Non-malignant perineural spread of epithelial tissue in the orofacial region. A 48 year-old male had two operations because of severe neuralgic pains in the region of the right infraorbital nerve. The first operative specimen consisted of connective tissue, striated muscle fibers and two myelinated nerve bundles, surrounded by a ring of well differentiated squamous epithelium. Initially the lesion was assumed to show perineural spread of cancer in this region. As the pain was not alleviated, a second operation was performed. The framework of the second specimen also consisted of connective tissue and muscle. It contained in addition an atheromalike cyst and some nerve bundles, ensheathed by well differentiated epithelial cells partly in a ring-, partly in a horseshoe-like pattern. The perineural epithelial sheaths could be traced to a rupture of the cyst, and to benign proliferation of its epithelial lining in the connective tissue and along the nerve bundles. Following the second operation the patient was relieved of his complaints. During the last five years he had repeated control examinations but no sign of malignant disease could be found; his state of health was perfect. Our finding of benign perineural spread of squamous epithelium has not been described previously. The nature of the so-called perineural lymph spaces is also discussed.


[Factor analysis in hypertension. Risks of coronary heart disease and hypertensive arteriolosclerosis (author's transl)]. Based upon factor analysis, initial findings of the risk factors for coronary heart disease are reported, following invesitgations performed on a large number of patho-anatomical cases which were selected for specified criteria. The so-called hypertensive form of arteriosclerosis was demonstrated in the spleen, pancreas, and adrenal gland. It was shown that diabetes mellitus is an influencing factor in arteriolosclerosis in the liver. Several types of arterial hypertension can be differentiated according to clinical features and findings in the heart. Renoparenchymatous and renovascular sclerosis, pyelonephritis, diabetes mellitus, and age are the factors correlated or associated with various types of hypertension. Primary (?) renal hypertension can be differentiated from the secondary (?) TYPE. The discussion suggests that the morphological findings of arteriosclerosis and its complications may be explained, to a certain extent, by the known risk factors of coronary diseases defined by the methods described.


[Coronary arteriosclerosis and risk factors in coronary heart disease (author's transl)]. A large number of cases were tested for the relevance of clinical risk factors in coronary heart disease with regard to coronary arteriosclerosis (atheroma, fibrosis; five different locations). The method applied was VARIMAX-rotated factor analysis. The resulting factors were interpreted as the multiple variables structures which are in different relationships to the risk criterion, coronary heart disease, and morphological vascular diagnosis of the coronary arteries. The importance of the known risk of the vascular diagnosis was estimated and the reterance of the clinically influencing criterion was discussed. It appears that in spite of limited methodology additional morphological criteria are required in order to be able to explain heart infarction which does not involve the epicardial branches of the coronary vascular system.


Fine structure of adrenal adenomata causing Cushing's syndrome. Adenomata taken from nine patients with Cushing's syndrome were observed  by electron microscopy. Agranular endoplasmic reticulum was prominently developed in all cases, occasionally fine dotty granules were observed in the tubules of agranular endoplasmic reticulum. Mitochondria showed a wide variety of changes in size, shape and internal structure, and somtimes contained electron dense droplets in their matrix. Mitochondria resembling those in the normal zona fasciculata intermingled with pathologically altered ones, suggesting that the adenomata which caused Cushing's syndrome were derived from the zona fasciculata. Fibrous structures were seen in the cytoplasm in one case. It is proposed that all of the changes in cellular organelles of the adenoma cells are correlated with increased secretory activity.


Unilateral renal hypoplasia with associated venous anomaly and hypertension. A study of the juxtaglomerular cells. A child with unilateral renal hypoplasia, high plasma renin levels and hypertension was found to have large numbers of juxtaglomerular granular cells in the affected kidney. They were seen adjacent to and sometimes in the interior of hyalinized glomeruli or, in loose nests scattered in the interstitium. Ultrastructurally they contained large numbers of crystalline protogranules in the Golgi region and also displayed other features suggestive of hyperactivity. Atrophic tubules, smooth muscle and mast cells were present in considerable numbers. Well-preserved renal cortex remained in the affected kidney with no demonstrable juxtaglomerular granularity. After unilateral nephrectomy the patient became normotensive and plasma renin levels became normal. Thus it appears that the juxtaglomerular cells are able to produce and release renin independent of the structural integrity of the juxtaglomerular apparatus and renal glomerulus.


[The usefulness of echocardiography in clinical cardiology (author's transl)]. The principle of the ultrasound examination of the heart is explained and the possible applications of this method are discussed. Three case histories are presented to exemplify the usefulness of echocardiography in clinical cardiology.


Eosinophil predominance in Hodgkin's disease. Re-evaluating 327 Hodgkin's disease biopsy specimens, 10 cases with dense eosinophilic infiltration, amounting to more than 50% of the cell population, have been found. This phenomenon of eosinophilic predominance, occurred mainly in the fibrotic types of Hodgkin's disease. The survival time of patients with eosinophilic predominance was significantly shorter than that of the controls. The possible role of eosinophils in Hodgkin's disese has been discussed.


On the histogenesis of osseous structures in epithelial tumours. A light and electronmicroscopical study illustrated at the so-called mixed tumour of the mammary gland in bitches (author's transl). The osseous areas of 126 canine mixed tumours of the mammary gland were studied by light microscopy. Seven cases were investigated in detail using the electronmicroscop. It is suggested, that these structures develop by enchondral ossification. There ist no indication that myoepithelial tumour cells play a role in formation of osteoid or osseous foci. The cells taking part in enchondral ossification in such tumours cannot be distinguished from cell normally found in enchondral ossification. They derive from the stroma growing into the chondroid matrix. Areas developed by enchondral ossification therefore cannot be considered as tumour tissue in the true sense.


Carcinogenesis tests of nitroso-N-methylpiperazine, 2,3,5,6-tetramethyldinitrosopiperazine, nitrosoisonipecotic acid and nitrosomethoxymethylamine in rats. Four nitrosamines; nitroso-N-methylpiperazine, 2,3,5,6-tetramethyldinitrosopiperazine, nitrosoisonipecotic acid and nitrosomethoxymethylamine, closely related in structure to potent carcinogens, were fed chronically to rats in drinking water for one year. No toxic effects leading to life shortening were observed. There was no significant incidence of any malignant tumor other than the endocrine tumors normally found in untreated animals of our colony. This indicated that the small changes in structure represented by these compounds were sufficient to reduce greatly, or eliminate, the carcinogenic action.


Therapeutic studies with BCG, cyclophosphamide and surgery alone and in combination on the autochthonous mammary carcinoma of the rat. In a randomized study the effects of BCG, cyclophosphamide and surgery alone and in combination on the mammary carcinoma (induced by 7,12-dimethylbenz(a)anthracene) of the rat were investigated. Surgical excision of the tumours increased the survival time. Cyclophosphamide retarded growth of tumours and delayed the appearance of relapses compared to surgery. A single, intravenous injection of BCG (10(7) viable organisms) showed no statistically significant retardation of tumours. Immunotherapy with BCG could not increase the effectiveness of cyclophosphamide or surgery or their combination.


[Intraepithelial spread of the squamous cell carcinoma of the uterine cervix into the endometrium. A contribution to the question of a surface spread of the cervical carcinoma]. Four cases have been reported in which a squamous cell carcinoma of the uterine cervix was spreading on the surface of nearly the whole endometrial cavity by expansive intra-epithelial growth. In one of these cases, in the portio, there was only a beginning invasion into the stroma, whereas in the other three cases the wall of the cervix was variably infiltrated. In two cases a change to infiltrating growth into the corpus uteri could be observed.


Experimental carcinogenesis in the resected colon of the rat. Until now, carcinoma of the large intestine resected previously for benign disease has not been published. However an increasing number of patients resected for Crohn's disease, diverticulitis or trauma may reach nowadays a high lifespan. On the other hand, it is known that the gastroenteral anastomosis is predisposed to cancer development. In this study, the question of whether the large intestine following colotomy or ileotransversostomy is sensitive to carcinogenesis is examined. Male Wistar rats, subjected to colotomy or resection and ileotransversostomy, were treated weekly by subcutaneous injection of 1,2-dimethylhydrazine (12 mg/kg body weight) for seven weeks. The animals were killed 54 weeks after the first injection. At autopsy, 21 out of 29 operated rats had developed adenocarcinomas of the remaining colon. Intact control animals had the same incidence of malignant degeneration of the large bowel. When the anastomosis is chronically irritated by inflammation or by formation of a diverticulum, development, of carcinoma near the stoma was observed. This was the case in three rats of 28 animals. The results demonstrate that the resected colon of the rat is not more sensitive to experimental carcinogenesis than the intact one.


Carcinogenicity of a food additive, AF-2, in hamsters and mice. The carcinogenicity of a food additive, 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide (trade name, AF-2), was studied. A diet containing AF-2 at a rate of 0.25% was administered to male golden hamsters and male ddY mice. The hamsters developed squamous cell carcinomas in the forestomach after the 49th day from the start of administration. In mice fed a AF-2 diet for 308 days, squamous cell carcinoma was observed in the forestomach after the 381th day from the start of the experiment; in some cases the carcinoma metastasized to the lung and liver.


Chronic oral administration of 1-nitrosopiperazine at high doses to MRC rats. 1-Nitrosopiperazine was fed to two groups of rats as drinking water solutions containing 400 mg/liter (3.5 millimolar) and 800 mg/liter (7.0 millimolar), respectively. The treatment was 20 ml per rat per day, 5 days per week for life. In both groups many animals died with olfactory tumors (mostly esthesioneuroblastomas), the first at 36 weeks in the higher dose group, the first at 64 weeks in the lower dose group. There was also a small number of liver tumors in both groups. None of these tumors was seen in the untreated controls. The similarity of this tumor distribution to that produced by 1,4-dinitrosopiperazine suggests that the observed carcinogenicity of 1-nitrosopiperazine may be entirely due to its disproportionation in the acidic medium of the rat stomach. Chemical data supporting this interpretation are presented.


Compared effects of N-hydroxyurethan, urethan and hydroxyurea on DNA synthesis. In vivo and in vitro studies. The effect of N-hydroxyurethan (HUR) on DNA synthesis has been tested both in vivo on various tissues and in vitro on concanavalin A (ConA)-stimulated rat thymocytes and compared with the action of urethan and hydroxyurea. HUR suppresses scheduled DNA synthesis, except that of non-stimulated spleen cells in vitro. The inhibition is efficient and rapid and takes place immediately if the drug is administered at the peak of the S-phase. UR inhibits DNA synthesis in vitro only at much higher doses and with different time course. It is effective or slightly effective if it is administered at the peak of the S-phase. A conversion of urethan into HUR the latter depressing DNA synthesis could partly explain the differences observed. No toxicity was found after treatment with drugs at the concentration employed. Finally, the relationships between drug doses and cell responses have been particularly observed in vivo.


Activation of chromatin-bound DNA-dependent RNA polymerase (E.C. 2.7.7.6.) in plant storage tissue slices. The synthesis of RNA by chromatin-bound RNA polymerase (E.C. 2.7.7.6.) from white potato tubers proceeds at a low rate, which is enhanced after slicing the tissue, however. Concomitantly DNA template availability as measured with saturating amounts of Escherichia coli polymerase is diminished drastically. Nearest neighbor frequency analysis proved that the RNA synthesized on chromatin of intact tubers is different from that synthesized on chromatin of sliced tissue. The RNA polymerase of white potato tubers is dependent on all four ribonucleoside triphosphates and a divalent metal ion such as Mg2+ or Mn2+ and totally inhibited by the presence of pyrophosphate. Actinomycin D blocks the formation of the RNA product, which could be shown to be a heteropolymer by nearest neighbour frequency technique. The Km of the chromatin-bound enzyme with regard to ATP, GTP, CTP and UTP was 5.1 X 10(-5) M, 1.6X10(-5) M, 0.9X10(-5) M and 0.45X10(-5) M/l respectively. alpha-amanitin inhibits the overall activity to about 50%, which indicates the presence of equal amounts of polymerase I and polymerase II.


13C NMR investigations on the stacking of 5'-AMP with tryptamine. Complex formation between 5'-adenosine monophosphate (5'-AMP) and tryptamine was investigated by measuring 13C chemical shifts and spin-lattice relaxation times. The chemical shift changes observed were attributed to ring current effects originating in the stacking of the two respective aromatic moieties and to puckering changes of the AMP ribose. Differences in the magnitude of the shifts of the aromatic carbons were related to the geometry of the complex and compared with those found for AMP selfassociation. Upon complex formation the relaxation times of especially the tryptamine indole carbons were greatly reduced, this was explained by an increase in the particle size. Small changes found for the AMP carbons in solutions without tryptamine result from AMP selfassociation. Deviations from isotropic motion observed for the non-aromatic moieties are discussed.


Competition between oxalate and phosphate during active calcium accumulation by sarcoplasmic vesicles. 1. During ATP supported active calcium uptake oxalate as well as phosphate are accumulated with calcium. The uptake of calcium exceeds that of both anions by a small quantity--accounting for calcium binding to vesicular proteins and lipids. 2. From assay media containing phosphate and oxalate--nearly exclusively either oxalate or phosphate are taken up together with calcium by the sarcoplasmic reticulum vesicles. The mutual exclusion occurs in a very narrow concentration range of the anions. 3. In solutions containing phosphate and oxalate, calcium phosphate or calcium oxalate precipitates are formed according to their solubility properties. 4. When phosphate prevents oxalate from being taken up, calcium transport is inhibited. Inhibition occurs, because the concentration of ionized calcium inside the vesicles rises approximately 100-fold when oxalate is replaced by phosphate. The activity of the calcium dependent ATPase parallels the calcium uptake activity. 5. It is excluded that the inhibition of calcium uptake produced by phosphate is caused by an enhanced permeability of the sarcoplasmic reticulum membranes for calcium in the presence of phosphate.


Renal aminoacylase, a zinc enzyme.

Renal aminoacylase, a zinc enzyme. Renal aminoacylase is inactivated by dialysis against metal complexing agents such as o-phenanthroline. Activity can be restored by addition of zinc ions. A zinc dissociation constant of about 10(-10)M at pH 7.8 is obtained by titration of the enzyme with a metal ion buffer. The reactivity of the SH groups of the enzyme is considerably affected by zinc ions. The enzyme contains two essential zinc ions per molecule.


Variability of conductivity changes in black phosphatidylserine membranes induced by proteins from erythrocyte membranes. The electrical conductivity of black phosphatidylserine membranes, in solutions of 100 mM NaCl, 10 mM sodium phosphate (pH 7.1), is strongly increased by the intrinsic proteins ("strongly bound" protein fraction) from human erythrocyte membranes. The magnitude of the conductivity increase is highly dependent on the maximum pH-value pH used during the preparation of the protein (8.0 less than or equal to pH less than or equal 11.8). For each pH, membrane conductivity lambdaf and protein concentration c are linked by the equation lambdaf=k-cs, k and s being functions only of pH. The value of s varies between 1.0 (pH 8) and 4.0 (pH 10). It is assumed that the protein-induced conducting sites, at least for protein pretreatment at pH less than or equal to 10, are assembled from four protein subunits. The incorporation of the subunits into the lipid bilayer is supposed to occur either as the final tetramer (pH 8) or as monomers (pH 10) and possibly dimers (pH around 9).


[Investigations of body fluids with low protein content by the combination of micro-disc-electrophoresis and electroimmunodiffusion (author's transl)]. Fluids of the human body with low protein content, i.e. aqueous humour, tears, cerebrospinal fluid, and urine were analyzed by a combination of micro-disc-electrophoresis and electroimmuno diffusion. By this method both qualitative and quantitative statements about the proteins of these fluids can be established.


Transfer of glycolipid between membranes of tissue culture cells, using dansylcerebroside as a model. Donor cells, which had incorporated dansylcerebroside in their membranes, could further transfer this glycolipid to monolayers of acceptor cells. The case of transfer varied among acceptor cells, BHK cells being the best and MDBK cells the poorest acceptors of the cells tested. The process of transfer seemed to be mediated by lipids rather than by proteins of the membranes. The mode of attachment between donors and acceptors, such as classified as loose contact, tight adhesion or binding by lectin, did not significantly influence the extent of glycolipid transfer. However, modification of plasma membranes by infection of acceptor cells with myxoviruses resulted in enhancement of glycolipid transfer in some cases. Various factors have been evaluated with respect to dynamics of cellular membranes.


Evolution of the transfer RNA molecule.

Evolution of the transfer RNA molecule. Base sequences of many transfer RNA (tRNA) species obtained from different sources contain homologous regions. These homologies, which are 6 to 20 nucleotides long, occur both within the same tRNA molecule and between many different tRNA molecules repeatedly. Since it is very unlikely an 80 or so nucleotide long tRNA molecule could have been formed at once, under primordial conditions, we propose that the homologous oligonucleotides found within the tRNA molecules to-day represent the earliest adapter from which tRNA molecules have evolved.


Isolation of messenger ribonucleoproteins from HeLa cells by affinity chromatography on poly (U) sepharose. Polysomes of HeLa cells were adsorbed on Poly(U)-Sepharose columns. This adsorption is probably due to poly(A) sequences at 3' terminus of the messenger. Stepwise elution initially removed ribosomal subunits thereafter mRNA and a set of proteins. These proteins are identical with the main components of the polysomal messenger ribonucleoprotein particles described previously. Thus, this method allows their rapid and easy separation from ribosomal and other proteins.


A method for the purification of large quantities of biologically active ribonucleic acid components from cowpea chlorotic mottle virus, a multicomponent plant virus. Cowpea chlorotic mottle virus RNA has been prepared in comparatively high yield (at least 50%) by a modified phenol extraction method. The preparation, which has high biological activity, has been resolved into four components by zonal centrifugation on a 15-40% (w/v) sucrose density gradient. The components obtained have been tested for biological activity against whole plants and plant protoplasts. Each of the two largest components RNA 1 and RNA 2 was by itself infective (50-90% of the specific infectivity of the whole genome) and produced virus-specific proteins (coat protein and P2) and RNAs ("RNA 3" and "RNA 4"). Contamination by small proportions (less than 10%) of neighbouring RNAs is presumed to be involved in this infectivity. The two smallest components were obtained in an almost pure form.


The structural components of hog cholera virus. Hog cholera virus grown in PK-15 cells and SK-cells was labeled with [35S]methionine and [3H]uridine. At least 3 polypeptides were resolved by polyacrylamide gel electrophoresis after disruption of the virus with sodium dodecyl-sulfate. The molecular weights of the structural proteins were determined to be 55000 (p55), 46000 (gp46), and 36000 (p36). The molecular weight of the viral RNA was determined to be about 4 X 10(6) in polyacrylamide-agarose-gel electrophoresis. In sucrose gradients the RNA has a S20,w value of 40-45S.


[Spontaneous leukemia of AKR mice. Successful passive immunization with goat antibodies against isolated glycoprotein gp71 of Friend leukemia virus]. The occurrence of fatal spontaneous leukemia in AKR mice could be drastically reduced by passive immunization with goat antibody against isolated murine Friend virus glycoprotein gp71, possessing high group specific reactivity. The success depended on the time of antibody application. The best results were achieved when mothers and babies were inoculated.


[Identification and determination of age of needle tracks in human skin (author's transl)]. Examination of enzymic activities and histochemical reactions on needle pricks can be used to determine the age of micro-injuries with sufficient exactness. Well preserved skin shows patterns of enzymes which also appear with other skin injuries and which were described in detail especially by Raekallio (1970, 1972). In autolytical changes of the skin the adenosinetriphosphatase-reaction is still reliable and can be successfully estimated. If one has sufficient experience it is possible to fairly exactly estimate the age of an injury within the first hour after the injury by preparation of the adenosinetriphosphatase-reaction. If the times of injections are known one frequently succeeds in determining the time of death by exactly determining the age of the injury. In legal expertises the histochemical reactions can rightly be regarded as useful indications of a certain age of the injury. But they do not allow an exact estimate "beyond a reasonable doubt".


[Significance of enzyme-histochemical examinations in the diagnosis of prostatic carcinoma]. With the help of literary data is reported on the results of the ferment histochemistry and its significance in the recognition of the biological behaviour of a tumour achieved during the experimental cancerogenesis. At the same time the value of this method in diagnosing the prostatic carcinoma is emphasized, taking into consideration the investigations carried out already on the prostate gland.


[Enamel bundles and lamellae under the scanning electron microscope]. Lamellae,  tufts and cracks were found in the enamel near the dentionenamel junction. When investigated by the scanning electron microscop, lamellae and tufts were very similar to each other as to their structure. Lamellae appeared in two kinds: 1. Organic material originating in the dentionenamel membrane filled the whole space. 2. The space was empty, yet an organic membrane was covering the walls of adjacent prisms. Tufts and lamellae differed merely in their lenght. The walls of the cracks lacked organic material, the prisms being damaged or their course interrupted.


[Treatment through special education].

[Treatment through special education]. The author discusses the problem of integration of disabled children, and he points out that the present practices of the Swiss invalidity insurance scheme have a counter-productive effect with respect to early detection and early treatment of children with behavioral disorders.


[Promotion of behavior disturbed children at the home for children]. The Home for Disturbed Children is a therapy centre with the main task to prepare later resocialisation in the children's previous environment. All the fields are conceived to this purpose. The new buildings are designed with respect to their pedagogic function, the rooms are clearly fitted for their end. The distribution of the children among the coeducatively led living communities (8-10 children) is done according to length of stay, possible cooperation with the parents and the structure of the respective group. The school (8 children per class at most) provides an education under the aspect of therapy, as the ability of the individual child can only be increased if his social maturity and his relationship with the environment are changed. In home therapy the manifold possibilities of appropriate attitude to work and adequate social behaviour are consciously included.


[Territorial differences in the occurrence of caries in Karl Marx Stadt children and adolescent after 12 years of water fluoridation]. Cariostatistical comparisons made since the start of drinking-water fluoridation in Karl-Marx-Stadt suggested territorial differences in the prevalence of dental decay. In the present paper an attempt is made to analyse the problems involved, with due consideration being given to both demographic and ecological factors.


[Evaluation of Noracryl 100 as a filling material]. There were carried out clinical, chemical and scanning electron microscopical investigations of the filling material Noracryl 100, a composite produced by the Soviet Union. This material is one of the composites of the first generation and there were discussed its advantages and disadvantages in face of other filling materials of that kind.


[Genetic studies in patients with trisomy 21 with special evaluation of morphology and pathogenesis in the orofacial region. Condition of periodontal and oral hygiene in trisomy 21]. The incidence and severity of parodontopathies and results of studies of the level of oral hygiene are reported, in terms of both subjective and objective parameters, for children and juveniles affected with trisomy 21. Also discussed are problems of age and sex dependence; causal, complementary, and reciprocal relationships; and possibilities of prophylaxis.


[The pathology of temporomandibular joint luxations--anatomical studies on temporomandibular joint preparations]. After a description of the published hypothesis of luxation and subluxation in the temporomandibular joint the preparations of five temporomandibular joints is described. The results refer to the movement of the discus and the capitulum mandibulae and to the effects of the musculus temporalis and of the facies articularis ossis temporalis. In addition a hypothesis is established according to which the temporomandibular-joint-luxation may be considered to occur in the menisco-condylar part of the joint.


[The synovial membrane of the temporomandibular joint. Histological and morphometric studies on 106 temporomandibular joints]. Thickness of synovial lining cell layers, cytological appearance of synovial cells, the grade of fibrosis, the distance between subsynovial blood vessels and synovial surface, possible inflammatory infiltrations etc. have been controlled in synovial preparates of 106 mandibular joints. The age dependent fibrosis of the synovial tissue has been demonstrated.


[Evaluation of split skin transplantation as a preprosthetic surgical measure]. The author, within the framework of a long-term research program, makes a careful analysis of the late results of plastic operations to the vestibulum oris, which were performed on 109 patients and where the wound surfaces were covered by free split-skin transplantation; in this, he uses both objectifiable methods of examination and biostatistical test methods. Patients are classified according to preoperative conditions. The method of operation may be assessed from a purely functional point of view.


[The closing of large residual palatal and velum clefts using tongue flaps]. The author, after outlining the problems associated with palatoplasty, gives a detailed description of present methods of operation for cleft palate and cleft velum palatinum. Experience gained in the treatment of six patients, where a pedunculated lingual flap was used to repair the oral defect, shows that this particular method is a valuable addition to the techniques already available to the surgeon.


[The problem of damage to the tooth germ by ionizing radiation]. Experiments on animals (four-week-old dogs) were conducted in an investigation made to study the possibility of dose-dependent tooth-germ damage produced by ionizing radiation. The individual doses were 50 r and 200 r, respectively, and they were administered once to three times at weekly intervals. Hyperemia and edemata could be observed on tooth-germ pulps from 150 r onward. Both of these conditions became more acute as the radiation dose increased (from 150 r to 600 r). Possible damage to both the dentin and enamel is pointed out.


[Experimental study on the effect of the model thickness and its profile on the behavior of the dimensions in cast crowns and bridge-work cast in one piece]. The dimensional response of cast objects as a function of the shape and thickness of their wax patterns was studied, the dimensions of investment patterns taken as null bodies being compared with the corresponding dimensions of cast crowns and bridges. The metal shrinkage values are discussed.


[Effects of hypertrophy on the behavior of potentials in isolated ventricular strips of the rat]. Potentiation of right-ventricular strips obtained from normal rats (NT-group) and from rats showing hypertrophic hearts as a result of long-time swimming (HT-group) has been investigated. Strength-interval relationships, poststimulation potentiation and the potentiation by paired stimulation has been tested. The behavior of the action potential in both groups showed no significant differences. Standardized strength-interval relationships of HT-group were steeper than those of the NT-group. Maximal potentiation in the HT-group occurred at shorter delay-intervals. Potentiation after long-time pauses was greater in the HT-group. The results are discussed on the basis of model considerations of electro-mechanical coupling.


[Synthetic inhibitors of serine proteinases. 13. Quantitative structure-activity relationship for inhibition of trypsin and thrombin by 4-amidinophenyl compounds with a ketone structure]. To establish quantitative structure-activity relationships for the inhibition of trypsin, plasmin and thrombin by 4-amidinophenyl compounds with a keto group, attempts have been made to detect correlations between data on inhibition and substituent constants. The inhibitor activity of the derivatives is described by lipophilic or steric substituent constants using linear free energy relationships. To describe the action of beta-ketones, an additional sigma I term is necessary. The lipophilic or steric term stands for binding of the inhibitor side chain to a second hydrophobic binding site of the enzyme. The electronic term describing inductive influences on the keto group suggests the contribution of the beta-keto group to the enzyme inhibitor binding via a tetrahedral conformation of the carbonyl carbon.


Anaphylactoid reaction to dextran---a report of 133 cases. From 1968 to 1975, the Swedish Adverse Drug Reaction Committee received 113 reports on anaphylactoid reaction to dextran 70, and 20 reports on the same reaction to dextran 40. For 1975, this would equal a reported incidence of anaphylactoid reaction to dextran 70 of 1:2,500. The median age of patients reacting to dextran 70 was 63 years. Median age increased with increasing severity of the anaphylactoid reaction: from 48 years in patients who died. Symptoms were noticed within 10 min of the start of the infusion, or before 100 ml had been infused in 96 patients (85%) with an anaphylactoid reaction to dextran 70. There was a tendency for severe reactions to be observed earlier than milder ones. Symptoms also tended to be observed earlier in conscious than in unconscious patients. Reactions reported to have occurred in unconscious patients tended to be more severe than those in conscious patients. Patients with anaphylactoid reaction to dextran 40 did not differ from those with reactions to dextran 70 with regard to age, severity of the reaction or time before onset of symptoms. There was one death in this group.


Treatment of Huntington's chorea with bromocriptine. The authors tested the effects of 2-Br-ergocriptine (bromocriptine, CB-154), a drug which exerts a mixed agonist-antagonist activity on the dopaminergic receptors, in 12 patients with Huntington Chorea in a double-blind crossover trial. This treatment significantly reduced the abnormal involuntary movements and the disease severity in most of the patients. Subjects who were slightly disabled showed a better response than the ones with more severe degrees of disability.


Phagocytosis of heat-killed radiolabelled mycobacteria in human mononuclear phagocytes cultured in vitro. Human mononuclear phagocytes cultured in vitro for 8 dyas were exposed to 125I-labelled, heat-killed Mycobacterium triviale. The microorganisms were apparently engulfed, but no digestion occurred within a period of 16 days after the engulfment, measured as release of radioactivity to the medium and observed microscopically. Attempts were made to stimulate intracellular digestion of the bacteria. Pre-incubation with BCG-stimulated lymphocytes or with supernatants from BCG-stimulated lymphocyte cultures did not increase the digestive ability of the cells. However, pre-incubation with BCG-stimulated lymphocytes or with supernatants caused detachment of the cells during the following digestion period, probably due to a cytotoxic effect of autologous, transformed lymphocytes on macrophages. When the macrophages were cultured in the presence of autologous lymphocytes and BCG, a similar effect was found.


[Allergen testing in juvenile rheumatoid arthritis]. 79 children with classical collagenoses, streptococcaldiseases, arthralgia of unclear genesis and infection arthritis as well as juvenile rheumatoid arthritis and 25 normal children were submitted to an intracutaneous allergentest with various collecting extracts (legumens and cereals, house allergens, vegetables). Positive reactions to cereals in a high percentage were observed only in patients with juvenile rheumatoid arthritis and fewer also in children with unclear arthralgia and infection arthritis.


[Age-dependence of the cellular immune reaction in childhood. 1. Studies on healthy children and disease pictures with secondary modification of the immune apparatus (without leukoses and tumors)]. The dependence on age of the rates of transformation of lymphocytes is due not only to the different number and degree of maturity of lymph cells, but also to the macrophageal function as well as the feedback mechanism of specific and nonspecific defense reactions. Premature and newborn infants do not differ in their cellular immunoreactions. Between birth and the fifth year of life there is a continuous increase in the rates of transformation of lymphocytes. This increase in rates of transformation is less marked between the fifth and twelfth years of life, with the transformation rate leveling off as age increases. Tests made using nonspecific antigens showed the rate of transformation to decrease with further increasing age. Testing with histocompatibility antigens showed no influences whatsoever. A striking result were higher rates of transformation observed in children with virus infections. The evaluation of cellular immunoreactions subsequent to infections or immunization is an important parameter for the immune system.


[Comparative studies on the sensitivity of smooth bronchial muscles to catecholamines during sensitization with various allergens]. An attempt has been made to compare the effects produced by adrenergic agents on smooth bronchial muscles of normal and BCG- as well as ovalbumin-sensitized guinea pigs. The method of determining the state of relaxation of the isolated bronchial tree was used to ascertain the degree of sensitivity to adrenergic agents of smooth bronchial muscles. Experiments conducted on a total of 34 guinea pigs showed a considerable decrease in the response of smooth bronchial muscles to novodrine, adrenaline, and noradrenaline subsequent to BCG and ovalbumin sensitization of experimental animals. In normal guinea pigs, minimal relaxation of smooth tracheal muscles was brought about by 7.10(-8) - 1.10(-7) G/ml novodrine, 1.10(-7) - 9.10(-7) g/ml adrenaline, and 1.10(-6) - 8.10(-6) g/ml noradrenaline. For BCG-sensitized animals, the data obtained were 3.10(-7) - these agents of smooth bronchial muscles of guinea pigs was more clearly evident in BCG-sensitized 2.10(-6) g/ml, 1.10(-6) - 2.10(-6) g/ml, and 3.10(-6) - 6.10(-6) g/ml, respectively. The decrease in sensitivity to bronchi during the process of sensitization is believed to be responsible for the decrease in response to animals than in ovalbumin-sensitized guinea pigs. A partial blockade of beta-adrenergic receptors of catecholamines. The degree of partial blockade is dependent upon the kind of sensitization.


Anaphylactic shock and contact urticaria after the patch test with professional allergens. It is reported on 3 patients of medical profession who suffered from anaphylactic complications after the patch test with penicilline G, aminophenazone and promethazinhydrochloride. The triggering of the IgE mediated allergy is explained by the quick and complete epidermal penetration of the haptens because their low molecular weight and optimal solubility. It could be proved by the positive mast cell degranulation test, whereas the IgE level was elevated in serum only in one case, but in tissue in no case. Prophylactically, if the careful exploration is positive, the open patch test is indicated. It should carried out in the clinic or ambulance with consecutive observation of the patients for 60 min and with the possibility of the treatment of shock.


[Correlation between total serum IgE and the remaining allergologic-diagnostic methods in childhood]. The authors found in studing of 60 allergic children on Dermatophagoides Pteronyssinus (D.P.) that besides all clinical allergological tests is extraordinary radioimmunological determinations of serum IgE in allergic patients. In small group of healthy children they found the mean value for serum IgE 499 U/ml (+/- SD - 242). In allergic children with bronchial asthma and vasomotoric allergic rhinitis with positive skin reaction +++ on D.P. and with positive provocation inhalation and nasal test found statistically significantly higher values for serum IgE in chidren with above mentioned diagnostic tests. Detail analyses of determination of total serum IgE showed that is necessary to start to determine also specific IgE with Phadebas IgE test for different inhalative allergens. The greatest advantage of determination of serum IgE in vitro is undengereous technique whereas other allergological diagnostical test especially in childhood are dangerous for live.


[Rheumatoid factor in systemic lupus erythematosus]. 1. Rheumatoid factors were found in 12 of a total of 105 SLE patients. 2. Rheumatoid factors were found especially in patients with additional chronic polyarthritis, whereas it was not possible to find a relation between these factors and the age of patients and the duration of disease, respectively. 3. There was no difference between SLE and progressive polyarthritis as regrads the cold precipitation of rheumatoid factors. 4. In vitro fixation of the complement to antinuclear factors was not hindered by rheumatoid factors. 5. Renal lesions and uremia were observed in SLE patients with and without rheumatoid factors, the percentages being roughly the same in the two groups.


[Cholinergic bronchial reactivity in patients with sarcoidosis]. The acetylcholine aerosol test was used for testing 65 patients suffering from sarcoidosis for cholinergic bronchial hyperexcitability. Among 46 patients with stage I and stage II sarcoidosis there was only one female patient where the acetylcholine aerosol test gave positive results; however, it was not possible to establish a relationship between bronchial hyperexcitability and sarcoidosis. In two other patients with stage III sarcoidosis, where the acetylcholine aerosol test also gave positive results, there obviously was a close relationship between bronchial hyperexcitability and sarcoidosis. It is considered that positive acetylcholine aerosol test results might be interpreted as being indicative of stage III sarcoidosis. It should be noted in this connection that the third or fibrotic stage of sarcoidosis was characterized by a very much smaller number of cases showing positive acteylcholine aerosol test results than are, in general, observed for those forms of tuberculosis which are accompanied by more or less widespread fibrous processes taking place in, and causing major alterations to, the lungs and which may be described as chronically hematogenously disseminated, fibrocavernous, and cirrhotic forms of pulmonary tuberculosis. Also discussed in detail are the possible reasons for this different behavior.


[Inhibition antibodies identified as anti-IgE]. Ten years ago the author described a precipitating agens which has been seen by immunreaction serum before and after desensitization. Now it was possible to identify it as Anti-IgE. Our first terminus was "Hemmantikörper" (inhibition antibody). Contrary to Cooke's "blocking antibody" (= IgG) Anti-IgE is an IgM-Antibody. According to earlier statement once more could be established that "Hemmantikörper" are specific to allergen but not specific to the individuum.


[Effect of leukeran on the local Shwartzman phenomenon]. A study has been made to investigate the effect of treatment with Leukeran (Chorambucil) on the development of what is known as a loval Shwartzman phenomenon. The experimental results show that it is only in those cases where the leukopoietic capacity of the organism has been fully exhausted that it is possible for the development of this particular phenomenon to be reliably prevented by immunsuppression brought about by treatment with Leukeran.


Effects of some polynucleotides on DNA synthesis in human lymphocytes. The effect of several single-and double-stranded synthetic polyribonucleotides on the 3H-thymidine incorporation in intact and PHA-stimulated human lymphocyte cultures was investigated. Only polyuridilic and polyguanilic acids were found to stimulate DNA synthesis in the intact cells. All other polynucleotides tested had much weaker or had no stimulating activity. PHA-activated lymphocytes responded to addition of polynucleotides by the decrease of 3H-thymidine uptake. The mostly profound inhibition of lymphocyte response to PHA was observed with polyguanilic acid.


Some characteristics of human lymphocyte responsibility to stimulation in vitro. Attempts were made to examine the input of some ecological and physiological factors into the fluctuation of the lymphocyte transformation assay results. The spontaneous and PHA-induced 3H-thymidine uptake in lymphocyte cultures of adult healthy persons and healthy or rheumatic fever children fluctuated at different seasons of the year with the maximum at summer. The activity of cultured women's lymphocytes depended on the phases of menstrual cycle of donors.


[About the elimination of thromboagglutinins from anti-lymphocytic serum (author's transl)]. The possible utilization of the effect of immunological tolerance for inhibition of formation of thromboagglutinins was studied, which dependent of the kind of antigen employed for immunization more or less contaminate antilymphocyte sera (ALS) or globulins (ALG). In the sera of pigs weighing 80-90 kg, immunized with human thrombocytes the thromboagglutinin levels in a) animals tolerated in adult age with an i.v. dose of 2.2 X 10(9) thrombocytes though the complete inhibition of thromboagglutinin formation failed even in these conditions. The attempted induction of tolerance in adult animals, similarly as in newborn piglets obtaining a dose of 1 X 10(9) thrombocytes, was of little success. Good results were recorded in animals tolerated in the perinatal period with a dose of 5 X 10(9) thrombocytes though the complete inhibition of thromboagglutinin formation failed even in these conditions. The authors suggest that of all possible methods for thromboagglutinin elimination, for ALS production the above technique, i.e. the induction of tolerance during the perinatal period seems most feasible, both from the viewpoint of effectiveness and thrombocyte consumption as well.


Quantitative study on the size of coronary artery supplying areas postmortem. The relative amount of myocardium perfused by the three large coronary arteries was determined in 171 human hearts postmortem. Roentgenograms of transverse serial sections of the ventricular myocardium enabled planimetrical measurements. With little variation, an average of 41.5 per cent of the entire ventricular myocardium was supplied by the left descending coronary artery. Both left branches supplied an average of 63.8 per cent and the right coronary artery supplied 36.2 per cent of the myocardium. The size of supplying areas, in particular that of the right coronary artery and the left circumflex branch, was mainly dependent upon the coronary artery types. As a rule cardiac hypertrophy did not influence the size of coronary supplying areas as much as did the coronary artery types. Only very few hearts revealed that the myocardium was supplied to a greater extent by the right coronary artery than by the left (5.3 per cent). There is a close relationship between the size of the myocardial supplying area and the lumen of the corresponding coronary artery.


Partial anomalous pulmonary venous connection (intact atrial septum) associated with mitral regurgitation. The association of partial anomalous pulmonary venous connection with intact atrial septum and isolated severe nonrheumatic mitral regurgitation is rare, this combination of lesions having been reported on only one other occasion. Two such cases have been presented, with each patient having experienced an episode resembling subacute bacterial endocarditis. At operation, however, the mitral valve had a congenital cleft in one case and was normal in the other. One patient underwent mitral valvuloplasty and the second patient had mitral valve replacement. The diagnosis of associated partial anaomalous pulmonary venous connection was established at cardiac catheterization, and successful surgical correction was achieved in each case by diversion of the anamolaous pulmonary venous drainage to the left atrium via a pericardial tunnel through a surgically created atrial septal defect.


Cytological differentiation of human fetal skeletal muscle. The ultrastructural differentiation of several different muscles was investigated in human fetuses ranging in age from 13 weeks to neonatal. At approximately 16 weeks of gestation cell cluster containing both myotubes and satellite cells lie enclosed by a newly formed basal lamina and show evidence of fusion. The development of organelles is evident in myoblasts, proceeds as the cells transform into myofibers, and continues in the neonate. Filament synthesis occurs primarily in the cell periphery where thin filaments appear to align themselves in relations to parallel arrays of ribosome-studded thick filaments: Z line formation follows the appearance of thin filaments. Intermediate filaments, approximately 10-12 nm thick, were also consistently observed in perinuclear regions and distal to filament assembly. Although sarcoplasmic reticulum (SR) development is closely related to fibril formation, connections between Z lines and SR are not consistent, thus supporting the conclusion that SR does not evoke the formation of the Z line. Bristlecoated vesicles appear to be the precursors of elements of the SR, possibly the lateral sacs. Development of the transverse tubules, as invaginations of the sarcolemma, is closely associated with the formation of lateral sacs since the latter occur along the sarcolemma as soon as transverse tubules appear. Cytological differentiation is similar, though not identical, in several different muscles. During the last trimester muscle fibers show some evidence of diversity mainly of variation in Z line width. In gerneral the results suggest that the sequence and stages of human myogenesis are similar to those of other species.


The Framingham Eye Study. II. Association of ophthalmic pathology with single variables previously measured in the Framingham Heart Study. Using the age-sex-specific data collected in the Framingham Heart Study 1948--1964 together with ophthalmic diagnoses made in the Framingham Eye Study in 1973--1975, the following variables were found to be associated with senile cataract: education, casual blood sugar, systemic blood pressure, height, vital capacity, serum phospholipid and hand strength; with senile macular degeneration: systemic blood pressure, height, vital capacity, left ventricular hypertrophy, hand strength and history of lung infection; with diabetic retinopathy: casual blood sugar, urine sugar and other specific elements of diabetes; with ocular hypertension: systemic blood pressure, height, casual blood sugar and pulse rate. No variables were identified as associated with open-angle glaucoma. The paper stresses the need for corroboration of these findings, which may be a mix of real and chance associations, and the need for additional analyses before any of these associations are considered evidence of factors related to risk of ophthalmic disease.


The evaluation of left ventricular function by echocardiography. Echocardiographic assessment of left ventricular size and function correlates well with that made by cineangiography. The technic is particularly suited to the early detection and serial monitoring of left ventricular hypertrophy and dysfunction in valvular heart disease, hypertensive heart disease and the cardiomyopathies. It also has advantages over angiography in experimental situations in which frequently repeated or continuous assessment of left ventricular size and function may be required. The limited usefulness of a single ultrasound beam in segmental heart disease, such as ischemic heart disease, may be overcome in the future with improvements in two-dimensional echocardiographic technics.


Experimental aortic lesions of acute serum sickness in rabbits. The mechanisms by which serum sickness cause lesions in the aortic intima are not known. The early aortic lesions of serum sickness detected by permeability to Evans blue dye were studied morphologically to determine the chronologic sequence of lesion initiation and immunochemically with fluorescein-labeled rabbit IgG and bovine serum albumin to detect the presence of antigen and antibody. The topographic localization of lesions and the morphologic changes observed suggest that endothelial injury occurs first, probably due to immune complex deposition, and that platelets play a secondary or reactive role in the process.


Mucopolysaccharide osmotic pressure in the measurement of interstitial pressure. Subatmospheric pressures were recorded from cotton wicks inserted into Wharton's jelly of human umbilical cords (mean=-7.6+/-5.0 (SD) cmH2O; n=10). Hyaluronate concentrations (mean=0.69+/-0.30 g/100 g) and wick pressures correlated negatively (r=-0.825; P less than 0.01) but calculated hyaluronate osmotic pressures (mean=4.0+/-2.7 cmH2O) were insufficient to explain the full wick pressure. In model systems composed of asbestos fibers (mean radius=0.5 micron) and 0.9% saline, subatmospheric pressures were recorded which varied with the volume of saline added. When hyaluronate (1 g/100 g) was substituted for saline, lower wick pressures were recorded at each volume. The pressure lowering effect of hyaluronate was not seen in a matrix of glass fibers (mean radius=1.0 micron). It is suggested that the effect of hyaluronate in asbestos fibers is due to its immobilization by the matrix and the consequent development of osmotic pressure recorded via the wick. In the coarser glass-fiber matrix, hyaluronate was not immobilized and therefore had no osmotic effect. These experiments support the hypothesis that subatmospheric interstitial pressures result from osmotic pressure of immobilized mucopolysaccharide macromolecules.


Na-K-activated ATPase: activity maturation in rabbit nephron segments dissected in vitro. Single, defined nephron segments were dissected in vitro from fresh slices of neonatal and mature rabbit kidney. Na-K-ATPase was quantified for six different tubule segments with an ultramicromethod. The enzyme distribution pattern in the neonatal nephron was similar to that in the mature nephron. Activity in distal segments was 2-5 times higher than proximal tubule activity referred to tissue dry weight, and 2 times higher referred to tubule length. Neonatal enzyme activity was lower than mature in all segments. Some segments carried only 23% of mature activity. Enzyme activity in the proximal convoluted tubule was constant during maturation when referred to the basal and lateral membrane area measured in the same developmental stages. In vitro activities of these tubules were similar to the enzyme activity measured previously in freeze-dried slices. The Vmax during development of Na-K-ATPase was higher by a factor of 5 in the mature tubule, whereas the Km was identical in the neonatal and mature tubule. The ouabain-insensitive ATPase did not show a maturational activity change.


Central neural influence on precapillary microvessels and sphincter. The responses to central nervous system (CNS) stimulation of consecutive segments of arterioles down to the precapillary sphincter were measured in the mesoappendix and/or cremaster of nine male rats with indwelling electrodes. Under pentobarbital sodium anesthesia, vasoactive sites were stimulated at threshold for maximal constriction or lumen closure of the precapillary sphincter and/or immediately preceding precapillary arteriole (metarteriole). In all experiments, CNS stimulation induced blood pressure elevation and constriction of three consecutive segments of precapillary vessels and of the sphincter. A threefold increase in rate of vasomotion of precapillary sphincter and metarteriole was the rule, but this was noted infrequently in larger arterioles. In addition to an overall influence of the CNS on microcirculation, the data show a gradient of responses to stimulation, the slope of which is negatively related to the size of the vessels and sphincter, in both tissues studied. A complete lumen closure of the metarteriole and precapillary sphincter (when present) in response to CNS stimulation implies active participation in the regulation of local blood flow. No evidence was foun for central neural regulation of the precapillary sphincter independent of arteriolar control.


An extracorporeal shunt for the measurement of coronary flow in the closed-chest dog. An extracorporeal shunt circuit interposed between the left carotid artery and the left coronary ostium employs an electromagnetic flowmeter to measure coronary blood flow in the closed-chest anesthetized dog. Flow may be measured with the animal's arterial pressure as the driving force; introduction of a roller pump, or a roller pump and a negative feedback pressure controller allows for constant flow or constant pressure modes. During occlusion of the circuit or cessation of pump flow, retrograde coronary blood flow can be collected for measurement. The construction of the circuit is relatively simple and inexpensive, using common laboratory materials and a commercially available electromagnetic flowmeter and probe.


Zero offset in electromagnetic flowmeters. In electromagnetic square-wave flowmeters, it should be theoretically possible to determine zero flow by turning off the magnet drive. In actuality, this is not possible. A major source of zero offset in many commercial flowmeters lies in the fact that the very large voltage transients, seen as the flowmeter drive switches polarity, are distorted by the input amplifiers. This can be corrected by improved amplifier design. A second source of zero offset when flow probes have been immersed in conducting fluids is resistive leakage between the drive voltage and the input electrodes. This can be minimized through the use of shielded coils, with shield grounded, and by the use of a magnet drive isolated from ground. If both of these sources of zero offset are corrected, offset is greatly reduced. Polarization of the flowmeter electrodes, which has previously been suggested as a cause of zero offset, was not detected.


Histochemical studies of respiratory muscles of chicken. The histochemical profiles of myofibrillar adenosine triphosphatase (ATPase), nicotinamide adenine dinucleotide diaphorase (NADDase), and phosphorylase (Pase) activities were studied in the respiratory muscles of the chicken. Most respiratory muscles contained fibers exhibiting 18 possible combinations of staining reactions (dark or light ATPase; dark, intermediate, or light NADDase; dark, intermediate, or light Pase). Fibers that stained light for ATPase constituted as little as 10% of the total population in rectus abdominis, but as much as 32% of the total in costosternalis pars major. Those fibers did not tend to be smaller than fibers that stained dark for ATPase in the respiratory muscles as a group. Assuming these staining characteristics are correlated with functional properties of the fibers, as they are in mammals, the majority of the fibers should contract rapidly (dark ATPase) and be fatigue resistant (dark and intermediate NADDase).


Further controlled evaluations of fenbendazole as a bovine anthelmintic. The efficacy of fenbendazole (methyl-5-(phenythio)-2-benzimidazole-carbamate) in cattle parasitized by the lungworm Dictyocaulus viviparus and in other cattle parasitized by Haemonchus, Ostertagia, Trichostrongylus, Cooperia, and Oesophagostomum was investigated in 3 controlled critical experiments. A single treatment with 5.0 mg/kg of body weight administered in the feed or in a 10% suspension exceeded 99% efficacy against these helminths. Dosages of 1, 0.5, 0.35, and 0.25 mg/kg of body weight administered for 5 days to individual calves in their feed were 99% efficacious against all helminths, except Haemonchus. The 1.0 mg/kg dose removed 99.5% of the Haemonchus, and the other 3 dosages had efficacies of 91.0, 93.7, and 95.6%, respectively. The small daily dosages were not evaluated against Dictyocaulus.


Surgical anatomy of the aponeurotic expansions of the anterior abdominal wall. Dissection of the anterior abdominal wall in 40 fresh cadavers, with confirmation of the anatomical findings at operation in 25 patients, has enabled the patterns of distribution of the aponeurotic expansions of the abdominal muscles to be traced and the relation of structure to function to be determined. It is pointed out that the linea alba should no longer be regarded as the line of insertion of the abdominal muscles but as the area of decussation of the tendinous aponeurotic fibres of the muscular strata passing from one side to the other, for which the name "midline aponeurotic area" is proposed. Two separate functional areas are described, a "parachute respiratory mechanism" in the upper abdomen and a belly support in the lower abdomen. Attention is drawn to the functional derangement that may follow some of the standard abdominal incisions and to possible mechanisms of herniation through the midline aponeurotic area.


Abdominal wound dehiscence. A 10-year survey from a district general hospital. The incidence of abdominal wound dehiscence at a district general hospital was found to be about 1.5%. Analysis of a group of 123 patients with dehiscence in 3 separate years during a 10-year period confirmed that disruption most commonly occurs during the second postoperative week. The suture material used for primary closure appeared to have no influence on subsequent dehiscence. After resuture the recorded incidence of incisional herniation was 19% and the mortality was 24%. Patients who survived resuture remained in hospital for a prolonged period.


Red and white muscle fibres in meniscectomy patients. Effects of postoperative physiotherapy. Clinical examination of the knee joint of 16 meniscectomy patients was performed and muscle biopsies were taken preoperatively and four weeks postoperatively from the vastus medialis of the quadriceps muscle. Corresponding investigations were performed in 15 healthy volunteer controls. One group of the meniscectomy patients was given routine postoperative physiotherapy, the other group intensive physiotherapy. Type I and II muscle fibres were determined from the muscle biopsies of the myosin-ATPase staining method. No difference was observed in the clinical and histochemical findings between the patients given routine and intensive physiotherapy respectively. Compared with the controls, the older patients had clinical quadriceps atrophy preoperatively, but there were no differences in the muscle fibre composition. After meniscectomy the patients developed even more marked quadriceps atrophy, which was more manifest in the patients with a good preoperative muscle status. The surface areas of the type I and II fibres of the operated patients diminished compared with the samples from the healthy volunteer controls. Only in the male patients was the decrease in the type I muscle area considerable. The present data indicate that meniscectomy is accompanied by a marked change in the clinical and histochemical appearance of the quadriceps muscle compared with the muscle status following meniscus injury; the extent of physiotherapy as carried out in the present study did not significantly modify the results.


[Effect of coamide on immunogenesis during antibiotic therapy]. The dynamics of the antibody-producing cells in the spleen and the titer of hemagglutinines in the blood of albino mice immunized with sheep erythrocytes and treated with various doses (250, 500, 1000 gamma) of oxytetracycline and monomycin and their combinations with coamide, a complex of cobalt with nicotinic acid amide at different periods after the immunization. It was found that oxytetracycline in doses of 500 and 1000 gamma and monomycin in doses of 250, 500 and 1000 gamma administered intramuscularly for 4 days had an inhibitory effect on both the antibody-producing cells and the titer of hemagglutinines in the immunized animals at various periods after the immunization. Consequently, oxytetracycline and monomycin had the immunosuppressive effect. Exposure of the animals treated with oxytetracycline and monomycin to coamide for 5 days provided an increase in the number of the antibody-producing cells and the titer of the hemagglutinines. The results of the study showed the perspectivity of coamide use in complex therapy of infectious diseases.


Mechanism of accumulation of the antitumor protein antibiotic neocarzinostatin in bladder tissue: intravenous administration, urinary excretion, and absorption into bladder tissue. Some aspects of the absorption, distribution, and excretion of neocarzinostatin (NCS), a proteinous antitumor antibiotic, were studied in rabbits. NCS was given intravenously (i.v.) via the auricular vein, or [(14)C]NCS was instilled directly into the cavity of the bladder by tubing. In both groups, ureterostomy was performed, so that the drug excreted in the urine did not pass through the bladder. The results showed extremely rapid renal clearance; namely, two-thirds of the total recovered was excreted in the first 5 min. It was also shown that drug infused into the bladder cavity could be recovered in urine from the ureterostomized ureter. Also, the level of biological activity of NCS in bladder tissues after i.v. administration is significantly lower when ureterostomy is performed. Thus, evidence is presented for the absorption of NCS into bladder tissue from the lumen of the bladder. The high levels of NCS in bladder tissue are due to this effect as well as to accumulation via the iliac artery. These data should encourage further trials of NCS in bladder cancer. A study of urine containing NCS derived from i.v. administration showed an increase in antibacterial activity upon incubation, followed by a decrease. These effects are probably due to proteolysis, as shown by the appearance of a low-molecular-weight fragment and by the absence of such an increase in the presence of inhibitors of proteolysis.


Hepatic glycogen synthetase deficiency. Definition of syndrome from metabolic and enzyme studies on a 9-year-old girl. In the 13 years since hepatic glycogen synthetase deficiency was first described in identical twins no further cases seem to have been observed. We report a child who had suffered from occasional morning convulsions since the age of 7. Three 24-hour metabolic profiles showed fasting hypoglycaemia, hyperketonaemia, but normal lactate. Hyperglycaemia and hyperlactataemia occurred after meals. Glucagon caused a rise in glucose 3 hours after a meal with a fall in lactate and alanine; no effect of glucagon was seen after a 12-hour fast. Normal increments in glucose followed oral galactose or alanine. Liver and abdominal wall muscle biopsies were taken. Glycogen content was subnormal in liver but normal in muscle. Glycogen synthetase (EC 2.4.1.11) was virtually absent from liver but fully active in muscle. Hepatic glycogen synthetase deficiency causing fasting hypoglycaemia has been confirmed. It is postulated that some children with "ketotic hypoglycaemia" may suffer from this disorder.


Gastroschisis treated with lyophilized dura. At the Royal Alexandra Hospital for Children, Sydney, we have found that primary closure in gastroschisis is usually successful. However, in a small number of cases such closure is found to be impossible. In such patients we have not been satisfied with silastic sheeting and have on two occasions successfully used lyophilized dura.


Synthesis and concentration of 5-phosphoribosyl-1-pyrophosphate in erythrocytes from patients with Down's syndrome. Plasma urate levels and erythrocyte glucose-6-phosphate dehydrogenase activity were not significantly different in patients with Down's syndrome when compared with control subjects with mental retardation. No significant difference was found in 5-phosphoribosyl-1-pyrophosphate (PRPP) concentration and synthesis of PRPP in erythrocytes from glucose between subjects with Down's syndrome and controls. The purine metabolism of Down's syndrome is discussed.


Replacement of the ascending aorta and aortic valve with a composite graft: results in 25 patients. Our experience with combined replacement of the ascending aorta and aortic valve with a composite prosthetic valve-Dacron tube graft in 25 patients from September, 1974, to December, 1976, is reviewed. The technique involves suture of the composite graft to the aortic annulus, to the aortic tissue surrounding the coronary ostia, and to the distal ascending aorta, closing the aortic wall over the graft before discontinuing cardiopulmonary bypass. Annuloaortic ectasia was the most common indication for operation (15 patients). Perfusion of the coronary arteries was used in the first 15 patients. In the remaining 20, internal and external myocardial cooling with one period of ischemic arrest (average, 67 minutes) was used. There was 1 hospital death (4%), and there have been 3 late deaths (12%) in the 27-month follow-up period. This technique appears to be applicable to most types of aneurysmal disease of the proximal ascending aorta associated with aortic valve incompetence. All aneurysmal tissue from the aortic annulus to the innominate artery is excluded, bleeding through the graft is eliminated, operative time is reduced, and the late results have been satisfactory to date.


Acute venereal arthritis. Comparative study of acute Reiter syndrome and acute gonococcal arthritis. Acute venereal arthritis, a syndrome of fever and inflammatory arthritis following recent sexual intercourse, is a frequently misdiagnosed arthritic presentation. Nearly half of 39 patients admitted with a diagnosis of acute gonococcal arthritis were subsequently recognized as having acute Reiter syndrome. A retrospective study of both diseases revealed differentiating features that, when prospectively applied to 21 consecutive patients, permitted a correct and prompt bedside diagnosis. Acute Reiter syndrome could be differentiated by characteristic mucucutaneous lesions, arthritis/tenosynovitis confined to lower extremities, massive recurrent knee effusions, low back pain, conjunctivitis, and genitourinary inflammation. Gonococcal arthritis could be differentiated by migratory arthralgias, high fevers, arthritis/tenosynovitis initially confined to upper extremities, typical cutaneous lesions, and dramatic defervescence to penicillin therapy. Laboratory data provided support for each diagnosis.


Effect of ouabain on mechanical and electrical properties of rat and guinea pig hearts at 180 C. The effects of ouabain 10(-6) M on rat and guinea pig hearts have been studied at 18 degrees C, in order to reduce almost fully both the Na+, K+-dependent ATPase activity and the ouabain induced inhibition of this enzyme. In isolated guinea pig hearts the positive inotropic response to ouabain obtained at 32 degrees C disappeared at 18 degrees C. On the contrary, the contractile strength of rat hearts was slightly reduced by ouabain and in the same manner at both temperatures. Current and voltage clamp experiments carried out at 18 degrees C in ventricular fibres revealed that ouabain 10(-6) M decreased both the action potential overshoot and the fast sodium current in rat and guinea pig, by reduction of the membrane sodium conductance. Ouabain did not change the calcium current in guinea pig preparations, whereas in rat heart muscle this current was reduced. The effects of ouabain on both the action potential plateau and outward repolarizing current indicated some inconsistencies from preparation to preparation and cannot therefore be considered as significant. The persistence of the ouabain induced alterations of g Na (in rat and guinea pig) and calcium current (in rat) at 18 degrees C supports the hypothesis of two ouabain cell receptors in heart muscle.


A continuous culture study of an ATPase-negative mutant of Escherichia coli. For anaerobic glucose-limited chemostat cultures of Escherichia coli a value of 8.5 was found for YmaxATP. For anaerobic glucose- or ammoniumlimited chemostat cultures of the ATPase-negative mutant M2-6 of E. coli YmaxATP values of 17.6 and 20.0 were found, respectively. From these data it can be concluded that in the wild type during anaerobic growth 51-58% of the total ATP production is used for energetization of the membrane. Using the YATP values obtained in the anaerobic experiments a P/O ratio of 1.46 could be calculated for aerobic experiments with the wild type. It is concluded that from the energy obtained by respiration in wild type E. coli about 60% is used for membrane energetization and only about 40% for the actual formation of ATP. No dramatic difference in the maintenance requirement for ATP or glucose has been observed between glucose- and ammonium-limited chemostat cultures of the mutant. The large difference in maintenance requirement observed for such cultures of the wild type is therefore supposed to be made possible by ATP hydrolysis by the ATPase.


The fine structural localization of adenosine triphosphatase activity on the taste bud in the fungiform papillae of the rat. The localization of Mg++ activated adenosine triphosphatase (ATPase) activity in rat fungiform taste buds was demonstrated by electron microscopic histochemistry. Reaction product was found on the cell membrane of the taste cells, but not within their cytoplasm. Especially strong reaction occurred in the taste pore. Besides, enzymes were observed in axon-Schwann cell and axon-type I cell interspace, but not in the contacts of the nerve fiber and type II cell. The taste bud could well be distinguished from the surrounding epithelium by the existence of the reaction product. ATPase activity was absent at the synaptic portion where type III cells faced nerve fibers. No reaction product was seen along the basal lamina. In fungiform buds, the nerve fibers were frequently shown to make contact with each other, and these sites were devoid of deposits for ATPase.


Ultrastructure of the parotid duct. Cytochemical studies of the striated duct and papillary cystadenoma lymphomatosum of the human parotid gland. To our knowledge, there are currently no reports in the literature that discuss the fine structure of the striated ducts of the human parotid gland. Papillary cystadenoma lymphomatosum (Warthin's tumor) is a benigh neoplasm found almost exclusively in the parotid gland that represents about 16% of all neoplasms of the gland. This neoplasm is believed to arise from the striated and/or excretory ducts, but there are contradictions with regard to the proposed origin and the cellular composition of some Warthin's tumors. Tissue was obtained at the time of surgery and examined ultrastructurally and cytochemically for the localization of alkaline phosphatase and adenosine triphosphatase. Myoepithelial cells were found ultrastructurally and cytochemically on the proximal aspect of the striated duct, with their cell bodies situated at the junction of the striated and intercalated ducts. Two Warthin's tumors were observed with cells that were structurally and cytochemically similar to myoepithelial cells.


The handicapped driver: an insurer's point of view. This paper reviews the approach used by one automobile insurer to underwrite and to medically evaluate a handicapped driver. Significant factors which must be carefully developed for each application for automobile insurance are discussed. In the final analysis. The extent of any physical or mental impairment must be considered along with information verifying the capability of the handicapped person to safely operate an automobile. Cooperation in research programs among many disciplines, namely, state motor vehicle bureaus, insurers, product manufacturers, health professionals and driver educators as well as handicapped drivers, is clearly indicated.


Sexual function restoration in the physically disabled: use of a private hospital room. For more than two years, a rehabilitation department in a large general hospital maintained a room adjacent to the ward as a site for evaluating and restoring sexual function of disabled patients. This report provides a description of the room, discusses its diverse purposes, and offers justifications of its feasibility in an acute hospital facility.


Electromyographic biofeedback for pain related to muscle tension. A study of tension headache, back, and jaw pain. We review the literature on the application of electromyographic (EMG) biofeedback to tension-related headaches, back and shoulder pain, and temporomandibular joint (TMJ) pain and present clinical treatment data on 18 patients with tension headaches, eight patients with back and shoulder pain, and six patients with TMJ pain. Electromyographic tension levels declined in all groups of patients; pain declined significantly in 12 of 18 patients with tension headaches and one of eight back pain patients, and decreased slightly in three headache patients, three back and shoulder pain patients, and two patients with TMJ pain. Conclusions suggest that EMG biofeedback is generally more effective in treating tension headaches, but much less effective in the treatment of back, shoulder, or jaw pain, although the numbers of patients are small in the latter two groups.


[The problem of the cardiomyopathies].

[The problem of the cardiomyopathies]. The author criticizes the tendency to broaden continuously the notion of "cardiomyopathy" and the attempts to cover by this term almost all etiological and pathogenetic variants of myocardial lesions. Classification of these variants by two groups is proposed: 1) idiopathic cardiomyopathies, etiology of which are either not known, or not established yet; 2) symptomatic cardiomyopathies the causes of which are known. The first group comprises congestive and hypertrophic cardiomyopathies. Their essential clinico-anatomical features and considerations concerning pathogenesis are set forth. Every variant of the second group of cardiomyopathies (symptomatic) is analysed separately according to the character of the pathogenic agent. The need for comprehensive study of myocardial pathology in the so-called cardiomyopathies is emphasized.


An adenosine triphosphate-dependent deoxyribonuclease from Alcaligenes faecalis. A deoxyribonuclease was purified approx. 800-fold from crude extracts of the bacterium Alcaligenes faecalis. The enzyme requires ATP and Mn2+; ATP could be replaced by any other ribo- or deoxyribo-nucleoside triphosphate, and Mn2+ could be replaced by Mg2+ in 0.1 M-Tris/HCl, pH 8.0 at 37 degrees C. The enzyme could degrade linear duplex or denaturated DNA, but was inactive with closed-circular duplex DNA from bacteriophase PM-2. In the course of nucleolytic activity, ATP was hydrolysed. We have measured deoxyribonuclease and adenoxine triphosphatase activity in the presence of various salts, and found that the amount of ATP hydrolysis associated with a given amount of deoxyribonuclease activity was decreased in the presence of tetraethylammonium ions. Since these ions decrease the stability of the DNA helix, we conclude that one function of the ATP hydrolysis is to unwind the DNA.


Comparison of glucose metabolism in the lactating mammary gland of the rat in vivo and in vitro. Effects of starvation, prolactin or insulin deficiency. 1. Measurements of arteriovenous differences across mammary glands of normal and starved lactating rats, and lactating rats made short-term insulin-deficient with streptozotocin or prolactin-deficient with bromocryptine, showed that only in the starved animals was there a significant decrease in glucose uptake. This decrease was accompanied by release of lactate and pyruvate from the gland, in contrast with the uptake of these metabolites by glands of normal lactating rats. 2. There were no marked differences in metabolite concentrations in freeze-clamped glands in the four conditions studied, apart from a decrease in [lactate] and [pyruvate] and an increase in [glucose] in the glands of the streptozotocin-treated group. 3. Acini isolated from the glands of starved, insulin or prolactin-deficient rats had a higher production of lactate and pyruvate from glucose than did glands from normal rats; this is in agreement with the reported decrease in the proportion of active pyruvate dehydrogenase in these situations [Field & Coore (1976) Biochem. J.156, 333-337; Kankel & Reinauer (1976) Diabetologia12, 149-154]. 4. Addition of insulin did not increase the uptake of glucose by acini from normal glands, but it caused a significant increase in the utilization of glucose by acini from glands of starved rats. Insulin did not decrease the accumulation of lactate and pyruvate in any of the experiments. 5. It is concluded that isolated acini represent a suitable model for the study of mammary-gland carbohydrate metabolism in that they reflect metabolism of the gland in vivo.


A mutation affecting a second component of the F0 portion of the magnesium ion-stimulated adenosine triphosphatase of Escherichia coli K12. The uncC424 allele. A new mutant strain of Escherichia coli in which phosphorylation is uncoupled from electron transport was isolated. The new mutant strain has a similar phenotype to the uncB mutant described previously; results from reconstitution experiments in vitro indicate that the new mutation also affects a component of the F0 portion of the Mg2+-stimulated adenosine triphosphatase. A method was developed to incorporate mutant unc alleles into plasmids. Partial diploid strains were prepared in which the uncB402 allele was incorporated into the plasmid and the new unc mutation into the chromosome, or vice versa. Complementation between the mutant unc alleles was indicated by growth on succinate, growth yields on glucose, ATP-dependent transhydrogenase activities, ATP-induced atebrin-fluorescence quenching and oxidative-phosphorylation measurements. The gene in which the new mutation occurs is therefore distinct from the uncB gene, and the mutant allele was designated uncC424.


Structure and metabolism of rat liver heparan sulphate. Rat liver cells grown in primary cultures in the presence of [(35)S]sulphate synthesize a labelled heparan sulphate-like glycosaminoglycan. The characterization of the polysaccharide as heparan sulphate is based on its resistance to digestion with chondroitinase ABC or hyaluronidase and its susceptibility to HNO(2) treatment. The sulphate groups (including sulphamino and ester sulphate groups) are distributed along the polymer in the characteristic block fashion. In (3)H-labelled heparan sulphate, isolated after incubation of the cells with [(3)H]galactose, 40% of the radioactive uronic acid units are l-iduronic acid, the remainder being d-glucuronic acid. The location of heparan sulphate at the rat liver cell surface is demonstrated; part of the labelled polysaccharide can be removed from the cells by mild treatment with trypsin or heparitinase. Further, a purified plasma-membrane fraction isolated from rats previously injected with [(35)S]sulphate contains radioactively labelled heparan sulphate. A proteoglycan macromolecule composed of heparan sulphate chains attached to a protein core can be solubilized from the membrane fraction by extraction with 6m-guanidinium chloride. The proteoglycan structure is degraded by treatment with papain, Pronase or alkali. The production of heparan [(35)S]sulphate by rat liver cells incubated in the presence of [(35)S]sulphate was followed. Initially the amount of labelled polysaccharide increased with increasing incubation time. However, after 10h of incubation a steady state was reached where biosynthetic and degradative processes were in balance.


The effects of starvation and experimental diabetes on phosphoenol-pyruvate carboxykinase in the guinea pig. 1. Approx. 85% of liver phosphoenolpyruvate carboxykinase is associated with the mitochondrial fraction in the fed guinea pig. Enzyme activity is unchanged in diabetes, but doubles during starvation. In contrast with earlier reports, both cytoplasmic and mitochondrial activities were found to be increased. 2. In kidney cortex, total enzyme activity is increased in both starved and diabetic animals. These changes are associated with increases in the cytoplasmic activity alone. 3. In diabetic animals the mean blood-glucose concentration was 23.1 mM. Other blood metabolites were lower than those in the rat, and the animals did not show significant ketosis. 4. Changes in the rates of gluconeogenesis from lactate and propionate paralleled those in phosphoenolpyruvate carboxykinase activity.


Left ventricular filling in hypertrophic cardiomyopathy. An angiographic study. In order to study left ventricular filling in hypertrophic cardiomyopathy, left ventricular cineangiograms of 20 patients were digitised frame by frame and compared with those of 10 normal subjects. Peak left ventricular filling rate was 770+/-260 ml s-1 (mean+/-1 standard deviation), not significantly different from normal. Mitral valve opening was delayed, occurring 140+/-40 ms after time of minimum cavity area, compared with 93+/-14 msec in normals (P less than 0-01), indicating abnormal relaxation. Peak left ventricular filling rate was correlated inversely with this delay (r = 0-69, P less than 0-01), which was greater in patients with angina (155+/-27 ms) than in those without (85+/-23 ms) (P less than 0-01). The rapid filling period was also abnormally prolonged in 8 patients. End-diastolic transverse dimension was normal (5-3+/-0-7 cm) but end-systolic dimension was reduced (2-4+/-0-4 cm) (P less than 0-01) because of abnormal cavity shape. Peak rate of change of dimension during filling (18-7+/-5-3 cm s-1) was greater than normal (11-3+/-3-9 cm s-1) (P less than 0-01), and correlated with peak filling rate (r = 0-82, P less than 0-001). Thus, peak filling rate is normal in hypertrophic cardiomyopathy, but the filling pattern may be abnormal, apparently because of impaired relaxation and abnormal cavity shape rather than mechanical obstruction to inflow.


Effects of ethacrynic acid and furosemide on phosphorylation reactions of kidney mitochondria. Inhibition of the adenine nucleotide translocase. Previous reports that ethacrynic acid and furosemide diminish mitochondrial P : O ratios and reduce (Na+ + K+)-ATPase activity suggested that these diuretics may inhibit mitochondrial phosphorylation reactions. This possibility was initially studied by determining the effects of ethacrynic acid and furosemide on [32P]ATP exchange activity of rat kidney mitochondria. Concentrations of both drugs at 10(-4) M or greater, significantly inhibited [32P]ATP exchange. To investigate the mechanism of this inhibition, the effects of ethacrynic acid and furosemide on the ATPase activity of intract mitochondria and sonicated submitochondrial particles were determined. Both diuretics inhibited ATPase activity of intact mitochondria at 10(-4) M. In contrast, ATPase of submitochondrial particles was significantly less susceptible to inhibition by the diuretics. These results suggested that ethacrynic acid anf furosemide inhibit adenine nucleotide transport across the mitochondrial membrane. This was directly tested by determining the effects of the diretics on the mitochondrial adenine nucleotide translocase. At 5-10(-4) M, both ethacrynic acid and furosemide significantly inhibited adenine nucleotide transport. These findings suggest that ethacrynic acid and furosemide may diminish renal tubular solute reabsorption by direct inhibition of adenine nucleotide transport across the mitochondrial inner membrane.


Formation of ATP by the adenosine triphosphatase complex from spinach chloroplasts reconstituted together with bacteriorhodopsin. The energy-linked ATPase complex has been isolated from spinach chloroplasts. This protein complex contained all the subunits of the chloroplast coupling factor (CF1) as well as several hydrophobic compoenents. When the activated complex was reconstituted with added soybean phospholipids, it catalyzed the exchange of radioactive inorganic phosphate with ATP. Sonication of the complex into proteoliposomes together with bacteriorhodopsin yield vesicles that catalyzed light-dependent ATP formation. Both the 32Pi-ATP exchange reactions and ATP formation were sensitive to uncouplers such as 3-tert-butyl-5,2'-dichloro-4'-nitrosalicylanilide, bis-(hexafluoroacetonyl)acetone and carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazone, that act to dissipate a proton gradient. The energy transfer inhibitors dicyclohexylcarbodiimide, triphenyltin chloride and 2-beta-D-glucopyranosyl-4,6'-dihydroxydihydrochalcone were also effective inhibitors of both reactions.


The three-state model for the elementary process of energy conversion in muscle. A three-state model for the elementary process of energy conversion in striated muscle is analysed; in two of the three states, the crossbridge is attached to an actin site, while the third is a detached state. This model accounts for the mechanical properties of steady shortening and lengthening processes as well as those of isometric and isotonic transient processes in a quantitative way. Moreover, qualitative agreement is obtained for the total energy liberation from muscle. Biochemical properties are also computed for transient processes. Comparisions are made with other models with "three states".


Action of alkyl cations and the natural ATPase inhibitor from mitochondria on soluble mitochondrial ATPase. The effect of the natural ATPase inhibitor and octylguanidine on the ATPase activity of soluble oligomycin-insensitive mitochondrial F1 were compared. Both compounds induced a maximal inhibition of 60-80% in various preparation of F1 studied. The inhibition was of the uncompetitive type with respect to MgATP, and the action of the compounds was partially additive. The data suggest that octylguanidine reproduces the action of the natural ATPase inhibitor. Alkylammonium salts also affect the ATPase activity in a similar form. F1 bound to Sepharose-hexylammonium is largely inactive, whilst free hexylammonium at higher concentrations induces only a partial inhibition of the activity. This suggests that the degree of immobilization of F1 is related to the magnitude of inhibition of ATPase activity induced by alkyl cations. The binding of F1 to Sepharose-hexylammonium is prevented by high concentrations of Na+ or K+.


A reconstituted Na+ + K+ pump in liposomes containing purified (Na+ + K+)-ATPase from kidney medulla. Liposomes containing either purified or microsomal (Na+,K+)-ATPase preparations from lamb kidney medulla catalyzed ATP-dependent transport of Na+ and K+ with a ratio of approximately 3Na+ to 2K+, which was inhibited by ouabain. Similar results were obtained with liposomes containing a partially purified (Na+,K+)-ATPase from cardiac muscle. This contrasts with an earlier report by Goldin and Tong (J. Biol. Chem. 249, 5907-5915, 1974), in which liposomes containing purified dog kidney (Na+,K+)-ATPase did not transport K+ but catalyzed ATP-dependent symport of Na+ and Cl-. When purified by our procedure, dog kidney (Na+,K+)-ATPase showed some ability to transport K+ but the ratio of Na+ : K+ was 5 : 1.


Levels of the ribonucleoside triphosphates and rate of RNA synthesis in Neurospora crassa. The levels of the four ribonucleoside triphosphate (ATP, GTP, UTP and CTP) have been determined in Neurospora crassa in three conditions of exponential growth (on glucose, acetate and glycerol) as well as in the course of a shift-up and a shift-down transition of growth between two of them. Although in some cases the pools appear proportional to the rate of synthesis of ribosomal RNA, this seems not to be strictly dependent on the level of the nucleotides.


On the interaction of alpha2-plasmin inhibitor and proteases. Evidence for the formation of a covalent crosslinkage and non-covalent weak bondings between the inhibitor and proteases. alpha2-plasmin inhibitor is a proteinase inhibitor in plasma which efficiently inhibits the lysis of fibrin clots induced by plasminogen activator. The nature of the binding of the inhibitor to trypsin or plasmin was studied by the chemical treatment of the enzyme-inhibitor complex with 7.5 M hydrazine at pH 10.0. With the hydrazine treatment, the complexes were degraded to proteins corresponding to the respective enzyme and inhibitor moieties. These results indicate that the covalent bond between the inhibitor and the enzymes is a carboxylic ester. The binding reaction of the inhibitor to active site-modified trypsin was also studied. The inhibitor formed complexes with anhydrotrypsin and carboxyamidomethylated trypsin. The complexes were dissociated in the presence of 1% sodium dodecyl sulfate, to the individual components: the respective enzyme and inhibitor moieties. The inhibitor, however, did not form a complex with diisopropylphosphorylated trypsin regardless of the presence or absence of the denaturing reagent. These results suggest the contribution of non-covalent interactions to the complex formation between the inhibitor and native enzymes.


Studies on the amino groups of myosin ATPase. IV. Effects of ATP and its analogs on the spectral properties of trinitrophenylated myosin and its active fragments. A considerable blue shift was observed in the absorption spectrum of the trinitrophenyl moiety attached to a functional epsilon-lysyl amino group of subfragment-1, heavy meromyosin and myosin on addition of ATP or ATP analogs. The resulting difference spectra showed a maximum at 320 and a minimum at 365 nm. The greatest spectral change was observed with a non-hydrolyzable ATP analog, adenosine 5'-(beta,gamma-imino)triphosphate and it decreased in the order adenosine 5'-(beta,gamma-imino)triphosphate, ATP and ADP. The ATP-induced difference spectrum changed to that of ADP upon the hydrolysis of ATP. The observed spectra were depended on temperature and ionic strength. Difference spectra were produced also by ITP, IDP and pyrophosphate while AMP was practically ineffective. Mg2+ also caused small spectral changes which are not identical with those induced by ATP analogs. On the basis of measurements carried out on a model compound, it is assumed that as a consequence of the reaction of ATP with a myosin head, the environment of the functional lysyl residue becomes less polar, i.e. it becomes buried in the hydrophobic core of the molecule. Changes on addition of ATP or its analogs were observed also in the circular dichroic (CD) spectrum of trinitrophenylated subfragment-1, which also points to conformational changes in the vicinity of the functional lysyl residue.


The cross-linking of rabbit skeletal muscle sarcoplasmic reticulum protein. Sarcoplasmic reticulum proteins have been cross-linked in situ with two reagents, the disulphide-bridged bifunctional imido ester, dimethyl-3,3'-dithiobispropionimidate dihydrochloride and the mild oxidant cupric phenanthroline. Analysis of proteins so cross-linked by electrophoresis on agarose/acrylamide gels reveals that a series of new polypeptides, up to a molecular weight of 900 000, are formed. These have molecular weights which are multiples of 100 000. Further analysis of samples by electrophoresis in a second dimensions containing a reducing agent revealed the monomeric polypeptides from which the cross-linked polypeptides were formed. With dimethyl 3,3'-dithiobispropionimidate dihydrochloride homopolymers of the Ca2+-stimulated ATPase, calsequestrin and/or calcium binding protein were formed. With cupric phenanthroline only the Ca2+-stimulated ATPase was involved in polymer formation. It has been confirmed on another gel system that these two proteins which are involved in Ca2+ binding are not cross-linked intermolecularly with this latter reagent. We conclude that the 100 000 dalton Ca2+-stimulated ATPase polypeptides are within 2 A of each other in the membrane while calsequestrin and/or calcium binding protein are within 11 A of each other. Although there appears to be no limit to the extent of cross-linking of any of these polypeptides there is not indication of heteropolymer associations between them.


Tissue specific distribution of sulfated mucopolysaccharides in mammals. A comparative study on the distribution of sulfated mucopolysaccharides in several tissues of five mammalian species is reported. It is shown that each tissue has a characteristic composition differing from each other regarding the relative amount, type and molecular size of chondroitin sulfate A/C, chondroitin sulfate B and heparan sulfate. It is also shown that the same tissue from different mammals has the same types and proportions of sulfated mucopolysaccharides, but with different molecular weights. Exception to this rule was observed for the distribution of heparin which was present only in a few tissues of the five mammals studied. The possible involvement of the sulfated mucopolysaccharides in cell recognition and/or adhesiveness is discussed in view of this characteristic distribution.


Changes in sulfated mucopolysaccharide composition of mammalian tissues during growth and in cancer tissues. The distribution of sulfated mucopolysaccharides in different tissues during growth and in cancer tissues is reported. It is shown that most of the tissues of 1 day-old rats and rabbits contain chondroitin sulfate A/C, chondroitin sulfate B and heparan sulfate in about the same proportions, whereas in adult animals chondroitin sulfate A/C decreases in concentration or disappears. Changes in the relative proportions of chondroitin sulfate B and heparan sulfate were also observed in most of the tissues. In rats, these changes occur in the first 25 days of extrauterine development. A great increase of chondroitin sulfate A/C was observed in human tumors of different origins when compared with the normal adjacent tissues. Changes in the relative proportions of chondroitin sulfate B and heparan sulfate were also observed in most of the tumors analysed. The possible role of chondroitin sulfate A/C in cell division is discussed in view of the present findings.


[5'-Nucleotidase activity of lymphocyte plasma membranes. Effect of concanavalin A]. The 5'-nucleotidase properties of isolated lymphocyte plasma membranes from young pig mesenteric nodes are described; nucleosides-5'-monophosphates are the substrates of this specific enzyme. Concanavalin A inhibits this enzyme; on the same membranes this mitogen does not affect alkaline phosphatase and activates the membrane bound (Ca2+) ATPase. The 5'-nucleotidase inhibition is due to a specific interaction of Con A with carbohydrate groups of the membrane; its high positive cooperativity suggests that the lectin promotes reorganization of the membrane bound 5'-nucleotidase. Solubilization of the 5'-nucleotidase does not prevent the effect of Con A and the solubilized enzyme is firmly bound by Con A-Sepharose 4B; these results suggest that Con A inhibits the enzyme by a direct interaction and that 5'-nucleotidase can be considered as an eventual receptor for the lectin.