We evaluated the arrays by access resistance measurements and gross and histological observations of the tissue beneath both nonstimulated and stimulated electrodes. A porous type matrix constructed of Dacron mesh proved to be the superior design because of its minimal compression of the cortical surface, facility of handling during implantation and autopsy, and satisfactory electrical characteristics provided by a good electrode-brain interface. (Neurosurgery, 5: 681--686, 1979).


Oesophageal ulceration due to slow-release potassium in the presence of left atrial enlargement.

Ulceration of the oesophagus was suspected clinically and confirmed radiologically in a patient with an enlarged left atrium while on treatment with slow release potassium chloride. Its discontinuation resulted in resolution of symptoms. This potentially serious complication of treatment should be considered in patients with enlargement of the left atrium who develop dysphagia. It is avoided by using soluble forms of potassium chloride replacement.


Ocular findings in cytogenetic syndromes.

Several cytogenetic syndromes are reviewed, and the salient ocular and facial abnormalities that might lead to a diagnosis are pointed out. Examples are given of mongoloid slant to the palpebral fissures, not only in Down's syndrome, but also in monosomy 9p, where, in addition, the triangular skull is almost diagnostic. Antimongoloid slant is found in trisomy 9p, where the eyes also have enophthalmos of monosomy 9p. Hypertelorism is another common finding in these syndromes; in monosomy 5p it is almost always present, although it occurs in other conditions as well, including trisomy 12p. The ring 22 syndrome has a distinguishing finding called "doe's eyes" because of the shape of the palpebral fissures. Trisomy 13 has numerous ocular findings as well as skull and facial involvements.


Psychological disturbance and pain report differences in both organic and non-organic low back pain patients.

Patients with undiagnosable low back pain have been observed to differ from patients with proven low back pain in their clinical description of pain and in their psychological status. More variable and diffuse pain qualities are emphasized in their clinical reports and more psychological disturbance characterizes them as a group, suggesting an association between pain expression and psychological disturbance. One hundred and two patients with low back pain were administered a standardized pain questionnaire to determine more systematically the association between pain expression and psychological disturbance in patients with and without demonstrable organic disease. Patients with psychological disturbance differed significantly from patients without psychological disturbance in the following ways. They used more words in their description of pain, distributed these words over more pain factors, and endorsed significantly more pain of the affective and skin pressure variety. The results underscore previous clinical impressions and suggest that patients without either organic or psychological findings may be cases of undiagnosed organic disease.


Skeletal muscle analysis of wheelchair athletes.

The present study reports the results of using the biopsy technique with members of the Canadian Wheelchair Internation Team. The results demonstrate that these athletes possess muscles with large fibre areas than seen in Olympic athletes.


Instantaneous measurement of glomerular filtration rate in the isolated perfused rat kidney.

In perfusion studies on the isolated cellfree perfused rat kidney, the glomerular filtration rate (GFR) can be controlled if the GFR can be measured instantaneously. This paper reports on a GFR meter which opens this possibility. Vitamin B12 is used as a marker for the GFR. A bubble flow meter determines urine flow rates ranging from 10 up to 200 microliter-min-1. A fiberoptic colorimeter measures vitamin B12 concentrations in the urine up to 400 mg-l-1. The flow meter and the colorimeter are described in detail. The reliability of vitamin B12 as a marker for the GFR is demonstrated and, moreover, the identity of GFR values obtained with the GFR meter and those from B12 spectrophotometry is demonstrated.


[Dictyocaulus viviparus in Denmark. A survey of 15 years' diagnostic examination of faeces samples (author's transl)].

On the basis of routine diagnostic examinations of 12424 bovine faeces samples for larvae of Dictyocaulus viviparus, performed during the period 1963 through 1977, some calculations and reflections have been made on the incidence and epidemiology of lungworm infection in cattle in Denmark. It seems justified to conclude that dictyocaulosis is an important disease in heifers and cows as well as in calves. A distinct seasonal variation in the incidence of lungworm infection is apparent, in that more than 85% of the faeces samples were submitted within the period July through October. Lungworm larvae could be demonstrated in faeces samples from cattle during the winter and spring- This is considered to be of great importance with a view to re-establishment of the infection in the following grazing season. Overwintering of larvae on pastures seems possible. too, since patent infections among calves were demonstrated already in May and June. A comparison of meteorological data with totals of samples submitted and with relative numbers of positive samples seems to confirm, that both the level and the spread of lungworm infections are influenced by the amount of rainfall during the period June through August.


[The repair of inguinal hernia by insertion of prosthetic material with tunnelisation of the spermatic cord (author's transl)].

A mersilene plate, cut according to the technique of Zagdoun, usually fixed to the conjoint tendon (in front of the latter) and to the inguinal ligament, is turned in front of the spermatic cord in the form of a cuff attached to itself and the aponeurosis of the obliquus externus. Thus strengthens the deficient deep and superfical anatomical layers in cases of large or recurrent inguinal hernia.


[Controlled therapeutic "evisceration" in so-called "terminal" peritonitis (author's transl)].

Absence of closure of the abdominal wound following reoperation for severe peritonitis is an additional therapeutic technique in dealing with peritoneal infection. However, this technique poses the problem of covering the loops of the small intestine in order to avoid fistulisation in the exposed viscera. The loops are initially protected by a "wound protector" or covered with a plate of polyurethane foam. Secondarily, when the peritoneal cavity is clean, the open wound is converted to an incisional hernia by a thin dermo-epidermal graft in strips, applied to the granulation tissue. This technique is effective and would seem to be simpler than detachments, plasties and relieving incisions.


Cleavage of single-stranded DNA by the A and A* proteins of bacteriophage phi X174.

The purified A protein and A* protein of bacteriophage phi X174 have been tested for endonuclease activity on single stranded viral phi X174 DNA. The A protein (55.000 daltons) nicks single-stranded DNA in the same way and at the same place as it does superhelical RFI DNA, at the origin of DNA replication. The A* protein (37.000 daltons) can cleave the single-stranded viral DNA at many different sites. It has however a strong preference for the origin of replication. Both proteins generate 3'OH ends and blocked 5' termini at the nick site.


Studies on the binding of lambda Int protein to attachment site DNA: identification of a tight-binding site in the P' region.

We have used three approaches to studying the interaction of lambda Int protein with bacteriophage attachment site DNA, POP': location of binding sites by retention of DNA fragments in a filter binding assay, reconstruction of a binding site by DNA synthesis and protection of a binding site from an exonuclease. Retention of restriction fragments on nitrocellulose filters in the presence of Int protein was used to locate binding sites. A high affinity binding site lies in P' between base pairs -6 and +173 from the center of the common core sequence, and low affinity sites are found in the 200 base pair region left of position -6. Reconstruction of the high affinity binding site region from the right using primed DNA synthesis and testing for filter binding in the presence of Int protein shows that sequences sufficient for tight binding of Int protein lie to the right of position +66. When attachment site DNA is protected by bound Int protein against digestion by exonuclease III, four Int dependent protection bands are seen in positions +58, +68, +79 and +88. This can be interpreted either as showing that four Int protein monomers bind to the high affinity region in series, or as evidence for wrapping of the DNA around Int protein, leading to structural changes resembling those occurring to DNA in nucleosomes.


Size fractionation of DNA fragments by liquid-liquid chromatography.

A method for the fractionation of double-stranded DNA fragments from 150 to 22000 b.p. in size by liquid-liquid chromatography is described. The procedure makes use of the fact that the partitioning of DNA in a polyethylene glycol-dextran system is size dependent and can be altered by alkali metal cations. Cellulose or celite are used as supports for the stationary, dextran-rich phase. Examples show the fractionation of digests of T7 DNA produced by Dpn II and Hind II restriction endonulceases as well as lambda DNA digests produced by Hind III and Eco RI restriction endonucleases.


Possible role of the serotonergic system in the behavioral effect of massed electroconvulsive shock in rat.

Massed electroconvulsive shock (ECS) inhibited escape in a one-way avoidance system and tolerance to this effect developed in rats shocked for 4 consecutive days (1, 4, 5 and 10 ECS respectively). Chronic treatment with p-bromo-N-methylamphetamine (V-III) as well as pretreatment with pCPA antagonized the behavioral disturbing effect of massed ECS strongly supporting the idea that 5-HT plays an important role in observed behavioral effects.


Molecular cloning of human epsilon-globin gene.

Human beta-like globin genes were investigated by use of rabbit beta-globin cDNA plasmid as a cross-species hybridization probe. Normal and beta 0/delta beta 0 thalassemic DNA were compared by filter hybridization procedures. It proved possible to demonstrate that the rabbit probe detected G gamma, A gamma, delta, beta, beta 0, and delta beta 0 human globin genes as well as an additional unidentified beta-like globin gene. By use of an agarose gel elution procedure, fractions of HindIII-digested DNA enriched for beta-like globin genes were purified. One of these fractions, 8.0 kilobases in size, was clonedinto lambda 788, and EK2 lambda HindIII vector. A positive clone was obtained and characterized by restriction mapping and sequence analysis. The sequence data obtained predicted an amino acid sequence that exactly matches a part of human epsilon-globin. The human non-alpha-globin locus is now nearly complete. delta, beta, and gamma human globin genes have already been cloned and analyzed. We describe here the cloning of the remaining non-alpha-globin gene, epsilon.


Dynein binds to and crossbridges cytoplasmic microtubules.

Dynein isolated from Chlamydomonas flagellar axonemes binds to microtubules assembled in vitro from 6S brain tubulin dimers. The dynein arms bind periodically along the length of the microtubules with a center-to-center spacing of 24 nm, equal to the periodicity of dynein arms on intact axonemes. The arms project from the in vitro assembled microtubules at an angle of approximately 55 degrees, thereby defining microtubule polarity. Dynein cosediments with microtubules through a sucrose gradient, as demonstrated by electron microscopy, gel electrophoresis, and ATPase analysis. In addition, dynein induces crossbridging between adjacent microtubules. Darkfield microscopy reveals that microtubules containing dynein are aggregated into large bundles; electron microscopy indicates that microtubules of the same polarity are crossbridged by a regular array of arms. Viewed by darkfield microscopy, addition of ATP to crossbridged microtubules causes their disaggregation; electron microscopy shows that the majority of these microtubules are no longer crossbridged. These observations are applicable to the determination of microtubule polarity and directionality of microtubule assembly in situ and suggest a role for dynein in cytoplasmic microtubule-based cellular movements.


Increased expression of a eukaryotic gene in Escherichia coli through stabilization of its messenger RNA.

The expression of a cloned eukaryotic gene [catabolic dehydroquinase (3-dehydroquinate hydro-lyase, EC 4.2.1.10) (qa-2+) from Neurospora crassa] is dramatically increased (as much as 100-fold) in Escherichia coli strains deficient in polynucleotide phosphorylase (pnp) (polynucleotide: orthophosphate nucleotidyltransferase, EC 2.7.7.8) and RNase I (rna). The increased expression is controlled primarily by the absence of polynucleotide phosphorylase and appears to be specific for the eukaryotic gene. No increase in the specific activity of either chromosomal or plasmid-borne prokaryotic genes has been observed. In polynucleotide phosphorylase-deficient strains of E. coli the half-life of plasmid (pVK88, ampr qa-2+)-encoded mRNAs increases from 1.0 to 2.8 min. This increase must be due primarily to stabilization of the aq-2 mRNA because no increase in the half-lives of pBR322 vehicle mRNAs was observed in polynucleotide phosphorylase-deficient strains. These results suggest that there are inherent structural differences between prokaryotic and eukaryotic mRNAs.


Gene expression of an Escherichia coli ribosomal RNA promoter fused to structural genes of the galactose operon.

The promoter region of the rrnB ribosomal RNA gene of Escherichia coli has been ligated within the epimerase gene (galE) of the galactose operon in a lambda phage vector. The recombinant lambda phage has been characterized by restriction mapping and assays of both galK (galactokinase) gene activity and galactose messenger RNA hybridization. In such lyosgens, expression of the fused galactose operon occurs as a function of growth rate in a manner characteristic of ribosomal RNA gene expression and is subject to stringent control by amino acid availability for protein synthesis. Galactose messenger RNA arising from the ribosomal promoter is not as metabolically stable as ribosomal RNA.


Role of thymidylate synthetase activity in development of methotrexate cytotoxicity.

Methotrexate (MTX) inhibition of the growth of mouse or human leukemia cells in culture was partially prevented by either thymidine (dThd) or hypoxanthine. 5-Fluoro-2'-deoxyuridine (FdUrd) also decreased the growth-inhibitory potency of MTX in the presence of small concentrations of 5-formyltetrahydrofolate (citrovorum factor) and sufficient exogenous dThd to support the synthesis of thymidylate nucleotides by salvage mechanisms. In addition, citrovorum factor-induced reversal of MTX was several orders of magnitude more efficient in the presence of both FdUrd and dThd than in the presence of dThd alone or in the absence of both nucleosides. Likewise, the presence of FdUrd (3 microM) and dThd (5.6 microM) completely prevented the lethality of 0.3 mM MTX to L1210 cells in culture medium supplemented with micromolar concentrations of citrovorum factor. We propose that this protection against the cytotoxic effects of MTX by dThd, hypoxanthine, and FdUrd have a common biochemical mechanism--namely, inhibition of the de novo synthesis of thymidylate by either a direct [FdUrd; inhibition of thymidylate synthetase (thymidylate synthase; 5,10-methylenetetrahydrofolate:dUMP C-methyl-transferase, EC 2.1.1.45)] or indirect (dThd and hypoxanthine; feedback inhibition by anabolites on ribonucleotide reductase and deoxycytidylate deaminase) effect. The resultant decreased rate of loss of reduced folates due to de novo thymidylate synthesis would allow a higher degree of inhibition of dihydrofolate reductase to be endured without damage to the cell.


Migration of Schwann cells and wrapping of neurites in vitro: a function of protease activity (plasmin) in the growth medium.

In vitro conditions were defined under which Schwann cells, from a population of dissociated embryonic chicken spinal cord cells, migrate along the growing neuronal fibers and wrap bundles as well as individual axons, in a pattern similar to that found in a developing peripheral nervous system in vivo. The migration of Schwann cells and their wrapping of nerve fibers was found to be a function of plasmin activity in the growth medium. It was determined that at least one cell type among the spinal cord cells is producing plasminogen activator, the enzyme that activates the plasminogen that is a constituent of any serum. It is concluded that, to achieve wrapping of neurons by Schwann cells in culture, it is essential to have an active plasmin-generating system in the medium. It is hypothesized that the Schwann cell produces plasminogen activator. The possible role of both the Schwann cell and the plasminogen possible role of both the Schwann cell and the plasminogen activator in the formation of the neuromuscular junction is discussed.


DNA from recombinogenic lambda bacteriophages generated by arl mutant of Escherichia coli is cleaved by single-strand-specific endonuclease S1.

When propagated on arl strains (a subclass of Escherichia coli hyper-rec mutants), lambda "Red-" duplication phages accumulated an enhanced potential for recombination. The physical properties of the recombinogenic phages thus obtained ("Arl-" phages) were similar to those of phages grown on arl+ bacteria. However, Arl- phage DNA was cleaved by endonuclease S1 under conditions such that the nuclease is specific for single-stranded DNA;DNA from control phages was S1-resistant. The number of S1 sites (defined by the apparent decrease in single-strand molecular weight) reached a maximum (seven to nine sites per strand of lambda DNA) after five or six rounds of growth on arl bacteria. Similarly, the recombinogenicity of Arl- phages reached a limiting value (recombination frequency, 15%) that was 5 times that of Arl+ phages. Recombinogenicity and S1 susceptibility were accumulated concomitantly during growth on arl+ bacteria. If all increased recombination occurred at the S1 sites, then these regions (about 40 bases each) were about 300 times as recombinogenic as normal DNA regions of the same size, and 1.5 times as recombinogenic as UV-induced lesions. Chromosomal DNA and plasmid DNA (pBR322) from arl cells were more susceptible to nuclease S1 than was DNA from arl+ bacteria. Analysis of the cleavage products suggests that the S1 sites on Arl- lambda phage DNA are located randomly.


DNA-directed in vitro synthesis of proteins involved in bacterial transcription and translation.

The in vitro synthesis of elongation factor (EF)-Tu (tufB), the beta beta' subunits of RNA polymerase, ribosomal proteins L10 and L12 directed by DNA from the transducing phage lambda rifd 18, EF-Tu (tufA), EF-G, and the alpha subunit of RNA polymerase directed by DNA from the transducing phage lambda fus3 has been investigated in a crude and a partially defined protein-synthesizing system. Proteins L10 and L12 are synthesized in the partially defined system almost as well as in the crude system. However, the synthesis of EF-Tu, EF-G, and the alpha and beta beta' subunits of RNA polymerase is far less efficient in the partially defined system. An active fraction that stimulates the synthesis of these latter proteins has been obtained by fractionation of a high-speed supernatant on DEAE-cellulose. Because previous studies showed that this fraction (1 M DEAE salt eluate) contains a protein, called L factor, that stimulates beta-galactosidase synthesis in vitro, L factor was tested for activity. Although L factor stimulates the synthesis of the beta beta' subunits, it has little or no effect on the in vitro synthesis of the other products studied. In the present experiments, the ratio of L12/L10 and of EF-Tu (tufA)/EF-G formed is 4-6. These values are consistent with in vivo results.


Identification of the lexA gene product of Escherichia coli K-12.

The Escherichia coli lexA gene encodes a product important in induction of the recA gene and the expression of various cellular functions, including mutagenesis and prophage induction. As a start in a biochemical analysis of the lexA function, a family of lambda transducing phages carrying lexA+, lexA3, lexA3 spr-54, and lexA3 spr-55 alleles of the lexA gene was isolated and characterized. Polypeptides synthesized by these phages were examined. lambdalexA+ made a distinctive protein 24 kilodaltons (kd) in size. Lambda lexA3, which encodes an active mutant form of the protein dominant to wild-type function, made a slightly larger protein 25 kd in size. The latter protein was shown to be the mutant lexA3 gene product by the fact that lambda lexA3 spr-55, which carries an amber mutation in lexA3, made the 25-kd protein in hosts with an amber suppressor but not in a suppressor-free host. In hosts carrying a multicopy lexA3 plasmid, neither the 25-kd nor the 24-kd protein was made. This result suggests that lexA is autoregulated and that expression of the 24-kd protein made by lambda lexA+ is subject to the same controls. This and other evidence argues that the 24-kd protein is the product of the wild-type lexA+ gene.


The delta subunit of Escherichia coli DNA polymerase III holoenzyme is the dnaX gene product.

The delta subunit of DNA polymerase III holoenzyme has been purified extensively with an assay for phi X174 DNA synthesis using core (pol III) and beta and gamma subunits. Either the purified delta subunit or the purified DNA polymerase III holoenzyme can complement a defective enzyme fraction from the conditional replication mutant SG133 described by Sevastopoulos et al. [Sevastopoulas, C.G., Wehr, C.T. & Glaser, D. A. (1977) Proc. Natl. Acad. Sci. USA 74, 3485-3489]. It has been established by Henson et al. [Henson, J.M., Chu, H., Irwin, C.A. & Walker, J.R. (1979) Genetics 92, 1,41-1059] that SG133 has two temperature-sensitive mutations, called dnaX and dnaY. The crude enzyme source from dnaX can be complemented by the delta subunit and by DNA polymerase III holoenzyme. By contrast, the core DNA polymerase III and the beta and gamma subunits are unable to complement this defective enzyme fraction. Thus, the delta subunit of DNA polymerase III holoenzyme appears to be the dnaX gene product of Escherichia coli.


Fluctuations in polarized fluorescence: evidence that muscle cross bridges rotate repetitively during contraction.

Particular thiols of the myosin subfragment 1 moieties of single glycerinated muscle fibers are covalently labeled with rhodamine. By using appropriate solutions such fibers can be relaxed, be in rigor, or develop active isometric tension. The rhodamine is excited by polarized 514.5-nm laser light; the greater than 580-nm fluorescence is resolved into orthogonal components and the intensity of each is measured by a computer-interfaced photon counting system. Fluctuations over-and-above noise appear in steady-state activity but not in relaxation or rigor and not when the fluorophore is actin-attached instead of myosin-attached. Fluctuations also appear in ratios of polarized intensities--quantities sensitive to fluorophore attitude but not to fluorophore number. The fluctuations are dominated by low (approximately 2 Hz) frequencies similar to separately measured ATPase frequencies. The fluctuations are ascribed to repetitive motion of the cross bridges to which the rhodamine is attached.


Presence of calmodulin in Tetrahymena.

Ca-dependent affinity chromatography on phenothiazine-Sepharose 4B has been used to isolate a pure protein from the ciliate Tetrahymena pyriformis. This protein has been identified as calmodulin by demonstrating three of the Ca-dependent activities attributed to calmodulins. Tetrahymena calmodulin also has physicochemical properties similar to those of the previously characterized mammalian, coelenterate, and plant proteins, except for a lower molecular weight (15,000) and slightly different CNBr fragments compared to bovine brain calmodulin. Calmodulin is a constituent of demembranated Tetrahymena cilia from which it can be extracted with the crude dynein fraction. Sucrose density gradient fractionation indicated its presence in fractions containing the 14S dynein ATPase. It is concluded that the essential properties of calmodulin have been highly conserved during much of eukaryotic evolution, and it is suggested that calmodulin plays a role in the control of ciliary motility in Tetrahymena.


Gene for the RNA polymerase sigma subunit mapped in Salmonella typhimurium and Escherichia coli by cloning and deletion.

The genes for the RNA polymerase sigma subunit (rpoD) and DNA primase (dnaG) of Salmonella typhimurium have been cloned into lambda vectors. Combined restriction, deletion and functional analysis of the cloned fragment allows us to map the genes precisely on the fragment, establishes the direction in which rpoD is transcribed, and reveals the existence of at least one new gene in the vicinity. A closely homologous, smaller fragment of Escherichia coli DNA, also cloned into lambda, contains rpoD and at least part of dnaG.


Operon-specific regulation of ribosomal protein synthesis in Escherichia coli.

We have cloned a DNA fragment harboring the genes for ribosomal proteins L2, L4, and L23 on a plasmid vector that contains a lac operator and promoter. The cloned ribosomal protein genes are now under the control of lacOP. Addition of a lac inducer to these cells results in a specific 5- to 10-fold increase in the synthesis of the proteins corresponding to the cloned genes. Within 10 min of this induction, the synthesis of ribosomal proteins S3, S19, L3, L16, L22, and L29 stops almost completely. The genes for all these proteins reside in the same chromosomal operon as L2, L4, and L23. We have seen no dramatic effect on the synthesis of any other ribosomal proteins. Thus, the induction of L2, L4, and L23 results in a specific and rapid decrease in the expression of all (or almost all) genes in their own transcription unit.


Impairment of antigen-presenting cell function by ultraviolet radiation.

UV light irradiation of BALB/c mice was found to result in impairment of antigen-presenting cell function. Adherent trinitrophenyl-derivatized cells from the peritoneal exudate cell population or the spleen of UV-treated donors could not induce hapten-specific delayed hypersensitivity responses in UV-irradiated syngeneic mice, whereas adherent trinitrophenyl-derivatized cells from normal mice were able to do so. The failure to induce immunity in UV-treated mice by utilizing UV-treated adherent antigen-presenting cells was associated with the development of antigen-specific suppressor T cells. The implication of these results for UV-induced carcinogenesis is discussed.


Influence of PCPA, shock level, and home-cage conditions on shock-induced aggression.

In a series of experiments, the effect of parachlorophenylalanine (PCPA) on shock-induced fighting was assessed rats raised and maintained under either a 12-hr alternating light-dark cycle (LD) or constant light conditions (LL). PCPA increased shock-induced aggression only in LL groups when testing was accomplished using a 2 mA shock; PCPA resulted in increased aggression in groups from the LD condition only when testing was done at 1 mA. A procedure that used castrated and intact cagemates to manipulate home-cage social experience provided evidence for a role for social experience in determining differences between LL and LD reared rats in shock-induced aggression. However, these data also suggested that home-cage social experience was not a factor in the lighting condition influence on the effect of PCPA on shock-induced aggression. Finally, a separate experiment demonstrated that diurnal rhythms in shock-induced aggression were disrupted by handling and vehicle injection in the control procedures, so the possible role of serotonin in diurnal rhythms of aggression behavior could not be assessed.


Effect of isatin (2,3-dioxoindoline) on audiogenic seizures in rats and its relationship to electrographic and behavioural phenomena.

In doses of 160 and 80 mg/kg, isatin (2,3-dioxoindoline) significantly reduced the total incidence of audiogenic epileptic seizures in rats highly sensitive to an acoustic epileptogenic stimulus. The number of severest forms of seizure (running, clonic convulsions) was higher than in the control tests, however. The acoustic epileptogenic stimuls was applied one hour after the i.p. injection of isatin. At that time some postural reflexes were still inhibited after 160 mg isatin/kg, while after smaller doses they were already normal again. One hour after administering isatin there were marked changes in the electroencephalogram, the chief ones being an increase in rhythmic episodic activity against a desynchronization background and a decrease in slow wave sleep activity.


A study of intestinal dipeptidases of rats: effect of in vivo mucosal exposure to vinblastine.

The mucosal population of small intestine of rats was exposed in vivo to various concentrations of vinblastine sulfate for 30 and 60 min and the activities of glycyl-L-valine and glycyl-L-leucine hydrolase were measured in the treated mucosa of the upper jejunal segment. A significant depression in the activity of these dipeptidases was observed which was further found to be dose dependent.


Effect of flavonoids on vitamin C activity of D-isoascorbic acid.

Large peroral doses of D-isoascorbic acid, a vitamin C stereoisomer (50 mg per animal per day), were retained in the guinea-pig organism to a smaller extent than the same doses of L-ascorbic acid (vitamin C). Simultaneous administration of the flavonoids rutin and epicatechin increased the amount of D-isoascorbic acid retained in the liver, brain and wall of the small intestine by up to 100%, but four weeks after its extraction from the food the amount of L-ascorbic acid left in the guinea-pig organism still exceeded D-isoascorbic acid reserves. This difference, which was found in all the organs studied, was the largest in the groups simultaneously given flavonoids. In guinea-pigs which, like man, are dependent on an exogenous vitamin C supply, D-isoascorbic acid was metabolized at a manifestly higher rate than L-ascorbic acid, irrespective of whether flavonoids were administered or not. In liver, brain and small intestine wall homogenates, the oxidized forms of both stereoisomers were reduced in the presence of reduced glutathione, but the reduction rate of D-isodehydroascorbic acid was higher and it was stimulated by the two flavonoids more strongly than the reduction of L-dehydroascorbic acid. The stuterospecific.


Electrophysiological analysis of retrieval of conditioned taste aversion in rats. Unit activity changes in critical brain regions.

Gustatory discrimination testing shows that rats with an overtrained conditioned taste aversion (CTA) to isotonic LiCl stop salt intake after 1 to 2 licks at the LiCl spout and move to the adjacent water spout within 0.7 s. Activity of 526 neurones from the nucleus of the solitary tract, gustatory thalamus, gustatory cortex, lateral and ventromedial thalamus, and amygdala was recorded in naive or CTA trained rats during the above gustatory discrimination. Post-stimulus histograms (PSH) triggered by water or salt licks or by spout switching were plotted for single units. Population responses of various regions were obtained by integration of the statistically significant excitatory and inhibitory intervals in the individual PSHs. Lick related changes of unit activity were orserved in 52% and 65% of neurones in control and CTA trained rats, respectively. The CTA training increased the incidence of units in which salt licking influenced the activity less than water licking. Presentation of the aversive fluid induced inhibition of unit activity in the gustatory cortex, ventromedial hypothalamus, and amygdala and excitation in the lateral hypothalamus. The changes started 100 to 150 ms after spout switching and culminated 100 ms later. Activity of the solitary tract nucleus and gustatory thalamus was affected less consistently. The results indicate that the gustatory cortex, amygdala and hypothalamus participate in CTA retrieval but a more specific identification of the electrical correlates of memory readout and of drinking control was not possible.


Electrophysiological analysis of retrieval of conditioned taste aversion. Physiological techniques and data processing.

New techniques suitable for electrophysiological investigation of retrieval of conditioned taste aversion (CTA) were developed. The gustatory discrimination apparatus consisted of two parallel drinking spouts (20 mm apart) equipped with photoelectric lick sensors. The spouts contained water or the aversive fluid (0.15 M LiCl), respectively, and their position could be rapidly (50 ms) interchanged with a reversive electromotor. Licking at either spout and the position of the fluids were recorded on one channel of a tape recorder. Unit activity was picked up with tungsten microelectrodes (40 micrometers) inserted into the brain of a freely moving rat with a head-mounted microdrive system (weight 2 g), fixed to an implanted guiding cannula. The electrode was connected through a head-carried FET signal follower to a wide band integrated circuit amplifier and the unit activity was recorded in the other channel of the tape recorder. The records were evaluated using an off-line computer program (LINC 8) consisting of a spike detection subroutine followed by amplitude histogram analysis. The mean (M) and SD values were computed for uni- or bimodal amplitude distributions of the principal spike components. Spike falling within the M+/-2 SD range of the selected parameter were identified as single units and used for construction of post stimulus histograms triggered by licking or by spout switching.


Urease activity in the contents and tissues of the sheep, pig and chicken gastrointestinal apparatus.

Urease activity, expressed as mg N-NH3/g dry weight per 30 min at 25 degrees C, was determined in the various parts of the sheep, chicken and pig digestive apparatus. The results were as follows. Sheep: contents--rumen 1.25"/-0.09, reticulum 0.78+/-0.02, omasum 0.44+/-0.02, abomasum 0.002+/-0.001, duodenum 0.003+/-0.001, jejunum 0.18+/-0.03, ileum 0.42+/-0.03, caecum 1.34+/-0.11, colon 0.76+/-0.08, walls-rumen 0.88+/-0.16, reticulum 0.38+/-0.04, omasum 0.11+/-0.02, abomasum 0.01+/-0.002, ileum 0.092+/-0.01, caecum 0.14+/-0.03, colon 0.16+/-0.02. Chicken: contents--jejunum 0.028+/-0.009, ileum 0.043+/-0.013, caecum 0.17+/-0.03, colon and cloaca 0.04+/-0.013. Pigs: contents--jejunum 0.02+/-0.01, ileum 0.14+/-0.08, caecum 0.62+-0.12, colon 0.43+/-0.06. No urease activity was found in the walls of the digestive apparatus or the contents of the duodenum in chickens, or in the walls of the stomach and intestine and the contents of the duodenum in pigs. The results show that urease activity in the digestive apparatus of pigs and poultry is lower than in sheep. Inadequate urease activity in the digestive apparatus explains why chickens and pigs are significantly less capable than ruminants of utilizing urea nitrogen as a substitute for some of the protein in the diet.


Endogenous urea secretion into the sheep gastrointestinal tract.

Urea turnover and the proportion of endogenous urea secreted and excreted in the saliva, the bile, the pancreatic juice and the urine and directly across the wall of the digestive tract was studied in 6 experiments, after a single i.v. dose of labelled 15N, in two adult sheep weighing 49 and 50 kg, with permanent biliary and pancreatic fistulus and with an exteriorized right parotid duct. It was found that, of the total amount of endogenous urea secreted into the animals' digestive tract (0.2694+/-0.0138 mg/min/kg b.w.), 10.27+/-0.94% reached the contents in the saliva, 2.12+/-0.28% in the bile and 0.66+/-0.08% in the pancreatic juice, and that 86.95+/-2.1% was secreted into the gastrointestinal tract, across its wall, from the blood capillaries. Exogenous turnover amounted to 0.3228+/-0.192 mg/min/kg. Of the total amount of 476.6 mg i.v. injected 15N urea, 274.1+/-8.86 mg was excreted in the urine 5.1+/-0.9 mg in the bile, 3.19+/-0.06 mg in the pancreatic juice, 4.96+/-0.76 mg via the right parotid gland and 9.34+/-1.09 mg in the faeces. The results show that the quantitatively most important part of the recirculation of endogenous urea is its passage from the blood across the wall of the gastrointestinal tract into its contents.


Postnatal development of postganglionic parasympathetic neurones in the heart of the albino rat.

Electrical stimulation of the sinoatrial node region of isolated atria in medium containing physostigmine (0.1 micrograms/ml) produces a negative chronotropic effect whose intensity and duration depend mainly on the amount of acetylcholine released from postganglionic parasympathetic fibres endings. This technique was used to study functional maturation of the given neurones during postnatal development of albino rats. Preparations from animals of different ages were stimulated with 2-second bursts of rectangular pulses (frequency 50 Hz, pulse duration 0.02 ms, voltage 22.5--27.5 V) and frequency changes of the preparation were registered by recording extracellular action potentials. At 10 days the negative chronotropic effect is very weak and at 15 days it is only slightly stronger, but at 18 days it is almost the same as in adult animals. At 24 and 34 days the reaction is somewhat stronger than in adulthood. It can be concluded from these observations that functional maturation of the postganglionic parasympathetic neurones innervating the sinoatrial node in albino rats occurs between the 10th and 20th day of postnatal life.


Postnatal changes in the amount of acetylcholine in the atrial tissue of the albino rat heart.

Changes in the acetylcholine (ACh) content and concentration in the atrial tissue of albino rats between the third day of postnatal life and adulthood were studied. The ACh content (ng in whole atria) rose during the whole of the period in question, from 5.6 ng at 3--4 days to 307.5 ng in adult rats. The ACh concentration (micrograms/g fresh tissue) rose up to the 53rd day after birth, when it attained adult values. The fastest increase in both the ACh content and concentration was observed between the 10th and the 17th postnatal day, when it amounted to over 46% of the total concentration increase between the third day of life and adulthood.


Postoperative causes of death of neonatal intestinal obstruction excluding mucoviscidosis and Hirschsprung's disease.

In contrast to the remarkable improvement in the results of operations for oesophageal atresia at the University Children's Hospital, Zurich, the death rate secondary to operations for neonatal intestinal obstruction has remained constantly high between the years 1960 and 1976. The results are distressing especially when it is realised that many of them occurred in infants with good general conditions. The causes of death are analysed and classified according the following criteria: 1. Deaths associated with trisomy 21. 2. Deaths due to the short gut syndrome. 3. Deaths due to severe associated malformations or other conditions. 4. Deaths probably due to surgical mistakes. 5. Deaths due to mistakes in management. The latter group can be subdivided further in deaths due to wrong decision at the primary operation, overlooked medical complications, overlooked surgical complications and mistakes made at subsequent laparotomies.


Gastroschisis and omphalocele.

A series of 100 patients with gastroschisis and omphalocele is presented. It is emphasized that gastroschisis generally has a strikingly homogeneous clinical presentation, while the omphalocele has a more heterogeneous clinical presentation, varying from the smallest to the largest, nearly incorrectable type. The main problem in the two groups is the problem of the closure of the defect. In gastroschisis there are, in addition, two problems related to the length of the intestinal tract and the tendency to peritonitis and septicaemia. In omphalocele, however, the major problem is the associated anomalies. The experience from the present material indicates that greater efforts must be used in the future in trying to avoid hypothermia, both during transportation and during operation. Furthermore, greater efforts must be made in closing the abdominal wall defect primarily in both groups of patients. More liberal use of respirator and total parenteral nutrition, mainly by peripheral veins, has obviously contributed to the improvement in our results from 1 60% mortality rate in the first nine-year period to a 37% mortality rate in the last nine-year period in the omphalocele group. Our best results have been obtained during the last 3 years with 2 deaths in the last 12 patients who all were treated by primary closure. In the gastroschisis group a survival rate of 69% in the whole series and of 74% in those who were primarily completely closed must be looked upon as progress in the light of earlier reports of survival rates of 36% to 43%.