Alterations in the cardiovascular system that occur in advanced age.

Recent information appears to solidify the concept that the left ventricle hypertrophies with age in normal adult man. The stimulus for this moderate increase in wall thickness has not been precisely determined but an attractive hypothesis suggests that the stimulus may be an increased load imposed by the peripheral vascular resistance. The mechanism for the well-documented diminished cardiovascular response to maximal exercise in normal aged man still remains unclear. Evidence in the canine model indicates that a diminished chronotropic response to catecholamines could in part explain a limitation in maximal heart rate response. The reflex change in heart rate in respone to hypercapnia, hypoxia, and sustained isometric handgrip in normal man is diminished with age. The precise mechanism of this age-associated phenomenon remains to be elucidated, but the chronotropic responsiveness to catecholamines is likely a contributing factor. Finally, there is evidence of slowed myocardial relaxation in hearts of aged animals and man. A decrement in the speed at which the sarcoplasmic reticulum from hearts of aged rats accumulates calcium has been demonstrated and appears to be involved in the mechanism of prolonged contraction in aged myocardium.


Effect of benzoyl peroxide on skin surface lipids.

Investigations have been performed on the effect of benzoyl peroxide on skin surface lipids by direct lipid extraction with petrol ether and quantitative determination. Though there was no change after 1 week treatment, after 4 weeks a significant reduction of the casual level as well as well as the replacement sum could be observed.


Oral treatment of pustulosis palmo-plantaris with a new retinoid, Ro 10-9359.

Ro 10-9359 is a retinoic acid derivative, selected for study because of a better tolerance than retinoic acid, shown in animal experiments. Earlier clinical experience has proved Ro 10-9359 to be an extremely potent antipsoriatic drug. The well-known association between psoriasis and pustulosis palmoplantaris was a motivation to evaluate Ro 10-9359 also in the last-mentioned disease, which is notoriously known to be resistant to treatment. In this study 30 patients were given either 75 mg/day of Ro 10-9359 or 200 mg twice every week according to a randomized pattern. All patients had suffered from the disease for at least 2 years without any spontaneous remission during the year preceding the trial. After a treatment period of about 2 weeks with Ro 10-9359 hyperkeratotic scales had usually disappeared, and 2 weeks later there were in general significantly less pustular lesions. The treatment continued for 8 weeks, and at this time the average reduction of the number of pustules was 80%. The daily dosage seemed to give better results and was also better tolerated than was the twice-weekly dosage. Side effects were common, but generally mild. On average, the remission lasted 1 month after cessation of therapy.


[Multiple granulomata pyogenica in a patient with acne vulgaris (author's transl)].

Multiple granulomata pyogenica are usually satellites of a primary lesion recently treated unsuccessfully. Disseminated pyogenic granulomas are very uncommon. In our case report, we describe a young man with six granulomata pyogenica over the chest, after treating his acne with tetracycline and vitamin A acid. In the discussion, we include infection, trauma and vitamin A acid as factors which can induce the vascular tumor in the region of a vascular dysplasia.


Subcutaneous emphysema of the abdominal wall from diverticulitis with necrotizing fasciitis.

The case history of a patient with subcutaneous emphysema of the abdomen from sigmoid diverticulitis is presented. The mechanisms for developing abdominal wall emphysema are reviewed. Thus when the gas originates from the gastrointestinal tract, mechanical factors are mainly responsible for this phenomenon. These inculde a direct communication through a colonocutaneous fistula. Gas may, however, also be spread into the abdominal wall by high intraintestinal pressures. Infection with gas-producing organisms may be associated with subcutaneous emphysema. This is particularly true when the emphysema develops 48 h or longer after onset of symptoms. Infection, however, is not the major cause for gas in these tissues.


Comparison of thymidine, fluorodeoxyuridine, hydroxyurea, and methotrexate blocking at the G1/S phase transition of the cell cycle, studied by replication patterns.

Cultures of human amniotic fluid cells and fibroblasts were temporarily blocked by the replication inhibitors thymidine (dT) surplus, fluorodeoxyuridine (FdU), hydroxyurea (HU), or methotrexate uridine (MU). The respective arresting point at G1-S transition and the homogeneity of the blocked cell population were determined by means of BrdU replication patterns. Most variation of patterns were found after HU. After MU, cells were arrested before the onset of replication, while with dT surplus of FdU an arresting point in early S seemed more likely.


Unstable telocentric chromosome produced after centric misdivision of a 21q/21q translocated element.

An unstable telocentric chromosome was found in an individual with Down's syndrome and an unusual chromosomal mosaic, 46,XX, t(21q21q)+,21-/46,XX,21q-/45,XX,21-. As the 21q/21q chromosome was of paternal origin, based on the characteristics of its centromeric heterochromatin and on the characteristics of both 21 chromosomes of the father, it was concluded that its formation involved centric breakage and loss of centromeric material. The cell line with the 21q- chromosome may have originated from the translocation by an asymmetric misdivision of the reduced centromeric material. Of the two telocentrics produced by this fracture, one, possessing the smaller amount of centromeric apparatus, would be immediately lost; the other would be retained, but complete activity of its centromere would not be restored. It would therefore be unstable and might be lost.


Effect of corn and sorghum diets in N1 methylnicotinamide excretion and hepatic enzymes in rats.

This study was carried out to compare the effects of corn (Zea mays) and sorghum (Sorghum vulgare) diets on urinary N1 methylnicotinamide (N'MN) excretion and on the activity of hepatic enzyme in young adult rats. Thirty rats, weighing an average of 174.3 g at the beginning of the experiments, were divided into three groups and studied for 13 weeks. The two experimental diets supplied 7% protein, and a casein diet was used as control. Niacin was excluded from the vitamin mixture used in the corn and sorghum diets. The activities of the following enzymes were studied: betaHOB-D, G6P-D, NADH2-TR, NADPH2-TR, and 3 HOA-0. Urinary excretion of N'MN was statistically different among the three groups, the corn group having the lowest level. The corn-fed animals appeared to have more obvious alterations in liver enzyme activity. The changes found in corn and sorghum-fed animals are different and cannot be explained as due to niacin deficiency. The different amino acid compositions of the two grains and their relationship with the discrepancies in the result are also discussed.


Improvement in the fertility of streptozotocin-diabetic male rats following treatment with insulin and human chrionic gonadotropin.

Diabetes was produced in male rats with streptozotocin. Some of them were subsequently treated with exogenous insulin, human chorionic gonadotropin (hCG) or both. The rats were tested six weeks later for fertility, testosterone secretion and spermatogenesis. Diabetes was found to inhibit all three parameters of fertility. Accessory gland atrophy was restodred following the treatment with insulin and much improved with insulin plus hCG. In a diabetic control group on restricted food intake, insulin alone did not significantly improve fertility, whereas hCG enhanced steroidegenesis and spermatogenesis but not fertility. Treatment with both hCG and sinulsin gave the best results.


Selective excitation of mithramycin or DAPI fluorescence on double-stained cell nuclei and chromosomes.

Fluorescence spectra of leukocytes stained by both mithramycin and DAPI showed that the fluorescence of the two dyes can be separated efficiently by using different excitation wavelengths, for instance the 435 nm and the 365 nm mercury lines. In human chromosomes the complementary ("reverse") banding pattern produced by these dyes may thus be observed on double stained chromosome spreads. In plants, for instance in Anemone blanda, the two dyes may reveal two different banding patterns. The results of absorption and fluorescence measurements suggest the existence of at least two binding sites, or types, for each dye, with different fluorescent yields and binding strengths.


The localization of enzyme activities in the pancreatic appendages of Sepia officinalis L. (Cephalopoda).

In this study, enzyme activities of the pancreatic appendages of the ductus hepatoPancreas (the so-called "pancreas") in Sepia officinalis L. have been demonstrated by light and electron micicroscopical methods: Malate dehydrogenase, monoamine oxidase, acid phosphatase, beta-glucuronidase, adenosine triphosphatase and carbonic anhydrase were shown by the former, and monoamine oxidase, catalase, glutamic oxalacetic transaminase, choline esterase (non-specific), alkaline phosphatase, acid phosphatase and carbonic anhydrase by the latter technique. The correlation between enzyme activity and distribution, and the presumed function of the two pancreatic epithelia is discussed.


Laparoscopy in zoological medicine.

The technique of laparoscopy was adapted and utilized in zoological medicine for various mammals, birds, and reptiles for reproductive and diagnostic studies as well as clinically related research. It was concluded that since anesthesia was routinely required for most manipulative procedures in zoo animals, and since laparoscopy adds little additional risk, the use of this technique provides an additional diagnostic aid when indicated. Laparoscopy was found to be effective for evaluating reproductive status, particularly ovarian anatomy and function, direct visual biopsy of internal organs, sex determination in selected birds, and as a surgical means of fertility control.


Requirement for membrane potential in active transport of glutamine by Escherichia coli.

The effect of reducing the membrane potential on glutamine transport in cells of Escherichia coli has been investigated. Addition of valinomycin to tris(hydroxymethyl)aminomethane-ethylenediaminetetraacetic acid-treated E. coli cells in the presence of 20 mM exogenous potassium reduced the membrane potential, as measured by the uptake of the lipophilic cation triphenylmethylphosphonium, and caused a complete inhibition of glutamine transport. Valinomycin plus potassium also caused a rapid decrease in the intracellular levels of ATP of normal E. coli cells, but had little if any effect on the ATP levels of two mutants of E. coli carrying lesions in the energy-transducing ATP complex (unc mutants). Yet both the membrane potential and the capacity to transport glutamine were depressed in the unc mutants by valinomycin and potassium. These findings are consistent with the hypothesis that both ATP and a membrane potential are essential to the active transport of glutamine by E. coli cells.


Nature of 6-methylpurine inhibition and characterization of two 6-methylpurine-resistant mutants of Neurospora crassa.

6-Methylpurine, an analog of adenine, inhibits the growth of Neurospora crassa. From kinetic studies it was found that 6-methylpurine is converted to its nucleotide form by adenine phosphoribosyltransferase (EC 2.4.2.7), and inhibits the de novo purine biosynthesis. Adenine relieves the growth inhibition caused by 6-methylpurine, whereas hypoxanthine is not very effective. Studies dealing with hypoxanthine utilization in the presence of 6-methylpurine indicated a severely reduced uptake of hypoxanthine and a general slowdown in its further metabolism. Two mutants (Mepr-3 and Mepr-10) which are resistant to 6-methylpurine were characterized. Studies of purine base uptake and the in vivo and in vitro conversion to nucleotides indicated that Mepr-10 may be an adenine phosphoribosyltransferase-defective mutant, whereas Mepr-3 may be a mutant with altered feedback response to 6-methylpurine. Both mutants showed a severely lowered hypoxanthine phosphoribosyltransferase activity, but because 6-methylpurine did not have any effect on the conversion of hypoxanthine to IMP in the wild type, it was concluded that 6-methylpurine resistance in these mutants cannot be due to lowered hypoxanthine phosphoribosyltransferase activity, but rather that the lowering of enzyme activity may be a secondary effect.


Genetic and physiological studies on the relationship between colicin B resistance and ferrienterochelin uptake in Escherichia coli K-12.

The Escherichia coli gene for the ferrienterochelin uptake and colicins B and D receptor protein is located at approximately 13 min, adjacent to or among genes for enterochelin biosynthetic enzymes. The two receptor functions (colicin and siderophore) are separable by mutation.


Binding of 30s dynein with the B-tubule of the outer doublet of axonemes from Tetrahymena pyriformis and adenosine triphosphate-induced dissociation of the complex.

The binding properties of dynein arms to the A- and B-tubules of outer doublets of cilia from Tetrahymena pyriformis were examined, with the following results: 1. When 30s dynein purified from Tetrahymena cilia was added to doublets deficient in dynein arms, it bound to both A- and B-tubules almost equally and formed arms along the edges. The overall length of arms bound to the A-tubule was 22 +/- 3 nm, and that of arms bound to the B-tubule was 24 +/- 3 nm. Each arm bound to the A- and B-tubules was pointed toward the base at angles of 55 degrees +/- 7 degrees and 48 degrees +/- 7 degrees, respectively. In the presence of sufficient amounts of dynein, the arms along the A- and B-tubules were located at intervals of 22.8 +/- 1.5 nm and 22.5 +/- 1.7 nm, respectively. 2. On adding ATP, only the arms bound to the B-tubule were dissociated from the doublet decorated with arms on both sides. The dissociated arms rebound themselves to the B-tubule after hydrolysis of the ATP. When several doublets decorated with arms along both A- and B-tubules were arrayed side by side, the interdoublet spacing increased from 14 +/- 2 nm to 17 +/- 2 nm on addition of ATP. 3. The turbidity of a suspension of trypsin [EC 3.4.21.4]-treated axonemes decreased rapidly on addition of ATP, then recovered partially. Observations by dark-field microscopy and electron microscopy showed that the doublets which had slid out from the axonemes on ATP addition formed large aggregates after hydrolysis of the ATP. The dynein arms were also solubilized from the axonemes upon addition of ATP, and rebound themselves to the B-tubule after hydrolysis of the added ATP. 4. The double-reciprocal plot for the ATPase [EC 3.6.1.3] activity of the trypsin-treated axonemes against ATP concentration was composed of two straight lines, from which the Km values were estimated to be 1.0 and 12.7 micrometer. The dependence of the decrease in turbidity of the axonemal suspension on ATP concentration indicated that the binding of ATP to sites with an apparent dissociation constant of 1 micrometer induced dissociation of the arms from the B-tubule.


Biosynthesis of glycogen in Neurospora crassa. Kinetic mechanism of UDP-glucose: glycogen 4-alpha-glucosyltransferase.

The kinetic mechanism of glycogen synthase [UDP-glucose: glycogen 4-alpha-glucosyltransferase, EC 2.4.1.11], glucose-6-P-dependent form, from Neurospora crassa has been investigated by initial velocity experiments and studies with inhibitors in the presence of sufficient levels of glucose-6-P. The rate equation was different from those of common two-substrate systems because one of the substrates, glycogen, is also a product. The reaction rates were determined by varying the concentration of one of the substrates while keeping that of the other constant. Double-reciprocal plots of initial velocity measurements were linear and showed converging line patterns. UDP was found to act competitively when the substrate UDP-glucose was varied, but noncompetitively when glycogen was varied. On the basis of these results, it is concluded that glycogen synthase, glucose-6-P-dependent form, from N. crassa has a rapid equilibrium random Bi-Bi mechanism. Rate constant and dissociation constants for each step of this mechanism were estimated.


Two calcium regulation systems in squid (Ommastrephes sloani pacificus) muscle. Preparation of calcium-sensitive myosin and troponin-tropomyosin.

The Ca-regulatory system in squid mantle muscle was studied. The findings were as follows. (a) Squid mantle myosin B (squid myosin B) was Ca-sensitive, and its Ca-sensitivity was unaffected by addition of a large amount of rabbit skeletal myosin (skeletal myosin) or rabbit skeletal F-actin (skeletal F-actin). (b) Squid myosin was prepared from the mantle muscle. It showed a heavy chain component and two light chain components in the SDS-gel electrophoretic pattern: the molecular weights of the latter two were 17,000 and 15,000. Actomyosin reconstituted from squid myosin and skeletal (or squid) actin showed Ca-sensitivity in superprecipitation and Mg-ATPase assays. EDTA- treatment had no effect on the Ca-sensitivity of squid myosin. (c) Squid mantle actin (squid actin) was prepared by the method of Spudich and Watt. Hybrid actomyosin reconstituted by using the pure squid actin preparation with skeletal myosin showed no Ca-sensitivity in Mg-ATPase assay, whereas that reconstituted using crude squid actin showed marked Ca-sensitivity. The crude squid actin contained four protein components which were capable of associating with F-actin in 0.1 M KCl, 1 mM MgCl2 and 20 mM Tris-maleate (pH7.5). (d) Native tropomyosin was prepared from squid mantle muscle, and it conferred Ca-sensitivity on skeletal actomyosin as well as on a hybrid actomyosin reconstituted from squid actin and skeletal myosin. (e) Squid native tropomyosin was separated into troponin and tropomyosin fractions by placing it in 0.4 M LiCl at pH 4.7. The troponin fraction was further purified by DEAE-cellulose chromatography. Squid troponin thus obtained was different in mobility from rabbit skeletal or carp dorsal troponin; three bands of squid troponin corresponded to molecular weights of 52,000, 28,000, and 24,000 daltons. It could confer Ca-sensitivity in the presence of tropomyosin on skeletal actomyosin as well as on a hybrid reconstituted from squid actin and skeletal myosin. (f) Squid myosin B, and two hybrid actomyosins were compared as regards Ca and Sr requirements for their Mg-ATPase activities. The myosin-linked regulatory system rather than the thin-filament-linked regulatory system was predominant in squid myosin B. Squid myosin B required higher Ca2+ and Sr2+ concentrations for Mg-ATPase activity; half-maximal activation of Mg-ATPase was obtained at 0.8 micron Ca2+ and 28 micron Sr2+ with skeletal myosin B, and at 2.5 micron Ca2+ and 140 micron Sr2+ with squid myosin B.


Myosin and actin from Escherichia coli K12 C600.

Myosin-like protein and actin-like protein from E. coli formed filaments very similar in structure to those of myosin and actin from skeletal muscle. At 0.2 M KCl, a large number of "thick filaments" of uniform size (about 0.6-0.7 micron long and about 20 nm wide) was present. These thick filaments aggregated as the KCl concentration decreased to less than 0.2 M. Filaments of actin-like protein were decorated with muscle heavy meromyosin, showing "arrowheads". The arrowhead structure disappeared in the presence of ATP. A mixture of E. coli myosin-like protein and rabbit skeletal actin exhibited a gelation phenomenon on the additon of ATP. The phenomenon was reversible and showed ATP specificity. However, the gelation phenomenon was not observed with the mixture of E. coli actin-like protein and E. coli myosin-like protein. These results provide compelling evidence that the E. coli myosin-like protein and actin-like protein we isolated are essentially identical to myosin and actin, respectively.


Coupling factor ATPase from Escherichia coli. An uncA mutant (uncA401) with defective alpha subunit.

Inactive coupling factor ATPase (F1) was prepared from an uncoupled mutant (uncA401) of Escherichia coli. Reconstitution of ATPase activity was observed when alpha subunit from wild-type F1 was added to the dissociated inactive F1 and the mixture was dialyzed against buffer containing ATP and Mg2+. ATPase was also reconstituted when the mixture of alpha subunit (wild type) and crude extract from the mutant was dialyzed against the same buffer. These results indicate that the mutant is defective in alpha subunit, suggesting that the uncA401 locus carries the structural gene for alpha subunit, and that this polypeptide plays an essential role in ATPase activity in F1 molecule.


Structure and function of chicken gizzard myosin.

In our previous study (Onishi, H., Susuki, H., Nakamura, k., and Watanabe, S. J. Biochem. 83, 835-847, 1978), we found it to be characteristic of chicken gizzard myosin that thick filaments of gizzard myosin are readily disassembled by a stoichiometric amount of ATP (3 mol of ATP per mol of myosin), and that the ATPase activity of gizzard myosin in the ATP-disassembled state is much lower than that of gizzard myosin disassembled by a high concentration of KCl. We now report the following findings: (1) Thick filaments of (unphosphorylated) gizzard myosin can be in a bipolar structure or in a non-polar structure, depending on the method of preparing the thick filaments. (2) Thick filaments of (unphosphorylated) gizzard myosin in either the bioplar or the non-polar structure are readily disassembled by ATP. (3) Addition of rabbit skeletal C-protein does not confer ATP resistance on thick filaments of (unphosphorylated) gizzard myosin. (4) Unphosphorylated) gizzard myosin in the ATP-disassembled state is in a dimeric form as determined by ultracentrifugation. Moreover, 0.2 M KCl-dissociated gizzard myosin in monomeric form is converted to a dimeric form by ATP. (5) The Mg-ATPase activity of (unphosphorylated) gizzard myosin is much lower in its dimeric form (less than one-tenth) than in its monomeric form. The activity depression observed around 0.15 M KCl is therefore due to the formation of myosin dimers. (6) Skeletal L-meromyosin can increase the very low activity of (unphosphorylated) gizzard myosin ATPase at low ionic strength (0.13 M KCl) by forming ATP-resistant hybrid filaments with (unphosphorylated) gizzard myosin, preventing the formation of myosin dimers. (7) Gizzard myosin in which one of the light-chain components is phosphorylated by myosin light-chain kinase can form thick filaments which are resistant to the disassembling action of ATP. (8) Even in the presence of ATP, thick filaments of phosphorylated gizzard myosin do not disassembled into myosin dimers. Accordingly, the ATPase activity of phosphorylated gizzard myosin does not show activity depression at low ionic strength.


Odontoblast alkaline phosphatases and Ca2+ transport.

The same isoenzyme of nonspecific alkaline phosphatase (APase), assayed with p-nitrophenylphosphate (p-NPP), was shown be present in different calcifying tissues, bone, calcifying cartilage, odontoblasts and enamel organ. Indications were also found that the enzymatic degradation of inorganic pyrophosphate (PPi) in calcifying tissues is mediated by APase. By using specific APase inhibitors, it was shown that two enzymes capable of degrading ATP exist. These were characterized in dentinogenically active odontoblasts, and it was concluded that one is the classical APase, the other is a Ca2+ and Mg2+ activated ATPase, named Ca2+-ATPase. The two phosphatases were solubilized from odontoblasts and separated. The localization of APase and Ca2+-ATPase in odontoblasts was investigated by subcellular fractionation and EM histochemistry. Routine methods for fixation were found to almost completely inactivate the enzymes. By using a mild fixation technique that preserved 80% of the enzyme activity, the main localization for both APase and Ca2+-ATPase was found to be in the membranes of intercellular vesicles located in the cell body and odontoblasts process. No activity was found in the cell membranes. It is concluded that there are at least two enzymes able to degrade phosphate compounds at alkaline pH in hard tissue forming cells. One is the nonspecific alkaline phosphatase (APase; EC 3. 1. 3. 1), which is active against p-NPP, PPi, glycerophosphates and ATP among other substrates. The other is a more specific Ca2+-ATPase (EC 3. 6. 1. 3). There seems to be an intimate relation between these two enzymes in the tissue. The function of APase in biological calcification is still obscure. In contrast, the finding of an ATP dependent, intravesicularly directed, transmembranous Ca2+-transport in vesicles derived from the microsomal fraction of odontoblasts may explain the role of Ca2+-ATPase.


Occurrence and significance of oxygen exchange reactions catalyzed by mitochondrial adenosine triphosphatase preparations.

The capacity of various ATPase preparations from beef heart mitochondria to catalyze exchange of phosphate oxygens with water has been evaluated. Oligomycin-sensitive ATPase preparations retain a capacity for considerable intermediate Pi equilibrium HOH exchange per Pi formed during ATP hydrolysis at relatively high ATP concentration (5 mM). Submitochondrial particles prepared by an ammonia-Sephadex procedure with 5 mM ATP showed more rapid ATPase, less oligomycin sensitivity, and less capacity for intermediate exchange. With these particles, intermediate Pi equilibrium HOH exchange per Pi formed was increased as ATP concentration was decreased. The purified, soluble ATPase from mitochondria catalyzed little or no intermediate Pi equilibrium HOH exchange at 5 mM ATP but showed pronounced increase in capacity for such exchange as ATP concentration was lowered. The ATPase also showed a weak catalysis of an ADP-stimulated medium Pi equilibrium HOH exchange. The results support the alternating catalytic site model for ATP synthesis or cleavage. They also demonstrate that a transmembrane protonmotive force is not necessary for oxygen exchange reactions. At lower ATP concentrations, ADP and Pi formed at a catalytic site appear to remain bound and continue to allow exchange of Pi oxygens until ATP binds at another site on the enzyme.


A nuclear mutation conferring aurovertin resistance to yeast mitochondrial adenosine triphosphatase.

A single gene nuclear yeast mutant was isolated whose mitochondrial F1-ATPase was resistant to the specific F1 inhibitor aurovertin. The mutant enzyme was not cross-resistant to other F1 inhibitors. The binding of aurovertin to F1 and to the two largest F1 subunits (alpha and beta) was measured by enhancement of aurovertin fluorescence. Aurovertin bound to wild type F1-ATPase and to its monomeric beta subunit with about the same binding constant. It failed to bind to wild type alpha subunit or to either F1 or F1 subunits from the mutant. The aurovertin-resistant mutant thus contains an altered nuclear gene which specifies the structure of the beta subunit of F1.


The cellular basis of the impaired autologous mixed lymphocyte reaction in patients with systemic lupus erythematosus.

The autologous mixed lymphocyte reaction is impaired in patients with systemic lupus erythematosus. This is because nonthymus-derived (T)-lymphocyte preparations from such patients do not stimulate autologous T-lymphocyte proliferation normally. This defect may explain the impaired generation of suppressor activity in systemic lupus erythematosus and thereby the occurrence of autoantibodies in this disease.


Mechanisms of lymphocyte activation: the role of suppressor cells in the proliferative responses of chronic lymphatic leukemia lymphocytes.

Binding of (125)I-leukoagglutinin (LPHA) to lymphocyte membrane receptors at equilibrium generated similar curvilinear Scatchard plots in 20 patients with bursa-derived (B)-cell-type chronic lymphatic leukemia (CLL) and 15 controls. If biphasic plots are assumed, the two linear components show markedly diminished receptor capacity (15 and 137 ng/10(6) lymphocytes) in CLL as compared to controls (60 and 668 ng). In contrast, affinity was similar in patients (1.0 x 10(8) M(-1) and 2.1 x 10(6) M(-1)) and controls (1.8 x 10(8) M(-1) and 1.5 x 10(6) M(-1)). Highly purified B cells from patients and controls generated binding data comparable to that obtained from the mixed lymphocyte (ML) suspensions from which they originated. Maximal DNA synthesis of highly purified, normal, thymus-derived (T) and B cells in response to LPHA stimulation was comparable to that of ML (mitotic index [MI] 19.9, 20.1, and 23.4, respectively), though B-cell responses were slightly delayed. In CLL the markedly decreased and delayed DNA synthesis by ML (MI 2.3), and by highly purified T (MI 1.6) and B (MI 1.9) cells seemed out of proportion to their decreased receptor capacity for LPHA. The impaired mitogenic responses of leukemic cells from five patients were not enhanced when cocultured with normal lymphocytes. In contrast, cells from eight patients inhibited cocultured normal lymphocyte responses to LPHA by 94.3%. Sera from these patients and supernates from their cultured cells did not mediate this suppressor effect. These observations indicate that the decreased DNA synthesis observed in CLL is not an attribute of B cells and does not represent the expected response of a few residual normal T lymphocytes, but rather reflects impaired responses by all CLL cells. The defect does not relate to the density or function of membrane receptors for LPHA, to the presence of inhibitors in these patients' sera, or to depletion of helper T cells. Our data strongly suggest that one mechanism for the immunoincompetence observed in CLL reflects excessive suppressor-cell activity.


Results following closure of ostium secundum atrial septal defects.

In a series of 41 patients of ASD (ostium secundum type) corrected by surgery, a clinical, radiological, electrocardiographic and echocardiographic follow-up study was performed. Good clinical results were obtained but some abnormalities can persist postoperatively: RV enlargement, dysrhythmias and mitral valve dysfunction.


Effects of the interpolated vibratory stimulation on the interdental dimension discrimination in normal and joint defect subjects.

No significant differences in the interdental dimension discrimination (IDD) ability were found between normal and joint defect subjects. Furthermore, vibration onto the mandible gave similar effects on the nature of IDD in both subject groups. Thus, the muscle spindles of masticatory muscles may contribute to IDD, but temporomandibular receptors may not.


Attitudinal differences of faculty and students regarding the care of special (handicapped) patients in a dental school clinic.

Faculty and students were surveyed as to their attitudes regarding the management of the special patient. This survey was completed after such a program was in existence for three years. Recommendations were made to better realize the overall goals of the program, especially that of encouraging the treatment of the special patients in the general practice of dentistry.


Eliminating office architectural barriers to dental care of the elderly and handicapped.

Methods by which the most common architectural barriers to dental care for the elderly and handicapped can be overcome are described. Some physiological and medical conditions that necessitate special provisions in location and design of the office management of patients have been described. The consequences of accessibility have been discussed and suggestions for management of elderly and handicapped patients are presented.


In vivo activity of a nonspecific T cell-replacing factor.

Nonspecific T cell-replacing factors prepared as supernatants from mixed lymphocyte cultures or concanavalin A-stimulated spleen cells are active in vivo iv injected into nude mice at least 3 days before antigen. The supernatants appear to act by enhancing the week IgM responses that occur in untreated nudes. Secondary responses and IgG antibody were not found.


Langerhans cells trap tick salivary gland antigens in tick-resistant guinea pigs.

In the infested skin of tick-resistant guinea pigs, indirect immunofluorescence techniques have revealed that antigens from the ticks' salivary glands are associated with discrete dendritic cells in the epidermis. Evidence is presented to support the suggestion that these antigen-retaining cells are Langerhans cells.


Differential cyclophosphamide sensitivity of precursor cells in allogeneic and H-2 restricted cytotoxic responses.

Spleen cells from cyclophosphamide-treated mice responded in vitro to allogeneic stimulator cells but not to TNP-coupled syngeneic spleen cells. Similarly, cells from female mice, primed in vivo with syngeneic male cells, could not respond in vitro to male spleen cell stimulation if the mice were pretreated with cyclophosphamide. These results suggest that the precursor cells for H-2-restricted cytotoxic responses belong to a different T-cell subpopulation than the precursor cells for allogeneic responses.


Enzyme histochemistry on skeletal muscle of the human foetus.

The differentiation of fibre types in developing human skeletal muscle was studied. The material consisted of muscle samples from different muscles of 86 foetuses (abortions) between 12 weeks gestation and delivery and 50 children 1 day to 7 years old. The latter samples were obtained at surgery. Histochemical stains for myofibrillar ATPase were made after preincubations at pH 4.3, 4.6 and 10.3 in order to identify the subgroups A and B of type II fibres and undifferentiated fibres (type II C). Stains for glycogen and lipids were also performed as well as for NADH-diaphorase and alpha-glycerophosphate dehydrogenase. After 20 weeks gestation a few large size type I fibers could be found in some muscles, but not until after the 30th week were some type II A fibres seen. During the last 3 months of gestation a very rapid further differentiation occurred, but at delivery the differentiation process was still not completed. At birth 15-20% of the fibres were classified as undifferentiated. This picture only gradually changed with a slow increase in the number of type I, II A and II B fibres. The stains for metabolic enzymes and substrates were pale until late in foetal life when some distinction between fibre types became discernible.


Some quantitative biochemical evaluations of developing skeletal muscles in the human foetus.

This study was performed to obtain a more precise quantitative estimation of oxidative and glycolytic potentials and stores of various substrates of the muscles in the human foetus. The material consisted of muscle samples from different muscles, a total of 166 muscle specimens from 65 foetuses and 55 skeletal muscle specimens from 53 infants and children. The latter samples were obtained at surgery. The activities for succinate dehydrogenase and phosphofructokinase were chosen as markers for mitochondrial and cytoplasmatic enzymes respectively. Glycogen, triglyceride and phosphagen levels were studied. Water and protein content of the muscle tissue undergo continuous changes during foetal life and were therefore also included in the study. The SDH activity was low during gestation and reached a value of 2-3 mmoles/kg w.wt. X min at delivery. The PFK activity was also low during gestation, but around 25 weeks gestation a value of 3-4 mmoles/kg w.wt. X min was common, and around delivery time about 7 mmoles/kg w.wt. X min. At 1-5 years the PFK activity was around 11-12 mmoles/kg w.wt. X min, which is similar to adult muscles. Glycogen content varied, but increased during gestation. In the last trimester of gestation a value of 62-92 mmoles units/kg w.wt. was found. The triglyceride content at the end of the gestation time was 3-16 mmoles glycerol/kg w.wt. The phosphagen levels were quite low all through foetal life, averaging between 0.5 and 3 mmoles/kg for ATP and CP concentrations.


Studies on levamisole, a potentially useful drug in the treatment of Behçet's syndrome.

The anthelmintic drug, levamisole, was shown to amplify the response of human peripheral blood lymphocytes to vegetable mitogens. A similar enhancement of blast formation in the mixed lymphocyte culture was also demonstrated. High concentrations of the drug led to depression of both of these responses. These observations led to studies in a rat breast cancer model in which immunopotentiation was demonstrated in vivo, and this effect was associated with tumor regression. As in the human in vitro studies, high doses of the drug were not associated with augmentation of the immune response and in this circumstance no inhibition of tumor growth was observed. Assuming that potentiation of immune responsiveness is of benefit to patients suffering from Behçet's syndrome, the development of clinical trials employing levamisole appears justified, as long as the drug dosage is carefully monitored.


Comment on "personality organization as an aspect of back pain in a medical setting".

The methodology and results of a recent investigation by Louks, Freeman, and Calsyn (1978) are reviewed. It is demonstrated that the results may have been confounded by inappropriate experimental procedures. Regardless of the methodological deficiencies associated with the experimental procedures, the results do not provide adequate support for the continued differentiation of individual low back pain patients with respect to the etiology of their pain. It is suggested that psychologists may best contribute to the assessment and treatment of individual pain patients by developing actuarial rules regarding the pain-related behavioral characteristics shared by members of various patient subgroups and the specific treatments to which subgroup members best respond.


Effects of brain serotonin alterations on prostaglandin E1-induced bradycardia in rats.

The vasodepressor and bradycardia responses of saline control, serotonin-depleted and serotonin-potentiated rats to an intravenous dose of prostaglandin E1 (PGE1) were assessed under the urethane anesthesia. Elevation of serotonin concentration in brain with either 5-hydroxytryptophan (a serotonin precursor) or chlorimipramine (an inhibitor of serotonin reuptake), although causing no changes in vasodepressor reuptake), although causing no changes in vasodepressor response, did enhance the PGE1-induced bradycardia in contrast, depleting serotonin concentration in brain with either p-chlorophenylalanine or 5,7-dihydroxytryptamine greatly reduced the PGE1-induced bradycardia without changes in vasodepressor response. Moreover, the reduced PGE1 bradycardia induced by p-chlorophenylalanine treatment was readily reversed by the replacement of the depleted brain serotonin with 5-hydroxytryptophan in combination with a peripheral decarboxylase inhibitor Ro4-4602. The data indicate that brain serotonergic systems play a role in the elaboration or modulation of the PGE1-induced bradycardia. Specifically, brain serotonin seems to facilitate the PGE1-induced bradycardia since its depletion causes a decrease and its potentiation or elevation causes an increase in the PGE1-induced bradycardia.


Trisomy 21 with 47,+18 lymphocyte cell line: double mitotic nondisjunction.

A patient with Down's syndrome was found to have 47,XX,+18/47,XX,+21 mosaicism. Chromosome 18 trisomy was found only in 18% of lymphocytes and not in skin fibroblasts. A likely interpretation is double nondisjunction in a single lymphocyte precursor of a trisomy 21 embryo. A brief review of other cases of mitotic multiple nondisjunction and double aneuploid mosiacism is presented.


Adverse reactions to cromolyn.

The frequency of adverse reactions (dermatitis, myositis, and gastroenteritis) to cromolyn sodium in asthmatic patients was 2% (B/375). Reactions were non-life-threatening and completely reversible. Immunologic evaluations, including skin and serum tests for immediate and delayed reactivity, all were negative. Adverse reactions to cromolyn do not appear to be based on an immunologic mechanism. Cromolyn appears to be a safe drug for the treatment of asthma.


Evidence for long-lasting tumor immunity in a syngeneic rat lymphoma model: correlation of in vitro findings with in vivo observations.

Previous studies concerning the tumor-host relationship in the (C58NT)D rat tumor system indicated that some T-lymphocyte responses against tumor antigens were only transiently detectable after tumor inoculation; however, more sensitive procedures for the detection of proliferative responses in the mixed lymphocyte-tumor interaction (MLTI ) have been developed. Upon reexamination of the kinetics of this response, positive responses were detected as long as 650 days after inoculation. Cytotoxic effector cells could be generated in MLTI with lymphocytes from immune WF rats as long as 1 year after inoculation, and evidence was provided which indicated that the persistence of the responses observed in vitro correlated well with the resistance of immune rats to rechallenge with (C58NT)D tumor cells in vivo.


Total correction of tetralogy of Fallot. How to deal with the complicated ascending aorta-right pulmonary artery anastomosis.

Ascending aorta-right pulmonary artery anastomosis may be complicated by deformity at the anastomotic site leading to discontinuity between pulmonary artery branches. Simple closure of such shunts through the ascending aorta is associated with residual stenosis and pressure gradients. An alternative approach which allows reconstruction of the entire intrapericardial pulmonary arterial system at the initial corrective operation is described. The transection of the ascending aorta facilitates the exposure necessary for this extensive repair. Two illustrative cases are presented.


Repair of pulmonary arterial stenosis after Waterston-Cooley anastomosis.

Within the spectrum of neonatal congenital cyanotic heart disease, emergent surgery is often necessary to correct profound pulmonary hypoperfusion. An ascending aorto-to-pulmonary artery anastomosis (Waterston-Cooley) has proved to be the preferred procedure in selected patients. A new technique to correct the occasional resultant pulmonary arterial deformity is presented which is performed concomitantly with definitive intracardiac correction.


Calcium sensitivity of myocardial actomyosin ATPase in young and mature male Fischer rats. A brief note.

Although myocardial actomyosin ATPase specific activity determined at Ca2+ levels of 1 x 10(-3) to 1 x 10(-2) M is consistently higher in two-month old male Fischer rats than in twelve-month old individuals, this difference can be eliminated if the enzyme is assayed at lower calcium concentrations. This suggests that the previously reported, declining actomyosin ATPase activity in the rat myocardium with advancing age may represent an age-related diminished ability of calcium to reverse the known inhibition upon actomyosin ATPase by the regulatory proteins.


[The inhibitor factor of leukocyte migration in acne vulgaris].

The inhibition factor of the leukocytic migration was studied in 26 patients with Acne Vulgaris, stages III and IV, being positive in all the cases. The LIF positive shows the mobilisation of lymphocytic population, answering an active and constant immunologic conflict. As the PA is antigenic, because it produces a blastification (TTL positive), we can say that it acts as antigen provoking immunologic mechanisms with help to explain the inflammatory process at the pilosebaceous follicle in the AV.


The effect of age on the character of immune complex disease: a comparison of the incidence and relative size of materials reactive with Clq in sera of patients with glomerulonephritis and cancer.

The impact of aging on the severity of chronic immune-complex glomerulonephritis was studied in 144 patients from whom diagnostic renal biopsies were obtained over a 3-year period. Glomerulonephritis was related to an antecedent streptococcal infection in nine of these patients. In 58, glomerulonephritis occurred in association with a systemic disease; 27 of these had lupus erythematosus. At the time of the renal biopsy, serum creatinines were more frequently abnormal in men over 40 years of age. Similarly, histological evidence of irreversible glomerular injury was more evident in men over 40. Histological indices of renal glomerular injury correlated with the presence of intense fluorescent antibody reactions specific for C3 and C4 and IgG in the glomeruli. High serum Clq binding activities (Clq BA), an indication of the presence of circulating immune complexes, also were found significantly more often in males over 40. High serum Clq BA correlated with renal functional and biopsy evidence of severe glomerulonephritis. The renal biopsies in 89 cases were tested with fluorescein-conjugated heat-aggregated IgG (FAIgG) to determine how many contained focal immunoglobulin deposits with antiglobulin activity. Antiglobulins were detected in glomeruli of 24 patients and were found significantly more often in biopsies which revealed histological evidence of severe and irreversible histological injury. Binding of FAIgG was not selectively associated with any sex or age groups. Thus, detection of circulating immune complex-like materials in sera and the presence of glomerular deposits with antiglobulin activity were both features associated with severe glomerular injury. Both correlated with the quantity of complement deposited in the glomeruli. But only serum Clq binding activity was age and sex related. Similarly, in cancer patients, abnormal Clq BA were found more frequently in sera of older men with cancer but not in age- and sex-matched controls. Examination of selected sera by sucrose density gradient ultracentrifugation revealed that the complexes from cancer patients were relatively small (less than 19S greater than 7S) whereas those in most nephritis patients were heterogeneous in size. Sera with relatively high Clq binding activity from patients with chronic glomerulonephritis tended to contain relatively greater quantities of Clq binding materials sedimenting more rapidly than 19S.


The cytoskeleton and cell movement: general considerations.

The cytoskeletal proteins, actin, myosin, tubulin, dynein, and their associated proteins, are discussed selectively with regards to their biochemical and structural properties. Particular emphasis is placed on the comparison of non-muscle proteins to their muscle counterparts, and on the various mechanisms for regulating actin polymerization, actin-myosin interaction, and tubulin polymerization. This review as well as the bibliography accompanying it is selective. An attempt is made to stress the most recent findings and to emphasize those areas which appear to hold the greatest promise for future research.


[Long-term complex plan for technical reorganization of technological processes].

New technological processes introduced in the manufacturing combine "Krasnogvardeets" and planned for adopting conformable to a long-range complex programme of technical reorganization of technological processes are briefly described.


[Experience in developing and introducing a system of defect-free work as a stage in creating a complex system of production quality control].

An experience in working out and introduction of a system of failure-free performance work as one of the most important steps in creating a complex system for the production quality control at the Leningrad combine "Krasnogvardeets" is described. Issues related to elaborating, introduction and further improving the system of the failure-free work, its pecuniary stimulation and setting up standards for the enterprise are discussed. Under consideration are also problems of organizing a unitized service for the quantity control, as an organ called to secure coordination and quidance over these operations at the combine in this industry.


[Experience in developing and manufacturing anesthetic-respiratory apparatus in the "Red Guard" combine].

Unification of basic subassemblies in the apparatus for inhalation anesthesia and artificial ventilation of the lungs is in wide practice. This helped achieve a high quality of the manufactured units with the diversity of models for the anesthetic-respiratory apparatus, put out by the Leningrad manufacturing combine "Krasnogvardeets".


Reversion and interallelic complementation at four urease loci in Neurospora crassa.

Analysis of heat stability of urease in extracts of 24 revertants, six for each of four ure loci, revealed that at least one revertant for each locus had a heat stability about one-third that of wild type. Similar results were obtained with urease formed by interallelic complementation at the ure-2 and ure-4 loci, but interallelic complementation at the ure-1 and ure-3 loci produced insufficient urease activity for analysis. The data are interpreted to suggest, as a tentative model, a structural function for each of the four ure loci.


Sterol content and enzyme defects of nystatin-resistant mutants of Neurospora crassa.

Non-saponifiable cell extracts of wild type and sterol mutants of N. crassa were analysed by means of gas-liquid chromatography. The wild-type contained ergosterol and episertol in a 10:1 ratio. None of the mutants was able to synthesize ergosterol. Three of the mutants carry single recessive gene mutations cauisng blocks in the terminal steps of ergosterol biosynthesis: erg-1 has an inactive delta 8 leads to delta 7 isomerase erg-2 has an inactive 24(28) hydrogenase, and erg-4 has an inactive C-24 methyl transferase. Some of the mutants accumulated novel sterols as a result of their enzyme defects. The genes erg-1 and erg-2 were mapped close to inl on the right arm of chromosome V.


Characterization of the plasma membrane ATPase of Saccharomyces cerevisiae.

1. The distribution of ATPase and several marker enzymes was examined after differential and sucrose gradient centrifugation of yeast homogenates. 2. An ATPase activity not sensitive to oligomycin is found exclusively associated with a particulate fraction equilibrating at densities of 1.23-1.25. This particulate material shows the chemical and enzymatic characteristics of the yeast plasma membrane. 3. The pH optimum of the plasma membrane ATPase is 5.6, as compared with 8.5 for the mitochondrial ATPase. In addition to oligomycin, the enzyme is not sensitive to other inhibitors of the mitochondrial ATPase as azide, dicyclohexylcarbodiimide and the mitochondrial ATPase inhibitor protein. It is inhibited by p-chloromercuryphenyl sulfonate, fluoride, quercetin and by the antibiotic Dio-9 but is not affected by ouabain. 4. The plasma membrane ATPase shows a high affinity for ATP (Km = 0.1 mM) and is very specific for this compound, hydrolyzing other nucleotide triphosphates less than 25% as rapidly. No activity was detected with ADP. 5. The enzyme requires a divalent cation for activity and Mg2+ is the most effective. It is not significantly stimulated by K+ or bicarbonate and Ca2+ is inhibitory. 6. The activity cannot be assayed in intact cells unless they are permeabilized with toluene. This suggest that the active site is on the cytoplasmic side of the plasma membrane.


["Ischias antica et postica." A scheme of neurological investigation (author's transl)].

A scheme of neurological investigation is presented which combines anamnesis, clinical findings, electrophysiological data, course and postoperative documentation for the radicular processes of the lumbo-sacral region (ischias antica et postica).


Biophysical studies on agents affecting the state of membrane lipids: biochemical and pharmacological implications.

The phospholipid requirement of membrane-bound enzymes may depend on several reasons. In our laboratory we have investigated lipids (1) as a bidimensional medium required for the movement of Coenzyme Q, a lipid-soluble cofactor of the mitochondrial respiratory chain, and (2) as a hydrophobic environment necessary to impose the proper conformation to membrane-bound enzymic proteins. We have found that Coenzyme Q, once reduced by NADH dehydrogenase, must cross the inner mitochondrial membrane; only quinones having long isoprenoid side chains can easily cross phospholipid bilayers, and this is the reason why a short chain quinone such as CoQ-3 inhibits NADH oxidation. The incapability of short quinones to cross lipid bilayers is due to their disposition in the lipid bilayer, stacked within the phospholipids. The conformational role of lipids has been investigated indirectly observing the kinetics of membrane-bound enzymes, e.g. the mitochondrial ATPase, and directly by circular dichroism. Lipid removal or lipid perturbation with organic solvents induce a decrease of alpha-helical content in mitochondrial proteins, and give rise to a series of kinetic changes in ATPase, including uncompetitive inhibition, increased activation energy, and loss of cooperativity in oligomycin inhibition. The recognition of a conformational role of lipids has allowed us to postulate a working hypothesis for the mechanism of action of general anesthetics. Such drugs have been found by us, by means of spin labels and fluorescent probes, to disrupt lipid protein interactions in several membranes, including synaptic membranes. The loosening of such interactions is believed to induce conformational changes, which will alter ion transport systems necessary to the propagation of neural impulses. Conformational changes induced by anesthetics have been found by us both directly by circular dichroism and indirectly by enzyme kinetics. The conformational effect of anesthetics is not directly exerted on the proteins but is mediated through the lipids. In agreement with this hypothesis we have found that membrane-bound acetylcholinesterase is inhibited by anesthetics, whereas the solubilized enzyme is not inhibited. However, binding of the solubilized enzyme to phospholipids restores anesthetic inhibition.


Reversal of impaired splenic function in patients with nephritis or vasculitis (or both) by plasma exchange.

By studying the clearance of autologous labeled antibody-coated or heat-damaged erythrocytes, we showed that reversible blockade of the splenic component of reticuloendothelial function existed in 14 of 15 patients referred for treatment of nephritis or vasculitis. In 10 patients treated by plasma exchange--alone in three and combined with steroids and cytotoxic drugs in six--reversal of splenic blockade followed in nine, and in the three patients treated solely by plasma exchange this reversal was demonstrated to occur within 48 hours of the procedure. Only gradual reversal of splenic blockade was found in three of five patients treated by steroids with or without cytotoxic drugs; no change in splenic function was observed in two. When circulating immune complexes were detected by a C1q-binding assay, there was, in serial studies, an approximate inverse correlation between splenic function and the level of C1q-binding material, though hyposplenism was also a feature of patients in whom the C1q-binding assay was negative.


Spinal subdural empyema: report of two cases.

Spinal subdural empyema (SSE) is a rare variety of intraspinal infection. SSE should be suspected in patients presenting with fever, back pain, and signs of cord or nerve root compression. Two patients with SSE are presented. The first patient complained of fever and back pain. She had no neurological deficit but was found to have SSE. The second patient, who presented with intracerebral hemorrhage in the fifth month of pregnancy and spontaneous abortion, was found to have SSE at lumbar puncture. The clinical manifestations and management are discussed.


Spinal subarachnoid hematoma after lumbar puncture producing acute thoracic myelopathy: case report.

A case of subarachnoid hematoma after a difficult lumbar puncture and anticoagulation is presented. Subarachnoid adhesions preventing the free flow of spinal fluid at the T-6 level served to limit the cranial progression of the hemorrhage and produced a transverse myelopathy at that level. The underlying pathology, clinical course, and myelographic findings are reviewed. Pertinent literature is presented.


The cornea in connective tissue diseases.

Even though lenticular and retinal abnormalities seem to dominate the ophthalmologic picture in Marfan's syndrome, the cornea shows significant abnormalities consisting of a striking flattening and corneal astigmatism. The use of conjunctival biopsies followed by histochemical and electron-microscopic evaluation shows low morbidity but an excellent yield of diagnostic information on storage diseases, and an ectopic collagen may be the basis of at least one type of keratoconus. Much more work has to be done on defining the collagens of the human eye in embryologic, fetal, and postnatal stages under normal and pathologic conditions. The yield of such studies may be high for an understanding of such diseases as myopia, retinal detachment, and keratoconus.


Counseling the parents of birth-defective children.

Parents of a child who is diagnosed as defective face a crisis for which they are usually unprepared. They need an opportunity to work through their intense feelings. In addition, they need specific information about how to be of use to their child. Self-help groups composed of parents of children with a similar handicap can be a resource of great value during this crisis as well as in the years that follow. When such groups are not available, parents can be placed in contact with a family that is effectively raising a child with the same handicap or an adult who has successfully coped with it. Physicians should be aware of their own feelings regarding handicaps and of the effect these may have on efforts to help parents.


The role of methylprednisolone in the modulation of cellular cytotoxicity and its relation to renal transplantation.

Inhibition of killer cell generation or suppression of their cytolytic capacity once formed represent fundamental mechanisms by which methylprednisolone may modulate cellular cytotoxicity in the transplant recipient. In vitro studies in mixed lymphocyte culture demonstrated that the presence of therapeutic concentrations of this agent (0.001-1 microgram/ml) during the sensitisation phase resulted in suppression of lymphocyte activation without cytolysis and marked or total inhibition of killer cell generation. A considerable individual variation in sensitivity to methylprednisolone-induced suppression was observed and killer cells once generated were resistant to this agent.


Cytogenetic analysis on children born of parents treated with immunosuppressive drugs.

Two women previously treated with cyclophosphamide had five pregnancies, resulting in seven normal offspring, including two sets of twins. All the babies had normal chromosome constitution and there was no significant chromosome damage. Apart from the twin pregnancies, which were induced, the pregnancies continued to full term and the birth weights were good. Men with renal transplants receiving azathioprine and prednisolone fathered 13 pregnancies, resulting in 11 offspring; one was a mongol; there were two spontaneous abortions, including a twin pregnancy. With the exception of the mongol, the babies had normal chromosome constitution and there was no significant chromosome damage. Two women with renal transplants receiving azathioprine and prednisolone have had four pregnancies, two ended in spontaneous abortion and two continue.


Interaction of RNA polymerase and rho in transcription termination: coupled ATPase.

We have previously described temperature sensitive rho mutants of Escherichia coli (e.g., rho15) that are defective in transcription termination at various signals, including an IS2 DNA insertion in the gal operon [Das, A., Court, D. & Adhya, S. (1976) Proc. Natl. Acad. Sci. USA, 73, 1959-1963]. In this paper, we report the isolation of mutants altered in the beta subunit of RNA polymerase (a class of Rifampicin-resistant mutants), which restore gal IS2 polarity in the rho 15 strain. It has been shown that one of these suppressor RNA polymerases (rpoB101) requires rho to terminate transcription of phage lambda mRNA. In contrast to the wild type RNA polymerase, the suppressor RNA polymerase also terminates lambda mRNA transcription in the presence of rho15 protein. We have isolated new rho mutants (e.g., rho112) that are defective in transcription termination in the rpoB101 strain. These results strongly support the notion that rho and RNA polymerase interact functionally during transcription termination. We have shown that rho15 catalyzes ATP hydrolysis during transcription with rpoB101 RNA polymerase, but not with wild-type RNA polymerase. Because rho 15 protein hydrolyzes ATP in the presence of free RNA, we suggest that rho may recognize the 3'-OH end of RNA. During transcription, this recognition involves an interaction with RNA polymerase, resulting in the displacement of the polymerase and the release of the nascent mRNA.


Natural killing and antibody-dependent cellular cytotoxicity are independent immune functions in the Minnesota miniature swine.

Peripheral blood lymphocytes from Minnesota miniature pigs were tested for natural killing (NK) and antibody-dependent cellular cytotoxicity (ADCC) in a 2- to 4-hr 51Cr release assay against human myeloid and lymphoid tumor target cells. Adult specific pathogen-free and germfree animals exhibited normal levels of activity in both assays. In addition, the NK and ADCC activities of peripheral blood lymphocytes from colostrum-deprived newborn piglets were examined. These animals were obtained by hysterectomy and previously shown to be immunologically "virgin." We found that these newborn piglets exhibited normal ADCC but lacked NK activity. The differences in the ontogeny of the two activities suggest that they are distinct. Preliminary effector cell characterization studies suggest that: (i) NK and ADCC in the pig are physically not separable; (ii) the majority of the cytotoxic activity on a cell-per-cell basis is mediated by the non-T lymphocyte fraction; and (iii) the rosetted T cells, which account for about 60% of the total pig peripheral blood lymphocytes, have low but demonstrable cytotoxic activity as well.


Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice.

Dendrite cells (DCs) are a new cell type initially identified in mouse lymphoid organs. Recently, DCs have been purified from mouse spleen. This paper demonstrates a functional role of DCs: they are potent stimulators of the primary mixed leukocytes reaction (MLR). As few as 300-1000 DCs doubled the proliferative activity of 5 X 10(6) allogeneic responder spleen cells, while 0.3-1.0 X 10(5) DCs induced a maximal stimulation of 30- to 80-fold. Between these extremes, the log of the MLR response increased linearly with the log of DC numbers. This dose-response assay was then used to compare the potency of purified DCs with that of other heterogeneous lymphoid populations, many of which gave dose-response curves with similar slopes. The potency of purified DCs as MLR stimulators was 100-300 times greater than that of unfractionated spleen cells. When spleen cells were fractionated by simple physical techniques, MLR-stimulating capacity in the subpopulations correlated closely with DC numbers. Removal of splenic B or T lymphocytes, by anti-immunoglobulin or anti-brain serum plus complement, did not reduce MLR-stimulating capacity. Finally, several populations, enriched in mononuclear phagocytes but lacking in DCs, stimulated weakly if at all. We conclude that DCs are a potent stimulating cell and are at least 100 times more effective than other major cell subclasses--i.e., B and T lymphocytes and macrophages.


Midabdomen abdominoplasty.

A simple technique is presented for removal of excessive supraumbilical and periumbilical skin.


Suture materials in otoplasty.

From my experiences in 101 otoplasties of the Mustardé type, the buried suture materials have shown individual variations, as regards granuloma and slippage complications. As a result, I now prefer 4/0 clear nylon for reconstruction of the anti-helix, 3/0 white Mersilene for concha-mastoidal fixation, and 4/0 chromic or subcuticular Vicryl for skin closure.


[Diagnosis and differential diagnosis of cardiac enlargement in the chest film. Systematic survey (author's transl)].

The pathological enlarged heart is attempted to define by roentgenologic criteria. The historical "heart lung quotient" continues to be an important measurement. Alterations of the heart size secondary to age, the systolic-diastolic difference of the heart size and the alterations of the heart size between two chest films are discussed. Differential diagnosis of enlargement and shape of the left and right heart are presented. Also the differential diagnosis of general cardiac enlargement especially valvular heart disease, combined left and right heart failure, pericardial effusion and myocardiopathy is considered.


The role of the fibrinolytic system in thromboembolism.

The present concept of physiologic fibrinolysis was reviewed. It was concluded that the nonspecific proteolytic activity of plasmin would essentially be limited to fibrin in vivo in view of (A) the specific adsorption of activator and of plasminogen onto the fibrin surface resulting in local generation of plasmin  and (B) the fact that plasmin, adsorbed to fibrin (in contrast to plasmin in the fluid phase) largely escapes from the action of antiplasmin. The hemostatic balance in the resting condition was discussed. It was concluded that under normal conditions, systemic intravascular fibrin deposition or formation must be either nonexistent or extremely limited. On the other hand, there is considerable evidence that a limited systemic fibrinogenolysis is going on in healthy individuals and that this process can be accelerated by simple physiologic procedures, such as strenuous physical exercise.


[Unusual localizations of hydatid cysts].

In a total of 448 hydatic cysts that have been treated in the I-st Surgery Clinic of Jassy between 1947 and 1977 rare localizations were noted in 61 cases. Of these 47 were primary echinococcoses and 14 were secondary. The clinical and therapeutic aspects are discussed for each particular localization: the splenic localization was encountered in 16 cases, the peritoneal one in 10 cases, the diaphragmatic in 6 cases. There were also 2 renal localizations, 3 retro-peritoneal ones, 3 ovarian and salpyngean localizations, 3 thyroid, 7 endo-thoracic but extra-pulmonary, 5 muscular and 6 subcutaneous localizations. Radical surgery had immediate and late results that were quite satisfactory. No deaths or recidives were noted.


[Intramedullary nailing with reaming. A critical analysis of Kuntscher's principle (author's transl)].

The authors have reviewed two of Kuntscher's principles relating to intramedullary nailing: the moment of elasticity of the nail should be close to the moment of elasticity of the bone and the suppression of rotation movements at the fracture site is due to locking of the nail by virtue of its elasticity. They have conducted an experimental study which does not confirm these views. They considered that rotary stability is due to muscle tone, the line of the fracture and the anchorage of the ends of the nail at the upper and lower end of the bone.


[Combined Kuntscher nailing and screw fixation (author's transl)].

The authors describe a technique of Kuntscher intramedullary nailing combined with screws driven through the bone and the nail above and below the fracture site. This technique gives better stability of the fracture and allows extension of intramedullary nailing to severely comminuted fractures, fractures with loss of bone and to proximal or distal fractures. Risks of rotational instability or shortening are diminished. The technique is fully described. With the use of correct ancillary instruments, x-ray exposure is minimal. Biomechanical experiments conducted to determine the best position of the screws for optimal locking of the nail are described. The results obtained in one hundred and sixteen cases are analysed. The technique was also used in the treatment of non-union and in the fixation of osteotomies.


[Autologous osteochondral graft: a method for resurfacing osteonecrosis of the medial femoral condyle in the elderly (author's transl)].

The author describes an original technique for resurfacing osteonecrotic medial femoral condyles. The centre and posterior part of the condyle is displaced anteriorly into the weight-bearing area. The indications for this technique are cases in which there is no deformity in the frontal plane and when the tibial articular cartilage is normal. Two cases were so treated. After a follow up of three and five years the results were very good.


[Evaluation of functional results after fractures of the calcaneus (author's transl)].

The author describes a scale of rating for the evaluation of the results of fractures of the calcaneus, similar to that used for the evaluation of hip function. Five points are given for walking ability, pain, mobility and triceps power. The last point is considered to be essential. This evaluation was tested on 232 cases. A close correlation was established between the four criteria.


[Correction of bowing in Paget's disease (author's transl)].

Thirteen tibiae and seven femora suffering from bowing due to Paget's disease have been streightened operatively. In the tibiae, the deformities were of metaphysial genu varum with bowing in the sagittal plane of an average of 30 degrees combined with some medial rotation. In the femora, the main curve was anterolateral with some medial rotation and coxa vara. Seventeen cases united uneventfully after osteotomy. In three cases, there were septic complications, union occurred after removal of the internal fixation. Bowing recurred in three cases. The recurrence appeared to be related to incomplete correction leading to persistent mechanical strain on bones affected by rapid bone turnover. Inadequate internal fixation may also be a factor. All other cases were functionally improved by correction. Oblique osteotomy is indicated for the correction of tibial deformity when there is moderate medial rotation. Transverse osteotomy with fixation by intramedullary nailing is indicated for correction of femoral deformities.


[Severe strains of the cervical spine operated on by a posterior approach (author's transl)].

The authors have operated on 18 cases of severe strain of the cervical spine (six cases of C1-C2 and 12 cases of level cervical spine). They point out the difficulty of an accurate diagnosis in emergency. They emphasize the importance of flexion-extension X-rays when conventional X-rays are not strictly normal. After an analysis of the results they suggest that recent cases should be treated by posterior grafting at the level of C1 and C2, posterior plating at lower levels. Old and irreducible cases should be treated by osteotomy and anterior grafting: banding with grafting at C1 and C2, posterior screwed plating at the inferior cervical level.


[Surgical treatment of stiff knee following femoral sepsis and septic arthritis of the knee (author's transl)].

The authors have studied the results of attempts to restore joint movement in stiff knees after septic non-union of fractures of the femoral shaft or after septic arthritis of the knee by arthrolysis and quadriceps release. Fifteen procedures were done on fourteen patients with severe limitation of movements. The results were gratifying; eight very good and four good. No case was made worse. The technique is described in detail and operative and post-operative complications described. A long-term follow-up study showed that the results tended to improve after several years. The prognosis can be based on the degree of flexion obtained during operation, though free flexion should be distinguished from forced flexion. It is concluded that the procedures used are worthwhile in spite of previous sepsis.


[Flexor tendon grafting. The use of a modified Hunter's technique (author's transl)].

The authors describe a modification of Hunter's technique of flexor tendon grafting. The operation is performed in two stages. At the first stage, a silastic prosthesis is inserted and the proximal end of the flexor digitorum profundus is sutured to the tendon of palmaris longus. This suture will represent the proximal suture of the future graft. At the second stage, six weeks later, the palmaris longus is divided proximally and the graft is passed distally to be sutured to the terminal phalanx. This modified technique allows a gain in time, a better blood supply to the graft and a safer proximal suture.


[Induction of experimental diabetes in frog (author's transl)].

The effect of diabetogenic agents, alloxan and streptozotocin, in frogs has been studied. These drugs were administered to the animals by injection into the dorsal lymph sac. Alloxan did not exert any effect at non-lethal doses. At 300 mg/kg alloxan caused death of most of the animals in an hyperglycemic state in less than 72 hours. Streptozotocin at doses lower than 1 g/kg was ineffective. At 1.5 g/kg, a non-lethal dose, about half of the animals became diabetic.


Reversible modification of rat liver F1-ATPase by a redox reaction.

F1-ATPase from rat liver mitochondria exhibited a change in properties when reduced by dithionite: an increase in activity together with a disappearance of its sensitivity to bicarbonate stimulation was observed. A complete reversion to the original properties was achieved with the oxidizing agent 2,6-dichlorophenolindophenol.


Rat liver mitochondrial F1-ATPase, an FAD containing ferroprotein.

F1-ATPase isolated from rat liver mitochondria has been found to contain approximately 1 mole of FAD and 6 g atoms of nonheme iron per mole of enzyme.


[Visceral larva migrans].

The clinical records of patients with visceral larva migrans confirmed through laparoscopy and other tests are reviewed. This review was prompted by the admittance of two patients with this affection in the last years. Medical literature was reviewed, and conclusions are made.


ATPase, an electron carrier and energy transducer: the missing link in oxidative phosphorylation?

A mechanism for oxidative phosphorylation is proposed. ATP synthesis would take place on a catalytic site of ATPase constituted by two irons with ligands ATP, ADP, and Pi. The interchange of ATP with ADP and Pi makes possible a redox cycle between two potentials permitting the energy transduction.


Intranasal ipratropium: inhibition of methacholine induced hypersecretion.

The submucous glands of the nose have an abundant innervation from the parasympathetic nervous system, and rhinorrhea, a symptom of perennial rhinitis, is in all probability caused by an increased activity in these nerves. Pharmacological blockade with atropine-like compounds will therefore be a logical method of treatment. Rhinorrhoea was brought about in the laboratory in 15 healthy experimental subjects by the intranasal application of methacholine. The experimental subjects were pretreated with Ipratropium (Atrovent, Boehringer-Ingelheim) or placebo in a double-blind trial and it was found that Atrovent could effectively inhibit the methacholine induced hypersecretion for up to 6 hours, without local or systemic side-effects. The methacholine induced hypersecretion could also be effectively blocked in 10 patients with perennial rhinitis, and an open clinical study demonstrated that Atrovent had an effect on the spontaneous rhinorrhoea of these patients.


Successful kidney transplantation in a man with Dacron "trouser" prosthesis.

The case history of a male patient, 62 years old, in preterminal uremia at transplantation with a cadaveric kidney is described. Twelve years before the transplantation he was operated on because of an aortic aneurysm where the abdominal aorta and both iliac arteries were substituted with a Dacron prosthesis. The kidney was anastomosed to this vessel substitute and functioned excellently for more than five years and the patient was completely rehabilitated.


Persisting hypertension after renal artery reconstruction. A follow-up study.

Twenty-four patients with persisting hypertension after renal artery reconstruction were re-investigated 1--8 years after surgery. They underwent renal arteriography, determination of plasma renin activity, renography and renal function studies in order to find the causes of the postoperative hypertension. Restenosis was found in 6 patients, in 3 of whom it was of functional significance according to the positive renin tests (renin ratio greater than 1.5). Positive renin tests were found in 2 other patients. One had occlusion of a renal artery branch and the other hypoplasia of the kidney due to chronic nephritis. No explanation of the persisting hypertension could be found in 19 patients at re-examination. In 10 of them, however, biopsy from the affected kidney obtained during operation showed nephrosclerosis, which may explain the outcome. Fourteen of the 19 patients had negative renin tests preoperatively. These negative tests indicate that renal artery stenosis was not the only cause of hypertension. It may be concluded that the renin test is of the utmost value in the selection of patients for renal artery reconstruction and should always be considered. A biopsy from the contralateral kidney may be necessary in order to detect other causes of hypertension than renal artery stenosis. The importance of re-investigating patients with persisting hypertension is confirmed by the present study.


Antibiotic susceptibility of Neisseria gonorrhoeae isolated in Johannesburg.

The susceptibility of 175 clinical isolates of Neisseria gonorrhoeae to penicillin G, ampicillin, erythromycin, tetracycline and spectinomycin was determined. Almost one-fifth of strains were relatively resistant to penicillin G. Relative resistance to penicillin G was significantly correlated with resistance to ampicillin, tetracycline and erythromycin, but not with resistance to spectinomycin. No penicillinase-producing or spectinomycin-resistant strains were encountered in this study. The relevance of the findings to the management of gonococcal urethritis is discussed.


Six years' experience in a children's hospital genetic clinic.

A genetic clinic has been held once a week at the Red Cross War Memorial Children's Hospital for the past 6 years. During the period 1971--1977, 579 patients were seen, of whom 56% had genetic conditions due to chromosome defects, Mendelian traits or a multifactorial type of inheritance. In these, genetic counselling was a prime importance regarding prognosis, risk of recurrence and possibility of antenatal diagnosis. A further 25% of patients seen had conditions of non-genetic origin and could be reassured, while in the remaining 19% no specific causation was detected.


Huntington's chorea in a black Rhodesian family.

Clinical features suggesting a diagnosis of Huntington's chorea in several siblings in a Black Rhodesian family are described. A progressive and eventually fatal mental deterioration accompanied by gradually worsening choreiform movements has until the present time occurred in only a single generation of this family, which precludes a definitive diagnosis based on the triad of family history, chorea and dementia. It is suggested that Huntington's chorea is the most likely diagnosis.


A new surgical procedure for the treatment of gastroesophageal reflux and hiatal hernia.

A procedure for the treatment of sliding esophageal hiatal hernia and gastroesophageal reflux has been successfully and safely performed upon 46 patients. It is based on the placement of a ringlike silicone prosthesis around the lower part of the esophagus, below the diaphragm.


Management of superior gluteal artery aneurysm by percutaneous balloon catheter occlusion: a case report.

A 19-year-old woman developed an aneurysm of the left superior gluteal artery following laparoscopy. Percutaneous insertion of a balloon catheter into the neck of the aneurysm for 48 hours resulted in permanent thrombosis of the aneurysm. Use of balloon catheters in the management of surgically inaccessible vascular lesions in discussed.


Spectinomycin in the treatment of anal gonorrhea: a retrospective study.

The authors conducted a retrospective study of 125 male patients treated for anal gonorrhea with 4 g of spectinomycin in a social hygiene clinic. Of those treated, nine (7.2%) still had cultures positive for Neisseria gonorrhoeae when tested again five to 14 days after treatment.


[Bacterial skin infections in the dog (author's transl)].

The most common bacterial skin conditions in dogs are reviewed in the present paper. An introductory part on the pathogenesis of pyoderma and some universal morphological dermatological concepts is followed by a systematic study of superficial and deep forms of pyoderma. In addition to the bacterial diagnosis, the results of bacteriological examination of fifty-three dogs with pyoderma submitted to the University Clinic of small animal medicine are reported. Moreover, a guide to the institution of adequate therapy is suggested.


Anomalous mixed lymphocyte culture reactivity between HLA--A, --B, --C, --DR identical siblings.

Complete HLA typing including HLA--A, --B, --C, --DR (D related B cell typing), --D, mixed lymphocyte culture (MLC), and primed lymphocyte testing (PLT), together with complete red blood cell (RBC), glyoxalase (GLO), GBG (Factor B), and phosphoglucomutase 3 (PGM3) typings were performed on a informative family. The five siblings inherited the four possible combinations of parental HLA haplotypes, and two of the siblings were HLA--A, --B, --C and --DR identical. Repeated MLC testing of the family revealed positive mixed lymphocyte reactivity in all combinations. B cell typing for the DR specificities demonstrated no variation from the expected inheritance pattern and specifically no recombination event. GBG and GLO typings militated against a recombination involving the paternal chromosome. HLA--D testing revealed that only one of the HLA--A, --B, --C, and --DR identical siblings gave typing responses to the HLA--Dw3 specificity present on that maternal haplotype. Utilizing HLA haploidentical combinations, lymphocytes were primed against the four parental haplotypes and the non-Dw3 haplotype of interest (Aw24--B8--DRw3--LDY) in the PLT. The sibling inheriting this haplo-type did not restimulate cells primed against the A2--B40--DRW6--LDY specificity. Furthermore, no discrimination was observed in the restimulation of lymphocytes primed against this haplo-type. Possible interpretations of these family data include: a spontaneous mutation, non-major histocompatibility locus (MHC) stimulation, and HLA--DR/D recombination.


HLA--Dw4 and rheumatoid arthritis.

Forty-seven patients with a "definite" or "classical" rheumatoid arthritis according to the ARA criteria were typed for the serologically detectable HLA--A, --B, and --C antigens and 36 of these patients were typed for the HLA--D antigens, Dw1, 2, 3, 4, 6, 7, and 8 by the MLC technique. The frequency of Dw4 was increased to 44.4% in the patients compared to 17.2% in normal controls (P = 8 X 10(-4)). The frequency of Dw1 and Dw7 was also increased although this was only of borderline significance. The frequency of Dw2 was remarkably low, especially in females, which is of interest, as the same antigen has a low frequency in some other autoimmune diseases. No significant deviations of the frequencies of HLA--A, --B, and --C antigens were found in rheumatoid arthritis patients.


[Local nicotinamide therapy in erosive lichen of the oral mucosa].

The local treatment of erosive lichen planus by means of subfocal injections of nicotinamide has been successful in 19 of 25 cases. Nevertheless, it is no true alternative of the systemic chloroquine-triamcinolone treatment. A therapeutical program is presented in which the more riskful use of corticosteroids and chloroquine ranks but second.


Followup of abdominal neourethra.

Abdominal neourethrostomy is a highly satisfactory form of urinary diversion for patients with irreparable urethral stricture or destruction. Normal renal function, structure and urinary continence have been observed in 7 patients for as long as 17 years.


Follow-up study of patients with cerebral palsy.

Of 319 patients with cerebral palsy recalled for reevaluation 15 years after the initial visit, 10 percent had died. Of the living, 55 percent had spasticity, 32 percent had athetosis, 4 percent had ataxia and 9 percent had mixed spasticity and athetosis; 38 percent had an intelligence quotient (IQ) less than 50, 24 percent between 50 and 79, and 38 percent had IQ above 80. There was a high correlation between overall functional outcome and intellectual level. Severity of physical disability, as measured by hand use, mobility and speech, also correlated with dependence, in part because increased severity of the disability was associated with decreased intellectual capacity generally.Twenty-five years after the initial visit, parental attitudes and personality intactness were evaluated (using the Minnesota Multiphasic Personality Inventory [MMPI]) and were correlated with satisfaction with status in life in 28 persons predicted to be independent on the 15-year study. Twenty (72 percent) of the 28 were satisfied with their status in life and of these, 16 were evaluated (with the MMPI) with 70 percent scoring in the normal range; 13 (65 percent) had parents with a positive attitude. Positive attitude was defined as parental feelings that the handicapped child was a worthy, valuable person, to be encouraged and assisted but not isolated from the world of nonhandicapped people. Careful serial assessment by professional teams combined with repeated long-term counseling of families can result in optimal outcome for the disability level involved, due to the primary role parents play in the development of a child's character and behavior.


[Cholestatic jaundice and hypophosphataemia in parenterally-fed premature infants--coincidence or causal connection? (author's transl)].

A report is presented of the chemical pathological findings in 14 premature and one full-term infant receiving almost exclusively parenteral nutrition during the first two weeks of life. Six infants developed cholestatic jaundice. The underlying diseases were the idiopathic respiratory distress syndrome in 10, gastroschisis in 3 and renal insufficiency in 1, while one was an otherwise healthy small for dates infant. After parenteral nutrition had been discontinued obstructive jaundice cleared by the third month of life except in one infant. Apart from the higher glucose intake during the second week, jaundiced infants principally differed from non-jaundiced infants by the development of significant hypophosphataemia. An attempt was made to correlate aetiologically the presence of cholestatic jaundice with the finding of hypophosphataemia on the possible basis of a disturbance of energy metabolism.


[Mucopolysaccharidosis V (Ullrich-Scheie syndrome) (author's transl)].

Mucopolysaccharidosis V (Scheie's syndrome, MPS-IS) is a very rare, autosomal recessively inherited metabolic disease. The degradation of dermatan sulphate and heparan sulphate is disturbed due to alpha-L-iduronidase deficiency, leading to intracellular storage and excessive urinary secretion of these substances. The characteristic clinical features are contractures (claw-like flexion of the fingers), umbilical and inguinal herniae, corneal opacity, hepatomegaly, myocardiopathy and minor skeletal malformations. A patient with Scheie's syndrome is now reported for the first time in Austria; the results of the clinical, biochemical, chromosomal, dermatoglyphic and electron optical investigations are described and discussed.


[Long-term cultures of trophoblast cells and mixed trophoblast cultures as a model for in-vitro studies (author's transl)].

Trophoblast cell-cultures provide a much promising model for qualitative and quantitative in-vitro-examinations of immunological, morphological and biochemical items. In the present paper an attempt has been made to analyze the light-microscopically identificable morphological modifications of the cultured cells under standardized culture-conditions in a temporary order. Furthermore, a number of single cases is presented in which mixed cultures of trophoblast cells with heterologous cells of embryonic origin and with cells derived from adult malignoma were tried.


Mode of binding of pyridoxal phosphate to 5-aminolevulinate synthase.

5-Aminolevulinate synthase of Rhodopseudomonas spheroides interacts with its cofactor, pyridoxal phosphate, and shows an absorption maximum at 430 nm with a probable shoulder at 320--330 nm. The enzyme-PLP complex absorbing at 430 nm is the predominant species at pH 7.2 and can be reduced by NaBH4 at neutral pH with a spectral shift of the absorption maximum to 325 nm. These data suggests the formation of a Schiff base rather than a substituted aldimine between the enzyme and pyridoxal phosphate. The decrease in absorption at 430 nm and increase in absorption at 325 nm by the addition of 2-mercaptoethanol seem to support Schiff base structures for the absorption bands at 430 nm and 320--330 nm. Both pyridoxal phosphate and glycine can equally protect the enzyme from inactivation by sulfhydryl reagents. The inhibition by p-chloromercuribenzoate versus PLP and glycine is noncompetitive and that by N-ethylmaleimide is noncompetitive with glycine and competitive with PLP. These results suggest either a conformational change in the presence of substrates or loss of affinity by the enzyme for PLP, rather than an interaction of PLP with a -SH group of the enzyme. The combined data seems to eliminate the possibility of the formation of a thiohemiacetal or a substituted aldimine and support rather strongly the formation of a Schiff base between the enzyme and pyridoxal phosphate.


Uracil catabolism by Escherichia coli K12S.

Experiments designed to elucidate the mechanism of uracil degradation by E. coli K12S showed that in contrast to uracil, dihydrouracil--the postulated intermediate of a reductive mechanism--did not stimulate the growth of bacteria as additional source of nitrogen, nor it was catabolized to ureido carbon dioxide. However, the chromatographic analysis of dihydrouracil metabolic products, revealed the presence of an enzyme converting dihydrouracil to beta-ureidopropionic acid. Results of growth and biochemical studies indicated that barbituric acid--the postulated intermediate of an oxidative pathway--is not involved in uracil degradation.


The kinetics of formation of metarhodopsin in intact photoreceptors of the fly.

The formation of metarhodopsin in fly photoreceptor no. 1--6 occurs at room temperature with a time constant of 125 microseconds (Q10 approximately 2.5). The formation of rhodopsin is faster by factor of 1/10 to 1/100 at least.


[Antibiotics from basidiomycetes, VI. Merulinic acids A, B, and C, new antibiotics from Merulius tremellosus and Phlebia radiata (author's transl)].

Three new antibiotics, merulinic acids A, B, and C, have been isolated from fruiting bodies of Merulis tremellosus and Phlebia radiata. They are closely related derivatives of beta-resorcylic and salicylic acid, carrying monounsaturated C17-alkyl side chains in 6-position. The merulinic acids are mixtures of the delta8'-compounds with minor amounts of the corresponding delta10'-, dehydro, and dihydro derivatives, separable only by means of HPLC. delta8'-Merulinic acid A (I) was synthesized via a biomimetic cyclization of a linear precursor. The merulinic acids inhibit a variety of bacteria and are not active against fungi. RNA, DNA, and protein synthesis in Bacillus brevis and Ehrlich carcinoma ascites cells are inhibited shortly after the addition of the antibiotics. Almost complete hemolysis of human erythrocytes is caused by 25 microgram/ml of merulinic acid B and C or by 73 microgram/ml of merulinic acid A.


Influence of ions and chelating agents on the haemolymphacetylcholinesterase of Mytilus edulis.

By use of different inhibitors as well as atomic absorption spectrophotometry it has been shown that the haemolymph-acetylcholinesterase (E. c. 3.1.1.7) of the sea mussel Mytilus edulis is a metalloprotein containing 2,95 Fe2+-ions per subunit. All inhibitors used (1,10-phenanthroline, salicylic aldehyde, 2,2'-dipyridyl, 8-hydroxyquinoline) showed a non-competitive inhibition, which was not pH-dependent. Some divalent cations caused a marked increase of the enzyme activity, some heavy metals inhibited the enzyme almost completely; monovalent inorganic cations did not influence the enzyme at all. Besides NaF and Na2SiF6, which showed a non-competitive inhibition comparable to the inhibition observed with the chelating agents, and NaN3, whose mode of action was not identifiable, no inhibition by different mono- and divalent inorganic anions was to be observed. Ammonium ions caused no enzyme inhibition, but length the inhibition power of substituted ammonium ions increased with an increasing C-chain. The influence of some organic solvents on the enzyme activity is demonstrated.


Differentiation of Rhizobium japonicum, III. Inhibition of nitrogenase derepression by chloramphenicol and rifampicin concentrations, not inhibiting growth.

Development of nitrogenase (40--140 nmol C2H4.mg protein-1.h-1) in Rhizobium japonicum 61-A-101 after transfer to special culture conditions (medium 20 P, 2% O2, 10% CO2, 88% N2 in the gas phase) is inhibited by chloramphenicol (6 X 10(-4)--10(-3) M) and by rifampicin (10(-5) M). These concentrations do not inhibit the slow growth of the cells under these conditions with a doubling time of the cell protein and living cell number of 3--5 d. Nitrogenase activity of previously derepressed cells is not inhibited by chloramphenicol. Growth of the cells under air in yeast extract-mannitol-glycerol medium (8 h doubling time) is affected significantly more by chloramphenicol (2.5 X 10(-4) M) than growth under nitrogenase derepressed culture conditions.


1H-NMR investigations on the hydrogen bond formation between the tranquilizers diazepam and nitrazepam and some nucleobases.

The formation of hydrogen bonds between the minor tranquilizers diazepam and nitrazepam and a few nucleobases was studied in deuterochloroform solution by means of proton magnetic resonance spectroscopy. The thermodynamic and spectroscopic data of the associations were evaluated on the basis of a dimer model, using the concentration dependent shifts of the protons involved in hydrogen bonds. The interactions of nitrazepam (deltaH0=-10 to -21 kJ/mol; deltaG025 -0.2 to -7.4 kJ/mol) were found to be stronger than those of diazepam (deltaH0=-10 to -13 kJ/mol; deltaG025=6.0 to 6.4 kJ/mol). The various binding sites of the benzodiazepines for hydrogen bonds are discussed.


Structural aspects of histone complexes and nucleosomes revealed by the accessibility of cysteine side chains.

Chemical modification with 5,5'-dithiobis-(2-nitrobenzoic acid) shows that histone H3 cysteines 110 (chicken) or 96 and 110 (calf) are completely protected in native chromatin and core particles but become unmasked simultaneously during a salt induced dissociation. In whole histone extracted from chicken erythrocyte chromatin, H3 Cys-110 residues experience a uniform environment at 2 M NaCl and pH 5.5. In whole histone extracted under the same conditions from calf thymus, H3 Cys-96 provides a more accessible thiol group than Cys-110. At higher pH values a conformational heterogeneity is induced causing a partial exposure of both cysteine side chains. The kinetic approach described in the present work provides a highly sensitive means to probe the homogeneity of H3 containing protein complexes.


Calculation of the circular dichroism of Chironomus hemoglobin in the light of the quality of its X-ray structure.

For the larval hemoglobin III of the insect Chironomus thummi thummi, the rotational strength of the B (Soret) and Q band is calculated with a monopole/monopole and a dipole/dipole approximation applied to the atomic co-ordinates of the X-ray structures at 2.5 and 1.4 A resolution. In previous calculations using the 2.5 A co-ordinates and with perturbing groups being restricted to aromatic side-chains, the dipole/dipole approximation clearly confirmed the negative sign observed by experiment. The predominant interactions were those of phenylalanine residues. Recalculation with X-ray data refined to the present limits of performance corroborates the negativity of the rotational strength, but now the most important contributions are due to the peptide bonds formerly neglected. Also for the 2.5 A coordinates it is learned that in contrast to earlier expectation the influence of the backbone in this hemoglobin is rather strong. A substantial contribution is further obtained for the perturbation by one of the propionic acid carboxylate groups of the heme. Perspectives and problems of the approach are outlined.


[Reactions of nascent quinones with methyl beta-alanate in glacial acetic acid and in aqueous solution (author's transl)].

In order to generate a model for the reaction of proteins with nascent quinones, catechol and 4-methylcatechol were oxidized with silver-I-oxide in glacial acetic acid or with mushroom tyrosinase (EC 1.10.3.1) in phosphate buffer, respectively. The structures identified indicate that not only the amine reacts with the quinone by the well known addition-oxidation-mechanism, but also that solvent molecules may participate in product formation. The main product of the oxidation of catechol in glacial acid is N-(2-carbomethoxyethyl)-phenoxaz-2,3-dione.