[Computerised axial tomography of the head (E.M.I. scan). Clinical experience with a new diagnostic method for examining the brain (author's transl)].

Computerised tomography of the head is a unique radiological method with an exceptional ability in demonstrating intracranial lesions. Increasing experience will ensure this method very wide scope in the diagnosis of neurological and neurosurgical diseases; it will make conventional methods, such as angiography, pneumo-encephalography and brain scanning largely superfluous. The frequency of incorrect diagnoses is acceptable and will be further reduced with increasing experience of the method.


[An apparatus for serial angiotomography (author's transl)].

A new casette for serial angiotomography is described; with it, one contrast injection can be used to show the arterial, capillary and venous phases in series. The examination is possible with any desired direction of the rays, without changing position of the head. The cranio-cervical region, the neck and the vessels in the upper thorax can also be tomographed.


[The scope and limitations in the demonstration of vessels by angiotomography; their relationship with contrast and size and between detail and direction of cut (author's transl)].

Experiments with models and post mortem angiograms have shown that the supposed advantages of angiotomography, such as determination of the depth of vessels, cannot be achieved with accuracy if there is repeated change in direction of the vessels. Blurring of superimposed vessels depends not only on their contrast and calibre, but also on their alignment in relationship to the direction of blurring. Vessels running in the direction of blurring produce undesirable shadows through a considerable depth, whereas vessels running across the direction of blurring are rapidly blurred if not in the selected plane. The demonstration of vessels running at right angles to the direction of blurring may at times be very difficult with simultaneous tomography. The clinical significance of this finding is pointed out.


[The scintigraphic diagnosis of meningiomas (author's transl)].

There is a scintigraphic trio which indicates, with a high degree of probability, the presence of a meningioma. It consists of intensive uptake of radio-pertechnitate immediately after injection, a level, or only slowly declining, time-activity curve over the tumour and corresponding intensive fluorine uptake of the skull, even in the absence of radiological or histological evidence of bone involvement.


[A comparison of osteotropic radiopharmaceuticals. II. Plasma clearance of 18F and 99mTc-EHDP (author's transl)].

Renal and extra-renal clearance of 18F and 99mTc-EHDP were compared in the same individuals. The 18F space is twice that of 99mTc-EHDP, as is its renal clearance. 99mTc undergoes glomerular filtration, 18F is excreted by glomerular filtration and tubular secretion. Extraction rate was determined indirectly by a comparison with extra-renal clearance, and for patients without bone disease it was four times as high for 18F as it was for 99mTc-EHDP. In patients with secondary hyperparathyroidism extra-renal clearance is greatly increased. This is explained by an increased extraction rate, which may be different for the two substances.


[99mTc-iron complex for demonstrating reflux without the use of a catheter (author's transl)].

99mTc-iron complex was used in 35 patients (20 adults and 15 children) in an investigation into ureteric reflux without using a catheter. The results were compared with the findings on micturating cysto-urethrography. Agreement in the findings was observed in 56 of the 69 kidneys examined. In only four kidneys, showing reflux radiologically, was this not observed on the isotope examination; in view of the low radiation dose, the catheter-free isotope method can be recommended as the most suitable investigation. The need for serial investigations or contrast allergies are important indications for using this method. The relatively high frequency with which reflux shown by the isotope method could not be confirmed radiologically (nine kidneys) indicates that the isotope is more sensitive than the radiological investigation.


[Radiation dose to the patient after administration of radioactive labelled colloids (author's transl)].

The radiation dose to the patient after injection of radioactive colloids is calculated for three substances: colloidal radiogold, 99mTc sulfur colloid and 113mIn colloid. For the calculation normal and pathological conditions were assumed.


[Renal blood flow after selective injection of different dosages of diatrizoate into the renal artery. An experimental study in the dog (author's transl)].

The characteristic biphasic renal haemodynamic response to diatrizoate injected into the renal artery was shown in the dog with the 133-Xenon washout technique. A brief increase in renal blood flow (RBF) during the first ten seconds is followed by a more prolonged period of diminuished RBF. A dose of 4 ml. diatrizoate 60% resulted in the maximum RBF increase of 43% after ten seconds, but even 1 ml. diatrizoate raised the RBF 24%. The initial vasodilator effect of diatrizoate compares well in its extent with the most potent renal vasodilators.


[Selective renal angiography with fractionated contrast medium injection. An experimental study in the dog (author's transl)].

Fractionated contrast medium was compared with the conventional technique in 96 selective renal angiograms in the dog. The only possible clinical significance might be that improved visualisation of the renal vein was obtained with this technique without increasing the total administered dose. The overall best result in this regard was obtained with 2 and 6 ml. diatrizoate 60% injected with an interval of five seconds. Compared with other vasodilators, contrast material reflux into the aorta was not reduced and the vasodilator effect on the main renal, segmental and interlobar arteries was not constant and less marked.


[Mesenteric vascularisation of malignant renal tumours (author's transl)].

Three angiographic observations showing partial mesenteric vascularisation of renal tumours were made. Problems in diagnosis and therapy arising from this are discussed.


[Retrograde renal phlebography with balloon occlusion of the renal artery. Technique and scope of a new method (author's transl)].

A new method of retrograde phlebography of the kidney is described; it is carried out by using a balloon catheter in the renal artery for occluding the circulation. The procedure has been carried out in 13 patients without complication. Early experience has provided very good results in the diagnosis of malignant renal tumours; invasion into the venous system can be demonstrated radiologically. In particular, in cases of carcinoma of the renal pelvis, this method represents a significant improvement of the hitherto unsatisfactory angiographic techniques.


[Para-ureteric cyst. A rare complication of abdominal surgery (author's transl)].

A para-ureteric pseudo-cyst of the middle third of the ureter was observed following a sympathectomy. Originally it was diagnosed as a renal tumour. The findings are described and the pathogenesis, symptomatology and diagnosis are discussed.


[Results of post mortem thyroid gland phlebography (author's transl)].

The anatomic course and variation of the thyroid veins used for retrograde thyroid phlebography were studied in 70 post mortem thyroid phlebograms. Comparison with pathological and anatomical findings showed good agreement in benign diseases of the thyroid with lesions of more than 1 cm. Infiltrating malignant changes could not be delineated with certainty and a post mortem proven parathyroid adenoma was also missed. The practical clinical significance of thyroid phlebography is therefore confined to the localisation of parathyroid tumours in primary hyperparathyroidism by selective parathoromone measurements.


[New bases and theories for improving angio-cine-densitometry. III Resolution of quotient cine-densitometry (author's transl)].

In the present paper, the degree of resolution which can be achieved with quotient cine-densitometry is described. The accuracy of the procedure is illustrated. The superiority of this method over video-densitometry is pointed out.


[Reduction in radiation scatter during radiographic magnification techniques (author's transl)].

The reduction in scatter during magnification techniques is compared with the effect of grids. The results of extensive measurements concerning scatter and distance in a water phantom are shown in 24 diagrams. The various factors were altered as follows: distance 0-1.5 m., phantom thickness 0-27.5 cm., area 5 cm. x 5 cm. - 30 cm. x 30 cm. and kilovoltage 50-150 kv. The amount of scatter immediately behind the phantom is compared with that through a grid by observing image quality for given amounts of scatter. This "grid-equivalent" image quality can be used to determine the circumstances under which a magnification technique can be employed without using a grid.


[A new method for localising non-palpable lesions of the female breast (author's transl)].

A new method for the localisation of non-palpable lesions of the female breast is described. It is uncomplicated, very accurate and simple, and requires a single puncture only. It enables a cytological diagnosis to be made, as well as preoperative marking of suspicious areas.


Epinephrine renal venography.

Experience with the use of epinephrine renal venography in 60 patients with various renal disease is reviewed. The technique offers an important supplement to selective arteriography. It is of particular value in the diagnosis of avascular infiltrative tumors of the renal parenchyma and pelvis. Further, it is of value in the detailed demonstration of renal vein thrombosis and in seeking the cause of unexplained gross hematuria. It can also aid in evaluating expansile avascular renal masses and renal parenchymal disease. The authors found only a relatively low value for epinephrine renal venography in the diagnosis of hypervascular renal tumors and the early detection of venous extension of hypernephromas.


[The pharmaco-kinetics of angiographic contrast media, with special reference to the extra-vascular space. An experimental study on dogs. Paper II. Pharmaco-kinetics of an angiographic contrast medium used for selective angiography (author's transl)].

Basic studies were carried out on experimental animals in order to investigate the pharmaco-kinetics of angiographic contrast media when used in various ways. Injections were carried out through angiographic catheters in a "physiological angiographic" manner. Measurements obtained by using radioactive compounds have shown that the distribution and excretion of the contrast medium are independent of the site of injection. The kinetics of the contrast within an organ do not differ, whether it is injected selectively or not. The results of all the experiments will be discussed at the conclusion of the third paper.


[The absorption of cholecystographic contrast media, following intraduodenal application; reasons for improved absorption due to sodium bicarbonate (author's transl)].

Three different cholecystographic contrast media in six dilutions were administered through a duodenal tube to six groups of five patients each. Blood samples were obtained up to five hours following the introduction of the contrast, in order to determine serum iodine levels as a measure of contrast concentration in the blood. At one, two, four and five hours, radiographs of the abdomen were obtained in order to evaluate the biliary passages and non-absorbed contrast. 1. The known effect of increased absorption of a microcrystalline suspension of Iosumet acid caused by sodium bicarbonate was enhanced by intra-duodenal application. 2. Following intra-duodenal application, there was no definite effect on the blood level of Iosumet acid microsuspension due to the addition of sodium bicarbonate. Thus there was no evidence of increased absorption. It therefore seems that the effect of sodium bicarbonate is due to accelerated transport of the contrast medium from the stomach into the duodenum. 3. The micro-suspension is very rapidly dissolved in the duodenum. Ingestion of an acid solution does not improve absorption. 4. Micro-crystalline suspensions of iopodinic acid and particularly iopanic acid are absorbed relatively slowly and incompletely. The sodium salt of iopodinic acid is absorbed much better than the free acid.


[The results of transvenous cholangiography (contrast media)].

Transvenous cholangiography is a method for the direct demonstration of the biliary passages described by Hanafee and Weiner; its main indication is in the investigation of obstructive jaundice. This method, which does not require immediate subsequent operation, was used in 41 patients. In three patients catheterisation of hepatic veins was unsuccessful. Of the remaining 38 patients, puncture of a bile duct was successful in 20. In 29 patients biliary obstruction was present, and this was demonstrated in 19. In the absence of obstruction the procedure was successful in only one case. The main complications were a sub-capsular liver haematoma, with rupture into the abdominal cavity and one case of haemobilia.


[The radionuclide hepato-angiography in the clinical diagnosis (author's transl)].

In 156 patients the dynamic liver perfusion study with 99mTc-sulfur colloid and the scintillation camera was performed. Out of the 81 cases with confirmed diagnosis, the rapid sequential liver study was only in one case to provide an additional information of clinical importance, which could not be demonstrated by static liver imaging. Except for 2 patients with carcinoid metastases of the liver and 3 cases of acute hepatitis, we did not find any significant difference in the activity appearance in the liver between normal subjects and patients with liver metastases and diffuse liver diseases.


[Splenic artery ligature and latero-lateral anastomosis in portal hypertension (author's transl)].

A new type of shunt for decompressing portal hypertension is described, consisting of ligation of the spleno-renal anastomosis. This reduces the pressure in the portal territory and in the dangerous gastric and oesophageal varices. In addition the procedure also abolishes the marrow inhibition due to splenic activity without removing the spleen and maintaining part of the portal circulation. The advantages and disadvantages of various decompression operations are discussed and compared with other methods in current use.


[Experience with a guidable catheter for angiography and bronchography (author's transl)].

Despite certain disadvantages, depending partly on the design of the catheter and partly on other problems, a guidable catheter is, in many cases, the only means for achieving a successful angiographic examination. The guidable catheter is therefore a valuable addition to the equipment used for angiography.


[Haustral changes in the colon due to diseases of the pancreas and stomach (author's transl)].

The radiological anatomy of the colon, as shown by double contrast enema, is described. Changes in the haustral pattern may often be due to lesions outside the colon.


[Double and multiple carcinomas of the colon (author's transl)].

Double or multiple carcinomas of the colon represent approximately 4% of all colon carcinomas. They may arise spontaneously or occur as a result of some predisposing disease. It is necessary to distinguish between double or multiple carcinomas arising synchronously or in sequence. Diseases such as ulcerative colitis, colonic polyposis and adenomatous polyps are pre-disposing conditions whereas familial polyposis is pre-cancerous.


[The effect of scatter on film quality in mammography (author's transl)].

The proportion of total radiation during mammography due to scatter was measured by film densitometry, and was found to average 44% (N = 16). The relationship between the geometry of the scattering object and the distribution of scatter was investigated experimentally. The relationship between gradation, amount of scatter and maximal resolution, as well as contrast, are discussed. The usual collimation and breast compression do not result in any significant reduction of scatter. The use of grids is described, but the technical problems involved have not yet been solved.


[A new basis and theories for improving angio-cine-densitometry. V. The effect of the injection method of the contrast on measurements during angio-cine-densitometry (author's transl)].

The theoretical basis for measuring speed of flow in vessels of conscious patients obtained by estimating dilution of injected contrast is described. Previously, measurements at two separate points had to be carried out in order to obtain a flow profile, but with the present method, a single measurement point is adequate. If contrast is distributed evenly in the circulation during its flow to the periphery, the measurement can be carried out at some distance from the point of injection. The ability to select ones point of measurement makes it possible to avoid areas covered by overlying shadows and eliminates the difficulties inherent in measurements in curved vessels.


[Theoretical investigations for optimising the quantum in radiodiagnosis (author's transl)].

On the basis of the present calculations, it is possible to determine the optimal exposure energies for any object of combination of materials. The results of the present investigation contradict present day practice. Calculated energies are sometimes much higher than those employed at present. This has certain definite advantages; reduced radiation dose to the object; a less sharp decline of contrast with high kilovoltage. Unfortunately it is only possible to guess at the causes of this difference. Further investigations, dealing particularly with the effect of spectral energy distribution under certain conditions, are in progress. Investigations into the sensitivity of intensifiers and film/screen combinations, combined with a comparison with calculated energies would be valuable.


The new special names of SI units in the field of ionizing radiations.

At its meeting in May-June 1975, the 15th Conference Generale des Poids et Mesures adopted two new special names of SI units; the becquerel, symbol Bq, equal to the second to the power minus one, s-1, for the quantity activity, and the gray, symbol Gy, equal to the joule per kilogram, J-kg-1, for absorbed dose and related quantities in the field of ionizing radiations. This action was preceded by a recommendation of the International Commission on Radiation Units and Measurements (ICRU) in 1974.


[Studies on the state of vitamins B1, B2 and B6 in Down's syndrome].

In 110 children-between 0-16 years of age-, 90 children with Down-syndrome and 20 controls the following metabolic parameter were analyzed: ETK (vitamin-B1-activating coefficient), EGR (vitamin B2), P-5'-P, EGOT (vitamin B6), GOT, GPT, pH, K, Na, Ca, Cl, uric-acid (HS). Among some important correlations between the different parameters it could be demonstrated-for the first time to our knowledge-that in Mongoloids a disturbance of the vitamin-B1-metabolism exists, certified by the so-called transketolase-test.


Islet transplantation in experimental diabetes in the rat. III. Studies in allogeneic streptozotocin-treated rats.

Diabetes of various degrees of severity was induced experimentally in rats by different doses of streptozotocin. These animals served as recipients for isolated islets of Langerhans from allogeneic donors. The islets were transplanted to different regions in the organism by paravascular or intravascular injection. As in pancreatectomized rats, the endocrine effect of the islets was only transient and consisted of disappearance of glycosuria, normalization of blood glucose and amelioration of intravenous glucose tolerance tests. When the islets were injected intravascularly (lung, liver) the influence of the transplanted islets was observable over a longer period than after subcutaneous or another paravascular transplantation. As in pancreatectomized animals, the period of survival was markedly prolonged in rats which had received a transplant compared to those which had not. The islets responded to glucose stimulation in vivo with insulin secretion similar to that of control rats, while only a very slight elevation of the low basis levels in streptozotocin-treated rats was observed.


Isolation and characterization of a mitochondrially synthesized polypeptide from Neurospora crassa cni-1 mutant.

A polypeptide with a molecular weight of 8 500 (HP 8 500) was isolated from the mitochondrial membrane of the nuclear mutant cni-1 of Neurospora crassa. This mutant is characterized by a cyanide-insensitive respiration and by a deficiency in the cytochromes aa3 and b. The polypeptide is synthesized on mitochondrial ribosomes. It has an extremely hydrophobic character; it is insoluble in aqueous media in the absence of sodium dodecylsulfate and is soluble in acid chloroform/methanol. It lacks histidine. The polar amino acids lysine, arginine, aspartic acid, glutamic acid, serine and threonine make up only 25% of the total amino acids on a mole-percent basis. The N-terminal amino acid is tyrosine. The possible function of this polypeptide in the mitochondrial membrane is discussed.


A subfraction of fragment D isolated from a plasmin hydrolysate of human fibrinogen.

Fragment D from a 4-hour plasminolysate of human fibrinogen was chromatographed on DEAE-cellulose and a nearly homogeneous subfraction obtained. It migrated as a single band in dodecylsulfate gel electrophoresis. Reduction yielded three peptide chains with approximate molecular weights of 45000, 295000 and 13000 as estimated from the electrophoretic migration rate in dodecylsulfate acrylamide gels. From these data the molecular weight of the Fragment D subfraction was calculated to be ca. 87500. The S-carboxymethylated peptide chains were separated by chromatography on DEAE-cellulose. They were correlated electrophoretically and their amino acid composition was determined. The peptide chains of molecular weight 45000 and 29500 showed a chromatographic microheterogeneity. The subfractions of these two chains, however, were not distinguished by their electrophoretic mobility in dodecylsulfate acry lamide gels and showed only insignificant differences in their amino acid composition.


Hereditary hemolytic anemia with erythrocyte phosphofructokinase deficiency: studies of some properties of erythrocyte and muscle enzyme.

A case of hereditary nonspherocytic hemolytic anemia associated with partial erythrocyte PFK deficiency without muscular symptoms is reported: erythrocyte enzyme activity in the propositus was 60% of normal. Kinetic studies of erythrocyte PFK revealed increased sensitivity to ATP inhibition and decreased sensitivity to citrate inhibition. Muscle PFK from the patient had a normal enzymatic activity, but was highly unstable to heat, dilution without stabilizer and urea; furthermore its starch gel electrophoretic mobility was markedly faster than the one of a normal control. The results suggested that a muscle type's subunit was deficient in the erythrocyte PFK. The authors hypothesize that there was no PFK deficiency in the patient's muscle because of the active synthesis of proteins by this tissue. In contrast, the deficiency of PFK would be easily detected in erythrocytes, because of the absence of protein synthesis.


Chromosome anomalies of infants dying during the perinatal period and premature newborn.

363 samples of different tissues were taken for cultivation from 118 antepartum deaths, 85 intrapartum deaths and 112 newborn dying during the first days after delivery. Successful growth of culture was noticed in 48.2% (15.4%) of antepartum deaths; 71.8% of intrapartum deaths and 68.1% of newborn dying during the first days of life. Among the 22 antepartum deaths 3 (13.6%) infants were found to have anomalies of karyotype; among 61 intrapartum deaths 3 (4.9%) infants were found to have karyotype anomalies; and among 92 early neonatal deaths 6 ones (6.5%) had karyotype anomalies. The total frequency of chromosome anomalies among the infants dying during the perinatal period was 6.9%. The final result of cytogenetic investigation of 607 premature infants was that chromosome anomalies were found among 2.5%, that is 3.5 times as much, as in the general newborn population. Among the types of chromosome anomalies the main defects were anomalies in the system of sex chromosomes and trisomy-21, and that is the proof of the fact, that other types of anomalies, found in newborn populations lead to earlier lethality.


Dosage effect of SOD-A gene in 21-trisomic cells.

SOD-A activity was measured by the polarographic method of catalytic currents in 30 subjects 10-24 years of age with a karyotype 47, + 21, and 30 age matched normal subjects. The ratio of the average amount of SOD-A in 21-trisomic cells to the average amount in normal cells is 1.4495. Statistical analysis confirms that this ratio does not differ significantly from the ratio 1.5 expected in the case of a simple gene dosage effect.


Plasma inhibitors of lymphocyte response to phytohaemagglutinin in children with recurrent infections.

A survey of the immunological status of 175 children with recurrent infections showed that the plasmas of fifteen patients contained an inhibitor of lymphocyte response to phytohaemagglutinin (PHA). The inhibitors could be subdivided into two groups. One type of inhibitor acted only on the patients' lymphocytes (autologous-only). The other type also inhibited the response of control lymphocytes to PHA and in the mixed lymphocyte reaction (homologous). Plasma inhibitors of both types inhibit the response of rabbit lymphocytes to PHA. Patients with a plasma inhibitor frequently have a raised resting lymphocyte DNA synthesis.


Phage group II staphylococcal strains with chromosomal and extrachromosomal genes for exfoliative toxin production.

Staphylococcal phage group 2 strain UT0007 was previously shown to contain a high-molecular-weight plasmid containing genes for exfoliative toxin (ET) and bacteriocin production. Phage group 2 strains UT0002 and UT0003 (Tox+Bac-) underwent a twofold and ninefold loss of ET activity, respectively, after growth at 44 C for 18 h. Strain UT0002 also lost total bacteriocin activity. Both strains contained (i) a 56S plasmid that was lost from those substrains showing reduced ET activity and (ii) a 21S plasmid with a gene for cadmium resistance that could be transduced into two recipient strains. Since the ET plasmid-negative substrains still made ET, it was postulated that this residual toxin was made from chromosomal genes. In characterizing the plasmid species from strains UT0002 and UT0003, the 21S but little or no 56S plasmid deoxyribonucleic acid could be isolated after centrifugation of cleared lysates from these strains on dye-buoyant density gradients. Treatment of cleared lysates from strain UT0002 with ethidium bromide, Pronase, or sodium dodecyl sulfate, but not heat at 60 C, induced conversion of the 56S closed circular ET plasmid to a 38S open circular form as determined after centrifugation on 5 to 20% neutral sucrose gradients.


Effects of enforced relocation on life adjustment in a nursing home.

A group of 75 institutionalized elderly patients was studied to determine the relationship of involuntary relocation to life adjustment in a nursing home. Data were collected by means of medical records and structured questionnaire. Patients who had experienced enforced relocation from other institutions expressed greater life dissatisfaction than those who had relocated voluntarily fissatisfaction was correlated with financial dependence, poor health, and limited social participation. Length of stay in the institution was not related to life satisfaction. The evidence suggests that involuntary placement, multiple moves, disruption of social networks, and financial dependence may contribute to life dissatisfaction among institutionalized elderly.


Determination of total choline in biological materials.

A microbiological eight-point parallel line assay for the determination of choline has been developed, using Neurospora crassa cholineless-1 as test organism. In the common procedure the mold is grown at 25 degrees C in 25 ml basal medium at pH 5.9-6.0. Growth studies showed, however, that a better log dose-response curve, with respect to the linear part of the curve, was obtained when the organism was grown at 30 degrees C, in 20 ml experimental volume and at pH 5.5. The proprosed eight-point assay was tested by comparison with the common procedure. Although repeated analyses of a test solution showed no significant difference in the mean values obtained, a greater scatter of the single values about the mean was observed when analyzing according to the common procedure. The developed procedure was also applied to different samples of biological material. The analysis of variance proved the parallelity and linearity of the dose-response curves. As a result of the variation between the replicates could be used as the experimental error of the assay when the confidence limits of the samples were computed.


[A new case of reticular hyperplasia connected with volatile oils].

An additional case of "reticular hyperplasia" is described. The clinical picture is trimorphic with grouped nodules, spinulosismus-like and parapsoriasiform lesions. Histologically there are dense lymphoreticular, partly eosinophilic infiltrates with leucocytoclastic cell aggregates, which, however, do not resemble mycosis fungoides nor a reticulosis. The causative agent was most likely the external use of remedy for an amputation stump containing ethereal oils, which had been used over decades. Positive provocation tests confirmed the diagnosis.


Histochemical localization of Mg2+-Na+-K+-adenosine triphosphatase in different stages of the sheep mesonephros.

Mesonephroi of sheep embryos ranging from 12 to 100 mm C.R. length were examined for the occurrence and localization of transport-ATPase. Native cryostat sections were incubated according to the technique of Guth and Albers for demonstrating the nitrophenylphosphatase activity of Mg2+-Na+-K+-adenosine triphosphatase. The basal cytoplasm of the collecting tubule of the narrow segment of the distal tubule exhibit strong activity, the wide segment of the distal tubule is moderately active. Glomeruli, proximal tubule, and Wolffian duct remain unstained. The basal labyrinths of the reactive nephron segments are believed to be the sites of a Na+-K+ exchange pump. In mature and regressing mesonephroi, the findings fully agree with biochemical data; in maturating mesonephroi, whose basal labyrinth is not yet fully established, the biochemical assay proves to be more sensitive. The specifity of the reaction was ascertained by diverse inhibitors and activating ions. The localization of Mg2+-ATPase is different to the above mentioned reaction pattern, as it shows moderate activity in the proximal tubule, too (mature mesonephros). Mesonephroi of very young embryos exhibit strongest Mg2+-ATPase activity in the proximal tubule; here the distal and collecting tubule stain only moderately.


Prolonged methanol fixation of soluble mucosubstances in mucopolysaccharidoses.

A simple and efficient method for the demonstration of highly water soluble acid mucosubstances in cold microtone sections is described. It consists of prolonged treatment of cold microtome sections with methanol (for at least 1 h) and subsequent staining with 0.1% azure A in distilled water or in 30% methanol. The procedure is recommended particularly for the bioptical examination of mucopolysaccharidoses.


Factors affecting the incidence of non-metrical skeletal variants.

Non-metrical variants of the human cranium have been studied in 186 London crania of known age, sex and date of birth. The incidence of several variants was different in the two sexes, and these results were compared with those of other workers from different parts of the world. Few variants persistently favoured one sex: the majority behaved inconsistently. Age dependency was only demonstrated for one variant, while year of birth, presence of rickets, and spina bifida occulta, showed negligible influence on variant incidence. 20% of vertebral columns examined included an anomalous vertebra, usually sacral spina bifida occulta. Although family studies were largely inconclusive, this investigation provides no reason to doubt the basic genetical control of these variants.


Skeletal muscle enzymes and fiber composition in male and female track athletes.

Muscle samples were obtained from the gastrocnemius of 17 female and 23 male track athletes, 10 untrained women, and 11 untrained men. Portions of the specimen were analyzed for total phosphorylase, lactic dehydrogenase (LDH), and succinate dehydrogenase (SDH) activities. Sections of the muscle were stained for myosin adenosine triphosphatase, NADH2 tetrazolium reductase, and alpha-glycerophosphate dehydrogenase. Maximal oxygen uptake (VO2max) was measured on a treadmill for 23 of the volunteers (6 female athletes, 11 male athletes, 10 untrained women, and 6 untrained men). These measurements confirm earlier reports which suggest that the athlete's preference for strength, speed, and/or endurance events is in part a matter of genetic endowment. Aside from differences in fiber composition and enzymes among middle-distance runners, the only distinction between the sexes was the larger fiber areas of the male athletes. SDH activity was found to correlate 0.79 with VO2max, while muscle LDH appeared to be a function of muscle fiber composition. While sprint- and endurance-trained athletes are characterized by distinct fiber compositions and enzyme activities, participants in strength events (e.g., shot-put) have relatively low muscle enzyme activities and a variety of fiber compositions.


Amino acid composition of dynein and comparison with myosin.

A comparison is made between dynein [flagellar ATPase; EC 3.6.1.3], purified from sea urchin sperm flagella, and muscle myosin. The amino acid composition of dynein was found to be statistically different from that of myosin. The same was true of their tryptic fragments retaining ATPase activity, i.e., Fragment A of dynein and heavy meromyosin. At low ionic strength, no superprecipitation took place when ATP was added to a mixture of dynein and actin, and stimulation of the Mg2+-ATPase activity of dynein remained below 50% even when a one-hundred-fold excess of actin was present. No viscosity drop was caused by adding ATP to a solution containing dynein and actin. Anti-myosin antiserum did not react with dynein, while anti-Fragment A antiserum formed no precipit-n line against myosin. Furthermore, the amount of dynein that combined with F-actin was less than one-fifth of the amount of dynein that fully combined with microtubules. These results are consistent with the dissimilarity in enzymatic and other physiocochemical properties of these two proteins.


The pre-steady state of Na+-K+-dependent ATPase after addition of Na+ ions. Transition of the phosphorylated intermediate from an ADP-sensitive to an ADP-insensitive form.

Na+-K+-Dependent ATPase [EC 3.6.1.3] was preincubated with ATP in the presence of a high concentration of MgCl2, and the phosphorylated intermediate, EP, was formed by adding a high concentration of NaCl. The following results showed that EP was converted from an ADP-sensitive to an ADP-insensitive form by a single turnover of the ATPase reaction. 1. After initiating the reaction by adding NaCl, almost all the EP was at first sensitive to added ADP, but its sensitivity to ADP decreased with increase in the time interval between the additions of NaCl and of ADP. 2. Both in the presence and absence of KCl, the time course of the replacement of ADP-sensitive EP by ADP-insensitive EP coincided with the time course of the decomposition of EP after addition of EDTA.


Change in the ultraviolet absorption of an adenosine triphosphate analog, beta-napht-yl triphosphate, during its hydrolysis by heavy meromyosin.

It was found that the absorption spectrum of beta-naphthyl triphosphate is different from that of beta-naphthyl diphosphate in the range 290-335 nm. Thus, beta-naphthyl triphosphate hydrolysis by heavy meromyosin can be recorded continuously as a function of time by means of a spectrophotometer. By analyzing the time course, the apparent kinetic parameters were easily and rapidly obtained. If necessary, the true kinetic parameters, including the product dissociation constants, can be estimated spectrophotometrically. Beta-Naphthyl triphosphate hydrolysis was inhibited competitively by ATP. By analyzing the time course, it was, therefore, possible to estimate the kinetic parameters of ATP hydrolysis indirectly, and resonable values were obtained. Beta-Naphthyl triphosphate hydrolysis by heavy meromyosin was performed under various conditions. Unlike that of ATP, the hydrolysis of beta-naphthyl triphosphate was inhibited monotonously by treatment of heavy meromyosin with p-hydroxymercuribenzoate.


Isolation and characterization of tryptic fragments of the adenosine triphosphatase of sarcoplasmic reticulum.

Exposure of sarcoplasmic reticulum to trypsin in the presence of 1 M sucrose results in degradation of the Mr = 102,000 ATPase enzyme to two fragments of Mr = 55,000 and 45,000 with subsequent appearance of fragments of Mr = 30,000 and 20,000. These fragments were purified by column chromatography in sodium dodecyl sulfate. Antibodies were raised against the ATPase and the Mr = 55,000, 45,000, and 20,000 fragments. There was no antigenic cross-reactivity between the Mr = 55,000 and 45,000 fragments, indicating that they were derived from a single linear cleavage of the larger enzyme. There was antigenic cross-reactivity between the Mr = 20,000 and 55,000 fragments, indicating an origin of the Mr = 20,000 fragment in the Mr = 55,000 fragment. None of the antibodies inhibited (Ca2+ + Mg2+)-dependent ATPase or Ca2+ transport. The Mr = 20,000 fragment and the Mr = 55,000 fragment were active in Ca2+ ionophore assays. The active site of ATP hydrolysis was labeled with [gamma-32P]ATP and the site of ATP binding was labeled with tritiated N-ethylmaleimide. In both cases radioactivity was found in the intact ATPase and in the Mr = 55,000 and 30,000 fragments, indicating that the Mr = 30,000 fragment was also derived from the Mr = 55,000 fragment. Amino acid composition data showed that the Mr = 45,000 fragment contained about 60% nonpolar and 40% polar amino acids, while the Mr = 55,000 fragment and the Mr = 20,0000 fragment contained about equal amounts of polar and nonpolar amino acids. Studies of the reaction of various antibodies at the external surface of sarcoplasmic reticulum vesicles showed that the ATPase was exposed, whereas calsequestrin and the high affinity Ca2+-binding protein were not. The use of antibodies against the various fragments indicated that the Mr = 55,000 fragment was in large part exposed, whereas the Mr = 20,000 and the 45,000 fragments were only poorly exposed. It is probable that the site of ATP hydrolysis in the Mr = 55,000 fragment is external, whereas the ionophore site is only partially exposed and the Mr = 45,000 fragment is largely buried within the membrane.


Purification and characterization of a DNA-dependent ATPase from Escherichia coli.

A DNA-dependent ATPase has been isolated and purified from an Escherichia coli cell-free extract. The ATPase has the following characteristics: preferential dependence on single-stranded DNA, specificity for ATP hydrolysis, Km value of 1.4 X 10-4 M for ATP, and molecular weight of approximately 69,000. The ATPase can be shown to bind to single stranded DNA. The resemblance between this ATPase and that isolated from vaccinia cores is discussed.


Alanine and glutamine synthesis and release from skeletal muscle. III. Dietary and hormonal regulation.

Alanine and glutamine formation and release were studied using the intact epitrochlaris preparation of rat skeletal muscle. Alanine release from skeletal muscle was increased by fasting (65%), cortisone (145%), thyroxine (200%), and diabetes (185%). Glutamine release was decreased by cortisone (37%) and diabetes (23%) but not significantly affected by fasting or thyroxine. Tissue levels of alanine were unchanged but tissue glutamine levels were markedly reduced (30 to 60%) in all treatment groups. Insulin added in vitro did not affect amino acid release even with preparations obtained from diabetic animals. Inhibition of glycolysis with 0.2 mM iodoacetate had no effect on the rate of alanine and glutamine formation in any treatment group. Pyruvate generation was increased by all treatments even in the presence of the inhibitor. Total skeletal muscle alanine, aspartate, and branched chain aminotransferase, glutamate dehydrogenase, and malic enzyme activities were not significantly altered in any treatment groups. The addition of 10 mM aspartate, cysteine, branched chain amino acids, and serine significantly increased alanine formation, whereas the maximal rate of glutamine formation in the presence of stimulating amino acids was reduced in each treatment groups--the most marked effects were noted with cortisone and diabetic preparations. Although accelerated muscle proteolysis is an important factor regulating alanine formation in skeletal muscle, the redirection of carbon flow from glutamine toward alanine formation observed in fasting, cortisone, thyroxine-treated, and diabetic rats, indicates that factors other than proteolysis also participate in the control of amino acid release from muscle.


Separation and characterization of the troponin components from bovine cardiac muscle.

The three major components of bovine cardiac troponin were separated by successive chromatography on sulfopropyl-Sephadex and DEAE-Sephadex columns in the presence of 6 M urea. All three of the bovine cardiac troponin subunits were necessary to restore full troponin activity in both skeletal and cardiac actomyosin ATPase assay systems. The 38,000-dalton subunit bound tropomyosin, and the 20,000-dalton subunit bound calcium, like skeletal TN-T and TN-C, respectively. The 28,000 component, although presumably analogous to skeletal TN-I, gave very little inhibition of actomyosin ATPase activity. Differences between cardiac and skeletal troponin subunits were also found in the elution patterns from ion exchange columns and in amino acid composition, thus demonstrating a significant muscle-type specificity.


Binding and precipitation of soluble collagens by chick embryo cartilage proteoglycan.

A sensitive radioactive assay has been developed to facilitate study of the binding to and precipitation of soluble collagen by embryonic proteoglycans. Using this assay it has been found (a) that chick embryo cartilageproteoglycan is reactive with types I, II, and III soluble collagen; and (b) that both the core-protein and chondroitin sulfate chains of the proteoglycan are necessary for this interaction.


Growth of cultured calf aortic smooth muscle cells on cardiovascular prosthetic materials.

The growth of cultured calf aortic smooth muscle cells on cardiovascular biomaterials was investigated, using native and oxidized polyacrylonitrile (orlon) fabrics, dacron velour, and Parylene-C coated polypropylene microfabric as substrates. By light microscopic evaluation, surface cell coverage was most complete on microfabric, followed by native orlon, dacron velour, and oxidized orlon. Native orlon supported the greatest total cell growth, as determined by chemically extractable protein, followed by oxidized orlon, dacron velour, and the microfabric. The observed differences appear to be related to the pore size and fiber thickness of the different substrates.


Reconstruction of the canine Achilles and patellar tendons using dacron mesh silicone prosthesis. I. Clinical and biocompatibility evaluation.

Surgical replacement of the Achilles and patellar tendons using Dacron mesh silicone prostheses was performed in 15 mature beagle dogs. This part of the study includes clinical evaluation, gross inspection at autopsy of regrown tendons, and histological determination of biocompatibility of prosthetic implants. Functional continuity and integrity of prosthetic patellar tendons have been established by evaluating the biologic-prosthetic interface and the mechanical properties of regrown tendon tissue around and through the Dacron silicone replacements. Results of prosthetic Achilles tendons were less satisfactory because of difficulties in suturing to a muscle and its fascia. Although the prosthetic tendon did not regrow through the tube, it provided a structure for regrowth around it. The regrown tendons became nearly ten times the normal cross-sectional area after three to four months and decreased to two to three times after 13 months. Histological studies indicate that in the absence of infection, the Dacron mesh silicone tendon was well tolerated for periods up to 13 months. Overall results are encouraging and warrant further investigation although the regenerative capacity of human patellar and Achilles tendons is unknown.


Ciliary inter-microtubule bridges.

Electron micrographs of both negatively contrasted and thin-sectioned lamellibranch gill cilia reveal several new features of ciliary fine structure, particularly in regard to those structures forming intermittent or permanent crossbridges between microtubules. Negative-contrasting reveals the presence of a 14-5-nm repeating bridge between the central microtubules. Frontal views of negatively contrasted dynein arm rows along subfibre A show that the arms (23-nm repeat) in the outer row are displaced in a left-handed manner by 3-4nm with respect to those in the inner row. This displacement is probably a direct reflexion of the helical tubulin subunit lattice of the subfibre. Interdoublet (nexin) links are seen connecting adjacent A and B subfibres at intervals of 86 nm along the doublet. Negative-contrasting shows thin, highly elastic connexions holding the doublets together. When seen in longitudinal thin sections, the interdoublet links are often tilted to considerable angles, indicating they may have an elastic response to interdoublet sliding.


The influence of gibberellic acid and abscisic acid on cell and tissue differentiation of bean callus.

Bean callus was induced to form roots (tissue differentiation) and vascular nodules (cell differentiation) by lowering the ratio of auxin to cytokinin in the growth medium. Both types of differentiation were inhibited by the addition of abscisic acid (at concentrations greater than I muM) to induction medium. Initiation of differentiation was inhibited, but its subsequent development was not, and the inhibition was not affected by the addition of gibberellic acid. Addition of gibberellic acid (GA) alone to induction medium stimulated tissue differentiation, although cell differentiation was unaffected (30 muM GA) or inhibited (45 muM GA) and its onset was delayed at both concentrations. Root initiation was also stimulated by gibberellic acid (0.I-45 muM) at an auxin-to-kinin ratio 10 times that normally optimal for cell differentiation. The phenylalanine ammonia lyase (PAL) activity of the calluses was closely correlated with the amount of cell differentiation which had occurred, and measurement of this confirmed that gibberellic acid delayed the initiation of cell differentiation. The increase and subsequent decline of PAL and betaI leads to 3 glucan synthetase activities, normally induced by transfer to induction medium, was abolished by abscisic acid. Addition of gibberellic acid did not affect the betaI leads to 3 glucan synthetase activity.


The determination of clioquinol in biological materials by extractive alkylation and gas-liquid chromatography.

Clioquinol, or 5-chloro-7-iodo-8-hydroxyquinoline (Vioform), and the internal standard, 5,7-dichloro-8-hydroxyquinoline are extracted from biological material in the form of their tetrahexylammonium salts into dichloromethane, where, in the presence of a methylating agent, both clioquinol and the standard are spontaneously transformed into their O-methyl derivatives. These derivatives can be purified by base-specific extraction and subsequently determined by gas chromatography; concentrations down to 10 ng per sample may be assayed. The method is compared with a previously reported procedure based on the O-acetyl derivatives.


Serum androgens in normal prepubertal and pubertal children and in children with precocious adrenarche.

Serum androgens testosterone (T), testosterone-like-substances (TLS), delta4-androstenedione (delta4), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) were measured in 85 normal girls and 101 normal boys grouped according to pubic hair development in Tanner stages I to IV/V. The pattern of change with puberty differed for each androgen. In boys T and TLS rose with the onset of puberty but showed a more abrupt rise later in puberty. DHT also was higher in boys in late puberty but did not demonstrate a steep rise. The other androgens did not show a sex difference at any stage of puberty. While delta4 steroids did not show an increase in the years before onset of puberty, DHEA was significantly higher in prepubertal children over 7 years than in those under 7 years (mean +/- SD 166 +/- 110 vs. 31 +/- 25, P less than 0.005). The most rapid increase of DHEA concentrations was observed with the appearance of pubic hair (Stage II) in boys and girls. This contrasted with the more gradual rise of delta4 in both sexes. The oldest boys and girls (Tanner stages IV/V) had mean concentrations of all androgens in the adult range except for DHT. Twenty-two girls with precocious adrenarche (PA) aged 3-8 years had mean concentrations of T, DHT, delta4 and DHEA that were significantly higher (P less than 0.05) than in prepubertal children, but similar to those of girls in stage II and significantly lower (P less than 0.02) than in late pubertal girls (stage IV/V). Longitudinal studies in 12 of the girls indicated fluctuation of androgen concentrations, especially DHEA, but in general no increase during the years of followup. Precocious adrenarche appears to be a non-progressive disorder associated with an advanced maturation of adrenal androgen to an early pubertal stage. A rise in all androgens measured was correlated with the development of sexual hair.


Degradation of cartilage proteoglycan by human leukocyte granule neutral proteases--a model of joint injury. I. Penetration of enzyme into rabbit articular cartilage and release of 35SO4-labeled material from the tissue.

The present work was undertaken to explore the effect of two purified neutral proteases derived from human peripheral blood polymorphonuclear leukocytes (PMN) on articular cartilage as a model of joint injury. Human leukocyte elastase and chymotrypsin-like enzyme, purified by affinity chromatography, released 32SO4 from labeled rabbit articular cartilage slices in vitro. Release of isotope was initially delayed, suggesting that either a lag in enzyme penetration occurs or that size of degradation fragments is a limiting factor in diffusion of label out of the tissue. The release of 35SO4 was inhibited by preincubation of elastase and chymotrypsin-like enzyme with human alpha 1-anti-trypsin, or with their specific chloromethyl ketone inactivators, and the action of elastase was also inhibited by a monospecific antiserum to PMN elastase, freed of major serum proteinase inhibitors. Immunohistochemical staining procedures revealed the presence of PMN elastase inside the matrix of cartilage slices after a 20-min exposure of tissue to either the pure enzyme or crude PMN granule extract. Serum alpha 1-antitrypsin failed to penetrate into the cartilage slices under identical in vitro conditions. In association with the results reported in the accompanying paper, these findings suggest a model of cartilage matrix degradation by PMN neutral proteases in which local protease-antiprotease imbalance, coupled with different rates of penetration of protease and antiprotease into target tissue, plays a key role in accounting for matrix damage.


Degradation of cartilage proteoglycan by human leukocyte granule neutral proteases--a model of joint injury. II. Degradation of isolated bovine nasal cartilage proteoglycan.

Extracts of human peripheral blood polymorphonuclear leukocyte granules, and two purified proteases derived from such extracts, an elastase and a chymotrypsin-like enzyme, degrade isolated bovine nasal cartilage proteoglycan at neutral pH. Viscosity studies indicate that the leukocyte granule extracts lack hyaluronidase activity and that their degradative effect on proteoglycan at physiological pH is due entirely to proteolytic action. Sepharose 4B gel chromatography and SDS-polyacrylamide gel electrophoresis of proteoglycan fractions treated with leukocyte granule enzymes at pH 7.0 indicate that they degrade one of the proteoglycan link proteins, release a fragment from the hyaluronic acid-binding portion of the proteoglycan subunit core protein, and break down the remainder of the proteoglycan subunit molecule into peptide fragments with varying numbers of chondroitin sulfate chains. Immunodiffusion studies indicate that the antigenic determinants of the proteoglycan subunit core protein and the link proteins survive treatment with granule proteases. Similar degradation of human articular cartilage proteoglycan by granule neutral proteases can be presumed to occur, in view of the similarity of structure of human articular and bovine nasal cartilage proteoglycans. The release of granule enzymes in the course of neutrophil-mediated inflammation can thus result in the degradation of cartilage matrix proteoglycan, leading to cartilage destruction and joint injury.


Development of a diagnostic checklist for low back pain patients.

The study of psychosomatic disorders implies that environmental variables, as well as attitudes and personality, can influence an individual's physical health. The present study developed a checklist composed of demographic and psychological variables to help to make diagnostic decisions related to chronic low-back pain. The need for the checklist stems from the situation that medical clinical evidence is often inconclusive to identify the etiology of patient complaints of low back pain. Cut-off scores on the checklist were able to discriminate with greater than 80% accuracy patients who received a specific medical diagnosis from patients who received a non-specific medical diagnosis. The findings provide additional support for procedures used to make difficult diagnoses of low back pain.


Echocardiographic study of the effects of acute left atrial hypertension on left atrial size.

This study was designed to investigate the effects of acute left atrial hypertension on left atrial size. Twenty-four patients with acute myocardial infarction were studied. The estimated mean left atrial pressure (LAm) was correlated with left atrial (LA) size obtained by echocardiogrphy. The LAm was elevated (greater than 12 mmHg) in 15 patients (Group I). The LA size was within normal limits in all but two patients who had minor increases. The LAm was normal in nine patients (Group II). The LA size was normal in each case. The LA size remained unchanged in those patients who had a stable LAm. We conclude that acute increases in LAm are not usually associated with LA enlargement beyond the upper limit of the normal range.


Enzymes of carbohydrate metabolism in human epidermal tumors 4. Enzymes of the pentose phosphate pathway.

The acitvities of six enzymes were determined by fluorometric micromethods in epidermal tumors (basal and squamous cell epithelioma, verruca seborrhecia and keratoacanthoma) and compared to the activities in the adjoining, apparently normal epidermis. Specific changes related to malignancy were not obvious.


Cellular mechanism of endotoxin unresponsiveness in C3H/HeJ mice.

B cells from C3H/HeJ mice fail to respond to an endotoxin (LPS K235) which is mitogenic for normal mice including the closely related C3H/HeN strain. The cellular basis for this unresponsive state has been investigated. The C3H/HeJ mice have normal numbers of B cells, which are capable of normal responses to other B cell mitogens, such as polyinosinic acid (Poly I). Addition of normal macrophages or spleen cells fails to reconstitute the normal response. Furthermore, neither macrophages nor spleen cells from the C3H/HeJ strain suppress the normal C3H/HeN spleen cells. Finally, spleen cells enriched for B cells by the removal of macrophages or T cells demonstrate the same differences in responsiveness to LPS. These results indicate that LPS unresponsiveness is a defect of the B cell itself and not due to suppressor cells or the absence of helper cells. When LPS is added to Poly I-stimulated cultures, there is additional enhancement of the response of normal C3H/HeN spleen cells. However, LPS causes a dose-dependent suppression of the Poly I response of C3H/HeJ spleen cells. This suppression is dependent on the time of addition of LPS to the Poly I-stimulated cultures. These data are interpreted as indicating that the binding of LPS to the membrane of C3H/HeJ B cells results in their inactivation or suppression, and that this is the basis of LPS unresponsiveness in this mouse strain.


Evaluation of topical anti-inflammatory steroid formulations in an Arthus model of inflammation.

Formulations of a number of steroids were evaluated after topical application in a reversed passive Arthus test (RPA) in rabbits. Four 21-chlorosteroids in the same cream base were investigated. The preparations of SQ 18,566 (halcinonide) and SQ 20,811 showed anti-edema activity, but those of SQ 15,361 and SQ 20,589 were less active. Ointment formulations of halcinonide also reduced edema in the RPA. These results, coupled with previously reported clinical data, suggest that the RPA might be utilized to distinguish good from poor formulations of anti-inflammatory steroids prior to screening tests or clinical trials in humans.


The effect of oral and topical tetracycline on acne severity and on surface lipid composition.

Groups of 20 males of high-school age with moderate acne were treated with oral tetracycline (500 mg/day), topical tetracycline (0.5% solution applied twice daily), or placebo for 8 weeks. The two panels treated with tetracycline showed a significant and equivalent reduction in acne severity as assessed by visual grading. The surface lipids in the panel treated with oral tetracycline showed a small but not statistically significant decrease in free fatty acid content, but the subjects receiving topical tetracycline showed no reduction in free fatty acids. Further, neither treatment was associated with a change in mass of surface lipid nor did the mass or weight percent of any component of the surface lipids change with the decrease in acne severity. These results show that acne severity can be reduced with tetracycline (both oral and topical) without any concomitant quantitative change in surface lipids.


Platelet contractile proteins: separation and characterization of the actin and myosin-like components.

Solution of thrombosthenin, the contractile protein complex isolated from pig platelets, have been studied by analytical ultracentrifugation and zone sedimentation in sucrose density gradients. Freshly prepared thrombosthenin in 0.6 M KCl shows a prominent peak in the ultracentrifuge with S degrees 20w about 5.5 and higher molecular weight aggregates (greater than 100S) sedimenting quickly to the bottom of the cell. Short term storage of high ionic strength solutions of thrombosthenin induces actomyosin-like gel formation and these gels dissociate with ATP and Mg2+ ions into two components of S degrees 20w 8.0 and S degrees 20w50. The supernatant,  after actomyosin gel removal, contains only the S degrees 20w5.5 protein. From results of Ca2+ ATPase activity measurements and SDS polyacrylamide gel electrophoretic mobilities of dissociated thrombosthenin separated into fractions in sucrose density gradients, it is concluded that the S degrees20w5.5 protein species is the myosin-like protein of thrombosthenin. The S degrees 20w8.0 protein is not fibrinogen but also has myosin-like properties and is believed to be myosin dimer. Species of higher S values seen in the presence of ATP and Mg2+ in the analytical ultracentrifuge and located in the higher density zones of the sucrose gradients all gave in SDS polyacrylamide gel electrophoresis a single band of molecular weight 46-47,000 daltons. These subunit proteins appear to be derived from a range of polymeric variants of the F-actin-like protein of the contractile complex. All these higher density F-actin-like proteins readily form superprecipitates and display syneresis when combined with rabbit skeletal muscle myosin or platelet myosin. They are also all capable of conferring upon these two myosins a Mg2+ activated ATPase activity. It is suggested that in thrombosthenin solutions a myosin monomer-dimer equilibrium state exists which can be directionally influenced by a number of factors. The coexistence in the solution of F-actin and Mg2+ ATP, for example, increases the propensity of the myosin-like protein to form the higher molecular weight aggregate. Such aggregation may be the initiating mechanism for the intracellular organization of the thick filaments of the actomyosin complex, preparatory to a contractile event.


Studies on the amino groups of myosin-ATPase. II. Localization of the amino groups.

1-5 of the epsilon-amino groups of myosin were trinitrophenylated by 2,4,6-trinitrobenzene sulphonate. The Mg2+-activated ATPase activity was found to increase twenty fold while the K+-activated ATPase was strongly inhibited as a result of this treatment. Myosin was dissociated by urea after trinitrophenylation and its heavy and light chains were isolated. Virtually all the introduced trinitrophenyl groups were found in the heavy chain indicating that the lysyl residues, the modification of which affects the ATPase activity, are located at the heavy core of the myosin molecule.


Immune complex orchitis in vasectomized rabbits.

The results of the present study show that bilaterally vasectomized rabbits with high levels of antibodies to sperm antigens frequently develop an orchitis associated with granular deposits of rabbit IgG and C3 in the basement membranes of seminiferous tubules. The immune deposits correspond in location to electron-opaque deposits seen by electron microscopy. The "membranous orchitis" is characterized by thickening of tubular basement membranes, acc-mulation of macrophages and a few polymorphonuclear leukocytes, and destruction of the basal lamina, of the Sertoli and spermatogenetic cells. The pathogenetic role of the immune deposits and the possibility that they contain antigen-antibody complexes is indicated by: (a) selective accumulation of IgG and C3 granular deposits along the basement membranes of seminiferous tubules in rabbits producing high and persistent levels of antibodies to sperm antigens; (b) the elution of immunoglobulins from tissues with chaotropic ion-containing buffers, acid buffers, or heat; (c) the observation that the immuno-globulins accumulated in the testis contain antibody to sperm antigens; and (d) the demonstration of sperm antigens in a location similar to that of IgG and C3. It is postulated that sperm antigen-antibody complexes are formed in the basement membranes of seminiferous tubules when antigens leaking out of the tubules react with specific antibody coming from the circulation. In two rabbits with higher levels of circulating antisperm antibodies and severe orchitis, granular deposits of IgG and C3 were also present in renal glomeruli. Immunoglobulins eluted from the kidneys contained antibody with antisperm activity. These findings are consistent with the hypothesis that in some vasectomized rabbits extratesticular lesions may develop by a mechanism comparable to that of chronic serum sickness.


The role of nonclassical Fc receptor-associated, Ag-B antigens (Ia) in rat allograft enhancement.

The ability of a hyperimmune Lew anti-BN serum (HIS) to induce enhancement of (Lew/BN)F1 kidneys transplanted into Lew recipients was compared to that of the same antiserum that had been depleted of hemagglutinating anti-Ag-B antibodies by absorption with Brown-Norway (BN) RBC-absorbed sera (RAS) or platelet-absorbed sera (PAS). The RAS and PAS were as effective as the unabsorbed HIS in abrogating early rejection as assessed by renal function and promotion of long-term survival. The absorbed sera retained the capacity to block the mixed lymphocyte culture (MLC) between Lew and BN lymphocytes and to a lesser degree the MLC between Lew and BUF, WF, AUG, and ACI lymphocytes; however, strain specificity was clearly evident at high antiserum dilutions. Similarly, these absorbed sera retained the capacity to block the Fc receptor of BN lymphocytes, and this effect was completely strain specific. In contrast, hemagglutinating and cytotoxic antibodies eluted from platelets used for antiserum absorption did not react with Fc receptors as assessed by rabbit antisheep (IgG)-coated SRBC (EA) rosette formation. F(Ab')2 fragments of PAS also blocked EA rosettes. On the other hand, complement rosettes (EAC) were not inhibited by the HIS. The antibodies were therefore directed against the Fc receptor itself or a structure spatially or functionally closely related to it. Both the Fc receptors and the enhancing capacity of the antisera were strictly specific for the BN genotype. It is suggested that the anti-"Fc receptor" antibody could play an important role in the induction of enhancement by impairing host T-B collaboration as a result of its binding to graft allogeneic "Fc receptors" which appear to be analogous to the major histocompatibility complex (MHC)-coded Ia antigens of the mouse.


Regulatory mechanisms in cell-mediated immune responses. III. I-region control of suppressor cell interaction with responder cells in mixed lymphocyte reactions.

Active suppression of mixed lymphocyte reaction (MLR) response is mediated by a soluble factor released by alloantigen-activated murine suppressor cells. Genetic restrictions controlling suppressor factor interaction with MLR responder cells were elucidated in this study. Non-H-2 genetic background was irrelevant to effective interaction. Using congenic strains and strains with intra-H-2 recombinants the genetic locus controlling suppressor T-cell-responder cell interaction was mapped in the I-C or S regions of the H-2 complex. Similarly, recombinant strains were used to exclude the presence of another suppressor cell-responder cell interaction locus in K,I-A, and I-B regions. It thus appears that the I-C subregion of the H-2 complex controls suppressive cell interactions in this T-cell-mediated immune response.


Two anaphylactic deaths after chemonucleolysis.

Chemonucleolysis is a procedure for treatment of low back pain due to discogenic disease in which the drug chymopapain is injected into lumbar disks to produce chemical dissolution of the nucleus pulposus. More than 15,000 cases have been treated by chemonucleolysis world-wide. Anaphylaxis after the injection of chymopapain occurs in about 1% of such cases. The two cases described in this paper are the only known deaths due to anaphylaxis. Both patients suddenly became hypotensive after injection of chymopapain into a disk. One patient died shortly after this, whereas the second patient died of the complications of prolonged shock.


[Epidemiological aspects of trisomy 21].

The authors analyse cytogenetic and epidemiological data of 4760 cases of trisomy 21 found in 22 European Centres of Genetics. This cytogenetic study is dealing with the frequency of regular free trisomies and those in mosaics and of trisomies by translocation. The frequency of the different types of translocation has been established thanks to an identification of the chromosomes through marking techniques. The risks and causes of recurrence are discussed. From the epidemiological aspect, the role of the mother's age was the subject of a special study which confirms the bimodal distribution of the trisomy 21. This distribution is discussed in association with the other epidemiological factors: X-ray, virus, auto-immunity and gynaecological disorders.


[Chromosome analyses in parents of children with trisomy 21[].

In connection with a comparative study between parents of trisomic 21 children and control parents, the authors discuss the eventual role of the increase of association rates between acrocentric chromosomes on the appearance of non-disjunctions and translocations affecting chromosome 21. The results are analyzed and compared with data found in the literature.


Relation between Genetic markers and oligoclonal IgG in CSF in optic neuritis.

Thirty patients with acute, unilateral optic neuritis (ON), where re-examination after a mean observation period of 5 years did not reveal any aetiology, were investigated with regard to laboratory abnormalities frequently observed in multiple sclerosis. Eleven patients had oligoclonal IgG in CSF. In 5 of these a measles virus antibody response within the CNS was demonstrable. The remaining 19 patients did not display oligoclonal CSF IgG, nor an antibody response. The major histocompatibility antigens HL-A3 and HL-A7 occurred at similar frequencies in ON and in controls, irrespective of the presence of oligoclonal CSF IgG. The HL-A7 associated MLC determinant LD-7a occurred in ON at a frequency between that observed in controls and in MS. However, an association of the same magnitude as observed in MS was found between ON with oligoclonal CSF IgG and the presence of LD-7a. This association was absent in those ON patients who lacked oligoclonal CSF IgG. The present data indicate that the finding of oligoclonal CSF IgG may increase the risk of developing MS.


Neurofibrillary tangles of paired helical filaments.

The abnormal aggregates of fibrillar material found in neurons in Alzheimer's disease, senile dementia, the Guam Parkinsonism-Dementia complex, Down's syndrome, and postencephalitic Parkinsonism were studied by means of tilt-stage electron microscopy and with X-ray images of scale models of a bifilar helix. The model fulfills the structural criteria established by electron microscopy. These studies showed that the "twisted tubule" which makes up the neurofibrillary tangle in many pathological situations is a bifilar helix made up of 130 A filaments.


Classification and response characteristics of muscle spindle afferents in the primate.

A study was made of the response characteristics of spindle afferents in the baboon soleus muscle. Afferents were isolated from the dorsal roots, their conduction velocities were determined, and their responses were recorded to muscle stretch at rates of 2.5-45 mm/s and amplitudes of 2-10 mm. Spindle afferents could be classified as primary or secondary on the basis of two criteria. The first criterion was conduction velocity. The conduction velocity histogram was bimodal, with peaks at about 45 and 80 m/s and an intermediate region from 55 to 70 m/s. The second criterion was the pattern of adaptation following the peak of ramp stretch. This latter criterion has the advantage of allowing units with intermediate conduction velocities also to be confidently classified as primary or secondary. The velocity and position sensitivities of primate spindle afferents were determined. The mean dynamic index and mean dynamic sensitivity of secondary afferents were about 45% of the corresponding values for primary afferents. On the other hand, the position sensitivities of primary and secondary spindle afferents in the baboon were not significantly different.


Effects of fusimotor stimulation on dynamic and position sensitivities of spindle afferents in the primate.

The effects of stimulation of single static and dynamic fusimotor fibers on the dynamic sensitivity and position sensitivity of primary and secondary spindle afferents have been studied in the soleus muscle of the baboon. Static fusimotor fibers decreased the mean dynamic sensitivity of primary afferents at all rates of stretch and stimulation. The magnitude of the decrease in dynamic sensitivity increased as the rate of fusimotor stimulation was increased. Qualitatively similar effects were observed in secondary afferents. Static fusimotor stimulation had a strong excitatory effect on spindle afferent resting discharge and greatly increased the mean position sensitivity of both primary and secondary afferents. Dynamic fusimotor fibers increased the mean dynamic index of primary afferents at all rates of stretch and stimulation. The effect of dynamic fusimotor fibers on the mean dynamic sensitivity, however, was dependent on the rate of muscle stretch; at rates below 15 mm/s the dynamic sensitivity was substantially increased, whereas at rates greater than 15 mm/s it was either unchanged or decreased. Dynamic fusimotor fibers slightly decreased the mean position sensitivity of primary afferents.


Classification of fusimotor fibers in the primate.

The classification and distinguishing characteristics of fusimotor fibres of the baboon soleus muscle have been studied by determining the effects of single fusimotor fiber stimulation on the response of isolated spindle afferents to muscle stretch. As in the cat, fusimotor fibres in the baboon were divisible into static and dynamic types on the basis of the effect of their stimulation at 200/s on the dynamic index of the primary afferent. Single fusimotor fibres had the same qualitative effect-static or dynamic-on all the primary afferents they were found to influence. All static fusimotor fibres produced at least 1 to 1 driving of primary afferent discharge at 50/s if the muscle length was adjusted to optimize conditions for driving. In contrast, 31 of 32 dynamic fusimotor fibres did not produce driving of primary afferent discharge even though all were studied at many different muscle lengths and frequencies of stimulation. Therefore, fusimotor fibres in the baboon could be classified as static or dynamic on the basis of their ability to produce driving of the primary afferent. The ratio of isolated static to dynamic fusimotor fibers was 1.5 to 1. The mean conduction velocity of static fusimotor fibers was 24.1 m/s and that of dynamics was 20.2 m/s. Although the difference between these two means was statistically significant (P less than 0.001), the conduction velocity histograms of static and dynamic fusimotors overlapped, precluding classification by this means. Secondary afferents with one possible exception were concluded to be exclusively activated by static fusimotor fibers. Poststimulus effects of fusimotor stimulation on primary afferent response to stretch were studied. With intervals between the end of stimulation and the beginning of stretch of 0.1 s, dynamic fusimotor stimulation produced facilitation of the primary afferent response to stretch, whereas static fusimotor fibers produced depression.


Dietary fatty acids on the control of glucose-6-phosphate dehydrogenase and malic enzyme in the starved-refed rat.

The role of dietary unsaturated fat in the control of hepatic glucose-6-phosphate dehydrogenase (G6PD) (EC 1.1.1.49) and malic enzyme (ME) (EC 1.1.1.40) was studied in rats subjected to one or two cycles of starvation-refeeding. Rats starved and refed a control (5% corn oil) diet showed a threefold increase in G6PD activity and a twofold increase in ME activity compared to ad libitum-fed rats. After a second cycle of starvation-refeeding G6PD and ME activities showed fourfold and threefold increases, respectively, as compared to ad libitum-fed rats. Feeding rats diets containing 8% linoleic acid (as triglycerides) prevented the increase in G6PD and ME activities upon starvation-refeeding, diets with oleic, palmitic, and stearic acis when fed did not prevent this increase. Feeding rats various combinations of linoleic, linolenic and oleic acids following starvation prevented the additional increase in G6PD and ME activities after a second starvation-refeeding cycle; however, linoleic acid fed alone during the first refeeding prevented the additional increase in ME activity but not in G6PD activity. It is suggested that the dietary control of these enzymes involves one or more specific polyunsaturated fatty acids.


The effects of muscle cooling and stretch on muscle spindle secondary endings in the cat.

1. The objectives of the investigation were to identify the muscle spindle endings which respond to cooling of the relaxed muscle and to study their response to stretch. 2. The discharge of single afferents from 162 de-efferented muscle spindles in the relaxed medial gastrocnemius muscle of the anaesthetized cat was studied in vivo during cooling of the muscle from 37 to 24 degrees C. Temperature measurements were made at the inner surface of the muscle, while cooling (never below 15 degrees C) was applied at the skin over the muscle. 3. The endings were classified as primary or secondary endings on the basis of their conduction velocity, the dividing line being set at 70 m/sec. A response to cooling was obtained only from endings with afferents conducting at velocities of 20-70 m/sec. These fifty-six endings (CR) represented 65% of the secondary endings studied; the remaining secondary endings (NCR) and the primary endings showed no activity during cooling of the relaxed muscle. 4. During maintained stretches of 4-12 mm, activity of the NCR and primary endings decreased when the muscle was cooled. Cooling affected the CR endings in the same way, but only if the muscle was stretched 6 mm or more. During a smaller maintained muscle stretch, cooling caused an increase in CR activity, superimposed on the response to stretch. 5. The response to a 10 mm stretch at velocities of 10-70 mm/sec was studied in twenty-six CR, eleven NCR and twenty-one primary endings. 6. The dynamic responses of CR endings were intermediate between those of the primary endings and NCR endings. For any velocity of stretch the mean dynamic index of the CR endings was significantly greater than that of the NCR endings but significantly less than that of the primary endings. 7. The mean static responses of the CR and primary endings, measured 0-5 sec after the end of ramp stretch, were the same and significantly greater than that of the NCR endings. 8. The results indicate that cooling of the relaxed mammalian muscle may be used to differentiate between primary endings and about two-thirds of the secondary endings. The remaining secondary endings can be recognized by their small dynamic and static response to stretch.


Analysis of activity of muscle spindles of the jaw-closing muscles during normal movements in the cat.

Recordings have been made of afferent activity from spindles of the jaw-closing muscles, together with jaw movement and e.m.g. from temporalis and masseter in conscious, unrestrained cats. 2. In the twenty-nine units studied, the pattern of spindle behaviour observed during eating and lapping was generally what might be expected of stretch receptors. Maximal firing frequencies were found during opening of the mouth (lengthening), while during active closing the discharge was progressively reduced or abolished. Nevertheless, changes in the relation of stretch to firing frequency in different movements indicated that fusimotor drive was not constant. 3. spindle afferents could be divided into two groups on the basis of their maximal firing frequency during eating. "High-frequency" units (range 240-600 impulses/sec) showed pronounced velocity sensitivity, which supports the proposal that they correspond to spindle primaries. 'Low-frequency" units (range 80-200 impulses/sec) showed predominantly length sensitivity and probably correspond to secondary endings. 4. Length sensitivity of low-frequency units was considerably greater in lapping movements than in eating, indicating increased static fusimotor drive in the former. Sensitivity in the opening phase of eating was indistinguishable from that recorded in deeply anaesthetized animals. 5. High-frequency units were generally silenced immediately active shortening commenced. 6. No simple relationship existed between temporalis or masseter e.m.g. and spindle firing. 7. These results imply that normal masticatory movements are not initiated or driven to any appreciable extent via the fusimotor route. Close alpha-gamma co-activation is not a feature of this situation. On the other hand, in some other movements, such as licking the lips, fusimotor drive could fluctuate so as largely to cancel the unloading effects of active muscle shortening.


Stoichiometry of sodium and potassium transport in erythrocytes from patients with myotonic muscular dystrophy.

1. 22Na and 42K radioisotopes were used to measure Na efflux and K influx in identical suspensions of fresh erythrocytes from myotonic dystrophy patients and matched controls under the same conditions and in the same time interval. K was present in concentration 10 mM in the suspending medium to prevent Na-for-Na exchange. Each flux was measured in the presence and absence of ouabain. The mean ouabain-sensitive Na efflux rate in controls (2-33+/-0-13, S.E. of mean, m-equiv/1. cells.hr) was significantly greater (P less than 0-001) than the corresponding rate in myotonic dystrophy (1-64+/-0-09). 2. No significant differences between myotonic dystrophy and controls in mean ouabain-insensitive Na efflux, mean ouabain-sensitive K influx, or mean ouabain-insensitive K influx were found. 3. The stoichiometric ratio (ouabain-sensitive Na efflux)/(ouabain-sensitive K influx) was determined for each flux experiment. The mean stoichiometric ratio determined in controls (1-46+/-0-08) reconfirms extensive previous evidence favouring a 3Na-for-2K active exchange in controls. 4. The mean stoichiometric ratio determined in myotonic dystrophy (1-01+/-0-06) is statistically significantly different (P less than 0-001) from that in controls. These findings are interpreted as indication of 2Na-for-2K exchange in erythrocytes from patients with myotonic dystrophy.


A simple technique of laparoscopic tubal sterilization.

In the last several years the use of laparoscopy in gynecological practice has become very popular. It is indicated for a number of conditions. However, sterilization of the female has been the main indication for laparoscopy and will remain so until more efficient and reversible techniques are developed. A simple technique of laparoscopic tubal sterilization is presented. In the opinion of the authors it offers several advantages over other methods. Only one instrument is used and only one type of electrical current applied. A small portion of the fallopian tube is removed and the surrounding tissue--the tube and mesosalpinx-- is sufficiently cauterized to secure hemostasis. The histological quality of the removed specimen is excellent. Finally, less than 2 cm of fallopian tube is destroyed, providing an excellent opportunity for reanastomosis.


Separate effects of mercurial compounds on the ionophoric and hydrolytic functions of the (Ca++ +Mg++)-ATPase of sarcoplasmic reticulum.

We have shown that a Ca++-ionophore activity is present in the (Ca++ +Mg++)-ATPase of rabbit skeletal muscle sarcoplasmic reticulum (A. E. Shamoo & D. H. MacLennan, 1974. Proc. Nat. Acad. Sci. USA 71:3522). Methylmercuric chloride inhibited the (Ca++ +Mg++)-ATPase and Ca++ transport, but had no effect on the activity of the Ca++ ionophore. Mercuric chloride inhibited ATPase, transport and ionophore activity. The ATPase and transport functions were more sensitive to methylmercuric chloride than to mercuric chloride. The two functions were inhibited concomitantly by methylmercuric chloride but slightly lower concentrations of mercuric chloride were required to inhibit Ca++ transport than were required to inhibit ATPase. Methylmercuric chloride and mercuric chloride probably inhibited ATPase and Ca++ transport by blocking essential -SH groups. However, it appears that there are no essential -SH groups in the Ca++ ionophore and that mercuric chloride inhibited the Ca++ ionophore activity by competition with Ca++ for the ionophoric site. Blockage of Ca++ transport by mercuric chloride probably occurs both at sites of essential -SH groups and at sites of ionophoric activity. These data suggest the separate identity of the sites of ATP hydrolysis and of Ca++ ionophoric activity.


Longevity in Down's syndrome in British Columbia.

Life Tables to age twenty for Down's syndrome cases born in British Columbia from 1952 through 1971 were constructed using data from the British Columbia Health Surveillance Registry. No significant difference in survival to age twenty between males and females was found either in the presence or in the absence of congenital heart anomalies. Data from the life Tables show that Down's syndrome patients with congenital heart anomalies experience higher mortality to age twenty than cases without congenital heart anomalies.


Genetic prognosis in severe mental handicap.

698 children below age sixteen years with severe mental handicap (below IQ50) who were admitted to hospital between 1956 and 1959 were surveyed for genetic prognosis. They were divided into 23.7% ascribed primarily to environmental factors, 50.9% unclassified aetiologically, 16.2% of Down's syndrome, 5.3% other genetic syndromes and 3.9% with congenital hydrocephalus. The incidence of a similar degree of mental retardation among the sibs of 660 whose families were traced, was 1.1% in the "environmental" group; 4.7% for the unclassified; 1.7% for Down's syndrome, 11.5% for other genetic syndromes and 4.3% for hydrocephalus with spina bifida. There were no affected sibs of the uncomplicated cases of congenital hydrocephalus. This survey underlines the fact that a high proportion of cases of mental handicap remain without aetiological diagnosis. It emphasises the value of such a diagnosis for genetic counselling. Advice given depends on the circumstances of the particular case which requires a detailed social history and sympathetic rapport by members of the team as well as appropriate clinical expertise (Kirman, 1971, 1972). When families with similarly affected new relative or previous severely mentally handicapped sibs are set aside, the recurrent risk for unclassified cases is reduced to three per cent.


A case of idiopathic Addison's disease and probable autoimmune thyroiditis in a mongol.

A case of idiopathic Addison's disease and probable autoimmune thyroiditis in a mongol is reported and the clinical features and significance of the changes in autoimmune competence, and their relationship to pathological ageing, are discussed.


The effect of institutionalisation on elevated IgD and IgG levels in patients with Down's syndrome.

Serum levels of IgA, IgD, IgE, IgG, IgM and levels of secretory IgA (S-IgA) in nasal specimens were quantitated by radial immunodiffusion in a group of forty-one institutionalised patients with Down's syndrome (all non-disjunctive trisomy-G karyotype) and their age, sex and race matched controls, consisting of institutionalised non-mongols and normal non-institutionalised subjects. Analysis of levels of all immunoglobulins by age and sex showed no differences within the populations. However, levels of IgA, IgD and IgG were found significantly higher in mongols than in the other two populations. The concentrations of IgM were lower in mongols than in other institutionalised retardates but higher than non-institutionalised normal controls. Levels of S-IgA or IgE were similar in all populations. It was shown that the length of institutionalisation was associated with elevated levels of IgA and depressed levels of IgM in mongols. However, elevated IgG levels in mongols did not appear to be associated with their length of institutionalisation. Similarly, elevated levels of IgD in mongols were not associated with their length of institutionalisation.


Disposable peak urinary flowmeter estimates lower urinary tract obstruction.

Peak urinary flow rate represents the highest flow rate achieved during a single urination and, as such, represents the patient's best effort at micturition. Peak flow rate, correlated with patient age and volume voided, effectively estimates lower urinary tract obstruction. The 63 normal and 368 abnormal male subjects urinated in privacy into a plastic sterile disposable device (the peakometer), which measured peak flow rate and volume voided. These data plus age, ultimate diagnosis and interval since last urination comprised our data base. Percentage distribution of diagnosis in this population was prostatic obstruction 47.3 per cent, stricture 19.3 per cent, normal 14.6 per cent, prostatitis 8.4 per cent, neurogenic bladder 2 per cent and miscellaneous 8.4 per cent. The average peak flow rate for normal male subjects reaches 27.6 ml. per second, which differs significantly from that for patients with prostatic obstruction--9.4 ml. per second, stricture--10.5 ml. per second, prostatitis--16.3 ml. per second and neurogenic bladder--13.9 ml. per second. The peak flow rate decreased progressively as the age of the subjects increased. We measured average decreases of 10 ml. per second peak flow for every 30 years after age 10. Peak flow rate increases as volume voided increases. Requirements of our measuring device combined with urodynamic responses caused us to select 100 ml. voided as the minimum acceptable volume. With volumes more than this any given individual may deviate plus or minus 10 per cent from the true mean peak flow depending upon volume voided. For practical purposes peak flow, age and volume must be considered to categorize voiding by peak flow rate. With these variables 2 graphs that compare peak flow, age and volume may be used to estimate voiding function for a given male patient. Comparison of peak flow rates, volume voided and voiding interval before and after surgical correction of obstruction documented significant increase in volume voided or in interval between voiding. Peak urinary flow rate measurement by this device predicted normality or abnormality with 90 to 95 per cent accuracy. Therefore, this represents a valid screening test but it does not in itself provide the diagnosis of abnormal urination.


Membranoproliferative glomerulonephritis with partial lipodystrophy: discordant occurrence in identical twins.

The course of disease of a patient with membranoproliferative glomerulonephritis and partial lipodystrophy is described. The case is further characterized by a deficiency of C3 and C3- activator, by normal values of C4, by evidence of the nephritogenic factor, by raised fibrin degradation products and by an unselective proteinuria. The course of the glomerulonephritis runs parallel to a pronounced susceptibility to infection (at first varicella, tonsillitis and measles, later pneumonia, meningitis, encephalitis and hepatitis). On account of a nephrotic syndrome and an initative impairment of the renal function, a cytostatic treatment was begun, which although raising the C3 level did not influence the further course of the disease. As the patient has a healthy identical twin sister without lipodystrophy, who shows no reduction in C3 and no nephritogenic factor, this case proves that these diseases are acquired and not genetically determined.


Intracellular collagen fibrils in cardiac valves of patients with the Hurler syndrome.

Ultrastructural study of thickened mitral and tricuspid valves from three patients with the Hurler syndrome disclosed collagen fibrils located within membrane-bound cytoplasmic dense bodies in small granular cells. These cells, which differ morphologically from the clear cells containing mucopolysaccharide deposits, are considered to be fibroblasts in advanced stages of degeneration. It is postulated that the elevated concentrations of dermatan sulfate in Hurler's disease lead to an abnormally high synthesis of collagen and to its polymerization in intracellular loci.


The ultrastructure of the glomerular slit diaphragm in autologous immune complex nephritis.

Morphologic alterations of the slit diaphram and glomercular epithelium were examined in rats with experimental autologous immune complex nephritis following perfusion fixation with tannic acid-glutaraldehyde.  The changes observed included a displacemnt by immune complex deposits of foot processes and associated slit diaphragms towards the urinary space.  With the onset of proteinuria, foot processes spreas, resulting in a decrease in spithelial cell surface area and a diminution in the length of interpithelial slits.  Concomiantly, the redundant slit diaphragm became folded and pleated in the residual interpithelial spaces.  No primary defect in the slit diaphragm was observed to account fo the severe proteinuria seen in this disease.  Instead areas of detached epithelial cells and an occasional slit pore lacking a slit diaphragm may consitute sites for substantial protein loss in the urinary space in autologous immune complex nephritis.


Surgical treatment of aneurysm of the ascending aorta with aortic insufficiency and marked displacement of the coronary ostia.

Six patients with a large aneurysm of the ascending aorta involving the root of the aorta and severe aortic valve insufficiency owing to marked annular dilatation were treated by replacement of the ascending aorta and aortic valve with a composite unit. It was also necessary to transpose the origin of the coronary arteries with the use of saphenous vein grafts. In 3 patients, the aneurysm was due to a chronic dissection. In one patient, the aneurysm extended beyond the arch of the aorta. There were no operative deaths. One patient died suddenly of pulmonary emboli 11 months after surgery. The remaining 5 patients are doing well, 5 months to 4 years postoperatively.


Low back pain patients in a psychiatric population.

Thirty-one patients with low back pain resistant to medical and surgical treatment were studied. On admission to the psychiatric service, these patients revealed apparent features of conversion and hysterical personality, as characterized also by the MMPI profile. During hospitalization, however, there was increased appearance and recognition of anxious-depressive features. We suggest that these patients should be treated by the combined approach of supportive psychotherapy and physiotherapy, with appropriate use of antidepressants.


Studies on the role of proteases in the biochemical mechanisms of tissue injury.

A complex of inflammatory protease with an inhibitor was found to be present in the early phase of Arthus skin lesions in guinea pig. From the extract of inflamed lesions a complex was partially purified by chromatography on DEAE-Sephadex A-50 and GE-cellulose, in that order. The inhibitor was finally dissociated rom the protease complex by treating them with cysteine followed by Sephadex G-50 chromatography. Active protease was recovered as a single peak which also contained some inhibitor activity. The isolated inhibitor was capable of inactivating inflammatory protease as well as papain. It was electrophoretically homogenous and was identified as protein or polypeptide in the serum alpha-1-globulin fraction. The significant role  of the inhibitor in regulating the acute phase of inflammatory process is emphasized.


Protective effect of tryptophan and 5-hydroxytryptophan on experimental phenylketonuria induced with phenylalanine+ p-cholorophenylalanine in rats.

An experimental phenylketonuria-like syndrome was produced in rats by oral administration of 1-phenylalanine (Phe, 500 mg/kg) and dl-p-chloro-phenylalanine (pCPA, 100-125 mg/kg) daily from the 2nd-3rd day of life to the age of 42 days. The effects of added dl-5-hydroxytryptohan (5HTP, 5 mg/kg) or 1-tryptophan (Trp, 100-125 mg/kg) were also studied. The groups receiving Phe+pCPA gained less weight than normal and less than the Phe controls. When tested during the last week of treatment the Phe+pCPA rats made more errors in the swim maze without changes in swimming times, and they showed significantly poorer learning of conditioned shock avoidance. These effects were partly antagonized by 5HTP or Trp. One to three weeks after the end of the treatments similar differences still remained in conditioned shock avoidance (and Trp and 5HTP prevented the effect of pCPA), but no more in maze learning, motor activity, or exploration on open field. Brain 5HT and 5-hydroxyindoleacetic acid (5HIAA) were lowered in all the pCPA treated rats during the treatment but returned to normal after it. Trp and 5HTP in the doses used only partly corrected the decrease of 5HT and 5HIAA. Brain noradrenaline did not change much.


[Onychomyosis caused by Trichopyton soudanense. 1st isolation in Venezuela].

Trichophyton soudanense is a dermatophyte wich is of highest incidence in Africa. Cases of tinea produced by this fungus have been described in England, Switzerland, Germany, Australia, the United States and Brazil. This investigation reports the first isolation of this fungus in Venezuela, from a lesion of the nail in a female patient who has always resided in Venezuela. The identification of this fungus was based on macroscopic and microscopic morphological characteristics; biological properties, scare or no growth when the only nitrogen source in the culture medium is provided by potassium or ammonium nitrate, and the production of dark pigment when inoculated in Lowenstein-Jensen medium. Experimental innoculation in animals produced an endothrix parasitism of the hair. Reference is made ot the incidence of the most frequently occuring dermatophytes in Venezuela.


[Punctate porokeratotic keratodermia associated with hepatic cirrhosis].

A case of non familial Punctate Porokeratotic Keratoderma in a man with liver cirrhosis is reported. The relation between both syndroms as well as the possible nevoid origin of this type of porokeratose is discussed.


[Experimental studies on seborrheic alopecia. II. Determination of the structural differences between testosterone transported cytosol protein of the bald and hairy areas].

By previous isolation of the testosterone transport cytosol protein in bald and hairy areas in patients with male pattern baldness, the author studies the differences concerning the protein citosol-testosterone complex, after fixation by means of labelled testosterone and electrophoresis, measuring the corresponding radioactivity curves. The results show that there are important structural differences for the cytosol protein between the hairy and bald regions.