[Clip markings of the uterus and the urinary bladder for the dosimetry of intracavity and percutaneous radiotherapy (author's transl)].

The exact marking of certain regional landmarks of the anatomy permits the determination of the co-ordinates of these points by stereoscopic diagnostic radiology. The mid-point of the upper margin of the symphysis is selected as the origin of the co-ordinates. The markings of the uterus are placed through the laparoscope with silver clips. The markings in the urinary bladder are placed close to the ureteral orifices through the cytoscope. The doses of radiation generated by the sources of radiation (tubes, colpostat, vaginal cylinder, cervical plate) can with this new marking technique not only be measured experimentally in anatomically well-defined points in the body but the dosage (the energy) can be calculated by the computer. In as many points in the body as desired. The maximal permissable dosage in the tumor can be determined with special consideration for the avoidance of radiation lesions to marked adjacent points such as the ureteral orifices.


[Medicogenetic study of isolates in Uzbekistan. II. Anthropogenetic characteristics, blood groups and serum proteins].

A study is carried out on the distribution of ABO, MN, Rh, P and Le blood groups systems, haptoglobins, and common anthropogenetic features in the population of two villages of the Samarkand district. The examined samples have appeared to be heterogenous for ABO, Rh and P systems. For MN and Le unification is possible. The summary data on the allotment of phenotypes are as follows: (%) 0-30.2, A-35.3, B-26.2, AB-8.3, M-33.9, N-26.2, MN-39.9, Rh- -1.5, P-78.6, Le(a-b+)-33, Le (a+b-)-22.2, Le(a-b-)-34.2, Le(a+b+)-10.6. Gene frequencies have are calculated. The occurrence with regards to haptoglobins in both the villages is the same. The summary data are as follows: Hp1=1-4.8, Hp1=2-36.2, Hp2=2-59%. Gene frequencies have been calculated. In the population of the village Karakent there is a change of the frequency in many features of dermatoglyphics. The frequencies of anthropogenetic features do not differ between the villages. The summary data are the following: the frequency of theelbow type of hand is 86.9%, the right type of "hand clasping"-55.0%, the right type of "arm folding"-50.4%, righthandedness-99.7%. The occurence of square lobe of the ear is 21%, spliced one is 26.2%, the hanging down is 52.7%. The frequency of the gene insensitivity for PTC taste is 0.47 in one village and 0.53 in the other.


[Empirical risk of oligophrenia in siblings of proband-oligophrenics in populations with high levels of inbreeding].

An investigation is carried out on 214 patients with oligophreny with regard to the secondary risk of the same disease for their four sibs. All patients were divided into 4 groups according to etiological symptoms, and it was found that maximal risk of the secondary disease with oligophreny was for the sibs of probably genetic group, and minimal one--for the sibs of the exogenic group. Maximal resemblance in the degree of the defect in the pair of proband-sibs was found both in probably-genetic and presumably-genetic groups. The risk of secondary oligophreny was significantly higher in sibs-probands with relatively lower degree of weak-mindedness than in those with severe mental defects. The frequency of the secondary oligophreny amond sibs of the inbred origin (18.9%) was more than twice as high (P less than 0.001) as in those of outbred origin (8.3%).


[Medicogenetic study of isolates in Uzbekistan. I. Statement of the problem and characteristics of the groups studied].

The paper comprises results of studying some demographic and populaton characteristics of the inhabitans of the Samarkand region as a whole and two villages, Karakent and Ishan, inhabited with Uzbeks-Khoja, a special religious-social caste in the past. It is shown that 87.4% of marriages in the Samarkand region are of international character (the information has been obtained on 7995 married couples). The frequency of consanguineous marriages is 11.6%, and among them 40.5% are first-cousin marriages and 39.1% are marriages of remote relatives. The coefficients of inbreeding are rather high among the Jewish, Tajik and Uzbek communities. The coefficient of inbreeding as a whole is F=0.0042 in this region and approaches to the maximal level, characterizing a panmix population. The average size of a family in the villages of Karakent and Ishan is approximately 4.0 persons. The values of reproductive performance, the nature of termination of pregnancies do not differ from those of panmix population. The percentage of intravillage and consanguineous marriages are 56% and 12.5% for the first village, and 25% and 2% for the second one respectively. The coefficient of inbreeding for karakent is F=0.0064, for Ishan--F=0.0014. Taking into consideration the historical development of the two villages and the cumulative data, the conclusion is drawn that Karakent is an isolate on a religious ground whereas Ishan is a disintegrated isolate.


Three new species of Gyrodactylus (Monogenoidea) from Varicorhinus capoeta gracilis (Keyserling) from the River Lenkoranka.

Three new species of Gyrodactylus Nordmann, 1832 are described from Varicorhinus capoeta gracilis (Keyserling) from the River Lenkoranka (Azebaijan SSR) as follows: G. varicorhini sp. n., G. capoetai sp.n. and G. mikailovi sp.n.


Two new species of Gyrodactylus (Monogenoidea) from Schizothorax intermedius McClelland from the River Kafirnigan.

Two new species of Gyrodactylus, namely G. kafirniganensis sp. n. and G. hemivicinus sp. n., are described from the fins and nostrils ofSchizothorax intermedius from the River Kafirnigan (Tajik SSR).


Effects of streptozotocin added in vitro on insulin biosynthesis and release in isolated rat islets.

The effect of different concentrations of streptozotocin was tested in vitro on isolated rat islets. The following parameters of islet-cell activity were measured: 1) incorporation of 3H-leucine into proinsulin and into total islet protein; 2) IRI release into the medium, and 3) islet proinsulin content. It appears from the preliminary results shown here that both insulin release and biosynthesis were decreased by streptozotocin in a way which was dose- and time-dependent.


Rates and correlates of expenditure increases for personal health services: pre- and post-medicare and medicaid.

This investigation of the increases in expenditures for medical care of the noninstitutionalized population of the United States in two recent periods suggests the following: Price increases contributed substantially more to overall expenditure increases in both periods than did use increases. Hospital price increases contributed most to overall price increases in both periods. Drug use in the first period and hospital use in the second period contributed most to overall use increases. The so-called "free services" made a substantial contribution to increases in use between 1963 and 1970, while apparently making no contribution in the earlier period. In the pre-Medicare/Medicaid period, use increase were greatest among the working-age and male population. However, increases in use also seemed to be relatively high among the low-income group. In the most recent period, use increases shifted not only to the elderly and the very young, but also to the group 55-64. The relatively high rate of use increase for males and the low-income group continued. These findings, then, suggest that institution of the Medicare and Medicaid programs was accompanied by acceleration of some trends that were already taking place, i.e., relatively high rates of increase in the use of health services for the low-income population and the aged. Some groups not considered to be target populations for the programs, such as those 35-54, showed a reduction in their use rates; others those 55-64, increased their use. Finally, the non-white population showed no greater rate of increase in use of health services than the white population, even though the former would presumably be considered a target group.


Arbitration of malpractice claims: a hospital-based pilot project.

In summary, the findings of this study indicate that the "simple existence" of an arbitration option and the logistical systems supporting it have produced positive results and have established significant trends in a group of hospitals participating in the Southern California Arbitration Project when compared to a group of Southern California hospitals that have not participated. Albeit inconclusive at this time, the concept may well be a feasible alternative to litigation in securing an expeditious and inexpensive resolution for malpractice cases. Arbitration, in and of itself, is most assuredly no panacea for the critical malpractice problem currently experienced throughout the country; however, its potential substantive contribution toward the resolution of malpractice claims is certainly one worthy of extensive experimentation and evaluation.


B and T cells in lymphoid tissues of human appendix.

Human appendix lymphoid cells (HAL) react very strongly to stimulation with concanavalin A, strongly to stimulation with phytohaemagglutinin, and weakly but definitely to stimulation with lipopolysaccharide. From the results of rosette formation assay, cytotoxicity tests with anti-T cell antiserum or anti-B cell antiserum, cell surface or intracellular immunoglobulin staining with fluorescein-conjugated rabbit anti-Fab of human immunoglobulin serum, and plaque-forming cell (PFC) assay, it was concluded that human appendix lymphoid tissue is a B cell pool but includes T cells. However, both direct and indirect PFC could not be significantly demonstrated against sheep red blood cells in a 5-day HAL culture.


Influence of the indigenous gastrointestinal microbial flora on duodenal Mg2+ -dependent and (Na+ + K+) -stimulated adenosine triphosphatase activities in mice.

Mg-dependent and (Na+ + K+)-stimulated adenosine triphosphatase (ATP-ase) activities were assayed in butanol extracts of duodenal tissue from germ-free, specific-pathogen-free, and ex-germfree mice associated with an indigenous microflora from specific-pathogen-free mice. In the germfree mice the levels of both ATPase activities were significantly higher than the levels in specific-pathogen-free mice. By contrast, the ex-germfree animals colonized by an entire indigenous microflora, the values fell to levels close to those for specific-pathogen-free animals. (Na+ + K+)-stimulated ATPase was not inhibited by ouabain in extracts from any of the three kinds of mice. These findings show that the indigenous microbial flora influences the intestinal ATPase activity of mice and, because of the connection between (Na+ + K+-stimulate ATPase and active transpoort, undoubtedly affects the process of absorption in the intestinal tract.


[Perioral dermatitis].

Intensive investigations between 1969-1974 on 245 patients with perioral dermatitis are reported. Results are discussed with special regard to clinical behaviour, histology, differential diagnosis and etiology of the disease. Eczematous sources, bacterial and mycotic infections can be ruled out as etiological factors. Therapeutical considerations are discussed.


[Occupational vitiligo caused by para-tertiary-butylphenol, a trias of vitiligo, hepatosis and struma].

In the period between 1956-1974 twelve cases of occupational vitiligo due to para-tertiary butylphenol were observed. In addition another 12 cases of vitiligo of other etiology occurred. Occupational vitiligo cannot be distinguished from ordinary vitiligo. 21 patients had, aside from their leukodermia a normal thyroid function, and 18 patients showed symptoms of chronic liver damage. The trias of vitiligo, hepatic disease and struma euthyreotica was noticeable. Autoimmunisation tests were positive in cases of vitiligo of unknown etiology. The localization of vitiligo may be compared to viscero-cutaneous reflexes.


Drug eruption associated with sulfonamide treatment of vertebral osteomyelitis in a dog.

Drug eruption was diagnosed in a 4-year-old German Shepherd Dog being treated with sulfonamides for vertebral osteomyelitis due to infection with Nocardia spp. The eruption was characterized by generalized, pruritic, eczematous dermatitis. Diagnosis was based on a history of repeated exposure to sulfonamides, skin biopsy findingd, and clinical recovery on cessation of sulfonamide therapy.


Mucopolysaccharides in hypothalamic neurons of the rat.

A study of the hypothalamic nuclei of the rat, using a variety of histochemical methods, has shown the distribution of mucopolysaccharides and neurosecretory material. In all the hypothalamic nuclei there are two types of neurons and in some a third type characterized by the presence of hyaluronidase-resistant acid mucopolysaccharides in the periphery of the perikaryon. These type III neurons also contain Gomori-positive material and neutral mucopolysaccharides. It is considered that hypothalamic nuclei with type III neurons have similar neurosecretory properties.


Acute hypercalcemic crisis.

Although hypercalcemia may be caused by extraparathyroid disease and controlled with various medications, acute hypercalcemic crisis is a surgical emergency. All nonperative measures are directed toward diagnosis of hyperparathyroidism and preparation for operation. Parathyroidectomy is indicated even in the absence of definite evidence of a functioning parathyroid tumor in patients when nonoperative methods fail. Prompt medical therapy and timely surgical intervention will result in success in the vast majority of patients with hypercalcemic crises.


An experimental model for the study of exercise-induced skeletal muscle hypertrophy.

A procedure for training laboratory cats to perform weight-lifting exercise has been developed. This program consists of operantly conditioning adult cats to move a bar a specific distance with their right forelimb to receive a food reward. Weights attached to the bar via a pully are lifted as the bar is moved. The cat is then exercised at the same load for 5 days before the weight is increased. A linear potentiometer, attached to the hinged bar, produces an analog voltage proportional to the bar movement. This voltage is then monitored by a general purpose computer using a real-time behavioral program. In this way, the numbber of times the cat moves the bar, the time required to move the bar, and the time between bar movements are all recorded. The total physical work accomplished and the average power expended by the cat during the weight-lifting exercise regimen can then be calculated. This procedure has the advantage of inducing significant gross muscle hypertrophy (from 7 to 34%) and muscle fiber hypertrophy in one limb, while the muscles of the opposite limb can be utilized for comparative studies. The striking morphological and histochemical transformations that occur during physiological hypertrophy are now available for experimental investigation using this model.


Direct Fick application for measurement of cardiac output in rat.

The direct Fick procedure for cardiac output determination in rat was validated by simultaneous comparison with electromagnetic flowmeter techniques. Significant coefficients of correlation were obtained between absolute  cardiac output values (r = 0.789, P less than 0.001), increases (r = 0.768, P less than 0.001) and decreases (r = 0.672, P less than 0.01)  in cardiac output detected by the two methods. As demonstrated in other species, cardiac output values of the Fick procedure in the rat  were between 40 and 58% greater than respective electromagnetic flow probe values; however, percent changes in cardiac output obtained by the two methods were similar. The larger  values of cardiac output obtained by the direct Fick method may be related, to a great extent, to the distribution of blood flow to the coronary and bronchial circulations. Fick cardiac output measurements were reproducible within rats, and the degree of variation in values among rats was similar to that obtained with the flowmeter procedure. The result indicate that the Fick meth  od provides a valid estimation of cardiac output in the rat, with the ability to detect moderate changes (22-36%) in cardiac output.


Lactate dehydrogenase changes following several cardiac hypertrophic stresses.

The effects of four different cardiac hypertrophic stresses on cardiac lactate dehydrogenase (LDH) isozyme composition and activity were examined. Altitude-induced right ventricular hypertrophy was accompanied by an increase of 10% in the M subunit of LDH in right ventricle, left ventricle, and atria. Left ventricular hypertrophy induced by aortic stenosis also produced isozyme changes in the ventricles, but of only half the magnitude. Biventricular hypertrophy, induced by running or swimming, was accompanied by 4-5% increases in M LDH in the ventricles only. We conclude that changes in LDH activity are directly related to changes in the M subunit in all three portions of the heart. No changes in H subunit were noted under any of the stresses. It appears that the magnitude of changes in cardiac LDH isozyme composition are only marginally related to extent of hypertrophy.


Isolation and identification of the conidial germination factor of Neurospora crassa.

The germination-essential substance (germination factor [GF]) that is lost from conidia of Neurospora crassa on exposure to solutions of low water activity has been isolated and identified as a group of iron-transport compounds, or siderochromes. The principal siderochrome of conidia is ferricrocin, a cyclic hexapeptide. A closely related substance, ferrichrome C, is tentatively identified as a minor constituent. The same substances are also present in extracts of mycelium along with small amounts of a third siderochrome, which has not been identified. The GF activity of culture filtrates is due to coprogen, the only siderochrome previously identified with N. crassa.


Fractionation of membrane vesicles from coliphage M13-infected Escherichia coli.

Membrane vesicles were prepared by osmotic lysis of spheroplasts from M13-infected Escherichia coli. Reduced nicotinamide adenine dinucleotide (NADH) oxidase (reduced NAD: oxidoreductase, EC 1.6.99.3) and Mg2+-Ca2+-activated adenosine triphosphatase (ATP phosphohydrolase, EC 3.6.1.3), which are normally localized to the inner surface of the cytoplasmic membrane, were 50% acceesible to their polar substrates in these vesicles. The major coat protein of coliphage M13 is also bound to the cytoplasmic membrane (prior to phage assembly) but with its antigenic sites exposed to the exterior of the cell. Antibody to M13 coat protein was used to fractionate membrane vesicles. Neither agglutinated nor unagglutinated vesicles had altered NADH oxidase and adenosine triphosphatase specific activities. This is inconsistent with such vesicles being a mixture of correctly oriented and completely inverted membrane sacs and suggests that NADH oxidase, adenosine triphosphatase, M13 coat protein, or all three proteins rearrange during vesicle preparation.


Relationship between the transport of iron and the amount of specific colicin Ia membrane receptors in Escherichia coli.

Strains of Escherichia coli K-12 defective in their ability to utilize exogenously supplied iron due to genetic defects in the entF, tonB, fes, or fep gene exhibited elevated levels of the specific outer-membrane receptor for colicin Ia when compared with parental strains. Although entF, fes, and fep strains showed a higher degree of Ia sensitivity than did the parental strains, tonB strains were resistant to colicin action. The colicin insensitivity of tonB strains was not due to hyperproduction of enterochelin. Growth in medium containing 101.8 muM Fe2+ led to a lowering of receptor levels in all the above strains and resulted in decreased colicin Ia sensitivity in all strains except tonB, which was already at maximal resistance. Growth in citrate plus iron (1.8 muM) or in ferrichrome resulted in a substantial reduction in both receptor levels and Ia sensitivity in ent, fes, and fep strains but had no effect on receptor levels in tonB strains. Growth in citrate did not lead to an alteration in receptor levels in a mutant specifically defective in citrate-mediated iron transport. The presence of enterochelin during growth led to a reduction in the number of receptors in the parental and ent strains but not in tonB, fes, or fep strains. Thus, in all cases examined, there was an inverse relationship between the number of colicin receptors per cell and the ability of the strain to take up iron from the growth medium. This suggests that under conditions of iron limitation there is a derepression of colicin Ia receptor biosynthesis. These results may point to a role of the colicin I receptor in iron uptake.


Isolation and characterization of membranes from a hydrocarbon-oxidizing Acinetobacter sp.

Membranes were isolated and purified from nutrient broth-yeast extract- and hexadecane-grown cells of Acinetobacter sp. strain HO1-N. Two membrane fractions were isolated from nutrient broth-yeast extract-grown cells, the cytoplasmic membrane and the outer membrane. In addition to these two membrane fractions, a unique membrane fraction was isolated from hexadecane-grown cells (band 1) and characterized as a lipid-rich, low-density membrane containing high concentrations of hexadecane. The outer membrane preparations of Acinetobacter, obtained from nutrient broth-yeast extract- and hexadecane-grown cells, exhibited a low ratio of lipid phosphorus to protein and contained phospholipase activity and 2-keto-3-deoxyoctulosonic acid. Phosphatidic acid cytidyltransferase, adenosine triphosphatase, and reduced nicotinamide adenine dinucleotide oxidase were recovered almost exclusively in the cytoplasmic membrane fractions. The cytoplasmic membrane fractions contained 20 to 25 polypeptide species on sodium dodecyl sulfate-polyacrylamide gels, and the outer membrane fractions contained 15 to 20 polypeptide species. A major polypeptide species with an apparent molecular weight of approximately 42,000 to 44,000 was found for all outer membrane fractions. The buoyant densities of the cytoplasmic membrane fractions and the outer membrane fractions were closely similar, necessitating their separation by differential centrifugation. Band 1 of hexadecane-grown cells had a ratio of lipid phosphorus to protein that was almost twice that of cytoplasmic membrane and a correspondingly low buoyant density (1.086 g/cm3). Enzyme activities associated with band 1 were identical to those associated with the cytoplasmic membrane. The electrophoretic banding pattern of band 1 was essentially identical to the banding pattern of the cytoplasmic membrane. The phospholipid and neutral lipid compositions of the isolated membrane fractions were determined as qualitatively similar, with significant quantitative differences. The ultrastructure characteristics of the respective membrane fractions were examined by the negative-stain technique.


Thiols of myosin. III. Spectrophotometric identification of the amino acid residue of myosin modified by rho-nitrobenzenediazonium fluoroborate.

As previously reported, rho-nitrobenzenediazonium fluoroborate strongly inhibits Ca2+- ATPase of myosin [EC 3.6.1.3] without appreciable suppression of its EDTA-K+- ATPase activity, and the presence of ATP in the reaction medium reverses the pattern of alteration in both ATPase activities, i.e., causing selective inhibition of EDTA-K+ -ATPase. Spectrophotometric studies on the azo-coupling products of 17 amino acids and their derivatives revealed that the amino acid residue of myosin modified by the diazonium dye was cysteine in both the presence and absence of ATP. It is also suggested that the number of cysteinyl residues responsible for the activity changes was one mole per mole of myosin subunit.


Temperature-dependent transitions of the myosin-product intermediate at 10 degrees during Mn(II)-ATP hydrolysis by myosin from rabbit psoas muscle.

The initial burst of Pi liberation during the hydrolysis of Mn(II)-ATP by heavy meromyosin from rabbit psoas muscle was investigated. Below 10 degrees, the initial burst of Pi liberation was inhibited by the pre-addition of ADP without any change in the steady-state activity, but it was not inhibited above 10 degrees. The burst size was about one mole per mole of heavy meromyosin. The initial burst of Pi liberation in Mg-ATP hydrolysis at 8 degrees, however, was not inhibited by the pre-addition of ADP. These results, obtained with psoas muscle heavy meromyosin, were almost the same as those obtained with heavy meromyosin from rabbit leg and back muscles (Hozumi and Tawada (1975) Biochim. Biophys. Acta 376, 1-12) and, therefore, indicate that in Mn-ATP above 10 degrees there is at the burst site a predominant myosin -product complex generated by ATP hydrolysis. Similarly, below 10 degrees there is a myosin-product complex identical with the one generated by adding ADP (and Pi) to myosin.


Chemical modification of the Ca2+ -dependent ATPase of sarcoplasmic reticulum from skeletal muscle. II. Use of 2, 4, 6-trinitrobenzenesulfonate to show functional movements of the ATPase molecule.

1. By changing the concentrations of Mg2+ and Ca2+ ions and ATP, the Ca2+, Mg2+-dependent ATPase [EC 3.6.1.3] of SR was converted to various enzymatic states, E, MgE, MgECa, MgEATP' CaECa, and CaECap at pH 8.0 and 0 degrees (cf. Eq. 1). 2. SR vesicles were allowed to react with 0.5 mM 2,4,6-trinitrobenzenesulfonate (TBS) at pH 8.0 and 0 degrees, keeping the ATPase in one of the enzymatic states listed above. Trinitrophenyl (TNP)-protein and TNP-lipid were separated by gel-filtration, and the amounts of TNP incorporated into protein and lipid were determined. 3. In all the enzymatic states of ATPase tested, the amount of TBS bound with SR protein increased exponentially with time, and reached a maximum level 10 min after starting the reaction. On the other hand, the amount of TBS bound to lipid increased with time, and did not reach a maximum level for at least 20 min. 4. The SR ATPase activity and the amount of EP formed decreased only slightly, even when the amount of TBS bound to SR protein reached the maximum level. 5. The maximum amount of TBS bound to SR protein varied on changing the enzymatic state of SR ATPase. Namely, about 2,3,1,3, or 4, and 3 moles of TNP were incorporated per mole of SR ATPase, when SR was allowed to react with TBS in the enzymatic states MgE, MgECa, MgEATP' CaECa, and CaECap, respectively. 6. When the enzymatic state was changed from MgE to MgECa 10 min after starting the reaction with TBS, about 4 moles of TBS was bound per mole of ATPase within 10 min, while the maximum levels of TBS bound in states MgE and MgECa were about 2 and 3 moles per mole of ATPase, respectively, as mentioned above. 7; When the enzymatic state was changed from MgE to MfEATP 10 min after starting the reaction with TBS, about 3 moles of TBS was bound per mole of ATPase within 10 min, while the maximum levels of TBS bound in states MgE and MgEATP were about 2 and 1 moles per mole of ATPase, respectively, as mentioned above. 8. When the enzymatic state was changed from CaECa to CaECap 10 min after starting the reaction with TBS, about 4 moles of TBS was bound per mole of ATPase, while the maximum levels of TBS bound in states CaECa and CaECap were about 3 or 4 moles per mole of ATPase, respectively. 9. A diagrammatic model of functional movements of the ATPase molecule coupled with elementary steps in the ATPase reaction is proposed on the basis of these results.


Isolation and characterization of proteoglycans from chick limb bud chondrocytes grown in vitro.

Chick limb bud mesenchyme cells from stage 23-24 embryos were isolated and grown in culture under conditions facilitating chondrogenic development. Dissociative extraction methods were used to isolate proteoglycans from Day 8 cultures, at which time the incorporation of [35S]sulfate into these macromolecules occurred at maximal rates. The monomer (D1) fraction contained 85 to 90% of the proteoglycans originally present in the matrix of the cultures. The  composition of this fraction was approximately 7 to 8% protein, 7% keratan sulfate, and 85% chondroitin sulfate. The proportions of nonsulfated, 4-sulfated, and 6-sulfated disaccharides in chondroitinase digests were about 11%, 31%, and 58%, respectively. The D1 fraction exhibited a single, polydisperse component on Sepharose 2B chromatography and in the ultracentrifuge (so = 19 S). In associative density gradients about 35% of the proteoglycans were recovered in a gel at the top of the gradient. The remainder were recovered at the bottom of the gradient in the aggregate (A1) fraction. The A1 fraction exhibited two components, aggregate (about 70% of the total) and monomer, upon Sepharose 2B chromatography and in the ultracentrifuge (so = 120 S for aggregate; 18 S for monomer). The aggregate preparation contained only one of the two link proteins (molecular weight of about 45,000) which occur in proteoglycan preparations from many hyaline cartilages.


Studies on heart phosphofructokinase. Use of fructose 6-sulfate as an alternative substrate to study the mechanism of action and active site specificity.

Fructose 6-sulfate was synthesized by direct sulfurylation of fructose and was isolated by two selective steps: (a) conversion of the 6-sulfuryl ester to fructose 1-phosphate-6-sulfate with phosphofructokinase; (b) conversion of fructose 1-phosphate-6-sulfate to fructose 6-sulfate by fructose-1,6-diphosphatase. Utilizing crystalline sheep heart phosphofructokinase, kinetic studies with the alternative substrate were carried out at pH 8.2 which is optimal for nonallosteric kinetics. The data are consistent with an ordered addition of the two substrates with the first, MgATP, being at thermodynamic equilibrium. The Vmax and Km obtained with fructose 6-sulfate were 0.03- and 100-fold, respectively, that obtained with the natural substrate. The study suggests that the divalent phosphoryl moiety is intimately involved in the active site conformation. Identification of the product of the reaction, fructose 1-phosphate-6-sulfate, was confirmed through studies with aldolase, fructose-1,6-diphosphatase, and by 31P NMR. The utilization of fructose 6-sulfate as a substrate by yeast glucose-6-phosphate isomerase could not be demonstrated.


Isolation and characterization of the affinity chromatography forms of human Glu- and Lys-plasminogens and plasmins.

Affinity chromatography forms, 1 and 2, were each isolated from human Glu- and Lys-plasminogens by gradient elution from a L-lysine-substituted Sepharose column with a linear gradient of epsilon-aminocaproic acid. Although each of the two zymogen forms contains two affinity chromatography forms, the relative concentrattions of these forms in each of the zymogen preparations depended upon the plasma sample or enriched plasma fraction used for the preparation of the zymogen. Specific analytical acrylamide gel electrophoretic systems were used for the characterization of the zymogen and enzyme forms, and their component affinity chromatography forms, 1 and 2. The four zymogen affinity chromatography forms, Glu-1-plasminogen, Glu-2-plasminogen, Lys-1-plasminogen, and Lys-2-plasmingoen, show distinct stepwise differences in their molecular size and charge. The Glu-1-form is the largest in molecular size and the most acidic, and the Lys-2-form is the smallest in molecular size and the most basic. The proteolytically altered Lys-1- and Lys-2- forms appear to be specifically df the zymogen affinity chromatography forms showed a different distribution of isoelectric forms. The major isoelectric forms isolated from Glu-plasminogen with pI values of 6.2, 6.3, 6.4, and 6.6, and the major isoelectric forms isolated from Lys-plasminogen with pI values of 6.7, 7.2, 7.5, 7.8, and 8.1, (Summaria, L., Arzadon, L., Bernabe, P., Robbins, K. C., and Barlow, G. H. (1973) J. Biol. Chem. 248, 2984-2991) were shown to be mixtures of the Glu-1- and Glu-2- forms, or the Lys-1- and Lys-2- forms, respectively. Although the sialic acid contents of the Glu- and Lys- forms appear to be similar, the isolated affinity chromatography forms show distinct differences. The sialic acid contents of the Glu-1- and Lys-1- forms are identical, and are substantially higher than the sialic acid contents of the Glu-2- and Lys-2- forms which are also identical to each other. It is possible that the charge difference between the zymogen-1- and -2- forms may be related to the differences in their sialic acid content. Each of the four zymogen affinity chromatography forms, when activated by urokinase in the presence of the plasmin inhibitor, Trasylol, was converted to an apparently unique and different enzyme form. The four enzyme forms show distinct stepwise differences in molecular size; Glu-1-plasmin is the largest in size whereas Lys-2-plasmin is the smallest in size. Each plasmin-derived carboxymethyl heavy(A) chain was found to be different in molecular size, but the two carboxymethyl light(B) chains found in each of the four enzyme forms appeared to be identical and of the same molecular sizes. The four heavy(A) chains show a stepwise difference in molecular size; the Glu-1-heavy(A) chain is the largest in size whereas the Lys-2-heavy(A) chain is the smallest in size...


Stimulation of proteoglycan synthesis in chick embryo sternum by serum and L-3,5,3'-triiodothyronine.

Incorporation of sulfate into alcian blue-precipitable glycosaminoglycan of 12-day-old chick embryo sterna is stimulated by addition, separately or together, of normal human serum and physiological concentrations of thyroid hormones (Audhya, T.K., and Gibson, K.D. (1975) Proc. Natl. Acad, Sci. U. S. A. 72, 604--608). We present evidence that this stimulation is due to increased synthesis of at least one proteoglycan, with minor alterations in the size and chemical composition of the glycosaminoglycans. Pulse-chase experiments showed no detectable loss of label during the chase, in control sterna or sterna incubated with serum and L-3,5,3'-triiodothyronine; thus, all incorporation was the result of synthesis of glycosaminoglycans. In double-label experiments, with 35SO4(2-) and [3H]acetate, the molar ratio of 3H and 35S incorporated into glycosaminoglycans was changed little, if at all, by addition of serum or triiodothyronine or both, at concentrations which increased incorporation up to 2-fold. Glycosaminoglycans isolated from these and other incubations gave similar elution patterns from agarose columns, and identical electrophoretic patterns on cellulose acetate. Digestion with chondroitinase ABC (chondroitin ABC lyase; EC 4.2.2.4.) showed that incorporation was into chondroitin sulfate and possibly hyaluronic acid, and that the proportions of non-sulfated, 4-sulfated, and 6-sulfated disaccharide units differed little between stimulated and unstimulated sterna. Incorporation of [3H]serine into glycosaminoglycans from papain digest of sterna paralleled incorporation of 35SO4(2-), and indicated a number average molecular weight between 21,000 and 25,000 for the newly synthesized chondroitin sulfate. This value was confirmed by gel filtration chromatography, which also showed that the average molecular weight of the newly synthesized chondroitin sulfate decreased up to 15% under conditions of 2-fold stimulation. Proteoglycans were extracted from sterna incubated with [3H]serine and 35SO4(2-) and analyzed by isopycinic centrifugation in CsCl and by zone sedimentation in a sucrose gradient. A major proteoglycan fraction could be separated by either method. Incorporation of both isotopes into this proteoglycan fraction, and into glycosaminoglycans isolated after papain digestion, was stimulated in a coordinate manner. Almost identical results were obtained with both separation techniques. The results indicate that the synthesis of the major proteoglycan, and probably also of a minor one, is stimulated by serum and triiodothyronine.


Mechanism of the urokinase-catalyzed activation of human plasminogen.

When human plasminogen (Glu-Pga) is activated by urokinase in the presence of pancreatic trypsin inhibitor, the plasmin produced (Glu-Pma) exclusively contains a heavy chain (Glu-Ha) derived intact from the original NH2 terminus of Glu-Pga. Similar activations, utilizing a low molecular weight synthetic plasmin acylating agent, p-nitrophenyl-p-(pyridiniummethyl) benzoate, still result in a plasmin molecule with approximately 50% of the plasmin heavy chain containing the intact NH2 terminus of the original Glu-Pga. Activations performed at high levels of urokinase in the absence of any inhibitors initially produce Glu-Pma. However, the final stable plasmin, Lys-Pmb, which is obtained contains a heavy chain (Lys-Hb) which arises by plasminolysis of a small peptide from the NH2 terminus of Glu-Ha. Alternatively, Lys-Pmb can be formed in a separate series of reactions initially involving plasminolysis of Glu-Pga to yield Lys-Pgb. The peptide removed in this step is identical to the peptide removed in the Glu-Ha to Lys-Hb reaction. Next, urokinase catalyzes the conversion of Lys-Pgb to Lys-Pmb without further loss of peptide material. This latter pathway involving Lys-Pgb is probably the major pathway for human Lys-Pmb generation. These studies support a mechanism of activation of human plasminogen which involves at least two bond cleavages in Glu-Pga. However, these same studies strongly indicate that the Nh2-terminal peptide need not be released from Glu-Pga prior to plasmin formation. Further, we feel that plasmin and not urokinase catalyzes cleavage of the NH2-terminal peptide bond from Glu-Pga and the Glu-Ha heavy chain of Glu-Pma.


Compartmental behavior of ornithine in Neurospora crassa.

In Neurospora cells grown on minimal medium, most of the large ornithine pool is found in osmotically sensitive organelles, the "vesicles." In this paper kinetic studies on the compartmental behavior of ornithine and its derivatives are reported. Analysis of the metabolism of a 10(-7) M pulse of uniformly labeled L-[14C] ornithine supports the following conclusions: (a) Over 98% of the cellular ornithine is in the vesicles. (b) The amount of ornithine normally in the cytosol is about 0.3% of the cellular ornithine, as shown by the kinetics of incorporation of 14C into putrescine via the cytosolic enzyme, ornithine decarboxylase (EC 4.1.1.17). (c) Mitochondria, the site of ornithine synthesis, contain about 1% of the cellular ornithine, as demonstrated by the kinetics of incorporation of 14C into citrulline via the mitochondrial enzyme, ornithine transcarbamylase (EC 2.1.3.3). (d) Considerable ornithine exchange, and a net efflux of ornithine, takes place across the mitochondrial membrane. (e) Ornithine aminotransferase (EC 2.6.1.13), a catabolic enzyme, may have a special relation to the cell membrane in cells grown in minimal medium. This enzyme uses ornithine efficiently while it enters from the medium, but very poorly after all the [14C] ornithine is within the cell. (f) Citrulline and proline are not compartmented with respect to the enzymes using them. (g) In contrast, arginine is distributed such that over 99% is in vesicles. We suggest that the vesicles; with their ability to sequester ornithine and arginine, are potentially significant in regulation.


Histones of Neurospora crassa.

Neurospora crassa chromatin isolated by a rapid method minimizing proteolytic degradation contains approximately one weight of acid-extractable basic protein per weight of DNA. This basic protein consists of five major polypeptide species which are similar in size to the histone proteins of higher eukaryotes and are present in approximately the same molar ratios. These five polypeptides have been purified by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Their electrophoretic mobilities in polyacrylamide gels and their amino acid compositions indicate that they are histones homologous, although not identical, to the H1, H2A, H2B, H3, and H4 histones of mammals. The first 3 residues in the amino acid sequence of Neurospora H3 histone are identical to the first 3 residues in calf and pea H3; Neurospora H1, H2A, and H4 histones have blocked NH2 termini, like their mammalian counterparts. The finding of recognizable H1, H2A, H2B, H3, and H4 histones in Neurospora extends the range of eukaryotes now shown to contain a full complement of these strongly conserved chromosomal proteins, and supports the view that histones became involved in chromosome structure at a very early point in the evolution of eukaryotes.


Localization of ionophore activity in a 20,000-dalton fragment of the adenosine triphosphatase of Sarcoplasmic reticulum.

The (Ca2+ + Mg2+)-dependent ATPase of sarcoplasmic reticulum has been shown to ast as a Ca2+-dependent and selective ionophore in artificial lipid bilayers. Four fragments of 55,000, 45,000, 30,000, and 20,000 daltons have been purified from tryptic digests of the enzyme and it has been shown that the 55,000- and 45,000-dalton fragments are obtained from a single cleavage of the 100,000-dalton ATPase, while the 30,000- and 20,000-dalton fragments are obtained subsequently by a cleavage of the 55,000-dalton fragment. The 55,000- and 20,000-dalton fragments have ionophore activity inhibited by ruthenium red and by mercuric chloride but not by methylmercuric chloride, an inhibitor of the hydrolytic site of the enzyme. Under standard conditions the 45,000-dalton fragment was not active as an ionophore, while the 30,000-dalton fragment acted as a nonselective ionophore. The 55,000- and 30,000-dalton fragments have been shown to contain the site of phosphorylation and of N-ethyl [2-3H]-maleimide binding indicative of the hydrolytic site in the enzyme, and this site is absent from the 20,000-dalton fragment. Therefore, the ionophoric and hydrolytic sites are localized in separate regions of the ATPase molecule and they have now been physically separated. The 20,000-dalton fragment was degraded with cyanogen bromide and fragments were separated by molecular sieving. Ionophore activity was found in fragments of molecular mass less than 2,000 daltons.


Mechanism of an active transport of calcium. Ethoxyformylation of sarcoplasmic reticulum vesicles.

Ethoxyformylation of sarcoplasmic reticulum vesicles is performed to study a possible role of histidine residues in the calcium translocation process. The influence of the chemical modification is evaluated on the Ca2+-dependent ATPase activity, and on the Ca2+ uptake parameters: VCa (initial rate of calcium uptake) and CCa (amount of cation accumulated at the steady state). The substitution of the amino acids is monitored by three different techniques: (a) by amino acid analysis of the ethoxyformylated material further submitted to modification by diazonium-1-H-tetrazole, or by sulfhydryl titration using 5-5'-dithiobis (2-nitrobenzoic acid); (b) by 14C labeling followed by the removing of labels after NH2OH or imidazole treatment at pH 7; (c) by spectrophotometric measurements at 230 nm. The ethoxyformylation reaction is not specific for histidine at pH 6.1 and 10 degrees. About 1 lysyl group/mol of ATPase is first modified. Then 1 (with a pseudo-first order rate constant of 240 (+/- 20) 10(-3) min-1) or 2 histidines are modified. No substitution of tyrosine or sulfhydryl groups can be detected under our experimental conditions. A decrease of the Ca2+-dependent ATPase activity correlated with the inhibition of both VCa and Cca corresponds to the chemical substitution of the histidine. No direct correlation between the decrease of the activities and the modification of the lysine can be found. After removing the ethoxyformyl group from the histidine, only the Ca2+-dependent ATPase activity is restored to its initial value. No protection is found when the reaction is performed in the presence of ATP or p-nitrophenylphosphate. These results can be explained if one assumes that the ethoxyformylation of the histidine residue(s) induces a conformational change modifying the affinity of the membrane for nucleotides.


Sodium- and potassium-activated adenosine triphosphatase of the nasal salt gland of the duck (Anas platyrhynchos). Purification, characterization, and NH2-terminal amino acid sequence of the phosphorylating polypeptide.

Sodium- and potassium-activated adenosine triphosphatase (NaK-ATPase) was purified from nasal salt glands of the duck (Anas platyrhynchos). Enzyme of specific activity 2,000 to 2,300 mumol of Pi/mg/hour was routinely obtained by sodium dodecyl sulfate treatment of a microsomal fraction of gland homogenate in the presence of 3 mM ATP followed by pelleting of the enzyme through a sucrose density gradient. Purified NaK-ATPase was stable for over 3 months at -20 degree. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration chromatography purified NaK-ATPase was shown to contain two polypeptide chains of molecular weight 94,000 and 60,000, the smaller of which was a glycoprotein. Purified enzyme of activity 2,300 mumol of Pi/mg/hour bound 3,600 pmol of ouabain/mg of enzyme protein. Reaction with [gamma-32P]ATP in the presence of Mg2+ and Na+ gave 7,025 pmol of acyl phosphate/mg of enzyme protein. The turnover number calculated from phosphorylation data was 5,460 min-1. Amino acid analysis of the polypeptide components of duck salt gland enzyme after separation by gel filtration chromatography in sodium dodecyl sulfate demonstrated strong compositional homology with highly purified NaK-ATPase preparations from other organs and species. The NH2-terminal amino acid of the 94,000-dalton component was glycine and of the 60,000-dalton component, alanine. With a combination of manual sequencing and automated Edman degradation, the NH2-terminal amino acid sequence of the 94,00-dalton catalytic subunit was found to be Gly-Arg-Asn-Lys-Tyr-Glu-Thr-Thr-Ala-()-Ser-Glu.


Acne arthralgia.

A syndrome of arthralgia associated with one form of acne is described. Orthopaedic surgeons should be alert to the association of profound arthralgia and myalgia with this particular variant of acne vulgaris. Thirteen patients are described, all of whom are adolescent boys with a chronic moderately active acne which suddenly became extremely aggressive and toxic. The symptoms and signs included proximal arthralgia and myalgia, fever, elevated sedimentation rate, and altered immunoglobulins. Control of acne and conservative physical therapy resulted in complete resolution of the musculoskeletal complaints.


Teleost chloride cell. I. Response of pupfish Cyprinodon variegatus gill Na,K-ATPase and chloride cell fine structure to various high salinity environments.

Certain euryhaline teleosts can tolerate media of very high salinity, i.e. greater than that of seawater itself. The osmotic gradient across the integument of these fish is very high and the key to their survival appears to be the enhanced ability of the gill to excrete excess NaCl. These fish provide an opportunity to study morphological and biochemical aspects of transepithelial salt secretion under conditions of vastly different transport rates. Since the cellular site of gill salt excretion is believed to be the "chloride cell" of the branchial epithelium and since the enzyme Na,K-ATPase has been implicated in salt transport in this and other secretory tissues, we have focused our attention on the differences in chloride cell structure and gill ATPase activity in the variegated pupfish Cyprinodon variegatus adapted to half-strength seawater (50% SW), seawater (100% SW), or double-stregth seawater (200% SW). The Na,K-ATPase activity in gill homogenates was 1.6 times greater in 100% SW. When 50% SW gills were compared to 100% SW gills, differences in chloride cell morphology were minimal. However, chloride cells from 200% SW displayed a marked hypertrophy and a striking increase in basal-lateral cell surface area. These results suggest that there are correlations among higher levels of osmotic stress, basal-lateral extensions of the cell surface, and the activity of the enzyme Na,K-ATPase.


Teleost chloride cell. II. Autoradiographic localization of gill Na,K-ATPase in killifish Fundulus heteroclitus adapted to low and high salinity environments.

The specific binding and inhibitory action of (3H)ouabain were employed to localize transport Na,K-ATPase in the euryhaline teleost gill, a NaCl-transporting osmoregulatory tissue in which both enzyme activity and transepithelial transport vary with environmental salinity. In killifish fully adapted to 10%, 100%, or 200% seawater, the gills were internally perfused and externally irrigated in situ. After suitable internal or external exposure to (3H)ouabain, individual gill arches were excised for Na,K-ATPase assay, measurement of radiolabel binding, or quantitative high-resolution autoradiography. Internal exposure to 50 muM ouabain resulted in essentially complete enzyme inhibition, and binding paralleled the increases in enzyme activity at higher salinities; in contrast, external exposure gave minimal and erratic results consistent with leakage of external ouabain into interstitial fluid. (3H)Ouabain autoradiographs demonstrated that, irrespective of exposure or salinity, most of the gill binding was associated with chloride cell. These cells increased in size and number with salinity and, at the subcellular level, the distribution pattern for bound ouabain was always identical to that for the amplified basal-lateral (tubular system) membrane. The combined physiologicmorphologic results constitute final direct proof that chloride cells are the primary site of gill Na,K-ATPase. More important, they provide convincing evidence for unexpected increases in basal-lateral enzyme at higher salinities and thus raise a fundamental objection to the long-postulated role of the Na pump in secretory NaCl transport.


[Mixed dacron-vein bypass. Apropos of 33 cases].

The use of a mixed dacron-vein by-pass is a technical device permitting one to palliate the impossibility of using exclusively venous material. 33 by-passes were thus carried out:--30 distal by-passes;--3 proximal by-passes. The interest of this technique is the possibility of implanting on a small caliber artery, e.g. profunda femoris, popliteal or femoral artery. The main technical point is the immediate anastomosis. Since this article was drawn-up, the indications for this procedure have been multiplied and, over a period of six months, we carried out 32 new mixed by-passes.--27 proximal by-passes;--5 distal by-passes.


Alteration in intracellular sodium concentration and ouabain-sensitive ATPase in erythrocytes from hyperthyroid patients.

The activity of the ouabain-sensitive sodium-potassium-activated component of the ATP-hydrolyzing enzyme system (ouabain sensitive ATPase) was studied in the erythrocyte membranes of 10 patients with hyperthyroidism, and found to be decreased in all 10 patients. The mean ouabain-sensitive ATPase activity was 43 +/- 4 nmol Pi/mg tissue/h in the patients, compared with 69 +/- 5 nmol Pi/mg tissue/h in the erythrocyte membranes of 10 paired control subjects. The mean concentration of sodium within the erythrocytes was 10.8 +/- 0.9 nmol/liter of red blood cells in the patients and 7.2 +/- 0.3 nmol/liter of red blood cells in the controls. The decrease in ouabain-sensitive ATPase activity did not appear to be associated with a change in the ligand sensitivity of ATPase, nor was there a difference in the activity of the ouabain-insensitive component of ATPase. Serial studies to follow the effects of treatment of hyperthyroidism on red cell membrane ATPase were performed repeatedly in one of these patients. There was a significant inverse correlation between L-thyroxine (T4) and ouabain-sensitive ATPase, as both variables returned to normal. Normal erythrocyte membranes were assayed for ATPase activity in the presence of varying concentrations of L-triiodothyronine (T3) and T4, and following pre-incubation with T4. No significant effect on erythrocyte membrane ATPase was demonstrated in either series of experiments. It can be concluded from these studies that the decreased sodium efflux in the erythrocytes of patients with hyperthyroidism is associated with a decrease in the activity of the ouabain-sensitive component of ATPase in the erythrocyte membrane. The failure to reproduce this effect in vitro suggests that it does not represent a direct effect of the thyroid hormones on the mature erythrocyte membrane.


Assay of pig growth hormone preparations for metabolic activities in the rat and in man.

The possible somatotropic effect in man of porcine growth hormone (pGH) and its plasmin digest has not been comprehensively studied before. For this purpose, pGH was digested with rat or human plasmin; acrylamide gel electrophoresis showed less than 10% native pGH remaining in the digests. Native pGH and the 2 types of plasmin digest possessed similar GH potency, as measured by the weight gain assay in the hypophysectomized rat: 1-2 IU/mg. In 7 GH-deficient children and 3 adults with myotonic dystrophy, we measured the capacity of human GH (hGH), pGH, and pGH plasmin digests to cause: a) the retention of N, P, K, Na, and Cl; b) a rise in plasma free fatty acids; c) a fall in plasma alpha-amino NL d) impaired glucose tolerance; and e) hyperinsulinemia. Human GH was active in all respects at minimal effective dosages of .0168 to 0.168 IU/kg BW(3/4) per day. The pGH preparations had no detectable effect at 0.532 I.U./kg BW(3/4)/day. The data show that in man pGH and its plasmin digests possess less than 1/30, less than 1/10, and less than 1/3 the anabolic, adipokinetic, and diabetogenic potencies of hGH, respectively.


Hepatitis B infection in health care personnel of an institution for mentally handicapped children and adults.

The health care personnel (HCP) of an institution for the mentally handicapped were serially tested for the presence of hepatitis B surface antigen (HBSAg) and antibody over a period of 1.5 years. HBSAg was present in 1.8% and anti-HBS in 20.8% of HCP. The prevalence of seropositive HCP appeared to be related to the age and the prevalence of seropositive residents cared for by the HCP. The occurrence of seropositivity was higher in the HCP who cared for children under 15 years of age, who demonstrated a high prevalence of HBSAg or anti-HBS. Although the prevalence of HBSAg-positive subjects was 4- to 8-fold lower in HCP than in residents, the degree of seroconversion in susceptible seronegative HCP and residents was strikingly similar. These observations suggest that HCP working in a closed institutional setting are at considerable risk of contacting hepatitis B infection.


Phage typing of Staphylococcus epidermidis.

Thirteen phages were isolated from lysogenic cultures of Staphylococcus epidermidis from a clinical laboratory and used to type 223 clinical isolates of this organism. The 18 phages isolated in The Netherlands were used to type these same cultures. No correlation was observed between phage type, biotype, or clinical source of isolation. At phage concentrations of 100 times the routine test dilution, 35.0% of the cultures were typable with out phages and 21.5% were typable with the phages from The Netherlands. When only cultures in biotype 1 were considered, 43.3 and 24.1% of 141 cultures were typable with our phages and those from The Netherlands, respectively. The lytic reactions obtained with our phages were generally stronger and easier to read and the lytic patterns were, almost invariably, shorter. The typability of untypable cultures was increased 12.0% by incubation at 45 C prior to phage typing and 20% by heat shock (55 C for 5 min) prior to typing. Phage typing 5 subcultures of 20 typable cultures on 5 successive days showed that the lytic patterns were reproducible. The present status of phage typing S. epidermidis and the work needed to obtain a set of typing phages for epidemiological studies of infections by this organism are discussed.


Prevention and reversal of cholera enterotoxin-induced intestinal secretion by methylprednisolone induction of Na+-K+-ATPase.

The relationship of the mucosal enzyme systems Na+-K+-activated adenosine triphophatase (Na-K-ATPase) and adenylate cyclase and their associated intestinal transport processes was studied in the rat ileum. Two ileal loops were constructed in each anesthetized rat; one loop was inoculated with saline, the other loop with choleragen. Net transport of water and electrolytes was measured in vivo after which enzyme activity was measured in the mucosa of the perfused loops. All doses of choleragen between 5 and 150 mug decreased water movement as early as 3 1/2 h after inoculation. A linear relationship between the dose of choleragen and the level of net water and electrolyte secretion was observed when choleragen doses between 5 and 150 mug were incubated in ileal loops for 4 h. Adenylate cyclase activity was always increased in secreting intestinal loops, whereas Na-K-ATPase was unaffected by choleragen. In animals pretreated with methylprednisolone acetate, 3 mg/100 g per day for 3 days before loop inoculation, saline loops had enhanced mucosal Na-K-ATPase activity had increased net water and electrolyte absorption; choleragen-exposed loops had increased adenylate cyclase and Na-K-ATPase activities, and net absorption of water and electrolytes 4 h after inoculation. These effects of methylprednisolone acetate were still present 19 1/2 h after inoculation. When a single injection of methylprednisolone acetate was given 3 1/2 h after choleragen inoculation, both adenylate cyclase and Na-K-ATPase were activated, and net intestinal absorption of water and electrolytes was observed 19 1/2 h after inoculation. These results suggest that methylprednisolone can prevent and reverse the secretory effects of choleragen by selectively stimulating a coexisting absorptive process.


A review and selection of simple laboratory methods used for the study of glycosaminoglycan excretion and the diagnosis of the mucopolysaccharidoses.

The current state of knowledge on the biochemical abnormalities in the mucopolysaccharidoses is reviewed. Methods for the estimation and identification of glycoasminoglycans excreted in the mucopolysaccharidoses are discussed and a selection of simple and reliable methods of value in a small hospital laboratory have been given in detail in an appendix.


Diseases and histological normality of the renal glomerulus: a clinicopathological study.

Thirty-seven percutaneous renal biopsies showing no significant abnormalities on light microscopy were studied electron optically and by immunofluorescence when available. Assessment of the pathological material was followed by analysis of the patients' clinical notes, and a clinicopathological correlation was carried out. Twenty-three patients fulfilled the clinical criteria of minimal change disease; 10 did not behave clinically as minimal change and showed immune complex deposition; two had benign recurrent haematuria; and two had myelomatosis. Our study shows that if diagnosis is based solely on the light microscope appearances of renal biopsy, diseases other than minimal change are likely to be overlooked. Accuracy of diagnosis in structural terms requires additional immunofluorescence and electron microscopic study; final clinical diagnosis also requires careful follow-up, and repeat biopsy may be necessary.


Staphylococcal scalded skin syndrome. An ultrastructural study.

The authors investigated the ultrastructure of the epidermis of two children who suffered from the staphylococcal scalded skin syndrome (or the Ritter's type of toxic epidermal necrolysis). This syndrome is attributed to the action of an exfoliative toxin produced by Staphylococcus aureus phage group II. A characteristic bullous cleavage was selectively observed at the level of the granular layer, without any damage in other epidermal layers. This cleavage was the result of disruption of of desmosomes between granular cells in two halves, each half desmosome conserving the tonofilaments which were attached to its attachment plaque. No remarkable cytoplasmic alteration occurred in the granular layer, with the exception of the development of thickened tonofilaments among dilated endoplasmic reticulum. Odland bodies were particularly numerous in the areas of desmosomal disruption. This syndrome must be considered as an entity clinically, histologically and ultrastructurally separate from the drug form of toxic epidermal necrolysis.


Surgical correction of intertriginous soft corns.

A new surgical technique for the excision of intertriginous soft corns with advancement of the floor of toe webs is presented.


Characteristics of permanent teeth in persons with trisomy G.

Tooth size and morphology have been studied in 35 participants with trisomy G. The control material was obtained from 33 dental students. Special attention has been paid to the mean cusp pattern of the upper first and second molars. The classification matrix for the linear discriminant function analysis between participants with trisomy G and controls, based on five selected variables that determine the cusp pattern, showed three misclassifications.


Conditions that mimic skin cancer.

There are several conditions that may clinically and microscopically mimic skin cancer. Some of the more serious and unusual differential problems are infections, neoplasms, non-infectious granulomas, and ulcers. Particular attention is given to giant keratoacanthoma dn the Buschke-Lowenstein wart.


Papillon-Lefevre syndrome: report of two cases in the same family.

Two cases of Papillon-Lefevre syndrome have been seen in the same family. The characteristic features of the syndrome are shown to be present in both children and the main characteristics are hyperkeratosis of the palms of the hands and soles of the feet; destruction of the periodontium of the deciduous teeth with subsequent premature loss of the teeth; and destruction of the periodontium of the permanent teeth and the premature loss of these teeth usually before 16 years of age.


[Influence of pre- and postnatal exercises on the abdominal wall].

The authors took a number of biometric measurements from two groups of young women who had had babies. A statistical study of the facts that were obtained shows that muscular strength and tone in the abdominal wall comes back quicker in women who have followed specialised courses of gymnastics before and after delivery.


Simultaneous localization of proteoglycan by light and electron microscopy using toluidine blue O. A study of epiphyseal cartilage.

The simultaneous localization of proteoglycan by light and electron microscopy was demonstrated by fixing epiphyseal cartilage in a glutaraldehyde toluidine blue O solution. Sections cut for light microscopy viewing and those cut for electron microscopy required no further staining, although, in the latter case, staining with uranyl acetate and lead improved the overall contrast. By this technique, electron-dense structures were seen concentrated about the cells which were actively synthesizing matrix, and these structures appeared to bind collagen fibrils. Similar structures were not seen in conventionally fixed tissue. They could also not be identified when the specimens were previously incubated with the proteoglycan-digesting enzyme, papain, prior to toluidine blue O fixation. The toluidine blue O fixation method, unlike conventional fixation and staining, retained proteoglycan in the pericellular areas of actively synthesizing cells and made it visible by light and electron microscopy. It appears that proteoglycans is both precipitated and stained by the presence of toluidine blue O during fixation.


Genetic studies in inbred rats. VI. Linkage relationships of mixed lymphocyte reactivity, serologically defined antigens (Ag-B, Ag-C) and the immune response to poly(Glu52Lys33Tyr15).

The Ag-B allotype, mixed lymphocyte reactivity (MLR) and the immune response to poly(Glu52Lys33Tyr15) were assayed in male rats from the F2 hybrid and two backcross generations of the F344 and DA strains in order to investigate the structure of the rat major histocompatibility complex. No disparity between Ag-B type and mixed lymphocyte reactivity was found in 263 animals. The immune response to poly(Glu52Lys33Tyr15) was closely linked to the Ag-B locus, and both antibody production and the delayed hypersensitivity response were under polygenic control. These results suggest that the genetic loci which determine these responses in the rat are closely linked and that recombinational events between the Ag-B and MLR loci are infrequent.


Diagnostic procedures in immunodermatology.

Most immunologic diseases are caused by the derailment of the humoral or cellular pathways of the immunologic defense system. This derailment results from numerous factors such as the inability of the patient to remove the pathogen; the consumption, defect, or deficiency in any component of these pathways, and the overproduction of any of the components. To diagnose these immunologic disorders one has to detect the pathogen and the reactions caused by it and to determine the cause of its nonclearance. The immunofluorescence techniques has been invaluable in detecting both the antigen that causes the disease and the reactions initiated by the antigen, such as the production of antibodies and the activation of the complement system. The immunoperoxidase technique has also been used for these purposes in certain instances. For detecting the circulating immune complexes which occur as intermediates in the chain of reactions initiated by the antigen, various physiochemical and biologic techniques have been used. However, none of these tests seems to be totally reliable for determining whether circulating immune complexes are present. The consumption of complement was detected by hemolytic estimations and radial immunodiffusion or rocket electrphoresis. These techniques were also useful in detecting the hereditary deficiencies in immunoglobulins and components of classical and alternative pathways of complement activation. Since these techniques cannot be used to estimate IgE, the radioallergosorbent test was used to measure such levels in the atopic patients. Cellular hypersensitivity was detected with skin tests together with methods which assess the ability of lymphocytes to produce mediators in response to antigen. Many of these mediator assays, however, are not suitable for this purpose. A satisfactory substitute appears to be to determine the factor in antigen-stimulated, lymphocyte culture supernatants which activates macrophages to take up radiolabeled colloidal gold or radiolabeled glucosamine. In contact allergic dermatitis, an increase in the IgD-bearing lymphocytes and granulocytes has also been correlated with cellular hypersensitivity. Lymphocytes and polymorphonuclear leukocytes coated with antibodies mainly directed against nuclear antigens of the basal layer cells of the noninvolved epidermis have invariably been encountered in psoriasis. The use of these findings for diagnostic purposes and for understanding the mechanisms of certain diseases is being explored.


Comparative studies on the structure and aggregative properties of the myosin molecule. I. The structure of the lobster myosin molecule.

Myosin purified from the abdominal flexor muscle of the lobster, Homarus americanus, has a number average length of 1559 +/- 218 A, a rod like tail 1335 A long and a globular head 225 X 45 A as determined from electron microscopic observations on platinum shadowed preparations. The mass of the molecule was determined to be ca. 486,000 daltons from high speed equilibrium centrifugation studies at neutral and alkaline pH, and by SDS-acrylamide gel electrophoresis. Both sedimentation equilibrium centrifuge studies at alkaline pH and SDS-acrylamide gel electrophoresis experiments, indicate that the molecule contains a heavy chain core (two polypeptide chains weighing ca. 210,000 daltons each) and ca. four light chains of two weight classes (ca. 16,000 and 20,000 daltons). The amino acid composition of the myosin was determined. The specific activities of the Mg2+ -activated, K+/EDTA-activated, and Ca2+ -activated ATPases of the myosin were determined. Kinetic analysis of the digestion of lobster myosin with trypsin suggests that lobster myosin contains three classes of lysine and arginine residues; slowly split (k = 2.07 +/- 0.31 X 10(-2) moles/min2), rapidly split (k = 11.0 +/- 1.83 X 10(-2) moles/min2) and trypsin insensitive. There are 187 +/- 22 slowly split residues, 280 +/- 35 rapidly split residues, and 144 +/- 41 trypsin insensitive bonds per molecule. Comparison of these molecular parameters with those for the vertebrate skeletal muscle myosin indicates that the two myosins are similar in terms of mass, shape and overall polypeptide chain composition but may be considerably different in terms of local polypeptide chain conformation or composition.


Effects of exogenous dehydroepiandrosterone sulphate on various enzymes and on steroid metabolism in the guinea-pig.

Treatment of male guinea-pigs daily with an oral dose of 2 mg dehydroepiandrosterone (DHA) sulphate/100 g body weight for 2 weeks significantly reduced the glucose-6-phosphate dehydrogenase (G-6-PDH) activity of erythrocytes, liver, kidney and testis. Lactate dehydrogenase activity in plasma also decreased, but L-aspartate: 2-oxoglutarate aminotransferase (GOT) and L-alanine:2-oxoglutarate aminotransferase (GPT) activity in plasma remained unaffected. In liver and kidney, however, a significant rise in GOT and GPT was observed. A 2- to 3-7-fold increase of C19-steroids was observed in plasma, liver and kidney. In extracts of liver and kidney more than 60% of steroids were isolated from the sulphatide fraction. Only minor changes were detected in the metabolic pattern of C19-steroids, 17-hydroxysteroids prevailing in the free and sulphatide fractions, while 17-oxosteroids predominated in the sulphate and glucuronide fractions. A slight rise of cyclic AMP concentrations in liver and kidney tissue was attributed to the inhibition of phosphodiesterase by the DHA/G-6-PDH system


Polarization variations induced by high hydrostatic pressures in the isolated frog skin as related to the effects on passive ionic permeability and active Na+ transport.

The effects of a wide range of hydrostatic pressures (from 50 to 1000 kg/cm2) have been investigated on the spontaneous potential difference (PD), the short-circuit current (SCC) and the activity of the membrane ATPases of the isolated abdominal skin from the frog Rana temporaria L. Two types of variations in PD are induced by pressure changes: short and transient potential variations which appear to be related to the pressure change (compression and decompression) and lasting variations which persist as long as pressure is applied and whose nature appears to be related to the pressure magnitude. Long-lasting potential changes have particularly been investigated. At pressures lower than 500 kg/cm2, the skin potential increases while a pressure over 500-600 kg/cm2 induces a depolarization. Both variations consecutively occur at 500 +/- 100 kg/cm2. These effects of pressure have been shown to be reversible up to about 800 kg/cm2. The question of the origin of the potential changes is discussed and it is proposed that the lasting hyperpolarization results from an effect on the passive permeabilities to Na+, K+ and Cl- ions inducing in turm a secondary readjustment (stimulation) of the Na+ active transport while the depolarization at high pressures reflects a direct inhibition of the Na+ pump. These interpretations are supported by experimental data on the effects of pressure on the short-circuit current and on the activity of the skin (Na+ + K+) ATPase.


The Fc receptor on thymus-derived lymphocytes. III. Mixed lymphocyte reactivity and cell-mediated lympholytic activity of Fc- and Fc+ T lymphocytes.

The involvement of Fc- and Fc+ T cells, separated on the fluorescence-activated cell sorter, in proliferative and cytotoxic responses to alloantigens was examined. The cytotoxic lymphocytes generated by in vivo exposure to allogeneic tumor cells were shown to express the Fc receptor. The proliferative responses to alloantigen exposure in mixed lymphocyte cultures was equivalent in intensity for unseparated T cells, the Fc+ T-cell fraction, and the Fc- T-cell fraction isolated from nonsensitized spleen cells. In contrast, the cytotoxic responses generated by the Fc- T-cell fraction (less than 1% Fc+) were much weaker than the cytotoxic responses generated by the Fc+ T-cell fraction (80-90% Fc+), and the responses of the Fc+ T-cell fraction were generally weaker than, or equal to the responses of unseparated T cells (Fc- T less than Fc+ T less than or equal to unseparated T). Mixtures of the Fc- and Fc+ T-cell fractions mounted stronger cytotoxic responses than the sum of the responses of either fraction alone. Examination of the Ly phenotypes of the synergizing populations revealed that the CL precursor activity (Ly-2+ T cells) resided in the Fc- T-cell population, and that the amplifier T-cell activity (Ly-1+ T cells) resided in the Fc+ T-cell population. The data are discussed in terms of T-cell heterogeneity, differentiation, and intercellular interaction.


Altered growth hormone release in Huntington's chorea.

Glucose tolerance tests have been performed on five patients with Huntington's chorea and no difference in response has been observed compared with seven controls. Insulin tolerance tests have been performed on 12 patients with Huntington's chorea and 10 controls. Blood samples were taken at regular intervals for 75 minutes and analysed for blood glucose, insulin, and growth hormone (HGH). There was no difference between the groups in the hypoglycaemia which developed. The patients, however, had an earlier elevation of HGH than the controls. The difference was highly significant (P less than 0.001, P less than 0.02) 30 and 35 minutes after the intravenous injection of insulin. The patients, although awake, ceased to have choreiform movements for at least the last 60 minutes of the insulin tolerance tests. Our observations of HGH release imply that hypothalamic activity is altered in Huntington's chorea. Further observations of HGH release may therefore be of value in its diagnosis.


Acetylcholine and choline in cerebrospinal fluid of patients with Parkinson's disease and Huntington's chorea.

Lumbar cerebrospinal fluid (CSF) acetylcholine (ACh) and choline (Ch) levels were measured in patients with Huntington's chorea (N=11), Parkinson's disease (N=8), and subjects at risk for Huntington's chorea (N=4), and all three groups were found not to differ significantly from normal controls (N=10). The values found for lumbar CSF ACh and Ch levels in the normal subjects were comparable with previously reported values. The use of physostigmine, a cholinesterase inhibitor, in collecting the CSF samples did not appear to make a difference with regard to ACh and Ch concentrations. Evidence suggesting a ventricular-lumbar gradient, with lumbar CSF Ch concentration being less than ventricular CSF Ch concentration, was found. Finally, ACh levels in CSF did not correlate with corresponding Ch levels.


Role of local hyperfibrinolysis in the etiology of chronic subdural hematoma.

The authors describe studies performed on material aspirated from chronic subdural hematomas. Patients were given 51Cr-labeled red cells prior to aspiration, and it was possible to demonstrate that the mean daily hemorrhage into the hematoma space amounted to 10.2% of its volume. Immunoelectrophoresis of the aspirated hematoma fluid by monospecific anti-human fibrinogen revealed the presence of fibrin and fibrinogen degradation products that, measured by hemagglutination-inhibition immunoassay techniques, varied between 5.0 and 10,500 mug/ml with an average of 2604 mug/ml in 18 cases. The tissue activator was demonstrated by Todd's histological localization in the outer membrane of the chronic subdural hematoma in 11 cases, but not in the inner membrane. These results indicate that if a clot in the subdural space causes the formation of neomembrane, and excessive fibrinolysis occurs, the subdural clot would not only liquefy, but also enlarge by continuous hemorrhage from the neomembrane. Therefore, local hyperfibrinolysis and continuous bleeding are important in the etiology of the chronic subdural hematoma.


Results of treatment of chronic low-back pain at the Portland Pain Center.

We have evaluated 100 consecutive patients with low-back pain admitted to the Portland Pain Center. The average patient had been disabled for about 6 years, and had had an average of two surgical attempts to improve his symptoms. Most of the patients considered had open claims with their Workmen's Compensation carriers. Significant gains were demonstrated in drug reduction, general well behavior, and increased range of motion and exercise tolerance. The Pain Center setting provides a multidisciplinary approach to the treatment of chronic low-back pain. Significant increases in functional capacity are demonstrated.


Thiocardenolides I: synthesis and biological actions of 3beta-thiocyanato-14beta-hydroxy-5beta-card-20(22)-enolide.

The synthesis of a 3beta-thiocyanatocardenolide is described. The compound exhibited about 0.1 times the cardiotonic effect of digitoxyigenin in the isolated frog heart preparation. At a dosage of 20 mg/kg in the intact rat, it elicited ECG changes similar to those seen with a 10-mg/kg dose of digitoxigenin. Studies also revealed the new cardenolide to be a reversible inhibitor of sodium- and potassium-activated adenosine triphosphatase.


An inhibitory role for brain serotonin-containing systems in the locomotor effects of d-amphetamine.

Locomotor activity induced by d-amphetamine was found to be potentiated by food deprivation, a tryptophan-free diet, p-chlorophenylalanine and drugs proposed to antagonize serotonin receptors in brain. Administration of L-tryptophan 1 hour prior to d-amphetamine injection was found to antagonize the enhanced response to d-amphetamine in starved rats and in rats which had tryptophan removed from their diet. However, tryptophan did not block the potentiated response to d-amphetamine in animals pretreated with p-chlorophenylalanine. These findings suggested that the antagonism of d-amphetamine-induced activity by tryptophan in starved rats and rats fed a tryptophan-free diet was not due to a nonspecific depressant effect of the amino acid. Since accumulation of d-amphetamine and its metabolites was not affected by any of the treatments which enhanced its activity, it seems unlikely that an alteration in the metabolism of d-amphetamine can explain these findings. The present work provides additional support for the view that serotonergic fibers play an important role in the actions of d-amphetamine.


Behavioral evidence for supersensitivity following destruction of central serotonergic nerve terminals by 5,7-dihydroxytryptamine.

Previous studies have established that a complex behavioral syndrome--consisting of tremor, rigidity, hindlimb abduction. Straub tail, lateral head weaving and reciprocal forepaw treading--is a specific reflection of the activity of central serotonin receptors. This syndrome was utilized in the present study to test for supersensitivity in the central serotonergic system. Specific destruction of central serotonin nerve terminals by intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT, 50 mug) in adult male rats pretreated with a catecholamine uptake blocking agent resulted in marked supersensitivity to serotonin precursors and agonists. The greatest degree of supersensitivity was observed in response to L-5-hydroxytryptophan, for which the ED50 for elicitation of the syndrome was 20% of the value for control rats. A lesser degree of supersensitivity was seen in response to L-tryptophan (following monoamine oxidase inhibition) and the direct-acting serotonin agonist, 5-methoxy-N,N-dimethyltryptamine, for which the ED50 was approximately 50% of the control value in both cases. Supersensitivity begins to develop within 24 hours and is relatively complete by 96 hours after 5,7-DHT. A marked subsensitivity to the serotonin releasing agent, fenfluramine, was found in 5,7-DHT-treated rats. In contrast to the marked supersensitivity to serotonin precursors and agonists which occurs following 5,7-DHT, chronic administration of a serotonin synthesis inhibitor, p-chlorophenylalanine (400 mg/kg every 3 days for a total of 24 days), did not produce supersensitivity to L-5-hydroxytryptophan or 5-methoxy-N,N-dimethyltryptamine. Possible pre- and postsynaptic mechanisms for the development of supersensitivity are discussed.


Post-tetanic hyperpolarization, sodium-potassium-activated adenosine triphosphatase and high energy phosphate levels in garfish olfactory nerve.

1. While much is now known about the Na-K-ATPase and the posttetanic hyperpolarization of nervous tissue, they have yet to be studied together in the same preparation. 2. The post-tetanic hyperpolarization was studied in desheathed garfish olfactory nerve. The rate constant of decay of the post-tetanic hyperpolarization was determined by monitoring difference potentials after stimulation at 1/sec for 2-3 min. 3. In membrane fractions prepared from these nerves, the ouabain-sensitive ATPase activity (Na-K-ATPase) was determined by spectrophotometric measurements. 4. Both the post-tetanic hyperpolarization and the Na-K-ATPase showed a similar sigmoidal dependence on K+ concentration. The sequence of cation specificities measured at the K-site of the enzyme was the same as that determined by post-tetanic hyperpolarization measurements in whole nerve. 5. The rate constants of the enzyme showed a dependence on Na+ concentration that paralleled the way in which the post-tetanic hyperpolarization rate constants varied as a function of the number of impulses. When Na+ was completely replaced by Li+, neither enzyme activity nor post-tetanic hyperpolarization could be measured. 6. The pH optimum for enzyme activity was between pH 7-0 and 7-8, while the optimal pH for post-tetanic hyperpolarization was above pH 8-0. 7. Metabolite levels in preparations of this nerve studied in vitro correspond to levels found in vivo. 8. High energy phosphate levels were measured fluorometrically in extracts of nerve samples that had been stimulated in air at 1/sec for various intervals. 9. During the first 2 min of stimulation, there was a significant accumulation of inorganic phosphate, and the ATP/ADP.Pi ratio dropped appreciably. 10. The accumulation of ATPase products was commensurate with the approach of post-tetanic hyperpolarization rate constants to their maximum level. This provides direct evidence for an ATPase functioning in active Na+ transport in nerve. 11. The garfish Na-K-ATPase is sensitive to the ATP/ADP ratio of the incubating medium, but is relatively insensitive to orthophosphate, Pi. The fall in post-tetanic hyperpolarization rate constants observed with continued nerve stimulation may have been partially due to the falling ATP/ADP ratio measured in nerve under similar conditions.


An inexpensive method for documenting laparoscopic findings.

This article discusses a method for endoscopic photography as recommended by Lesesne. He presented his experience with this technique in the field of gastrointestinal endoscopy. This communication reviews his method and shows it also to be applicable to laparoscopy.


Scalp hair patterns in mental subnormality.

Scalp hair patterns have been examined in 1901 healthy subjects and 1789 severely subnormal patients. Patients with Down's syndrome had a highly significant excess of midline occipital whorls and a deficit of right-sided occipital whorls. Five out of 44 patients with microcephaly had a distinct 'up-sweep' of the frontal hair, a much lower proportion than found previously. Patients with unspecified mental subnormality had a highly significant deficit of multiple occipital whorls. Cutis verticis gyrata was noted incidentally in 15 subnormal patients, 13 of whom were males. Observation of hair patterns in individual patients with mental subnormality is of theoretical interest but is unlikely to be of great practical value.


Child development and disability: competency-based clerkship.

The training of medical students in the subject of mental retardation is important in broadening the physician's role in dealing with chronic disability. A competency-based training model is presented which specifies competencies, achievement methods, and evaluation procedures for a clerkship. The focus for training is on developing practical skills and a positive orientation toward developmental problems. Evaluative measures for 12 students rotating through the clerkship showed positive knowledge and attitude changes. Competency-based training is recommended as a model for preparing physicians to serve as advocates and resources for persons with chronic conditions.


Cystometric, sphincter and electromyelographic abnormalities in Parkinson's disease.

Bladder function was studied in 24 patients with a diagnosis of parkinsonism using cystometry, sphincter electromyography, flowmetry and electromyelography. A high incidence of disturbances in detrusor function and sphincter control was documented and the signal tracing studies showed prolonged conduction times, giving evidence of peripheral neuropathy. The abnormalities of detrusor function were ascribed to the lesion of the basal ganglia, whereas the sphincter disturbances indicate impairment of the corticospinal tract as a result of Parkinson's disease.


The "athletic heart". Prevalence and physiological significance of left ventricular enlargement in distance runners.

To evaluate the prevalence and importance of "physiological" left ventricular hypertrophy (LVH) in athletes, 30 marathon runners were studied. Electrocardiographic evidence of LVH, present in 24 subjects, was associated with concomitant echocardiographic evidence of a thickened left ventricular (LV) posterior wall in five, with an enlarged end-diastolic LV diameter in three, as well as with roentgenographic evidence of cardiomegaly in three subjects. Echocardiographic evidence of superior LV function was noted in six. Maximal treadmill stress provoked no ischemic change. Cardiac hypertrophy and dilatation commonly develop in well-conditioned athletes, but the changes in LV size are slight. This "physiological" type of LVH does not lead to an ischemic response during exercise, in contrast to that which is seen in pathological forms of LVH. Physiological LVH may, however, contribute to superior ventricular function.


Fitz-Hugh-Curtis syndrome. A laparoscopic approach.

Four of our patients had classical Fitz-Hugh-Curtis syndrome. Persistent right upper-gradrant pain prompted extensive medical evaluation; anibiotic therapy fialed to relieve the symptoms. In each case, laparoscopy proved to be an ideal method for obtaining definitive diagnosis and therapy. Typical perihepatic violin-string adhesions were cauterized and divided under direct vision with dramatic resolution of symptoms.


Tyrosine-induced eye and skin lesions. A treatable genetic disease.

Tyrosine-induced eye and skin lesions in man are an autosomal, recessive, inherited syndrome associated with tyrosinemia, tyrosinuria, and increased urinary excretion of tyrosine metabolites. Patients have mild to severe keratitis and erosive and hyperkeratotic lesions on the palms and soles. The degree of involvement was variable in the small number of patients studied. Mental retardation is frequently a part of the syndrome. A low-tyrosine low-phenylalanine diet lowers blood tyrosine level and leads to healing of the skin and eye lesions. Early dietary treatment may prevent mental retardation.


Echocardiographic recognition of the cardiac mural tumor.

An abnormal echocardiographic signal was detected in the myocardium on the echocardiographic examination of the septum and posterior left ventricular wall in a patient found to have lymphosarcoma which was diffusely infiltrated in the myocardium. This echocardiographic abnormality was well correlated with the autopsy findings. Echocardiography appears to be one of useful methods in diagnosing cardiac mural tumor antemortemly.


An autopsied case of Eisenmenger syndrome complicated by recurrent thromboembolic phenomena in postpartal period.

Dyspnea, back pain, edema, and cyanosis developed suddenly in a 23-year-old woman during the last trimester of her first pregnancy. Although she had been noticed to have the enlarged heart and exertional shortness of breath to a slight degree, she had been apparently in good condition without any significant heart murmurs. Clinically, recurrent episodes of disseminated intravascular coagulation, including pulmonary thrombosis, were thought to be superimposed to Eisenmenger syndrome associated with toxemia of pregnancy. Anticoagulant and fibrinolytic treatments were tried, but their effectiveness was limited by hemorrhagic diathesis. She died of respiratory and circulatory failure after delivery of a moribund baby. Autopsy revealed Eisenmenger complex (a defect in the membranous portion of the interventricular septum and pulmonary vascular disease) and many fresh hemmorrhages in both lungs with a lot of new and organized thrombi. Fresh thrombi were also seen in the heart, the pancreas and the kidneys. The high peripartal mortality in Eisenmenger syndrome could be attributed to pulmonary thrombosis, which may be related to DIC, as well as to peripartal changes in circulatory function.


A clinicopathological study on the electrical axis of the heart in 1,000 autopsy cases.

The electrical axis of the heart in 1,000 aged people more than 56 years of age was classified as normal axis in 58%, left axis deviation in 17.4%, mild left axis devaition in 21.9%, and right axis deviation in 2.7%. Pathological examination disclosed that left axis deviation was associated with myocardial infarction in 20%, right bundle branch block in 16%, but showed no significant relationships with coronary sclerosis, myocardial fibrosis and cardiac hypertrophy. Right axis deviation was associated with right bundle branch block in 66.7% and right ventricular hypertrophy in 22.2%


Potassium-induced changes in the electromechanical and ATPase activity of guinea pig heart.

The effects of various concentrations (0, 0.5, 1, 2, 4, and 8 mM) of potassium chloride on the simultaneously recorded action potential and contractility; and Mg++-dependent, Na++-K+-stimulated membrane ATPase of guinea pig's heart were studied. In KCl-free solution, the inhibition of the Na+-K+-ATPase was associated both with a shortening of the duration of action potential and an increase in the contractility. There was a decrease in the overshoot of action potential and an increase in the resting potential. Potassium chloride produced a concentration dependent lengthening of the action potential duration; decrease in the contraction and resting potential; and an increase in the overshoot of action potential and Na+-K+-ATPase activity. The changes in the action potential and contraction were associated with the changes in the Na+-K-ATPase activity. The changes in the ATPase activity preceded the changes in the action potential and contractility. The involvement of ATPase in the genesis of the resting potential; overshoot and duration of action potential; and contraction has been discussed.


Malignant hypertension and microangiopathic hemolytic anemia.

The fourth case found in Japan manifesting the features of malignant hypertension and microangiopathic hemolytic anemia (MHA) was reported. In this case, bilateral nephrectomy brought down the blood pressure and relieved MHA. The patient has since been maintained alive and well on hemodialysis up to the time of this report.


Difference between inhibitory actions of papaverine and dehydroepiandrosterone on the isolated guinea-pig ileum.

Dehydroepiandrosterone (DEA), a metabolite of steroid hormone in the urine, differed from papaverine in the mode of inhibitory action on the isolated guinea-pig ileum. Papaverine inhibited both phasic and tonic contractions induced by an agonist, while DEA inhibited the phasic contraction without apparent fatigue of the tonic phase. The main action of papaverine seems to be predominatly a metabolic inhibition similar to that of metabolic inhibitors, but the action of DEA could not be ascribed to that of metabolic inhibition. In the presence of papaverine or metabolic inhibitors the height of maximal contraction of an agonist tested by the cumulative method was greatly depressed and less than that by a single method. The longer the time involved in the cumulative doses, the lower was the maximal contraction.


[Comparative study on the effect of anticholinergic substances on basic gastric secretion as well as on gastric secretion stimulated by pentagastrin or hypoglycemia (author's transl)].

The effect of orally administered ipratropiumbromide and propanthelinbromide on the basic gastric secretion as well as on the gastric secretion stimulated by pentagastrin or hypoglycemia due to application of insulin was tested intraindividually in a double blind comparative study. Drug dosage and time after the drug effect was measured varied. In addition the anticholinergic effect of ipratropiumbromide on the basic as well as on the gastric secretion stimulated by pentagastrin was compared to that of oxacepam. The inhibitory effect of ipratropiumbromide on the basic gastric secretion as well as on the secretion stimulated by pentagastrin and hypoglycemia is more pronounced than that of propanthelinbromid. The effect on the basic secretion reached its peak 450 min after drug application whereas the maximal effect on pentagastrin stimulated secretion showed earlier. The effect described was only seen with a dose of the anticholinergic drug of at least 30 mg. A combination of ipratropiumbromide+oxacepam has no effect stronger than ipratropiumbromide alone. On the contrary, it rather seems to have an augementative effect on pentagastrin stimulated gastric secretion that may be compensated completely by ipratropiumbromide. On the basic of these results a direct influence of anticholinergic substances on the parietal cell is discussed.


A comparative pathology study of myocardial lesions and atherosclerosis in Japanese men living in Hiroshima, Japan and Honolulu, Hawaii.

Autopsies were conducted on Japanese men from 45 to 71 years of age in Hiroshima, Japan (191 patients) and in Honolulu, Hawaii (298 patients). They were performed according to a common protocol. In both locations the patients studied were representative of decedents from population-based cohorts with respect to age and cause of death. The degree of atherosclerosis in the coronary arteries and aorta, assessed according to the panel method, was found to be substantially more severe in men in Hawaii than in those in Japan. Areas of recent myocardial necrosis were 3.5 times more frequent in men in Honolulu than in those in Hiroshima. Large myocardial scars were 1.5 times more frequent in the men in Honolulu. It was characteristic of men in Honolulu that severe atherosclerosis and myocardial lesions appeared at younger ages than in those in Hiroshima. These data demonstrate that there is an increase in the frequency and severity of ischemic lesion in the myocardium of Japanese who have migrated to Hawaii and that this increase is the result of atherosclerosis of the extramural segments of the coronary arteries.


The valve of chemotherapy in the treatment of testicular dysembryoplastic tumors.

Chemotherapy appears to be of help in treating dysembryoplastic testicular tumors. It seems better to treat first by surgery (lymphadenectomy) if possible, then (a) if no nodes are involved or only one has been discovered by microscope examination, with chemotherapy for one year; or (b) if two or more  nodes are involved, with irradiation of the nodes and chemotherapy. Even if lymphadenectomy is not possible, one course of chemotherapy followed by cobalt and more chemotherapy can bring results in some cases.


Inhibition of mixed lymphocyte reaction by thoracic duct lymph: removal of inhibitory effect by thoracic duct drainage in lung cancer.

The inhibitory effect of the thoracic duct lymph of a patient with lung cancer on the "one-way" mixed lymphocyte reaction without cytoxicity is unequivocally demonstrated. The effect seems to be dose related. A moderate inhibition of mixed lymphocyte reaction is still observed, even if the responding cells are preincubated in the thoracic duct lymph for 1 hr only prior to the addition of stimulating cells. The inhibitory effect of thoracic duct lymph on the mixed lymphocyte reaction is no longer evident when the material is added 1-4 days after the beginning of culture. These observations suggest that the mechanism of the inhibitory effect of thoracic duct lymph may be a simple attachment of inhibitory factors to the receptor sites on the responding lymphocytes, causing interference in cell to cell interaction. The inhibitory effect of thoracic duct lymph collected 1 week after the thoracic duct drainage on mixed lymphocyte reaction is significantly lower than that of thoracic duct lymph collected at the beginning of the procedure. This indicates that the blocking effect of thoracic duct lymph can be easily removed by this technique; which is technically feasible in man. The interrelationship of the tumor-specific blocking factor, thoracic duct drainage, and tumor growth pattern are discussed with respect to the potential usefulness of this procedure as adjuvant immunotherapy in the management of patients with neoplastic diseases.


Immunologic and chemical studies on mucopolysaccharide derived from murine lymphosarcoma.

Mucopolysaccharide was prepared from media in which the Gardner's lymphosarcoma cells were cultured. Multiple intraperitoneal injections of the preparation into syngeneic mice resulted in enhancement of the tumors which were inoculated prior to the injections. Sera of these hosts contained antibodies reacting with antigens of the outer layer of the tumor cells. Chemical analyses of the preparation showed that the mucopolysaccharide is composed of hexosamine, uronic, acid, hexose, and proteins. The mucopolysaccharide was shown to possess unique migration rate on electrophoresis and thin layer chromatography.