Effect of dichloromethylene diphosphonate on morphology, enzyme activity, and ash content of bones of thyroparathyroidectomized rats. Dichloromethylene diphosphonate (Cl2MDP) was given at doses of 4 mg/kg and 10 mg/kg daily for 7 days to adult thyroparathyroidectomized rats fed a low calcium diet. Primary metaphyseal trabeculae in Cl2MDP-treated rats were more numerous and longer than in controls. The light and electron microscopic appearance of osteoblasts, osteocytes and osteoclasts were unaltered by Cl2MDP. Bone alkaline phosphatase was significantly elevated in rats given Cl2MDP but adenosine triphosphatase activity was unchanged. Bone fat-free weight, fat-free minus ash weight, and bone calcium and phosphorus concentration were reduced significantly in rats given 10 mg/kg Cl2MDP compared to controls. Bone magnesium concentration was significantly elevated in rats given 10 mg/kg Cl2MDP. Serum calcium and phosphorus concentration were lower in Cl2MDP-treated rats. These results suggest that Cl2MDP is capable of altering bone remodeling, enzyme activity and mineral content, without significantly altering bone cell morphology, independent of the effects of parathyroid hormone, calcitonin, and dietary calcium.


Neurospora endoexonuclease and its inactive (precursor?) form. Two nuclease activities which were shown previously to copurify from extracts of log-phase Neurospora mycleia, a single-strand specific endonuclease activity (with DNA and RNA), and a strand nonspecific exonuclease activity (with DNA only) have been found to be associated with a single polypeptide. The enzyme has therefore been classified as an endoexonuclease. In logphase extracts, about 75% of this enzyme was found to exist in an inactive form which was activated in vitro either by endogenous phenylmethylsulfonyl fluoride sensitive proteinase(s) or by exogenous trypsin. The inactive form of endoexonuclease has been purified 45-fold in 15% yield free of the active enzyme. On electrophoresis in 6 M urea--polyacrylamide gels, it migrated at a much slower rate than the active enzyme, indicating that it is a less acidic and(or) larger protein than the active nuclease. The strong adsorption of this inactive enzyme on octyl-Sepharose suggests that the protein may have a relatively large hydrophobic domain. The protein may be a precursor of the active enzyme (a pronuclease) or a strong complex of enzyme with a proteinaceous inhibitor that is not dissociated in 6 M urea or during a variety of chromatographic procedures.


Assembly of the sarcoplasmic reticulum. Synthesis of calsequestrin and the Ca2+ + Mg2+ -adenosine triphosphatase on membrane-bound polyribosomes. Membrane-bound and free polyribosomes were isolated from skeletal muscle of neonatal rats and messages were translated in a rabbit reticulocyte lysate treated with Ca2+ -dependent nuclease to reduce endogenous messenger translation. Newly synthesized calsequestrin and adenosine triphosphatase (ATPase) sere isolated by antibody precipitation, followed by separation of the precipitates in SDS-polyacrylamide gels. Radioactivity in calsequestrin and the ATPase  were counted in gel slices. Calsewuestrin and the ATPase were both found to be synthesized on membrane-bound polyribosomes. Since calsequestrin is a glycoprotein, localized in Golgi regions in early stages of muscle cell differentiation, it is probable that its synthesis follows the pathway for synthesis of secreted proteins except that its destination is the luminal space of a cellular organelle. The disposition of the ATPase during synthesis is, as yet, unknown.


Binding of the Ca2+,Mg2+-activated adenosine triphosphatase of Escherichia coli to phospholipid vesicles. Incubation of the Ca2+,Mg2+-activated adenosine triphosphatase of Escherichia coli with phospholipid vesicles resulted in binding of the enzyme to the lipid. Binding was observed with vesicles of soybean phospholipid (asolectin), phosphatidyglycerol, phosphatidylserine, phosphatidylcholine, and cardiolpin. Binding was not affected by alterations in pH in the range of pH 6.5 to 8.5, by ionic strength, or by the presence of Mg2+. Loss of the delta subunit from the enzyme had no effect on binding. However, removal of the delta and epsilon subunits by treatment of the enzyme with trypsin prevented binding to phospholipid. This treatment also removed a small portion (less than 2000 daltons) of the alpha subunit. It is concluded that the ATPase of E. coli binds to phospholipid vesicles mainly by nonpolar interactions through the alpha and (or) epilson subunits of the enzyme.


Lymphocyte transformation in patients with staged mycosis fungoides and Sézary syndrome. Lymphocyte transformation was studied in patients with mycosis fungoides and the Sézary syndrome with particular reference to the stage of disease. Phytohemagglutinin-induced lymphocyte blastogenesis was normal in stage II, became depressed in stage III and was greatly reduced in stage IV disease. Similar abnormalities were found in patients with the Sézary syndrome once the proportion of abnormal cells in the peripheral blood exceeded 10%. It is concluded that stag III mycosis fungoides is probably a critical period in determining dissemination of the disease.


Comparison of biochemical and biological effects of four nitrosoureas with differing carbamoylating activities. Four chloroethylnitrosoureas with differing degrees of carbamoylating activity were compared for their effects on incorporation of radioactive precursors into macromolecules. The comparisons were made with concentrations that, for each drug, produced a defined biological effect, either an 0.5-log or a 2-log reduction in cloning efficiency from a 1-hr drug exposure. Dose-dependent inhibition of incorporation of labeled precursors into nucleic acids and proteins was observed during the 1-hr drug exposure with either of the two strongly carbamoylating nitrosoureas, 1-3-bis(2-chloroethyl)-u-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea; the most extensive inhibition involved incorporation into DNA. No inhibitions were observed during exposure to a weakly carbamoylating nitrosourea (chlorozotocin) or during exposure to 1-(2-chloroethyl)-1-nitrosourea, a compound the carbamoylating activity of which is not agreed upon. By 4 hr after removal of 1-3-bis(2-chloroethyl)-1-nitrosourea or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea from the extracellular medium, the cells had partially recovered from the earlier inhibition of radioactive thymidine incorporation. This recovery was, however, dependent upon an undefined factor present in serum. The inhibitions that were observed during the 1-hr drug exposure are clearly not essential to the cytotoxic effect of chloroethylnitrosoureas since no inhibitions occurred with two of the four compounds studied.


Susceptibilities of normal and malignant human lung cells in culture to the cytocidal action of antitumor agents. Cultured normal and malignant human lung cells were examined for their different sensitivities to the cytocidal action of nine antitumor and three non-antitumor agents. The malignant cells were killed preferentially at lower concentrations and in a shorter time with each antitumor agent, Adriamycin, neocarzinostatin, bleomycin, actinomycin D, mitomycin C, carboquone, 1-beta-D-arabinofuranosylcytosine, 5-fluorouracil, and 5-fluorodeoxyuridine. Among these, Adriamycin, 5-fluorouracil, and 5-fluoro-deoxyuridine exhibited a higher differential lethal action on the malignant cells than did the other antitumor agents. The two cell lines exhibited little difference in cytolytic sensitivity to non-antitumor cytotoxic agents such as amphotericin B, G-strophanthin, and alph-amanitin.


Alteration of nucleolar dispersion in prophase by 5-FUdR treatment. The action of 5-Fluorodeoxyuridine (FUdR) used as an inhibitor of RNA synthesis on the nucleolar evolution during mitosis, has been studied in meristematic cells. Under FUdR treatment the nucleolar dispersion appears as a continuous process, but generally it is not completed and nucleolar remnants remain throughout the whole mitosis. The nucleolar material which was dispersed is transported by the mitotic chromosomes, and in telophase contributed to the formation of the new nucleolus. The non-dispersed part persisted in the cytoplasm during telophase, coexisting with both the prenucleolar bodies and the new nucleolus which was being formed. Our results suggest the necessity of some kind of RNA synthesis, preferentially blocked by FUdR, for nucleolar dispersion to take place.


[New data on serotonin control of sexual receptivity in the rat]. Serotonin was shown to be involved in the mechanisms whereby olfactory bulbs controlled sexual receptivity between 18 and 19 hrs. on prooestrus in 4-day cyclic female rats.


[Production of prostaglandins in mixed lymphocyte cultures (MLC) between allograft donors and recipients]. A prostaglandin-like activity, as evaluated by a bio-assay using the fundus of Rat stomach, has been demonstrated in supernatants of lymphocyte cultures. This activity undergoes a striking increase in supernatants of mixed cultures of allograft donor and recipient cells, when compared with control supernatants of donor or recipient cells cultured alone. This phenomenon is observed after 24 hrs. of culture. It disappears if the supernatant is dialyzed. Little or no increase in prostaglandin-like activity is found in supernatants of primary mixed lymphocyte cultures (without previous allograft), at lest in the first two days of culture.


An approach to the planning and evaluation of a parental involvement course. This paper reports the organization, content and evaluation of a parental involvement course. The course was designed to fulfill the expressed needs of parents whose children attended a local authority day ESN(S) school. The course was directed by Educational Psychologists working closely with the staff from the special school. One particular method of collecting data on the effectiveness of such a course is illustrated and discussed.


Extraction and analysis of coffee bean allergens. Workers in the coffee industry can develop occupational allergic disease upon exposure to dust associated with coffee manufacturing. Since controversy exists as to the source or chemical nature of these allergens, the mouse model of reaginic antibody production was used to assess the potential sources of allergens in samples obtained from a local coffee manufacturing plant. Mice were immunized with extracts of coffee dust and beans and the resulting reaginic antibody response determined by the passive cutaneous anaphylaxis reaction. Cross-reacting allergens were detected in samples of coffee dust, cleaner can debris and green coffee beans, but not in chaff or roasted coffee beans. None of the allergens detected in coffee samples cross-reacted with extract of castor beans, although these extracts contained the potent castor bean allergen. Green coffee bean allergens partially purified by gel filtration were heterogeneous with respect to molecular size, although quite similar in their reactivity with reaginic antiserum. These results suggest that the green coffee bean is the major source of allergen in coffee manufacturing plants. This allergen is heterogeneous with respect to size and heat lability, and is immunochemically different from the castor bean allergen.


Families with handicapped children--who helps whom and how? So much has been written about handicapped children and their families that one hesitates to add to this, but, equally, relatively little seems to have been discussed about all the various professions who are together concerned with helping these children and their families and how this can best be achieved. Secondly, it seems even more important that the caring professions should be aware of what these families feel about "the help" which they are given--only by knowing this can we all learn how to work more effectively together.


Sensory deprivation in young children.

Sensory deprivation in young children. The importance of the role of intentional movement and active exploration in the development of a child's knowledge concerning his body, his movement and his surrounding is recognized. Senoristasis is defined and the concept applied to deprivation studies with animal and human subjects. It is suggested that the principle can be used to explain behavioural patterns found in two groups of children who may suffer from sensory deprivation; namely those who live in environments which provide insufficient stimulation and those who lack the necessary mobility to explore the environment in which they live. The importance in a young child's development of a rich sensory environment and opportunities for exploration are stressed.


Observations of young normal and handicapped children. An observational study was made of 1-2-year-old children, and of mentally handicapped children functioning at a similar level, to determine the extent to which they involved themselves in play with toys and other objects and the extent to which their day was "empty". Observations of normal children were made in their homes and in day nurseries; observations of mentally handicapped children were made at home, in day care centres (special schools) and in the schools and wards of subnormality hospitals. In no setting were children interacting with adults for more than 20% of their non-routine time. These findings seem to justify concern over independent play with toys and other objects. The handicapped children in all settings had "emptier" days than the normal children, this being accounted for by greater amounts of inattentive handling of objects and self-stimulation and lesser amounts of social interaction and attentive play. However, attentive play scores for the handicapped children varied markedly with setting. In appropriate circumstances, there can be as much spontaneous contact with objects in handicapped children as in normal children at a similar development level. Despite current concern over the effects of day care on the development of very young children, normal children in day nurseries did not differ from normal children at home, either in attentive play scores or in the proportion of nonroutine time spent interacting with adults.


The effects of kwashiorkor serum on lymphocyte transformation in vitro. The serum from twelve children with kwashiorkor was deficient in its ability to support lymphocyte transformation in vitro, whereas lymphocytes from these children responded to phytohaemagglutinin and al-ogeneic lymphocytes in a relatively normal manner when cultured in normal serum. This serum abnormality improved with therapy and could not be clearly correlated with the degree of malnutrition, the presence or absence of infection or other laboratory manifestations of kwashiorkor. These observations indicate that defective cellular immune reactions in kwashiorkor may be symptomatic of a lack of some humoral factor and do not necessarily reflect an intrinsic cellular defect.


Changes in immunological activity of rat lymphoid organs during pregnancy. Immune reactivity in lymhoid organs of rats during the last week of syngeneic (Lewis: L x L) or allogeneic (females Lewis x males Wistar: L x W) pregnancy was compared with that found in non-pregnant animals. The thymus weight was slightly reduced and the response of thymic lymphocytes to phytohaemagglutinin and concanavalin A was slightly, but not significantly, elevated in pregnant rats. By contrast, the response of lymphoid cells from spleen and mesenteric lymph nodes to the mitogens was reduced in rats during advanced pregnancy. The immune response of lymphocytes from pregnant L x W rats to allogenic (Brown-Norway: BN) or semiallogeneic (W) irradiated cells was tested by the mixed lymphocyte culture (MLC) assay. The MLC response of para-aortic lymph nodes towards the unrelated BN cells was elevated over that of non-pregnant rats on day 15 of pregnancy. No significant enhancement was observed at the same time in the MLC response of mesenteric lymph nodes. On day 20 of pregnancy, a reduced MLC response towards BN cells was found in the mesenteric and para-aortic lymph nodes. On day 15 of pregnancy, the MLC response of mesenteric and, more markedly, that of para-aortic lymph nodes to paternal (W) cells was enhanced, as compared to that of non-pregnant rats. On day 20 of pregnancy, the response of mesenteric lymph nodes was suppressed, while the response of para-aortic lymph nodes was similar to that found in non-pregnant rats. Since the latter lymph nodes are the most directly exposed to antigenic stimulation from the uterus, it seems unlikely that the suppression in response to T-cell mitogens observed in the spleen and mesenteric lymph nodes during pregnancy accounts for the survival of the foetus. It seems more plausible that local factors in the vicinity of the uterus protect the foetus from being rejected.


Occupational allergic contact dermatitis to isophorone diamine (IPD) used as an epoxy resin hardener. Three patients employed in the manufacture of plastic tennis rackets developed allergic contact dermatitis to isophorone diamine (IPD), an epoxy resin hardener, and concomitantly to epoxy resin. Patch tests were positive to IPD at 1, 2 and 5% in olive oil and to IPD at 1, 2 and 5% in ethanol. Investigations were conducted in control subjects to confirm the allergic nature of reactions. A review of the literature about IPD and related compounds is presented.


Alantolactone sensitivity in chrysanthemum contact dermatitis. A case of occupational chrysanthemum contact dermatitis is reported. Patch tests showed the patient to be sensitized to Chrysanthemum morifolium (Chr M) leaves, flowers, and stems (alcoholic extracts) and to alantolactone. An attempt at desensitization appears to have been successful. Gas chromatography indicated the presence of alantolactone in all the various parts of Chr M, mostly in the flowers. The "maximization test" succeeded in sensitizing guinea pigs to alantolactone.


Occupational dermatitis from DNFB with cross sensitivity to DNCB. A case of occupational dermatitis in a research biochemist provoked by the Sanger reagent (DNFB), used to mark the terminal amino acid of polypeptides and proteins, has been studied. The patient showed cross sensitivity to DNCB.


Occupational allergic contact dermatitis to virginiamycin, an antibiotic used as a food additive for pigs and poultry. A warehouseman aged 31 working in a pharmaceutical factory got an occupational contact dermatitis to virginiamycin (factor M), an antibiotic used as a food additive for pigs and poultry. A review is made of contact dermatitis to virginiamycin and to pristinamycin.


The effect of chondrocyte growth factor on membrane transport by articular chondrocytes in monolayer culture. Chondrocyte growth factor (CGF), a contaminant of pituitary glycoprotein hormones, stimulates growth of cultured lapine articular chondrocytes while depressing SO4-proteoglycan synthesis. To study its effect on membrane transport, NIH-bTSH and two other preparations with comparable CGF activity were employed. In early log phase (36 hr) cultures CGF (64 microgram/ml) did not alter thymidine (dThd) uptake during the first 5 min. By 15 min however, TCA-precipitable dThd was 4-fold greater than in controls while the TCA-soluble fraction remained the same. CGF increased deoxy-glucose (DG) uptake in 36-hr old cultures. At 66 hr, CGF reduced DG transport. The transport of cycloleucine (CL) and aminoisobutyric acid (AIB) was reduced by CGF in 36 and 66-hr old cultures. There was a dose dependency between CGF concentration, the lowered uptake of DG, CL and AIB, and cell protein content. The effect of CGF on DG transport and dThd incorporation into DNA was not immediate but required prior exposure of the cells to CGF. CGF did not alter DG transport in rabbit or mouse fibrocytes or Chang liver cells. This and the reported finding that pituitary fibroblast growth factor (FGF), increases amino acid transport in other cells suggests that the biological specificity of CGF may not be identical to that of FGF.


The multicomposite structure of tendon.

The multicomposite structure of tendon. A revised morphological model for the crimp structure of tendon is presented. The 300-500 mu diameter tendons of the mature rat tail are comprised of from one to more than ten substructures, called fascicles, of 80-320 mu diameter. Fascicles each possess a "crimp structure" demonstrable in the polarizing microscope and neighboring fascicles within a tendon usually exhibit crimp registry. The fascicle itself is shown to be a cylindrical array of planar-zig-zag crimped 500-5000 A diameter collagen fibrils. The approximate cylindrical symmetry of the fascicle is domonstrated by SEM not equal to and polarizing optical microscopy. A method of replacing native water with other liquids of refractive index near to that of collagen is utilized to reduce or eliminate light diffusion and therby greatly improve OM observations. Small bunches of collagen fibrils removed from the tendon are shown to exhibit the simple planar zig-zag morphology described in previous literature. The planar crimping of collagen fibrils and their assemblage into cylindrically symmetric fascicles is verified by small angle X-ray diffraction.


Ultrastructural deformation of collagen. Ultrastructure deformation studies of reconstituted and native rat tail tendon collagen revealed that deformation occurs primarily in the non-staining and presumably non-polar proline rich regions for all ages examined. At low deformation (tension and compression) the deformation occurs somewhat more between the a2 and b1 and b2 and c2 bands than within the rest of the d period. At moderate elongations (greater than 40%), the deformation becomes localized between the c2 and d bands, with subfibrils on the order of 3-15 nm being drawn across the openings between the c2 and d bands. At high elongations (100% or greater) d period splitting occur on a regular basis between the c2 and d bands, along with a retraction of the 64 nm repeat period into 60 nm segments. It is in this deformation region that the effects of molecular slip and the apparent association of the acid mucopolysaccharides can be noted. These results suggest that crosslinking, if increasing as a function of age, does not affect the deformation characteristics of the individual fibrils and that changes with age in mechanical properties should be sought in changes in the fibril size and their interaction with the surrounding matrix.


Simultaneous morphological and stress-strain studies of the fibrous components in wet heart valve leaflet tissue. Simultaneous morphological and stress-strain studies have been carried out on heart valve leaflet tissue maintained in its unaltered functional condition. A microtensile tissue testing device is described which inserts directly into the stage of an optical microscope fitted with a Nomarski interference contrast facility. Glutaraldehyde fixation of tissue subjected to different levels of loading reveals that the current stressed state of the collagen fibers is "frozen" in by crosslinking process, and as a consequence marked alterations in the preserved tissue properties are produced. This is shown to be relevant to the preparation of the glutaraldehyde treated heterograft heart valve. The mechanical roles of the collagen and elastin components are investigated and a "complementation" mechanism is postulated whereby the widely different mechanical properties of the two types of fibers are combined in a non-competing manner to produce a diversity of composite tissue characteristics.


The determination of small amounts of collagen hydroxylysyl glycosides. Glucosylgalactosylhydroxylysine (GlcGalHyl) and galactosylhydroxylysine (GalHyl) in alkaline hydrolysates of insoluble collagens were separated on 130 x 0.6 cm and 45 x 0.6 cm columns of Chromobeads A resin (Technicon) and simultaneous analyses with ninhydrin and orcinol-H2SO4 were performed. Ninhydrin, which is the standard reagent in existing methods, gave erroneously high results with both columns due to overlapping, resistant peptides. A rapid and more accurate procedure employing the smaller column, the orcinol-H2SO4 reagent and a new internal standard was developed. The losses of the glycosides in alkaline hydrolysis, especially in the presence of collagen peptides, were much larger than had been reported previously. A shorter alkaline hydrolysis following digestion of the collagen with papain was effective and allowed more reliable corrections to be made. Purging with nitrogen reduced the losses further. Mature bovine skin collagen contained less GlcGalHyl than embryonic skin collagen whereas the differences in GalHyl were insignificant.


Evidence for increased protease activity secreted from cultured fibroblasts from patients with pseudoxanthoma elasticum. Abnormal polyanion metabolism in cultured fibroblasts from patients with pseudoxanthoma elasticum (PXE) was studied by incubating normal and PXE fibroblasts in culture medium containing 35SO4 for 96 hr and measuring differences in secreted 35SO4-labelled proteoglycans (35S-PG). PXE medium contained less high molecular weight (MW) 35S-PG and more low MW 35S-labelled molecules than normal medium. Addition of diisopropylfluorophosphate (DFP), a serine protease inhibitor, to the media after the 96 hr incubation resulted in no change in the MW distribution of 35SO4-labelled molecules in normal media. However, DFP treated PXE medium contained significantly more high MW 35S-PG than either untreated PXE medium or DFP treated normal medium. High MW 35S-PG was isolated from PXE fibroblast culture medium and incubated with serum free medium from either normal or PXE fibroblast cultures. There was significantly more degradation of this 35S-PG to low MW 35S-labelled molecules by PXE medium than by normal medium. 32P-DFP, which binds to the active site of serine proteases, was added to serum free medium from normal and PXE cultures. The specific radioactivity of PXE medium was 4 times greater than that of normal medium. These lines of evidence are consistent with the hypothesis that a biochemical defect in cultured PXE fibroblasts is the increased secretion of a serine protease that can degrade sulfated proteoglycans.


Chromosomal polymorphism in Equus hemionus. The first cytogenetic studies of the Turkmenian kulan, Equus hemionus kulan, are reported, and a polymorphism in diploid chromosome number is described. Chromosome fusion is apparently involved in the alterations of the karyotype of E. hemionus kulan (2n = 55, 54) when compared to the karyotype of the onager, E. hemionus onager (2n = 56). Additionally, the rearrangement involved has been identified in animals unrelated through captive breeding; inheritance of the fusion chromosomes has also been observed.


Immunohistochemical changes of somatostatin cells in the pancreatic islets of rats after streptozotocin administration. By the enzyme-labeled antibody method, cells containing somatostatin (SRIF) as well as insulin or glucagon were identified in pancreatic islets of the rat. SRIF antiserum was raised in rabbits followin immunization with synthetic SRIF coupled with human serum alpha-globulin and did not cross-react with hypothalamic, pituitary or gastrointestinal hormones using our immunoassay method. In the control rats, SRIF-containing cells were scattered in the periphery of the islets in close proximity to the outer glucagon containing cells. These latter cells were distributed in the outermost periphery of the islets. Insulin-containing cells were located in the central portion of the islets and dominantly occupied most of the islet. In the streptozotocin-diabetic rat, SRIF-containing cells were significantly increased in number whereas insulin-containing cells were markedly reduced. It is suggested from these findings that the number as well as the distribution of SRIF-, insulin- and glucagon-containing cells was important to the physiological and pathophysiological functioning of the islet.


On the kinetics of the reaction between human antiplasmin and a low-molecular-weight form of plasmin. The reaction between antiplasmin (A) and a low-molecular-weight form of plasmin (P) proceeds in at least two steps: a fast reversible second-order reaction followed by a slower irreversible first-order transition, and may be represented by: P +A k1 in equilibrium k-1 PA k2 leads to PA'. The low-Mr plasmin, which is obtained by limited elastase digestion, is composed of an intact B chain and a small A chain lacking the lysine-binding sites. The k1 of the reaction is (6.5 +/- 0.5) x 10(5) M-1 s-1 which is 30--60 times smaller than that for normal plasmin and antiplasmin. The dissociation constant of the first step is 1.9 x 10(-9) M which is 10 times higher than for normal plasmin and antiplasmin. The rate constant of the second step is (4.2 +/- 0.2) x 10(-3) s-1 for both normal and low-Mr plasmin. Low Mr plasmin which has substrate bound to its active site does not react or reacts only very slowly with antiplasmin. The reaction rate, however, is only slightly influenced by 6-aminohexanoic acid in concentrations up to 1 mM which decrease the reaction rate of normal plasmin approximately 50-fold. The findings further indicate that the lysine-binding site(s) of plasmin are of great importance for the rate of its reaction with antiplasmin.


Polyamine-induced actin polymerization.

Polyamine-induced actin polymerization. Muscle actin has been found to polymerize reversibly upon addition of low concentrations of polyamines. This polymerization, studied by centrifugation, has shown a linear relationship between the actin polymerization yield and the chain length of the polyamine. Among the biological polyamines tested, spermidine and spermine are the most efficient. The polymerization of actin can also be induced by the corresponding mono or diguanidine derivatives of these polyamines but monoamines or amino acids are inactive at the same concentration. The transformation of actin from a globular to a fibrous from upon addition of spermidine is also demonstrated by the changes in the near-ultraviolet circular dichoroic spectrum of this protein. Moreover, the polyamine-induced F -actin exhibits the same properties as the salt-induced F -actin: it strongly activates the Mg2+ -ATPase of myosin, its specific viscosity is enhanced to the same extent and electron micrographs show homogeneous thin filaments.


Reaction mechanism of non-allosteric phosphofructokinase. The reaction mechanism of the non-allosteric phosphofructokinase from Lactobacillus plantarum was investigated by initial-rate bisubstrate kinetics and product inhibition kinetics adn by the measurement of equilibrium isotope exchange in the presence of various substrate and product concentrations. The reaction mechanism is clearly sequential. The product inhibition and equilibrium isotope-exchange patterns are consistent with an ordered bi-bi reaction sequence with fructose 6-phosphate as the leading substrate and ADP as the first product released from the enzyme.


8-Azido-adenosine 5'-triphosphate as a photoaffinity label for bacterial F1 ATPase. 1. 8-Azido-adenosine 5'-triphosphate (n83ATP) is a suitable photoaffinity label for F1 ATPase from Micrococcus luteus. The nucleotide is a substrate in the presence of bivalent cations and inhibits the enzyme irreversibly upon irradiation with ultraviolet light above 300 nm. 2. More than 80% of the label is covalently bound to the beta subunits in the presence of bivalent cations. Labeling and inactivation is decreased by protection with ADP, ATP or adenyl-5'-yl imidodiphosphate. To a much smaller degree the alpha subunits also become labeled. 3. n83AMP does not specifically bind to the beta subunits upon irradiation. Like n83ATP and n83ADP, it also labels the alpha subunits to a small extent. 4. The F1 ATPase is inactivated after a single beta subunit per F1 complex has become labeled. A cooperativity of the beta subunits carrying nucleotide binding sites is suggested.


Initial events of light-dependent ATP synthesis in spinach subchloroplast particles. The kinetics of 32Pi incorporation into adenine nucleotides by subchloroplast particles in the light is studied with a continuous flow apparatus allowing measurements between 3 and 200 ms. After a short lag time from 1 to 3 ms ATP synthesis proceeds with a constant rate. During the first few milliseconds a faster labelling of ADP is detected. This labelling of ADP reaches a constant level up to 1 molecule ADP labelled per molecule of coupling factor present. The labelling pattern in ATP indicates that the labelled ADP does not equilibrate with free ADP. The addition of 32Pi to a phosphorylating system during the light phase (32Pi pulse) exhibits unchanged kinetic characteristics for labelling of ATP and ADP. These results indicate a phosphorylation of AMP to ADP being an intermediate step in photophosphorylation. In experiments carried out in the dark no label is found in ATP within the time analysed. However the labelling of ADP occurs in the same way as in the light.


The dicyclohexylcarbodiimide-binding protein of rat liver mitochondria as a product of the mitochondrial protein synthesis. A product of mitochondrial protein synthesis in rat liver mitochondria, characterized by a low molecular weight (Mr is less than 10000) and an unusually high hydrophobicity, has been identified as the dicyclohexylcarbodiimide-binding protein and as a peptide of the hydrophobic sector of the mitochondrial ATPase complex. The purified protein still possesses the ability of bind dicyclohexylcarbodiimide.


Evaluation of chamber and myocardial compliance in pressure overload hypertrophy. The effect of pressure overload hypertrophy on isolated myocardial muscle preparations remains controversial. Moreover, the ultimate effect on the diastolic function of the left ventricle in the pressure overload states of man and the relative changes in chamber and myocardial stiffness remain incompletely studied. We review here the methods as well as results of dynamic diastolic stiffness analysis in 18 patients with valvular aortic stenosis and 5 normal subjects based upon the pressure-volume and circumferential stress-strain relations obtained by simultaneous left ventricular micromanometry and high-speed cineangiography. In addition, complementary analysis of dynamic diastolic stiffness findings in chronically instrumented animals, before and after the induction of hypertrophy, are reviewed. Increased diastolic intracavitary pressures during concentric hypertrophy were found to be attributable to both increased muscle mass as well as enhanced myocardial stiffness. However, both chamber and myocardial stiffness changes during hypertrophy were quite variable with some patients (and 2 of 6 dogs) showing no enhancement of stiffness parameters. In the chronically instrumented animals where dynamic, instantaneous stiffness changes and strain rates are more readily studied than in man, viscous (velocity dependent) effects were noted to be enhanced during hypertrophy. It is postulated that variable increases in diastolic stiffness during concentric hypertrophy in the intact heart results from varying degrees of myofiber architectural distortion and/or inconstant collagen content, and further correlative studies of morphology and mechanical function are needed.


Relaxation in heart muscle: some morphological and biochemical considerations. In striated muscle the transition from the active to the resting state requires a reduction in the cytosolic concentration of ionized calcium (Ca2+), achieved by a rapid sequestration into the sarcoplasmic reticulum and the return of some Ca2+ to the extracellular phase. Morphologically the sarcoplasmic reticulum (SR) is heterogeneous. Specialized regions occur whenever the limiting membranes of the SR approach those of the plasmalemma. These specializations include a narrowed lumen, relative to that found in non-specialized parts of the SR, the presence of electron-dense 'feet' extending into the junctional gap separating the facing membranes of the plasmalemma and the SR, and the occurrence of intraluminal densities. These specializations can assume a variety of configurations, some of which appear to be species specific. The accumulation of Ca2+ by the SR, is a rapid process and the required energy is derived from the hydrolysis of ATP via a Ca2+-activated ATPase in the limiting membranes of the SR. Impaired relaxation in heart muscle can result either from an inadequate supply of ATP, Ca2+-overload, failure of the Ca2+-activated ATPase enzyme, leakage of Ca2+ from the SR, or the failure of the cell to return Ca2+ back into the extracellular phase. Evidence will be presented to show that the rise in resting tension that is caused by an inadequate supply of oxygen involves a mobilization of Ca2+ from the internal stores, and insufficient ATP to drive the ATPase enzyme in the SR, rather than a malfunction of the enzyme. Likewise ouabain-induced contractures have been found to be associated with diminished tissue stores of ATP, the rise in tissue Ca2+ occurring as a late phenomenon.


Incidence and prognosis of rheumatic carditis in a Belgian hospital. A 10-yr review (1965-1974). 106 cases of first attack of acute rheumatic fever were recorded during a decade (ending in 1974) in a Brussels pediatric clinic. 56 patients were Belgian and 50 were children of immigrants. The incidence of acute carditis was 23% among the former, 46% among the latter (P less than or equal to 0.01), and 34% among the whole group. The frequency of residual heart disease after a 3-yr antistreptococcal prophylaxis fell to 20% among the whole group. The difference in morbidity observed between Belgian children and children of immigrants calls for a prospective epidemiological study.


Effect of d-amphetamine on tryptophan and other aromatic amino acids in brain. The investigation examined the mechanism of the increase in brain tryptophan concentration of rats treated with d-amphetamine. Certain well recognised influences upon brain tryptophan have been excluded as responsible. Thus, the effect is not associated with changes in the plasma concentrations of NEFA or free tryptophan. It is probably not due to a tryptophan-specific mechanism, because amphetamine increases the ratio of brain/plasma concentrations not only of tryptophan but also of tyrosine and phenylalanine. The concentration ratios for liver/plasma also rose, as did the liver tryptophan concentration, but these changes were less striking than for brain. Both alpha- and beta-adrenergic blocking drugs opposed the changes in brain, but in different ways. Thus, after treatment of rats with phentolamine, amphetamine decreased the plasma concentrations of the three aromatic amino acids; however, as the brain concentrations were little altered, the brain/plasma concentration ratios rose. Propranolol (and the dopamine blocker pimozide) opposed the increases of the ratios, so that the brain concentrations again altered little. The increased brain/plasma ratios resulting from the administration of amphetamine were associated with hyperthermia. Propranolol, pimozide and the diabetogenic drug streptozotocin opposed the changes in both plasma and brain; phentolamine affected neither. Despite the increase in brain tryptophan caused by amphetamine this drug had relatively little concurrent effect on 5HT synthesis. Experiments with adrenergic blockers suggest that the small rise of plasma insulin after the injection of amphetamine into rats did not cause the brain changes; these are probably a consequence of hyperthermia. The findings with streptozotocin suggest that the hyperthermic effect of amphetamine is manifested only in states of normal insulin secretion.


Lack of interaction of spironolactone with ouabain guinea pig isolated heart muscle preparations. The effect of spironolactone on ouabain action was studied in experiments on guinea pig isolated heart muscle preparations. There was no effect of spironolactone on the ouabain-induced positive inotropic or toxic effects in isolated papillary muscles. This was accompanied by a lack of spironolactone effect on myocardial ouabain uptake. Only rather high spironolactone concentrations (1 X 10(-4) M) led to a reduced cardiac ouabain uptake (about 10%). The subcellular distribution pattern of ouabain, however, remained unchanged under these conditions. Studies on ouabain binding to a cardiac NaK-ATPase supported the conclusion that a direct interaction of spironolactone and cardiac glycosides at the myocardium could be ruled out.


[The effect of concomitant administration of dehydroepiandrosterone with progesterone on decidual growth in the rat (author's transl)]. Studies were made on the effect of concomitant administration of dehydroepiandrosterone acetate (DHA-Ac) with progesterone on decidual growth in the rat. Virgin female rats of Wistar strain weighing about 250 g were used. Daily vaginal smears were recorded and, during the time of vaginal cornification, the animals were made pseudopregnant by tapping the uterine cervix. Day 1 of the pseudopregnancy was designated as the day that the vaginal smears contained primarily leucocytes. On day 4 of the pseudopregnancy, each animal was laparotomized midventrally, and bilateral ovariectomy and scratching of the uterine endometrium were performed. Progesterone, alone or in combination with DHA-Ac, was injected from day 4 of the pseudopregnancy (immediately after ovariectomy) through day 8. On day 9 of the pseudopregnancy all animals were killed. The weights of the uterus, and the deciduoma-inducing score, etc, were estimated. Massive deciduomata weighing 2768 +/- 84 mg per uterus were induced in intact pseudopregnant rats. Treatment with 2 mg progesterone evoked maximal responses of only 754 +/- 101 mg. The concomitant administration of 20 mg DHA-Ac with 2 mg progesterone reproduced the decidual weight observed in intact rats, but 2.5 mg or 5 mg DHA-Ac in combination with 2 mg progesterone was only slightly effective. The weights of the uterus, the deciduoma-inducing score, the histological findings, and the effects of the DHA-Ac were discussed.


[The determination of plasma and urinary estetrol (E4) for assessing fetal and neonatal prognosis (author's transl)]. As estetrol (E4) is believed to be the steroid most likely to wholly dependent on fetal origin, we developed a radiommunoassay for unconjugated and conjugated E4 (E4-U and E4-G) and investigated plasma and urinary levels serially throughout the second half of pregnancy to establish their validity by means of monitoring or screening tests to assess fetal well-being. E4 exhibits a remarkable increase during the latter half of pregnancy. At term, the mean E4-U level in maternal peripheral plasma was 0.67 +/- 0.33 ng/ml, a five fold increase from that at 28 weeks; E4-G was 4.57 +/- 2.84 ng/ml, showing a four fold increase; and E4-G levels in maternal urine were 1.68 +/- 0.96 mg/day, showing a three fold increase from that at 28 weeks. E4-U and E4-G levels showed no diurnal change. The coefficient of the correlation between plasma E4-U and E4-G was 0.699, which is satisfactory, but no correlation was found between urinary and plasma E4 levels. A significant correlation was shown between maternal and umbilical E4-U (r=0.820) and E4-G (r=0.608). No relationships between E4 levels and birth weight were detected. Pre-eclampsia, Rh-isoimmunization and diabetes mellitus are common complications of pregnancy which may cause latent fetal distress. Prenatal fetal assessment was performed by serial daily evaluations of these E4 values. In pre-eclampsia resulting in a small full term baby, E4 levels were mostly below normal mean values or failed to show an increased pattern. In addition, the E4 levels decreased in one case of neonatal death. In Rh-isoimmunization, plasma E4-G levels were lower in the group affected severely by the hemolytic desease. In a patient with diabetes mellitus delivered of a healthy baby, E4 levels were within the range of a normal pregnancy. In order to evaluate fetal and placental reserve capacities as well as feto-placental function, the dehydroepiandrosterone sulfate (DHA-S) loading test was performed by loading selected subjects with 50 mg of DHA-S, then serially measuring the E4 in the maternal plasma and urine. Intravenous infusion of 50 mg of DHA-S was completed in 60 minutes. A rapid and sharp increase of plasma E4 was observed, reaching maximal concentrations at 120 minutes in normal pregnancies. However, urinary levels showed patterns similar to those reported for estriol (E3). In some abnormal pregnancies, no increased or delayed patterns were observed in plasma E4-G levels, while the serial levels remained within the normal range. This possibly suggests that in these pregnancies, fetal functions had been inhibited or had reached their limit. It is concluded that the simultaneous determinations of serial E4 levels accompanied by the DHA-S loading test may be of value in assessing fetal well-being and reserve capacity and may therefore improve fetal and neonatal prognosis in abnormal pregnancies.


Effect of Propionibacterium acnes or BCG on enzyme activities in spleen lymphocytes of Donryu strain rats. Immunopotentiated rats, which were injected with Propionibacterium acnes or BCG, had the 50% survival twice as long as those in untreated controls after intravenous inoculation of Sato lung carcinoma (SLC) cells. The amount of labeled tumor cells in the lung of the adjuvant-treated rats decreased significantly in the first 20 hr after intravenous injection of 51Cr-labeled tumor cells compared to that of control animals. The elevated activities of ATPase and acid phosphatase in the whole nucleated spleen cells as well as spleen lymphocytes separated by Ficoll-Conray gradient were also demonstrated in adjuvant-treated groups. These data suggested that the elevation of ATPase and acid phosphatase activities in nucleated spleen cells as well as spleen lymphocytes has an important role for the suppression of tumor growth in adjuvant-treated rats.


DNA repair in human leukemic leucocytes treated with neocarzinostatin. Neocarzinostatin, an antineoplastic agent which is effective against human leukemia, induced unscheduled DNA synthesis in human leukemic leucocytes. This indicated the existence of repair process against at least a part of DNA damage caused by the agent. The extent of unscheduled DNA synthesis increased in parallel with the concentration of Neocarzinostatin up to 5 microgram/ml, followed by a decline at more than 5 microgram/ml. Leucocytes from patients with chronic myelogenous leukemia had higher repair synthesis after Neocarzinostatin treatment compared to those from patients with acute leukemia. The amount of repair synthesis correlated well with the proportion of immature leucocytes among chronic myelogenous leukemia samples, but such correlation was not found among acute leukemia samples.


Mixed lymphocyte--tumor cell culture reaction in cancer patients. To measure immunological reactivity or recognition of tumor antigens, mixed lymphocyte--tumor cell culture reaction (MLTR) was studied using a micromethod. The peripheral lymphocytes of cancer patients were mixed in vitro with autochthonous tumor cells that had been irradiated with 60Co at a dose of 6,000 rad just before use. The lymphocyte blastogenic response was estimated by the incorporation of 3H-thymidine in the acid-insoluble fraction and expressed as counts per minute. The stimulation index equal to or greater than 2.0 was arbitrarily expressed as positive blastogenic response in the present experiment. Positive blastogenic responses to autochthonous tumor cells were observed in 10 of 34 patients with various solid tumors. The intensity of blastogenic response to tumor cells was correlated with that of the non-specific responses to PHA (r=0.4732, P less than 0.01). These results indicated that non-self tumor-associated antigens, which could induce in vitro blastogenic response of autologous lymphocytes, were present in some part of human tumors.


Laparoscopic cholangiography in the diagnosis of cholestasis: experience with 103 cases. The results of 103 laparoscopic cholangiographies performed in patients with cholestasis are reported and the technique used is described. Minimal or no secondary effects were noted. A correct diagnosis was reached in 92 cases, 53 of which presented cholestasis of an extrahepatic nature and 39 of intrahepatic origin. In the latter group, the technique made exploratory laparotomy unnecessary. The procedure allows a roentgenologic examination of the biliary system, a direct evaluation of the liver and gallbladder and, if necessary, a liver biopsy.


[Prenatal diagnosis in pregnancies at advanced maternal age (author's transl)]. Among 113 prenatal diagnoses in pregnancies at advanced maternal age (mothers older than 37 years) 7 aberrant fetal karyotypes were found (6.2%). Detailed reports of one case of trisomy 21, 18 and 13 each, as well as of XXY-, XYY- and XXX gonosomal constitution respectively are presented in the following. The frequency and severity of chromosome aberrations occurring in fetuses from elder women are discussed with respect to data from the literature. It seems that this group bears a higher risk for chromosomally abnormal offspring than has been suggested before.


An apparent connection between histidine, recombination, and repair in Neurospora. Two mutants of Neurospora crassa, uvs-3 and mei-3, share four properties--UV sensitivity, inhibition by histidine, meiotic blockage when homozygous, and increased duplication instability (due to mitotic crossing over, to deletions or to both). The present paper shows that a third nonallelic mutant, uvs-6, exhibits the same four properties.--Also, the instability of duplications in the absence of any UV-sensitive mutant is increased by the presence of histidine in the growth medium.


[Medico-genetic study of the population of the Samarkand region. II. Population-genetic description of 4 kishlaks of the Urgut district]. This report is a second one in a series of works devoted to the medico-genetical screening of Uzbekistan populations. The paper comprises the results of the analysis of the populational structure of one of the village councils (soviets) of the Urgut District of the Samarkand Region. The main parameters of the population studied were as follows: total number 1529 persons, the average number of inhabitants of one village--328. The proportion of the inhabitants studied--56%, the average number of persons per family--5.22; the average period between subsequent generations--30-35 years, the gametic index--0.8, the inbreeding coefficient inferred from pedigrees--0.018899--0.00781, Fst = 0.03577, the average genetic distanse according to Edwards--0.0231-0.0671. The distribution of Mendelian markers (ABO, Rh, Hp and Ptc) was studied. The observed ratio between a high degree of inbreeding and a relatively low extent of isolation of populations permits to explain satisfactorily the distribution and frequencies of hereditary pathology in the Urgut District of the Samarkand Region pointed out in the previous report.


[Abdominal laparoscopy, experience in 1,400 cases studied]. Laparoscopy is a simple and sure method of diagnosis for the gastroenterologist. Laparascopy does not oppose exploratory laparatomy and can often substitute it advantageously. In fact it causes less morbility and mortality, less discomfort to the patient, requires only local anesthesia, permits leaving the hospital within 4 hours, and when done by an experienced and able person provides data of great usefulness in diagnosis, prognosis, and treatment. A laparoscopy can confirm or refute various doubtful clinical diagnoses. It is hoped that the thecnic demonstrated and seen through the laparoscopy will lead to a greater use of this valuable diagnostic examination.


[Diagnosis of acute abdomen by means of laparoscopy (experience in 6,400 cases)]. A study of 6,400 cases of Emergency Laparascopy (E.L.) was made in the Instituto de Gastroenterología de Habana, Cuba. The objective of the E.L. is to provide a diagnosis when other methods have been unable to do so. The most frequent diseases found were: gynecological problems, acute appendicities, and acute cholecystopathies. The E.L. is of great usefulness as in many cases an exact diagnosis is possible thus avoiding unnecessary surgery. The reliability of the method is good, permitting an exact diagnosis in 98% of the cases. In all the authors' cases the diagnosis was confirmed by either surgery or the evolution of the disease. The authors recommend the creation of emergency laparascopy services in which all the resources would be centralized: sufficient medical staff to ensure 24-hour service, specialized technicians, and the necessary material. They add that even though in their country it is of little importance, their experience leads to the conclusion that this type of organization is medically profitable.


The effect of various dietary restricted regimes on some immunological parameters of mice. To test the effect of dietary protein restriction on mitogenesis and the mixed leukocyte reaction in the mouse immune system two protocols were followed: 1) a 4% protein diet ad libitum and 2) a standard diet of 24% protein fed only on alternate days, Monday, Wednesday, and Friday (intermittent feeding). The effect of dietary restriction was tested on weanling animals, placed on the dietary regimes for 1 and 6 month periods and adult animals (17 months of age) for 6 months of restriction. The results indicate that dietary restriction has a profoundly suppressive effect on mitogenesis and MLC1 during the first months of growth (i.e. weanling animals tested after 1 month of restriction). After 6 months of continued restriction suppression was no longer observed in the weanling animals. The 17 month old animals placed on restricted dietary regimes for 6 months showed results similar to the control group. The intermittently fed animals present a more complex picture. Initial suppression of the responses, observed in weanling animals after 1 month of restriction gave way to responses which are significantly higher than control levels after 6 months of dietary restriction. The results are discussed in terms of a general model of immunological stress.


Experimental spongy degeneration of the white matter induced by 6-aminonicotinamide intoxication. Spongy state and degeneration of the white matter in the 6-aminonicotinamide intoxicated rats were studied neuropathologically and electromicroscopically. Young albino rats, four weeks of age, received 0.1% of 6-aminonicotinamide solution intraperitoneally as a single dose of 10 mg/Kg of body weight. Four hours after the administration, paralysis of the hind limbs occurred in the rats. Neuropathological investigations revealed a characteristic spongy and degenerative change of white matter as well as gray matter of the central nervous system. Corpus callosum, cerebellar cortex, and optic nerves showed edematous and spongy degeneration in the early stage of the experiment. Ultrastructural changes of myelin sheath were initially seen in the vicinity of severely damaged oligodendrocytes. The vacuoles in the myelin, i.e. intramyelinic vacuoles, were formed by splitting between the innermost myelin lamellae and axon. Axons remained usually unchanged in the early stage. The pathogenesis of ultrastructural changes of the white matter in the 6-aminonicotinamide intoxication was discussed.


[The pulmonary ligament (pulmo-diaphragmatic ligament) (author's transl)]. The paper considers the appearances of the contour of the diaphragm and of the normal irregularities of the diaphragm. The hitherto existing opinion of ill defined or tented diaphragmatic outlines always being the result of pleurodiaphragmatic implications in inflammatory or fibrotic processes in the basis of the lung needs to be corrected: In a great number of p.a. chest roentgenograms of healthy persons a more or less obvious ill definition or tenting of the medial part of the diaphragma can be found, caused by a variation of the pulmonary ligament characterized by its connection with the diaphragmatic pleura. Ill definition and tenting of the diaphragmatic outline caused by this variation of the pulmonary ligament are called physiological alterations, contrary to similar pathological (e.g. adhesive) ones. Only if this anatomical variation exists a pulmonary ligament can be roentgenologically visualized directly.


[A comparison of various mammographic techniques using freshly amputated breasts (author's transl)]. In order to compare the performance of various mammographic techniques, xeroradiograms were obtained of sixteen freshly amputated breasts using tungsten and molybdenum rotating anodes. A film without screens (Kodak Definix Medical) and a film-screen system (screens: MR50, film Mammoray RP 3 PE FW) were employed. Exposures during xeroradiography were varied in that, when using the tungsten tube, a 2.5 mm. aluminium filter was added to the 0.5 mm. aluminium filtration inherent in the tube; when using the molybdenum tube, there was a choice between 0.03 mm. Mo. and 0.5 mm. aluminium filtration. The xeroradiograms obtained with the molydenum tube and molybdenum filter were of good quality, as were those obtained with this type of tube and nonscreen film. In view of the carcinogenetic risk of mammography, it is open to discussion whether one should aim at optimal film quality, since improved quality is associated with a higher radiation dose to the breast, or whether one should be satisfied with "adequate" quality. In our series the quality produced by the film-screen combination was, in general, acceptable. Compared with all other procedures, this system produces the lowest radiation dose of any mammographic technique. For this reason further improvements in technique, such as automatic exosure devices, film-screen packs suitable for routine use and improved quality of image are of practical interest.


[Reduction of radiation dose during film mammography using a new film-screen combination. Inital report (author's transl)]. The first results of using a new film screen combination are reported; it consists of an industrial film and a fine grain screen. Film quality approximates that of conventional industrial film, but radiation dose is only 27.5%. The reduced film costs compensate for the greater complexity.


[Dose reduction during radiological examination using high intensity rare earth screens or increased kV (author's transl)]. Using a procedure which resembles actual practice, it has been shown that an increase in kV. results in a reduction of radiation dose similar to that obtained by using the new high intensity rare earth screens while maintaining similar detail. In practical terms this means that there is only limited usefulness for the new rare earth screens. An exception to this is the screen which reduces dose while producing similar, or better, detail than a standard screen. We could demonstrate this for the film-screen combination Trimax alpha4XD.


[Developments in ionography (author's transl)]. Common aspects and differences of xeroradiography and ionography are reviewed briefly. Tendencies connected with latent image formation in ionography, and the development of electrostatic latent images are set out. Apart from gaseous absorbers, liquid or solid absorbers may be employed for latent image formation. A sensitivity increase in gaseous inography may be achieved by charge amplification, although with reduced resolution. As an alternative to aerosol and liquid development methods based on the distortion of deformable layers are described. A procedure yielding multiple copies with different image characteristics (edge contrast) via copies of the latent image is outlined. Finally possible closed ionography systems are mentioned which are necessary for real time imaging.


[Serial observations on pulmonary emboli/infarcts with computerised tomography (author's transl)]. Fourteen patients with pulmonary emboli/infarcts were observed for at least three months by means of computerised tomography. In the acute phase all patients showed minimal changes radiologically, which were not diagnostic of pulmonary emboli; at the same time, computerised tomograms showed definite changes in attenuation in the pulmonary parenchyma and of blood vessels and pleura. A relatively constant and diagnostically valuable sign appears to be a triangular area of attenuation which indicates the presence of an infarct. Serial observations are valuable where there is a clinical suspicion of pulmonary emboli. It is possible to observe regression of the thrombus (due to recanalisation or thrombolysis) and to evaluate the effects of treatment.


[Functional scintigraphy during contraction of the left ventricle. II. Evaluation of background correction (author's transl)]. During evaluation of cardiac function using 99mTc human serum albumen (functional scintigraphy during contraction of the left ventricle), it is necessary to take account of the background radiation which is derived from the lungs and great vessels overlying the heart. Only after correction of the background radiation is it possible to evaluate the severity of various types of cardiac insufficiency; this can be obtained by integrating the impulse during systole and subtracting this from the impulse rate over the left ventricle during a complete cardiac cycle. Apart from the background correction derived from the systolic-diastolic variation, it is necessary to obtain adequate resolution by examining 100 frames per second, an adequate picture matrix (4-K) in order to obtain adequate spacial resolution and accurate measurements of systole and diastole. The latter should be obtained not from the E.C.G., but directly from the volume curve of the left ventricle as determined by the isotope method.


[The accuracy of 201 thalium scintigraphy of the heart under conditions of stress (author's transl)]. The results of 201 thalliumszintigraphy under stress condition in patients with coronary heart disease with or without myocardial scars have not been uniform. We could show that pathologic stress szintigrams were only found in patients with a singular stenosis in one branch of the left coronary artery. In all those cases who had similar stenosis in both branches of the left coronary artery the stress szintigram appeared to be unchanged or normal. Therefore an unchanged stress szintigram allows no conclusion on the condition of the coronary arteries. A normal stress szintigram can be found as well in patients with normal coronary arteries as in patients with severe coronary heart disease. The examination of 201 thallium szintigrams under stress conditions therefore needs some critical evaluation.


[Sympathetic arthritis. A contribution to plasma cell osteomyelitis (author's transl)]. Sympathetic arthritis is a sterile, non-pyogenic complication due to adjacent bone disease, particularly chronic inflammatory osteomyelitis. Radiologically it is manifested as an arthrosis or serous arthritis (painful effusion), or as a chronic destructive arthitis. In the latter case, there is a lymphatic and plasma cell synovitis which may persist, clinically and radiologically, for a period of months or years before definite radiological signs of a chronic osteomyelitis become apparent. Observations of patients with plasma cell osteomyelitis and chronic destructive sympathetic arthritis indicate a special set of findings due to plasma cell osteomyelitis: metadiaphyseal ossifying periostitis, extreme demineralisation of the adjacent epiphysis with spotty focal sclerosis of the spongiosa and a chronic arthritis.


[The radiological findings of caisson-induced bone infarcts. The relationship between acute arthralgia and bone infarcts (author's transl)]. The radiological features, such as calcification in long bones due to infarcts, resulting from Caisson disease are described by the author on the basis of an extensive experience. The similar localisation of acute "arthralgia" and bone infarcts make it appear probable that the infarcts play a primary role in the production of "osteo-articular" pain. The author stresses the advisability of examining the adjacent portions of the tibia and femur at the initial pre-employment examination, since bone infarcts can be caused by a variety of conditions other than work in Caissons.


[A correlative retrospective study of the histological findings and arthrograms in degenerative disease of the meniscus (author's transl)]. The ability to diagnose degenerative changes of the menisci by means of arthrograms was studied retrospectively by correlating the histological and operative findings and arthrographic appearances in 45 cases. It was shown that degenerative changes, as indicated histologically, could be diagnosed by arthrography, but that the arthrogram gave no certain indication of its severity. On the other hand, it appears that fairly severe changes must be present before they become radiologically visible. In negative cases the presence of degenerative changes in bone and cartilage may indicate meniscus degeneration. Problems in the diagnosis of cartilage abnormalities in the arthrogram are discussed.


[The value of lateral views of the cervical spine in the diagnosis of chronic cervical myelopathy (author's transl)]. Factors in the production of chronic cervical myelopathy are considered to be developmental narrowing of the cervical spinal canal and the development of osteochondrotic changes. Lateral view of the cervical spine are a valuable survey method to be used before employing more invasive techniques. In four out of five patients with chronic cervical myelopathy, the quotient of lateral spinal to vertebral diameter was less than 0.8. In a control group this was found in only one out of four patients. Conversely, a quotient below 0.8 in men and 0.9 in women is associated with chronic cervical myelopathy or chronic cervical root damage in half these subjects.


Anterior intervertebral disc herniations (report of six cases). Six new patients with anterior intervetebral disc herniations are reported. This is probably one of the most common causes of back pain in children. Excessive sport activity and osteoporosis are probably two main causes of anterior intervertebral disc herniations. Anterior intervertebral disc herniation is a severe complication of prolonged, mild trauma.


[Pseudo-achnodroplasia in two brothers (author's transl)]. The authors describe two brothers with pseudo-achondroplasia. The literature is reviewed and the clinical and radiological features and differential diagnosis are discussed.


[Ulnar aplasia (author's transl)].

[Ulnar aplasia (author's transl)]. Aplasia of the ulna is a rare malformation of the forearm. A woman patient with such malformation was presented in our clinic on the occasion of a banal dream. In addition to ulnar aplasia, her entire ulnolateral hand was missing. This findings is compared with the relatively few cases described in literature, reporting on the forms of ulnar aplasia observed so far and their additional local malformation. Assumptions regarding the possible origin of such malformations are mentioned, the combined malformations in other body regions as mentioned in literature are described, and brief reference is made to methods of treatment.


[Bone mineral estimation (Hydroxyl apatite equivalent) by direct measurement of photo absorption in the upper extremity (phalanges, radius and ulna) (author's transl)]. The x-ray source of the apparatus developed by the authors for bone mineral estimations consists of a small anode tube with a silver anode. The value of the procedure has been tested by in vitro and in vivo experiments. The in vitro measurements were carried out on a bone reference system consisting of a model bone (Reiss) as well as on a macerated tibia embedded in a resin (Heuck). The results were compared with the values obtained by Rassow. It has been shown that the artificial resin is of only limited value as a connective tissue equivalent. The method of mineral estimation using phalanges is described and its reproducibility was tested on 17 parameters. The absorption coefficient of the spongiosa proved to be particularly critical. Finally, measurements, using the forearm, by Cameron's method are discussed briefly.


[Bone density measurements by computer tomography (author's transl)]. The suitability of the E.M.I. mark I computer scanner for carrying out bone densitometry has been tested, using the forearm. Within the region of interest there was an almost linear relationship between CT densities and the concentration of the bone equivalent substance K2HPO4. By means of a special computer programme, the spongiosa and cortex of both forearm bones could be analysed quantitatively. The reproducibility of the results (coefficient of variation 5%) was similar to that of other procedures in current use. The advantage of the method lies in the fact that it is possible to estimate the spongiosa and cortex separately. Investigations on patients with normal bones have shown that senile demineralisation affects the cortex most severely. On the other hand, in renal osteopathies of chronically dialysed patients, demineralisation in the forearm predominantly involves the spongiosa.


[The diagnosis of annular pancreas (author's transl)]. Annular pancreas is a rare congenital malformation of the gut; frequently it becomes manifest in adult life. The clinical picture and radiological appearances are dominated by stenosis of the duodenum. The only method for diagnosing annular pancreas up to the present was the barium meal. Its diagnostic accuracy, however, is limited. A knowledge of the characteristic radiological appearances is helpful unless other abnormalities confuse the interpretation. E.R.C.P. is an important advance in diagnosis. The diagnosis of annular pancreas can be made by demonstrating an accessory duct system. The literature is reviewed.


[Duodenal stenosis in chronic relapsing pancreatitis (author's transl)]. Duodenal stenosis in chronic relapsing pancreatitis occurs in 20% of our patients. In 21 of our cases, the stenosis was always in the descending portion of the duodenum, and in two-thirds it caused an obstruction. The stenosis is always concentric with destruction of the mucosal pattern, widening of the neighbouring folds, irregular contours, and, possibly, straightening of the medial margin of the duodenum. There may be widening of the duodenal loop and frequently the duodenal loop is dilated. The causes for these appearances vary, but a peri-pancreatitis or duodenitis are most frequent. There is no close relationship with the severity of the pancreatitis. Our findings are compared with the small number of reports to be found in the literature.


[Rare arterial variations during upper abdominal and pancreatic angiography (author's transl)]. Selected cases showing rare variations of the arteries of the upper abdomen indicate how difficult the exact identification of individual vessels can be. In the presence of such variations, which usually involve several vessels, it is essential to find and demonstrate all vessels in the upper abdomen. Vessels which are not seen easily must also be specially searched for. In the presence of anomalous vessels, angiography may prevent the surgeon from ligating the incorrect arteries during operation on the pancreas, the liver, stomach, spleen or colon.


[Ultrasound diagnosis of mural infiltration of the intestinal tract (author's transl)]. Gastro-intestinal mural infiltration can be diagnosed by ultra sound from a typical pattern of echos. This consists of a strong central echo surrounded by a circular structureless margin which indicates thickening of the gut wall. In the present paper, the significance of this appearance is discussed with particular reference to the differential diagnosis. The phenomenon is an important diagnostic criterion where there is suspicion of the presence of malignancy as a result of radiological or endoscopic examination. This is particularly important in cases where the suspicion of malignancy cannot be confirmed by biopsy and histology. It is to be expected that the routine use of ultra sound, and paying attention to the above phenomenon, will lead to further diagnostic measures in difficult diagnostic cases, such as intensive radiological examination or endoscopy with biopsy. This will lead to more rapid and more economical diagnoses.


[Nephrosonography during pregnancy (author's transl)]. In a consecutive series of 128 pregnant patients with sound kidneys the physiological changes of the renal cavity during gravidity with regard to primiparae and multiparae as well as to the stage of pregnancy have been investigated ultrasonographically. We found a dilatation of the renal cavity based on mechanical as well as on hormonal factors with the ultrasonographic picture of obstruction. The aim of this study is to identify border-line conditions in order to avoid false positive findings and to distinguish pathological stages from physiological changes. The ultrasonography represents an excellent technique to recognize macromorphologic changes of the kidney during pregnancy.


[Extragenital gonococcal infections. A review]. In many cases gonorrhea is overlooked and not treated due to an unusual course of the disease. The longer this infection exists the greater is the danger of dissemination of the  gonococci. Gonorrhea, if not diagnosed, may cause a series of local and general clinical manifestations, such as: the dermatitis-arthritis syndrome whose pathogenesis is not yet completely clarified: the Fitz-Hugh-Curtis syndrome which is often seen in females with chronic gonococcal adnexitis;gonococcal pharyngitis which nowadays occurs more often due to less conventional sexual practices of contemporary society; gonococcal conjunctivitis which represents the best known extragenital gonococcosis. This paper deals with the clinical manifestations and their treatment.


[The pathogenesis of psoriasis. Autoradiographic in vitro studies on cell proliferation in psoriasis vulgaris and other normal and hyperproliferative states of epidermal and dermal human cells]. In the epidermal cells of patients suffering from psoriasis we found a significant prolongation of DNA-synthesis time (ts) in uninvolved skin, very early lesions, and fully developed plaques. In uninvolved psoriatic skin ts in addition increased significantly within 6 hours after stripping of the horny layer. In normal epidermis and in other states of epidermal inflammation and hyperproliferation (akanthosis by petrolatum, toxic dermatitis, chronic allergic ekzema, neurodermitis, allergic patch test reaction) a comparable prolongation of ts was not ascertainable. This prolongation is most distinct in the early lesions and proceeds the development of hyperproliferation and akanthosis. A dermal infiltrate with increased proliferative activity seems to be a stimulus, in the sense of a Koebner-phenomenon. The abnormal psoriatic epidermis, with disturbed DNA-synthesis, reacts to this infiltrate as well as to other irritants not with a limited hyperproliferation but with the development of psoriatic plaque.


[Staphylococcal toxic epidermal necrolysis]. Staphylococcal toxic epidermal necrolysis is a well defined disease and can be ideally reproduced in a mouse model. It is due to the action of a staphylococcal exotoxin (exfoliatin) which is produced by phage group2 staphylococci. Exfoliatin acts on a hitherto unknown target site which is likely to be located in the cell membrane of keratinocytes of the subgranular layer. Sensitivity to exfoliatin is common to only few mammals and appears to be genetically determined. Exfoliatin leads to loss of intercellular adherence resulting in acantholysis; cellular morphology and function remains unimpaired. The action of exfoliatin on the epidermis is not influenced by serum factors nor by the mesenchyme. It is also not age dependent although adult humans as well as adult mice do not develop systemic disease. This is due to suppression of growth of staphylococci and rapid renal excretion of exfoliatin in the mature, immunologically competent organism.


Silver stain reveals nucleolus organizer regions on a satellited Yq chromosome. Chromosomes from a patient with a satellited Yq were stained with a silver procedure that differentially stains nucleolus organizer regions. The Yqs stained heavily in all cells examined, indicating the presence of ribosomal cistrons at this region. The Yqs also entered into satellite associations with the D and G group chromosomes at a frequency greater than would be expected through chance.


Trisomy 9p and unusual translocation mongolism in siblings due to different 3:1 segregations of maternal translocation rcp(9;21)(p11;q11). Two sisters are described, each with a specific retardation syndrome due to a balanced reciprocal translocation 9p;21q in the mother. As a result of different 3:1 segregations, one of them has a trisomy 9p with all typical features; the other one reveals a typical Down's syndrome having an unusual translocation karyotype.


The occurrence of a ring 18, an accessory bisatellited fragment, and trisomy 21 within one sibship. A family is presented in which there were three different chromosome abnormalities in the children although the parents were cytogenetically normal. The proband had the karyotype 46,XX, r(18) (p11q23), a phenotypically normal brother was 47,XY,+mar, and another brother was a typical case of Down's syndrome, karyotype 47,XY,+21. There is nothing in the parents' history that provides grounds for a hypothesis to explain the coincidence of the abnormalities.


Replication of chromosomal DNA in cultured abnormal human cells. The replication of chromosomal DNA in a series of abnormal human cell cultures has been studied by means of DNA-fiber autoradiography. In lymphocytes with trisomy 21, in fibroblasts of 45,X;47,XXX;49,XXXXY; and 49,XXXXX chromosomal constitution, and in fibroblasts from a patient with xeroderma pigmentosum (De Sanctis-Cacchione syndrome), the rate of DNA replication does not differ from that in normal cells, varying in a single fork from 0.2 to 1.0 micrometer/min with a mean of about 0.6 micrometer/min. In fibroblasts with trisomy 7 the rate of DNA replication is greater, varying from 0.3 to 1.2 micrometer/min with a mean of about 0.8 micrometer/min. The sizes of replication units in all cells examined are from 80 to 500 micrometer with a mean of about 200-300 micrometer.


Suppression of lymphocyte proliferation by a nonspecific factor produced by the Burkitt lymphoma-derived lymphoblast cell line. The DAUDI lymphoblast cell line derived from a patient with Burkitt lymphoma was obtained from two different sources. One of these (DAUDI-I) produced a factor that inhibited lymphocyte proliferation in both human and mouse regardless of the stimulator, i.e. allogeneic lymphocytes or mitogens. Glutaraldehyde treatment eliminated production of the factor and demonstrated that DAUDI-I was capable of stimulating normal lymphocytes in MLR. A second DAUDI cell line (DAUDI-S) did not produce the inhibitory factor and was capable of MLR stimulation.


Siderophore production by Vibrio cholerae. Vibrio cholerae produces a phenolate-type siderophore that stimulates growth of the organism in low-iron medium. This compound is similar, but not identical, to enterochelin, the siderophore produced by Salmonella and Escherichia coli.


Immune response to persistent mycobacterial infection in mice. Mycobacterium marinum has been recommended as a possible model of M. leprae for use in laboratory studies of antileprosy immunity. M. marinum introduced into the footpads of normal mice underwent a steady decline in viability, with less than 1% survival after a 30-day period. Small numbers of viable bacilli were recovered from the footpads of these mice up to 12 months later. Similarly, mice infected with M. simiae exhibited bacterial populations that persisted for up to 18 months with little change in viability. Injection of M. simiae into the footpads was followed by an extensive redistribution of the organisms in the tissues. Eventally, bacterial counts for footpads and draining lymph nodes stabilized, with small numbers of bacilli still present in the footpads 18 months later. Persistent growth, with little sign of any immune response, was also observed in mice infected with several strains of M. avium, as well as with one strain of M. intracellulare. Other strains of M. intracellulare, as well as M. vaccae and M. nonchromogenicum, failed to establish persistent infections in normal mice, regardless of whether they were introduced by an intravenous or subcutaneous (footpad) route. The relevance of these findings is discussed in relation to antileprosy immunity in experimental animals and in humans.


In vitro radiosensitivity of human T and B lymphocytes evaluated using lymphocyte transformation tests and rosette formation tests. The influence of irradiation upon human lymphocytes was studied using lymphocyte transformation tests and formation of E and HEAC rosettes. Irradiation was given in vitro using doses between 0 and 50,000 rad. It was shown that blast transformation after stimulation with T-cell stimulating agents (as PHA, PWM, Con.A and PPD) was suppressed by irradiation. The effect of irradiation upon T lymphocytes was also shown in different kinds of MLC experiments. Both the effect of irradiation upon rosetts formation and the influence of irradiation upon already formed rosettes were analyzed. The ability of lymphocytes to form E rosettes was affected after irradiation with 500 rad: there were fewer E rosettes with 3 SRBCs, decrease in total number of E rosettes and more null cells, with no depression of the number of HEAC rosettes formed. Already formed E and HEAC rosettes were totally unaffected of irradiation, and this radioresistance was also observed for 18-hour-old rosettes. The ability to form spontaneous E rosettes was decreased after irradiation of the lymphocytes with 100 rad; increasing doses did not cause further depression, and already formed spontaneous E rosettes were radioresistant. The mechanisms involved in E-rosette formation thus seem to be radiosensitive.


Risk factors of breast cancer in Burma.

Risk factors of breast cancer in Burma. A hospital-based case-control study of breast cancer was undertaken in Rangoon. The age-standardized incidence rate, 25.1 per 100,000 woman-years and the shape of the age-incidence curve show that Rangoon women have an intermediate level of breast cancer risk compared to women of other countries in the world. The analysis is based on 193 cases and 400 controls. Breast cancer risk was found to be directly related to educational attainment. There was an increased risk associated with early menarche and late menopause. The most striking finding was the strong inverse relationship between risk and parity; women who had six or more children have only one-third the breast cancer risk of married women who had less than four children. This association is not confounded by case-control differences in age at birth of first child. The association of breast cancer risk with age at first birth was not striking; only women with a first birth after age 30 were at increased risk. Breast cancer risk was unrelated to lactation. Overall, the epidemiology of breast cancer in Burma is similar to that in most other countries. However, the possibility of an unusual relationship of risk to parity and age at first parturition warrants further exploration.


An analysis of conditions allowing Corynebacterium parvum to cause either augmentation or inhibition of natural killer cell activity against tumor cells in mice. We have analyzed the impact of in vivo administration of Corynebacterium parvum on the mouse immune system against murine tumors, using the natural cytotoxic ability against tumors of normal mouse lymphoid cells as a baseline. A striking difference was found depending on the route of administration. Intravenous inoculation of bacteria would result in a significant decrease or sometimes complete abolition of natural cytotoxicity toward tumor cells of the spleen cells of treated mice. On the other hand, the intraperitoneal route of administration resulted in a dramatic increase in cytolytic ability of the peritoneal exudate cells. Both routes of treatment had the most significant impacts on  the local cell population (IV = spleen, IP = peritoneal exudate cells) with only minor effects on other cell populations. Analysis of the spleen cell population from IV-treated mice did also demonstrate a significant reduction in the T lymphocyte function, but in contrast to the natural cytotoxicity this could be corrected for by the removal of suppressor cells of an adherent nature. The lytic cells induced in the peritoneal exudate by the Corynebacterium parvum bacteria were all found to be natural killer, NK, cells with no significant activity found amongst macrophages using short-term cytolytic assays.


Pulmonary fibrinolytic activity: development of a sensitive radiochromatographic assay. Pulmonary fibrinolytic activity was determined by a column assay which uses antibovine fibrinogen antibody covalently bound to cyanogen bromide-activated Sepharose 4B and 125I-labeled fibrinogen immunologically bound to the antibody. Fibrinogen-degrading enzyme (plasmin) was passed through the immobilized substrate; the released 1252I-labeled fragments were counted in a gamma-scintillation counter. A positive correlation was found between enzyme concentration and release of fibrinogen degradation products. The assay was sensitive, reproducible and particularly useful for measuring low enzyme activity in dilute bronchopulmonary lavage fluids.


Mechanics of the human diaphragm during voluntary contraction: statics. We related diaphragm electromyographic activity (Edi) to transdiaphragmatic pressure (Pdi) in man during graded inspiratory efforts. Estimates of rib cage and abdominal volume displacements were based on their anteroposterior (AP) diameter changes. The diaphragm was assumed to contract isometrically when subjects performed inspiratory efforts against a closed airway at specified abdominothoracic configurations, increasing Edi and Pdi while holding lung volume and rib case and abdominal AP diameters constant. The relationship between Pdi and Edi depends primarily on abdominothoracic configuration rather than lung volume. For  equal increments in lung volume, the Pdi developed at constant Edi is four to eight times more sensitive to changes in abdominal than in rib cage AP diameter. We demonstrate an isofunctional state of the diaphragm at different lung volumes, when increases in lung volume and rib cage AP diameter are compensated for by slight decreases in abdominal AP diameter, resulting in a constant relationship between Edi and Pdi. We conclude that diaphragm shortening is reflected more directly in abdominal displacement than in lung volume change.


Papillary muscle rupture following nonpenetrating chest trauma: report of a case with hemodynamic and serial echocardiographic findings and successful surgical treatment. The pre- and postoperative echocardiographic features of a patient with severe mitral incompetence due to rupture of a papillary muscle following nonpenetrating chest trauma are presented. The mitral valve echocardiogram showed chaotic diastolic flutter suggestive of a ruptured papillary muscle or ruptured chordae tendineae. The preoperative ultrasound recording of the left ventricle revealed left ventricular enlargement and excessive motion of the interventricular septum. The echocardiogram taken 7 weeks after mitral valve replacement showed considerable regression of the left ventricular enlargement.


Cardiac hypertrophy in response to dynamic conditioning in female athletes. Ten female field hockey players were studied to determine if prolonged dynamic conditioning results in an increased left ventricular internal dimension at end diastole (LVIDD) and if this increase correlates with maximal oxygen consumption (VO2max). At peak season, echocardiograms were obtained and VO2max determined during maximal treadmill exercise. VO2max, LVIDD index (LVIDD/body surface area (BSA)), and ventricular septal and posterior wall thickness were compared to agematched nonathletic women. Mean LVIDD index was significantly greater in athletes than in controls: 29.3 +/- 0.9 mm/m2 vs. 26.3 +/- 0.6, P less than 0.005. Echocardiographic wall measurements did not differ significantly in the two groups. Mean VO2max for the athletes was significantly greater than controls: 51.7 +/- 4.0 ml O2.kg-1.min-1 vs. 41.2 +/- 2.1, P less than 0.001. VO2max correlated significantly with LVIDD index; r = 0.92, P less than 0.001. Female athletes show an increased LVIDD in response to dynamic conditioning similar to that seen in male athletes. The proficiency of athletic performance as measured by VO2max may be related to the heart's ability to increase LVIDD since there is a high correlation between VO2max and LVIDD index.


Cellular adaptations of the ventilatory muscles to a chronic increased respiratory load. It is not known whether cellular adaptations of the ventilatory muscles are induced by increased respiratory loads. A chronic respiratory load was produced in rats by tracheal banding. Five weeks after the imposition of this increased load, biochemical and histochemical analyses were performed on the diaphragm and intercostal muscles. The oxidative capacity, as indicated by succinate dehydrogenase (SDH) activity, increased 38% in the diaphragm. The capacity for beta-oxidation fatty acids, as indicated by 3-hydroxy-acyl-CoA dehydrogenase (HADH) activity, increased 29%. The glycolytic capacity, as indicated by phosphofructokinase (PFK) activity, did not change. Similar enzymatic adaptations were observed in the intercostal muscles. The proportion of slow-twitch muscle fibers, as indicated by the myofibrillar adenosine triphosphatase (ATPase) stain, increased in the diaphragm, but not in the intercostal muscles. Thus, these ventilatory muscles responded with an increase in their oxidative capacity, and the diaphragm reponded with an increase in the proportion of muscle fibers having the myofibriller ATPase staining characteristic of slow-twich fibers. We conclude that cellular adaptations are induced in the ventilatory muscles by chronic increased respiratory loads.


Developmental pattern of muscle fiber types in human ventilatory muscles. Premature infants tolerate respiratory loads poorly. This may reflect incomplete development of the ventilatory muscles (VM) causing poor resistance to fatigue. To study the developmental pattern of human VM, 31 postmortem specimens of diaphragm and intercostal muscles were obtained. Individual muscle fibers were classified as type I (slow-twitch, high-oxidative) or type II (fast-twich, low-oxidative) using histochemical staining methods for myofibrillar adenosine triphosphatase (M-ATPase) (pH 10.30) and nicotinamide adenine dinucleotide (NADH) tetrazolium reductase. In the diaphragm, premature infants (less than 37 wk gestation) had only 9.7 +/- 1.3% type I fibers, full-term newborns 25.0 +/- 1.1%, and older subjects (greater than 2 yr of age) 54.9 +/- 1.3%. There was no further increase after 8 mo postpartum. In the intercostal muscles, premature infants had only 19.0 +/- 4.8% type I fibers, full-term newborns 45.7 +/- 1.3%, and older subjects 65.2 +/- 2.6%. There was no further increase after 2 mo postpartum. These findings suggest the ventilatory muscles of newborn infants are more susceptible to fatigue than those of older subjects. This may contribute significantly to respiratory problems in the neonate.


Spectinomycin modification. IV. 7-deoxy-4(R)-dihydrospectinomycin. 7-Deoxy-4(R)-dihydrospectinomycin (7) has been prepared and its structure firmly established by proton magnetic resonance and high resolution mass spectrometry. This spectinomycin analog is devoid of antibiotic activity.


Evaluation of succinyl neocarzinostatin in vivo. The toxicity of the bis-succinyl derivative of the protein antibiotic, neocarzinostatin, was compared with the parent compound, neocarzinostatin (NCS), in rats. The derivative was found to be about two to five fold more active than NCS in vivo. The antitumor activity in rats bearing eleven distinct Yoshida hepatoma ascitic cell lines was tested under four possible combinations with regard to sites of drug and tumor cell administration. The results indicate that the antitumor spectrum of the derivative had changed slightly. Antitumor activity in mice was also tested with L1210 and P388 lymphatic leukemia, and with B16 melanocarcinoma. When the effect of the derivative was compared with parental NCS at the molecular level with respect to the inhibition of DNA synthesis in vitro, the specific activities of the two were found to be almost identical. These results were interpreted to indicate that the succinyl derivative of NCS was more stable to inactivation and proteolytic break-down in vivo than NCS as observed previously in in vitro studies.


The effects of storage of sarcoplasmic reticulum fragments on the Ca2+, Mg2+-ATPase. The effects of K+ and Na+ on the Ca2+,Mg2+-ATPase of sarcoplasmic reticulum fragments (SRF) were investigated at 1 mM ATP. There was an alteration of the sensitivity of the ATPase to the monovalent cations during storage of the SRF preparation. The Ca2+, Mg2+-ATPase of freshly prepared SRF was slightly activated by 5-10 mM K+ and Na+. Mg2+-ATPase was inhibited by both the monovalent cations to the same extent, and this response to the ions was independent of the freshness of the preparations. After storage of SRF, however, the Ca2+,Mg2+-ATPase was markedly activated by higher concentrations of K+ and Na+ (0.2-0.3 M). K+ and Na+ reduced the Ca uptake at the steady state in freshly prepared SRF, but did not affect pre-steady state uptake. In the presence of oxalate, the rate of Ca accumulation both in fresh and stored preparations was activated by 0.1-0.2 M K+ and Na+. The Ca2+, mg2+-ATPase with oxalate, so-called "extra ATPase," showed the same response to the ions as did the activity without oxalate during storage.


Effect of light and oxygen on neocarzinostatin stability and DNA-cleaving activity. The in vitro DNA-cleaving activity of neocarzinostatin, a protein antibiotic, is strongly but reversibly inhibited by anaerobiosis. Half-maximal activity is seen in the presence of 0.25 mM O2. The stability of neocarzinostatin, as demonstrated by its ability to cleave DNA, is significantly reduced in light. Inactivation by light is complete and irreversible.


The mode of inhibition of oxidative phosphorylation by efrapeptin (A23871). Evidence for an alternating site mechanism for ATP synthesis. Results are presented that confirm and extend earlier findings that efrapeptin is a potent inhibitor of oxidative phosphorylation. Binding of efrapeptin is shown to be reversible, and a dissociation constant for the enzyme-inhibitor complex is estimated to be 10(-8) M under conditions for either ATP synthesis or hydrolysis. Fifty per cent inhibition of the ATP hydrolysis activity of submitochondrial particles is obtained at a ratio of 0.56 mol of inhibitor/mol of enzyme. Studies of efrapeptin binding under pseudo-first order conditions show that the onset of inhibition is first order with respect to efrapeptin. Combined with the inhibition titer, these results indicate that there is one inhibitor binding site per molecule of enzyme. Steady state velocity studies using a substrate regenerating system show that efrapeptin is competitive with both ADP and phosphate during ATP synthesis. However, during ATP hydrolysis, a distinctly different mode of inhibition is indicated with respect to ATP. Data are presented which suggest that ATP promotes the binding of efrapeptin to the enzyme. Indications that efrapeptin is a catalytic site inhibitor make these results difficult to reconcile with a simple mechanistic scheme involving a single independnet catalytic site for ATP synthesis and hydrolysis. Our results are discussed in terms of support for catalytic cooperativity between adjacent subunits as recently proposed by Kayalar et al. (Kayalar, C., Rosing, J., and Boyer, P. D. (1977) J. Biol. Chem. 252, 2486-2491).


An ATP stimulation of T4 DNA polymerase mediated via T4 gene 44/62 and 45 proteins. The requirement for ATP hydrolysis. An in vitro replication system reconstituted from six purified T4 bacteriophage proteins, each of which is essential for T4 DNA replication in vivo, requires ATP. Because of the complexity of the complete system, we examine in this report the involvement of ATP in two subsystems of the overall DNA synthesis reaction. One subsystem consists of the T4 DNA polymerase (gene 43 protein) and its "accessory proteins," the gene 44/62 and 45 products. An even simpler subsystem consists of the gene 44/62 and 45 proteins alone, which together have a DNA-dependent ATPase activity. The combination of the 44/62 and 45 proteins hydrolyze ATP to ADP and inorganic phosphate in the presence of DNA. These essential accessory proteins have been previously shown to increase T4 DNA polymerase activity on primed, single-stranded DNA templates. In this report we use nucleotide analogues to demonstrate that this polymerase stimulation requires hydrolysis of the beta,gamma-phosphate bond of ATP. However, our data suggest that the mechanism of accessory protein stimulation is such that less than 1 ATP molecule need be hydrolyzed per 10 deoxyribonucleotides incorporated by the DNA polymerase into DNA.


Amino acid sequence of beta-galactosidase. VI. Limited tryptic digestion of the citraconylated protein and sequences of tryptic peptides. Hydrolysis with trypsin of citraconyl-carboxy-methyl-beta-galactosidase was carried out under limiting conditions. No Asp-Arg-X sequences were cleaved and many large peptides were produced. Butanol extraction from dilute acid proved very useful for separating the more hydrophobic fragments. Peptides were purified and sequenced. From this digest and two earlier preparations, all 80 theoretically possible tryptic fragments have been isolated and their structures determined.