[Effect of 7,8-benzoflavone on the incidence of skin tumors induced by polycyclic hydrocarbons].

Tumours were induced in CBA mice or (C57BL X CBA)F1 hybrids by the application of benz(a)pyrene (BP), 6-methylBP, 6-formylBP or 7,12-dimethylbenzanthracene (DMBA) to the skin. 7,8-benzoflavone (BF) used in combination with the mentioned agents decreased the carcinogenic action of methyl-substituted hydrocarbons--DMBA and 6-methylBP and had no effect on the carcinogenic action of BP and 6-formylBP. It is suggested that the inhibitory action of BF on carcinogenesis induced by methyl-substituted hydrocarbons was due to the inhibited oxidation of the methyl group.


[Smoking as a psychological and social problem].

1. The ill-effects of smoking on health not only concern the smoker but the entire population living in the same society and sharing the economy. Smoking is associated with a general increase of costs involved with increased morbidity, lowering of the social product and excess mortality. 2. The main prolem in weaning from smoking is related to the origin of smoking which is in large measure unknown. Smoking habits should not be analyzed on an individual basis only. It represents a "minor addiction" with the origin within the society. This is the result of an analysis of motives leading to smoking. Social habits, examples, deprivation of senses, dullness, anxiety, stress, and smoking as a symbol of status play a major role. 3. Stress carries a dual risk, it encourages to smoking and it exerts direct effects an organ function. 4. Smoking is enhanced by its somatic effects which activate in turn again smoking. Weaning from smoking does not affect the origin of the addiction thereby remaining symptomatic treatment. 5. There is a constant replacement of old smokers with smokers originating in the young generation. Smoking habits have the tendency to spread out of the smoking population over the non-smokers. A combat against this infiltration can only be successful by creating new values and by producing a new habit of non-smoking.


Loss and recovery of reactivity to noxious stimuli in monkeys with primary spinothalamic cordotomies, followed by secondary and tertiary lesions of other cord sectors.

Cebus albifrons monkeys were trained to escape electrical stimulation of either leg at five intensities, spanning a range from mild tingle to intense but tolerable pain, as judged by human observers who experienced the same stimuli. The average duration of stimulation received by the animals at each intensity was plotted for each leg during the period required for recovery of responsiveness to noxious electrical stimulation following ventrolateral spinal cordotomy. Recovery of escape responding was observed similarly following subsequent lesions to the spinal cord, in an attempt to define the pathways that subserve pain conduction after readjustment from cordotomies that produced substantial deficits of escape behaviour. The most enduring elevations of duration of stimulation by lesion I (left cordotomy) were produced by lesions that involved all of the ventrolateral column and most or all of one or both ventral columns. Secondary lesions of the dorsal columns, Lissauer's tract and the dorsolateral columns, in various combinations, did not produce long-term effects on escape responding. In contrast, a complete ventral hemisection produced a pronounced bilateral deficit that did not recover fully over three hundred and five post-operative days. The major conclusions are: (1) that the dorsal pathways do not play a major role in the rostral conduction of information critical for pain perception in monkeys, even though these pathways receive input from high threshold receptors; and (2) in order to produce a lasting decrease of pain sensitivity in primates by spinal surgery, the lesion must be bilateral and must involve both the ventrolateral and ventral columns.


Rehabilitation following early malnutrition in the rat: body weight, brain size, and cerebral cortex development.

Sprague-Dawley rats were malnourished by giving their mothers an 8% casein diet starting at day 10 of gestation, while controls were fed a 24% casein diet. Starting at postnatal day 20 (P20), rehabilitation of the malnourished animals was attempted by: (1) feeding both mother and young a 24% casein diet, (2) leaving the pups with their mothers until they were 40 days old, and (3) reducing the litter size from 8 to 4 pups. Observations were made on aldehyde-perfused tissue from animals 20, 40 and 70 days old. The somatosensory cortex from one hemisphere was embedded in Araldite, and that from the other side was processed fro Golgi staining. At 20 days of age the body weight of the malnourished animals was 21% that of the controls, but at 70 days it was no longer different. The anterior-posterior length, the width, and the height of the cerebral hemispheres were also significantly reduced at P20, but the differences had disappeared by P70. The thickness of area 3 of the cerebral cortex was measured in 1 micron sections. It was significantly reduced in the malnourished animals at P20, but at P40, following rehabilitation, the difference was no longer statistically significant. In tangential 1 micron sections the fraction of the volume of tissue occupied by neuropil was measured in layers II through IV. At P20 it was significantly reduced only in the upper half of layers II/III of the malnourished animals; at P40 this difference was no longer present. The mean volume of upper layer II/III cell bodies was estimated and found to be significantly reduced in the experimental animals at P20 but not at P40. In the Golgi preparations, pyramidal cells in upper layer II/III were studied. Their estimated volume, as well as the thickness of their basal dendrites, was significantly reduced in the 20 day malnourished animals, but not in the rehabilitated animals. These results show that animals severely malnourished until 20 days of age can reach normal body weight and attain cerebral hemispheres of normal size when proper nutrition is provided. The effects of malnutrition on the cerebral cortex of these animals are most apparent in upper layer II/III which, during the time of nutritional restriction, is the least developed of the cortical layers. However, when proper nutrition is provided, the cerebral cortex may attain normal morphology.


The pathology of tumors. Part II: Diagnostic techniques.

Frozen section diagnosis of cancer is generally used to 1) determine the type and extent of treatment while the patient is in the operating room and 2) to confirm the adequacy of surgical excision. Frozen section diagnosis forms the basis for further surgery. Because of the pathologist's role in this decision, he should be as familiar as possible with pertinent clinical data (e.g., previous biopsy or surgery) prior to operation. In some cases he may wish to observe the lesion in situ or suggest an area to be biopsied. Frozen section is very reliable in cancer diagnosis. A recent review of 2,240 consecutive sections has shown an overall accuracy of 99.3 percent with 13 false-negatives and only five false-positives. The technique is useful for most specimens, even tissue from needle biopsies. When the pathologist receives the gross specimen he must orient it and describe the color, consistency and size of the tumor and record its appearance prior to sectioning. The specimen must be carefully examined for any indications of inadequate tumor excision. Specimens may have critical areas close to the wound limits and the sections must be careflly oriented to prove or disprove adequate excision. Specimen roentgenography is very useful in evaluating excision and in pinpointing the tumor area. Microscopic description of tumors includes details of pattern, nuclear changes, stroma, and many others. However, only the microscopic findings which have prognostic or therapeutic significance should be emphasized to the surgeon. Summarizing the pertinent findings in a final paragraph of the pathology report can translate routine microscopic description into constructive clinical information which will give the surgeon a clear idea of the probable behavior of the tumor. In addition to the standard procedures for preparing and examining specimens for final diagnosis, there are some special techniques which are extremely useful. These include immunohistochemical staining, electron microscopy, tissue culture and biochemical studies.


Distribution of the perilacunar hypomineralized areas in cortical bone from patients with familial hypophosphatemic (vitamin D-resistant) rickets.

The perilacunar areas of low mineral density in microradiographs from cortical bone of patients with hypophosphatemic (vitamin D-resistant) rickets are not evenly distributed throughout the bone tissue. Their frequency and distribution were determined in bone from 9 patients with this disease. It was found that the lesion was more frequent in haversian bone than in interstitial bone, and along the inner circumference of growing haversian systems as compared with outer circumference. These findings indicate that the lesion is the result of retarded mineralization, and that mineralization slowly proceeds in these areas as the bone becomes older. A relatively high frequency of the lesion was also found in osteons with an elliptical cross section along the long axis of the ellipse. The cause of the abundance of the lesion at these sites is not clear, but it is possible to explain the uneven distribution in elliptical osteons by assuming an unequal rate of bone formation in these structures.


Age-related changes in the density and tensile strength of human femoral cortical bone.

In order to ascertain whether the intrinsic strength of human bone changes with age or not, we have determined the ultimate tensile strength and density of strips of femoral cortical bone. These femora were collected from cadavers varying in age from 13 to 97 years. The results show that both density and intrinsic strength of bone increase up to about the fourth decade of life and then decrease with age. However, the rate of decrease of strength is greater than that of density. This indicates that the density of bone is not the sole determining factor of its strength, and that some other factors play an important part.


Noninvasive measures of bone bending rigidity in the monkey (M. nemestrina).

The in vivo bending rigidity and bone mineral content of monkey ulnae and tibiae were measured. Bending rigidity in the anteroposterior plane was measured by an impedance probe technique. Forced vibrations of the bones were induced with an electromechanical shaker, and force and velocity at the driving point were determined. The responses over the range of 100-250 Hz were utilized to compute the bending rigidity. Bone mineral content in the cross section was determined by a photon absorption technique. Seventeen male monkeys (Macaca nemestrina) weighing 6-14 kg were evaluated. Repeatability of the rigidity measures was 4%. Bone mineral content was measured with a precision of 3.5%. Bending rigidity was correlated with the mineral content of the cross section, r = 0.899. Two monkeys were evaluated during prolonged hypodynamic restraint. Restraint produced regional losses of bone most obviously in the proximal tibia. Local bone mineral content declines 17 to 24% and the average bending rigidity declines 12 to 22%. Changes in bones leading to a reduction in mineral content and stiffness are discussed.


Comparative uptake of fluoride from sodium fluoride, ammonium fluoride, and barium fluoride in rat teeth when predominantly administered in the pre-eruptive stage of development.

A comparative study was undertaken which focused on the systemic uptake of sodium fluoride (NaF), ammonium fluoride (NH4F), and barium fluoride (BaF2) in rat pups. Two critical achievements made this comparative study possible: (a) the demonstration of significant increases in fluoride (F) uptake-deposition in the treatment group pups relative to control group rats as a result of stomach tube feeding; and (b) the demonstration of clear-cut differences in F concentration levels between the treatment groups as a result of this stomach tube-systemic uptake. Data were reliable and significant enough to suggest that, of the 3 compounds in question, NH4F is absorbed most successfully in a systemic fashion, whereas BaF2 is the least absorbed.


Studies on the incongruent solubility of hydroxyapatite.

The solubility of hydroxyapatite was examined in calcium phosphate mixtures produced by combining Ca(OH)2 and H3PO4 in varying proportions under a wide variety of conditions. Analyses of supernatants for calcium, phosphorus, and pH provided the data for solubility calculations. Alteration of the solid/liquid ratio by removing supernatant or by evacuating water from equilibrated mixtures had little effect on the solubility product. However, when precipitates separated from some mixtures were reequilibrated at various solid/solution ratios in either water, acetate buffer, or supernatants obtained from previous equilibrations, incongruent solubility was demonstrated and was attributed to the formation of other calcium phosphate phases which coated the apatite. The experiments indicated that hydroxyapatite has a thermodynamic solubility product between 10(-57) and 10(-60), but the exact value is difficult to determine because of the formation of surface coats.


Effect of 1-alpha-hydroxyvitamin D3 on osteoporosis in rats induced by oophorectomy.

Fifty adult female rats were used to study the effect of 1-alpha-hydroxyvitamin D3 (1alpha-OH-D3) on bone after oophorectomy. The experimental period was 6 months. At the end of the experiment the femurs and the tibias were investigated for bone mass and composition. Significant signs of osteopenia occurred as a result of oophorectomy. The treatment with 1alpha-OH-D3 induced only minor changes in blood chemistry but increased bone mass significantly. The findings support the view that 1alpha-OH-D3 may be a valuable tool in the treatment of osteoporosis resulting from ovarian insufficiency.


Precipitation of calcium phosphates under conditions of double diffusion in collagen and gels of gelatin and agar.

One-dimensional double diffusion was applied to determine critical concentrations at which the precipitation of calcium phosphates occurs in reconstituted connective tissue collagen and agar gels at 37 degrees C and in gelatin gels at 25 degrees C. Experiments were performed in the presence of unbuffered 0.15 mol dm-3 NaCl, or 0.15 mol dm-3 NaCl-veronal adjusted to pH 7.4. It was found that critical concentrations of precipitation of both precipitating components, CaCl2 and phosphate buffer (pH 7.4), were equimolar and independent of the ratios of initial concentrations of the components. Critical concentrations of precipitation were not affected by the concentrations and kinds of gels used. The first-formed precipitates showed amorphous structure by X-ray diffraction analyses. Infrared (IR) spectra of the precipitates indicated CaHPO4 . H2O to be their predominant species. The molar Ca/P ratio obtained by chemical analyses was 1.08. This precipitate transformed in time into octacalcium phosphate. In all experiments, two very thin membranes of precipitate were formed in the gel column at the onset of precipitation simultaneously on both sides of the actual disc of precipitate. IR spectra and chemical analyses showed that both membranes were identical to the actual precipitation discs.


Identification of phosphopeptides and gamma-carboxyglutamic acid-containing peptides in epiphyseal growth plate cartilage.

Uncalcified cartilage from the epiphyseal portion of bovine scapulae, both distant and adjacent to the epiphyseal growth plate, and the calcified cartilage of the epiphyseal growth plate itself were analyzed for the presence of O-phosphoserine [Ser(P)], O-phosphothreonine [Thr(P)] and gamma-carboxyglutamic acid (G1a). Only trace amounts of these Ca2+-binding amino acids or the peptides containing them were found in the unmineralized tissues. In contrast, whole calcified cartilage, and especially the most mineralized fraction obtained by density centrifugation, contained considerable amounts of all three amino acids. Essentially all of the G1a and the majority of the Ser(P) and Thr(P) were present in non-collagenous, non-diffusible proteins extractable in EDTA at near-neutral pH.


Bone fluoride concentrations associated with fluoridated drinking water.

Recently published bone fluoride values from Iowa are very high compared to earlier reports, suggesting an increase in fluoride intake. Reanalysis of the Iowa specimens shows levels one-fourth those reported by the Iowa laboratory indicating an error in the original report. Seventeen bone specimens, collected from long-term residents of Rochester, New York, drinking 1 ppm F- water, had a mean value of 2085 +/- 270 ppm F- on an ashed-weight basis. This value is not significantly different from that predicted by the data of Zipkin et al. in 1958. These data, therefore, do not support the contention that there has been an increase in fluoride intake.


A proposed nucleotide sequence for the 5S ribosomal ribonucleic acid of rainbow trout (Salmo gairdneri).

Rainbow trout cell cultures have been exposed to 32P-labelled inorganic phosphate and the labelled RNA has been isolated. The 5S ribosomal ribonucleic acid (5S rRNA) was purified by polyacrylamide gel electrophoresis, then digested with RNase T1 or pancreatic RNase. The products of complete digestion were separated and their sequences determined. These analyses have allowed a sequence to be proposed which differs in eight positions from that of mammalian 5S rRNAs.


Aminopeptidase I activities in several microorganisms.

Aminopeptidase I activity which was found to be localized in the same subcellular fraction and to be similarly heat stable was partially purified by a common procedure from Escherichia coli B, Escherichia coli K12, Enterobacter aerogenes, Salmonella typhimurium, Serratia marcescens Pseudomonas aeruginosa, and Proteus vulgaris. The enzyme preparations were shown to contain a single animopeptidase active toward both leucylleucine and methionylalanylserine by mixed-substrate initial-velocity kinetic analysis. The Km value for leucylleucine was virtually identical for the aminopeptidases of all of the organisms, as was the Km value for methionylalanylserine.


The 2.8 A resolution structure of Streptomyces griseus protease B and its homology with alpha-chymotrypsin and Streptomyces griseus protease A.

The 2.8 A (1 A = 0.1 nm) resolution structure of the crystalline orthorhombic form of the microbial serine protease Streptomyces griseus protease B (SGPB) has been solved by the method of multiple isomorphous replacement using five heavy-atom derivatives. The geometrical arrangement of the active site quartet, Ser-214, Asp-102, His-57, and Ser-195, is similar to that found for pancreatic alpha-chymotrypsin. SGPB and alpha-chymotrypsin have only 18% identity of primary structure but their tertiary structures are 63% topologically equivalent within a root mean square deviation of 2.07 A. The major tertiary structural differences between the bacterial enzyme SGPB and the pancreatic enzymes is due to the zymogen requirement of the multicellular organisms in order to protect themselves against autolytic degradation. The two pronase enzymes, SGPB and Streptomyces griseus protease A (SGPA), have 61% identity of sequence and their tertiary structures are 85% topologically equivalent within a root mean square deviation of 1.46 A. The active site regions of SGPA and SGPB are similar and their tertiary structures differ only in three minor regions of surface loops.


Antibody to an artificial disaccharide antigen cross-reactive with Neisseria gonorrhoeae lipopolysaccharide.

An artificial antigen was prepared from 4-O-beta-I-galactopyranosyl-D-glucose (lactose) and 8-ethoxycarbonyloctanol. Covalent attachment to bovine serum albumin provided an antigen that elicited antilactose antibody in rabbits and goat. These antibodies were active against Neisseria gonorrhoeae lipopolysaccharide in passive hemagglutination tests. The same antibody agglutinated cells of Streptococcus faecalis, strain N, and precipitated the lactose-containing cell wall diheteroglycan of this organism. Fractionation of rabbit and goat antibody raised against the synthetic antigen of S. faecalis vaccine provided two antibody fractions only one of which, eluted from the immunoadsorbent by galactose, was active against N. gonorrhoeae lipopolysaccharide.


Rieger's anomaly with congenital glaucoma a case presentation of postnatal anterior segment maturation.

We describe an unusual case of Rieger's anomaly with congenital glaucoma in an infant in whom significant maturation of the anterior segment occurred postnatally. Medical treatment of the glaucoma was successful. The control of the glaucoma coincided with the maturation of the angle, suggesting that the two events could be related.


Evidence for a periplasmic location in Comamonas terrigena of the inducible tyrosine sulfate sulfohydrolase.

The location of the inducible and constitutive forms of tyrosine sulfate sulfohydrolase in Comamonas terrigena was investigated by subjecting resting cells to osmotic shock and to treatment with lysozyme in the presence of EDTA. The bulk of this enzyme present in induced cells was released by these procedures, suggesting that the induced form is cell wall associated. The constitutive form present in noninduced cells was not released under these conditions. Evidence was also presented which suggests that SO4(2-)release by intact cells during exposure to tyrosine sulfate was primarily due to the action of the inducible form of the enzyme.


Protection of mammalian cells from diphtheria toxin by exogenous nucleotides.

Exogenous nucleotides were found to protect mammalian cells from the lethal effects of diphtheria toxin. Protective potency of a given nucleotide was base specific and phosphate chain length dependent. Full expression of protective potency required an intact nucleotide, but the effect did not appear to be mediated by nucleotide-induced phosphorylation. Nucleotides antagonized the binding of diphtheria toxin to its cell surface receptor in a manner that correlated with the degree of protection. It was concluded that cellular protection from diphtheria toxin by nucleotides results from inhibition of toxin-receptor binding and that nucleotides therefore may serve as valuable research tools for future studies.


Response of various cell lines to Escherichia coli toxic products.

Seven cell lines were compared with Y-1 and Vero cells for morphological response to E. coli toxic products. FL and WI-38, like Y-1 and Vero, responded to heat-labile enterotoxin. FL, HEp-2, HeLa, and BGM, like Vero but not Y-1, responded to heat-labile cytotoxin. FL was comparable to Vero in sensitivity to these two toxic products.


Release of rhodanese from Pseudomonas aeruginosa by cold shock and its localization within the cell.

Whole cells of Pseudomonas aeruginosa possess rhodanese activity. The enzyme can be released by rapidly resuspending the cells in cold Tris--HCl buffer. Approximately 95% of the rhodanese activity is released by cold shock. Release of the enzyme can be inhibited either by preincubating the cells with Mg2+ or by incorporating Mg2+ into the shocking buffer. The effect of Mg2+ can be reversed by washing the cells twice with buffer prior to cold shock. While rhodanese can be released from P. aeruginosa by cold shock, lactic dehydrogenase, a cytoplasmic enzyme, remains within the cell. Diazo-7-amino-1,3-napthalenedisulfonic acid, a compound which does not penetrate the cytoplasmic membrane, completely inactivated rhodanese and alkaline phosphatase, a periplasmic enzyme, whereas lactic dehydrogenase retained its full activity. These data suggest that rhodanese in P. aeruginosa, like alkaline phosphatase, is located distal to the cytoplasmic membrane in the periplasmic space. Electron micrographs also show that portions of the lipopolysaccharide outer membrane are shed from the cell during cold shock, while cells preincubated with Mg2+ did not release segments of their outer membrane.


The extraction and analysis of lipopolysaccharides from Pseudomonas aeruginosa strain PAO, and three rough mutants.

Three spontaneously arising rough mutants of Pseudomonas aeruginosa have been isolated by selection for resistance to virulent lipopolysaccharide (LPS) specific bacteriophages. In addition, the first phages specific for rough mutants of P. aeruginosa were isolated. Using these phage and autoagglutination patterns in 4% NaCl and acriflavine, these mutants could be clearly distinguished from the wild-type strain and each other. Chemical analysis of the LPS together with chromatographic resolution of the polysaccharide moieties showed alterations in both O-specific side chains and core regions.


Activation of serum prophenoloxidase in arthropod immunity. The specificity of cell wall glucan activation and activation by purified fungal glycoproteins of crayfish phenoloxidase.

This study shows that the activation of crayfish serum prophenoloxidase by carbohydrates was specific for beta-1,3-glucans. Fractionation of the beta-1,3-glucan laminaran into laminaran M and laminaran G showed that both activated the proenzyme, but the G-chain had somewhat higher affinity for the proenzyme. Methylation analysis of these two fractions revealed that there were no 1,6-linkages present. Laminaripentaose, a linear pentasaccharide composed of (1 leads to 3)-linked beta-D-glucopyranosyl residues was also active but had a lower affinity for the proenzyme than laminaran G. Laminaran completely inhibited the activation of prophenoloxidase by the pentaose. In the concentrations tested, laminaran was not inhibitory to the phenoloxidase activity. Purified extracellular glycoproteins of the parasitic fungus Aphanomyces astaci also strongly activated crayfish serum prophenoloxidase. Only high molecular weight glycoproteins were effective. Exo-beta-1,3-glucanase treatment decreased the activating capacity, suggesting that at least part of the glycoproteins consisted of beta-1,3-glucans. The significance of these results in the defence against parasitic fungi in crayfish is discussed.


Lymphoplasmacytic myeloma: an immunological, immunohistochemical and electron microscopic study.

An unusual case of a light chain plasma cell myeloma is described. The disease was initially characterized by a diffuse lymphoplasmacytic bone marrow involvement, but subsequently developed widespread extramedullary metastases with anaplastic tumors in the skin which histologically resembled a "histiocytic lymphoma." Electron microscopic examination, in vitro protein synthesis of bone marrow lymphoidal cells, chemical and immunochemical studies of serum and urine proteins, and intracellular immunoglobulin study by the immunoperoxidase technique on the skin biopsy and postmortem tumor tissue demonstrated evidence for lambda light chain synthesis and secretion. These findings provide further support to the notion that the wide spectrum of diverse morphologic patterns seen in lymphoplasmacytic disorders originates from the same progenitor B-lymphoid cell. Distinguishing anaplastic variant of plasma cell myeloma from other undifferentiated neoplasms offers a challenge.


Pseudolymphoma of breast.

A lymphoid infiltrate in the breast of a 77-year-old woman exhibited histological features warranting a diagnosis of pseudolymphoma. Detection of surface markers on cell suspensions of the lesion revealed approximately equal numbers of B aand T cells and kappa and lambda light chains in the immunoglobulins of the former. This represents ancillary evidence that is consonant with the pseudolymphomatous nature of the infiltration. Recognition of pseudolymphoma of the breast as an entity appears significant from practical and theoretical standpoints and is relevant to considerations concerning the incidence of so-called primary lymphoma of this organ.


Pathologic stage I and II Hodgkin's disease, 1968--1975: relapse and results of retreatment.

Sixty-seven previously untreated patients with Hodgkin's disease, pathologic stages I and II, seen during a 7-year period were evaluted with respect to initial staging and treatment, as well as relapse and retreatment results. The initial treatment consisted of radiation therapy (RT) to an involved field (IF) or an extended field (EF) for patients with stages IA and IIA, or RT and, in recent cases, combination chemotherapy [cyclophosphamide, Oncovin, procarbazine, and prednisone (COPP)] for patients with stages IB and IIB. Nineteen of the 67 patients relapsed (28%), including 11 of 56 patients with stages IA and IIA (20%) and 8 of 11 patients with stages IB and IIB (73%). Seventeen of the 19 relapses occurred within 24 months after completion of the initial therapy (89%). The relapse-free survival at 5 years was 75% for the A patients and 25% for the B patients. The actuarial survival of stage IA and stage IIA patients at 5 years was 91%; there was no significant difference between patients treated initially with either IF or EF. The actuarial survival at 5 years for the patients with stages IB and IIB was 88%, as most responded to a second program of induction therapy. No correlation could be found between the pattern of relapse and the initial pathologic stage or the mode of treatment.


Covalent binding of polycyclic aromatic hydrocarbons to adenine correlates with tumorigenesis in mouse skin.

Mouse epidermal homogenates were utilized to convert various polycyclic aromatic hydrocarbons to metabolites capable of binding covalently with nucleic acids. Poly(G) showed the highest capacity to bind covalently with the hydrocarbons; however, there was no correlation between binding to poly(G) and mouse skin tumorigenicity. On the other hand, covalent binding to poly(A) correlated well with values obtained for binding to DNA and mouse skin tumorigenicity. The order of binding to poly(A) was; 7,12-dimethylbenza[a]anthracene greater than benzo[a]pyrene greater than dibenz[a,h]anthracene greater than dibenz[a,c]anthracene.


The induction of sister chromatid exchanges by dihydrodiols derived from 7,12-dimethylbenz[a]anthracene and 3-methylcholanthrene.

The in vitro induction of sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells by the polycyclic hydrocarbons, 7,12-dimethylbena[a]anthracene and 3-methylcholanthrene and some of the related dihydrodiols was investigated. Increased numbers of SCEs were seen in the chromosomes of cells exposed to non-K-region dihydrodiols. The most active compounds were the 3,4-dihydrodiol of 7,12-dimethylbenza[a]anthracene and the 7,8- and 9,10-dihydrodiols of 3-methylcholanthrene: the parent hydrocarbons and their corresponding K-region dihydrodiols were relatively less active. The results are consistent with others that suggest that the metabolic activation of both hydrocarbons proceeds through the conversion of non-K-region dihydrodiols into vicinal diol-epoxides.


The effects of weak or non-carcinogenic polycyclic hydrocarbons on 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene skin tumor-initiation.

Benzo[e]pyrene (B[e]P) inhibited 7,12-dimethylbenz[a]anthracene (DMBA) skin tumor-initiation in mice by 84%, whereas pyrene and fluoranthene inhibited DMBA initiation by 50 and 34%, respectively. However, B[e]P, pyrene and fluoranthene had either no significant effect or a slight enhancing effect on benzo[a]pyrene (B[a]P) skin tumor-initiation. In addition, B[e]P had essentially no effect on the initiating ability of (+/-)B[a]P-7 beta,8 alpha-diol-9 alpha,10 alpha-epoxide. As a tumor-initiator, B[e]P was found to have very weak activity at a 252 microgram/level (0.4 papillomas/mouse at 40 weeks) and no activity at 100 microgram. When given at a dose of 100 microgram twice weekly, B[e]P induced 2.1 papillomas/mouse at 30 weeks, and 25% of the mice had carcinomas at 40 weeks. However, B[e]P carcinogenic activity is weak when compared to B[a]P, which can induce a comparable tumor response at a dose of 5 microgram twice weekly. When B[e]P was tested as a tumor promoter at a dose of 100 microgram twice weekly after DMBA initiation, it induced 4.5 papillomas/mouse at 30 weeks and a 45% carcinoma incidence at 40 weeks, which was approximately twice as effective as B[e]P alone. The data show that B[e]P is a very weak tumor initiator, a weak complete carcinogen, a moderate tumor promoter, possibly a weak co-tumor-initiator when given with B[a]P, and a potent anit-tumor-initiator when given with DMBA. The anti-tumor initiating and co-tumor-initiating effects of B[e]P appear to be related to its ability to modify the conversion of the tumor initiator into an electrophilic intermediate(s) which are capable of covalently binding to DNA. In addition, B[e]P induced epidermal cellular proliferation which may be related to its promoting ability.


Collagen synthesis in capsules surrounding dimethylbenzanthracene-induced rat breast tumors and the effect of pretreatment with beta-aminopropionitrile.

Collagen synthesis is increased over three-fold in capsules surrounding dimethylbenzanthracene-induced rat breast tumors compared to the tumor parenchyma and over six-fold compared to normal breast connective tissue. Increased collagen synthesis is independent of the rate of tumor growth and final tumor size. Pretreatment of animals with beta-aminopropionitrile to inhibit collagen cross-linking caused an 82% decrease in tumor formation and a significant reduction in tumor volume (approximately 0.4 cu cm) compared to controls (approximately 10 cu cm). The four small tumors that did develop in the lathyritic animals had increased collagen synthesis in the interior tumor stroma and reduced collagen synthesis in the tumor capsule. These findings suggest that the collagenous capsule surrounding dimethylbenzanthracene tumors functions as a physical barrier to protect the tumor from the immune system of the host. The apparent antitumor effects of beta-aminopropionitrile may be due to immunopotentiation and/or cytotoxic actions of the drug.


Interactions of the carcinogen 4-nitroquinoline 1-oxide with the non-protein thiols of mammalian cells.

The carcinogen 4-nitroquinoline 1-oxide (4-NQO) was found to rapidly deplete non-protein thiols (NPSH) from Ehrlich ascites tumor cells and V79 Chinese hamster fibroblasts. The effects of NPSH on 4-NQO metabolism were studied by measuring 4-hydroxyaminoquinoline 1-oxide formation, CN- -insensitive oxygen consumption, and reduction of ferricytochromes c + c1 in normal cells and in cells pretreated with the thiol reagent N-ethylmaleimide. Removal of thiols before treatment with 4-NQO resulted in increased production of 4-hydroxyaminoquinoline 1-oxide and increased production of nitro radicals. The NPSH thus appeared to play a significant role in 4-NQO detoxification. Glutathione, when present in culture medium during 4-NQO treatment, protected V79 cells from 4-NQO toxicity. Several mechanisms for reaction of 4-NQO with intracellular NPSH were indicated. Both V79 and Ehrlich cells contained appreciable amounts of glutathione S-transferase (EC 2.5.1.18), which catalyzes the nucleophilic substitution of the nitro group of 4-NQO with thiols. Greater thiol loss under oxic than under hypoxic conditions suggested oxidation by superoxide, peroxide, or hydroxyl radical formed in the course of 4-NQO reduction. In addition, reaction of thiols with nitro radicals or with nitrosoquinoline 1-oxide was indicated by the inhibitory effect of glutathione on oxygen consumption in solutions of 4-NQO and sodium ascorbate.


Experimental animal models of adriamycin cardiotoxicity.

Since patients exhibit both acute and chronic cardiac toxic effects from Adriamycin, the salient characteristics of the reported animal models for both acute and chronic cardiotoxicity are reviewed. This review reveals that while the pathology of these models is often well-characterized, the physiologic, biochemical, and nutritional variables are, in general, poorly defined.


Types of degenerating geniculocortical axon terminals and their contribution to layer IV of area 17 in the squirrel monkey (Saimiri).

Radiofrequency lesions were made in the lateral geniculate nuclei of six squirrel monkeys. The resulting degenerating terminals and their postsynaptic structures in layer IV of area 17 were quantitatively categorized on photomontages covering large areas of neuropil. Two to five days after the lesion, numerous axon terminals were affected by a variety of degenerative changes, i.e., enlargement and distortion of synaptic vesicles, neurofilamentous hyperplasia, electron-lucent and electron-dense reactions. Based on the aggregation of electron-dense material beneath the postsynaptic membrane, the degenerating terminals were considered to be of the asymmetric type. Among the degenerating boutons were the largest axon endings that occur in layer IV. Three days postoperatively, degenerating boutons contributed an average of 16.2% to the total synapse population; five days postoperatively, the average had increased to 19.3%. The percentage of degenerating boutons on individual montages, however, amounted to as much as 29%. This amount probably reflects more closely the actual contribution of the geniculocortical fiber system to layer IV of striate cortex. The postsynaptic structure most frequently contacted by degenerating axon endings was the dendritic spine, followed by dendrites of small diameter. To account for the diversity of degenerative changes in the same fiber system, we offer the tentative suggestion that heterogeneously degenerating axon terminals arise from a heterogeneous population of neurons in the lateral geniculate nucleus, i.e., from magnocellular versus parvocellular laminae.


Sequence organization of two recombinant plasmids containing genes for the major heat shock-induced protein of D. melanogaster.

We have isolated recombinant DNA clones which include cDNA and chromosomal DNA sequences of the major heat shock-inducible gene of Drosophila. With the cDNA fragments used as specific hybridization probes, DNA:DNA reassociation and in situ hybridization analysis demonstrated that the DNA sequences are repeated approximately 7 times in the haploid Drosophila genome, and that gene sequences are present at both the 87A and 87C loci on the cytological map. The cloned cDNA and homologous cloned chromosomal DNA hybridized to mRNA which translated in vitro into the major 70K heat shock-specific protein. Here we summarize a study of the organization of genes coding for the 70K heat shock-specific protein contained in the two recombinant chromosomal DNA plasmids pG3 and pG5. On the basis of R loop hybridization experiments and restriction enzyme analysis, we conclude that a 14 kb fragment, G3, contains three copies of the gene coding for the 70K protein. A second 9.2 kb fragment, G5, contains one copy of the gene coding for the 70K protein. Hybridization of labeled poly(A)-containing RNA to restriction endonuclease-cleaved DNA indicates that the mRNA coding regions in G3 and G5 are each approximately 2100 bp long. The three tandemly repeated genes of G3 are separated by approximately 1400 bp of spacer DNA. The two internal spacer regions in G3 appear to be identical, whereas differences in restriction enzyme sites indicate that the sequences adjacent to the cluster differ from the internal spacer and from each other.


Identification and time of synthesis of chorion proteins in Drosophila melanogaster.

The chorion of Drosophila melanogaster consists of proteins secreted by the follicular epithelium during late oogenesis. Petri, Wyman and Kafatos (1976) have described six major protein components of the Drosophila chorion and reported the synthesis of these proteins in vitro by mass-isolated egg chambers. We have used two-dimensional gel electrophoresis to identify approximately twenty components in highly purified chorion preparations. The synthesis patterns of these proteins in vivo were determined by isolating egg chambers of different developmental stages from flies injected with 14C amino acids. Chorion proteins constitute a large fraction of the protein synthesized by ovarian egg chambers in stages 12--14. The sizes and times of synthesis of the chorion proteins correlate closely with the production of poly(A)-containing RNAs by the follicle cells (Spradling and Mahowald, 1979).


A 9.6 kb intervening sequence in D. virilis rDNA, and sequence homology in rDNA interruptions of diverse species of Drosophila and other diptera.

A large proportion of the 28S ribosomal RNA genes in Drosophila virilis are interrupted by a DNA sequence 9.6 kilobase pairs long. As regards both its presence and its position in the 28S gene (about two thirds of the way in), the D. virilis rDNA intervening sequence is similar to that found in D. melanogaster rDNA, but lengths differ markedly between the two species. Degrees of nucleotide sequence homology have been detected bewteen rDNA interruptions of the two species. This homology extends to putative rDNA intervening sequences in diverse higher diptera (other Drosophila species, the house fly and the flesh fly), but hybridization of cloned D. melanogaster and D. virilis rDNA interruption segments to DNA of several lower diptera has been negative. As is the case with melanogaster rDNA interruptions, segments of the virilis rDNA intervening sequence hybridize with non-rDNA components of the virilis genome, and interspecific homology may involve these non-rDNA sequences as well as rDNA interruptions. There is, however, evidence from buoyant density fractionation of DNA that the distributions of interruption-related sequences are distinct in D. melanogaster and D. virilis genomes. Moreover, thermal denaturation studies have indicated differing extents of homology between hybridizable sequences in D. virilis DNA and different segments of the D. melanogaster rDNA intervening sequence. We infer from our studies that rDNA intervening sequences are prevalent among higher diptera; that in the course of the evolution of these organisms, elements of the intervening sequences have been moderately to highly conserved; and that this conservation extends in at least two distantly related species of Drosophila to similar sequences found elsewhere in the genomes.


Physical map of two D. melanogaster DNA segments containing sequences coding for the 70,000 dalton heat shock protein.

The isolation of the two hybrid plasmids 56H8 and 132E3, which contain D. melanogaster (Dm) DNA sequences complementary to the mRNA coding for the 70,000 dalton heat shock protein, has been reported (Schedl et al., 1978). Here we compare the sequence arrangement in the two cloned Dm DNA segments by restriction, cross-hybridization and heteroduplex analysis. The results show that the two cloned DNA segments derive from nonoverlapping regions of the Dm genome; that they contain homologous regions present once in 56H8 and twice in 132E3; and that each homologous region is composed of three distinct contiguous sequence elements, x, y and z, which together define a 3 kb common unit. While the 2.5 kb z elements show a high degree of sequence homology in all three common units, the three x and y elements display an intriguing relationship. The localization of the mRNA coding sequences within each of these common units is presented in the accompanying paper (Artavanis-Tsakonas et al., 1979).


In vitro synthesis of a 5S RNA precursor by isolated nuclei of rat liver and HeLa cells.

Isolated rat liver nuclei were incubated under appropriate conditions in the presence of 0.5 micrograms/ml alpha-amanitin and an RNAase inhibitor prepared from cytosol fraction, together with alpha-32P-UTP or alpha-32P-CTP and three other nucleoside triphosphates. RNA extracted by an SDS-hot phenol procedure was fractionated with sucrose density gradient centrifugation followed by acrylamide gel electrophoresis. Fingerprint analysis of the in vitro synthesized "5S" RNA, which was slightly larger than mature 5S RNA on gel electrophoresis, showed that it contained all the sequences of mature 5S RNA except for the oligonucleotide at the 3' end. Instead, it contained two additional spots which were not present in mature 5S RNA. Analysis of the extra spots revealed that they were derived from the 3' end of the in vitro synthesized "5S RNA, which were sequenced tentatively as -CUUGAUGCUUoh (extra sequence underlined). The 5' end of the product was (p)pGU--. Isolated HeLa cell nuclei synthesized similar sized "5S" RNA under the same conditions. We conclude from these results that in isolated nuclei of these mammalian cells RNA polymerase III starts transcription of 5S RNA gene at the same site as the 5' end of mature 5S RNA, proceeds toward the 3' direction and stops at a site probably 8 nucleotides downstream from the 3' end of mature 5S RNA. Experiments with a short pulse and with various "chases" have demonstrated the presence of a short-lived precursor 5S RNA which is similar in size and sequence to in vitro "5S" RNA, suggesting that 5S RNA is synthesized in vivo as a longer precursor molecular as demonstrated in this in vitro system, and is rapidly processed into mature 5S RNA.


Tandem promoters direct E. coli ribosomal RNA synthesis.

To determine the special feature of ribosomal RNA promoters that might account for the highly efficient and regulated synthesis of rRNA in E. coli, we have analyzed the beginnings of two ribosomal RNA operons, rrnD and rrnX. DNA sequences for 425 bp preceding those specifying mature 16s rRNA are reported. In vitro transcription of restriction endonuclease fragments containing this region from either operon reveals the presence of two promoters about 110 nucleotides apart; they are denoted P1 and P2. RNA synthesis from P1 is initiated with GTP at position -284 (relative to 16s sequences) in rrnD and with ATP at position -285 in rrnX. At P2, the RNA starts with CTP primarily at position-176 in both operons. The DNA sequences of the two operons are identical for 231 bp preceding the 16s rDNA (including a substantial region around P2); they then diverge almost completely, except for a notable 18 bp homology just preceding the transcription start site for P1. Certain sequences implicated in the recognition of promoters by E. coli RNA polymerase are clearly identifiable in both P1 and P2; other features include an extended region preceding P1 which is strikingly rich in AT base pairs. Possible mechansims by which these tandem promoters contribute to the high frequency of rRNA transcription and to the differential expression of the E. coli rrn operons are discussed.


Genes for the 70,000 dalton heat shock protein in two cloned D. melanogaster DNA segments.

Two hybrid plasmids, 56H8 and 132E3, which contain D. melanogaster (Dm) DNA segments coding for the 70,000 dalton heat shock protein, have been isolated (Schedl et al., 1978). The analysis of the sequence arrangement presented in the accompanying paper (Moran et al., 1979) shows that both Dm segments contain homologous regions composed of three distinct sequence elements which together define a common unit. We report here that the sequences complementary to the 70,000 dalton protein mRNA appear to be confined to a major portion of the largest element of the common unit and that the other sequence elements are located at the 5' end of the gene. We have also determined the cytogenetic location of the 70,000 dalton protein genes and have investigated whether these sites are transcriptionally active in salivary gland chromosomes.


Transposition of elements of the 412, copia and 297 dispersed repeated gene families in Drosophila.

The stability of elements of three different dispersed repeated gene families in the genome of Drosophila tissue culture cells has been examined. Different amounts of sequences homologous to elements of 412, copia and 297 dispersed repeated gene families are found in the genomes of D. melanogaster embryonic and tissue culture cells. In general the amount of these sequences is increased in the cell lines. The additional sequences homologous to 412, copia and 297 occur as intact elements and are dispersed to new sites in the cell culture genome. It appears that these elements can insert at many alternative sites. We also describe a DNA sequence arrangement found in the D. melanogaster embryo genome which appears to result from a transposition of an element of the copia dispersed repeated gene family into a new chromosomal site. The mechanism of insertion of this copia element is precise to within 90 bp and may involve a region of weak sequence homology between the site of insertion and the direct terminal repeats of the copia element.


Polymorphisms in the chromosomal locations of elements of the 412, copia and 297 dispersed repeated gene families in Drosophila.

The number and chromosomal locations of elements of the 412, copia and 297 dispersed repeated gene families differ extensively when the genomes of four D. melanogaster strains are compared. Differences among individuals from the same laboratory stock in the arrangement of these elements are also observed. In contrast to these polymorphisms, the structures of the elements themselves are closely conserved. Our results indicate that 412, copia and 297 are capable of evolutionarily rapid transpositions to new chromosomal sites.


Structural and image analysis of a crystalline layer from dipteran eggshell.

A crystalline layer has been identified as a constituent of the eggshell in the dipteran Drosophila melanogaster. This 400A thick intermediate chorionic layer (ICL) is composed of eight 50A thick sublayers and lies between the vitelline membrane and the endochorion. Whole mount views of isolated ICL after negative staining reveal P2 planar periodicity which, when analyzed further by optical diffraction and filtering, showed 1st (100A), 2nd, 3rd and 4th order reflections.


[Tuberculosis in patients deceased of renal insufficiency in a long-term hemodialysis program].

Eight cases of tuberculosis were seen in a series of patients dying of renal insufficiency after having been subjected to a long-term haemodialysis. In 5 cases Mycobacterium tuberculosis was successfully cultivated (4 were typed as human, 1 as bovine). In 5 cases the disease affected mainly the lymph nodes, not the lungs. In 3 of these a prevalence of abscessing specific granulomas with the presence of leucocytes was noted on microscopical examination. The findings have been regarded as possibly related to an impairment of cellular (lymphocytic) immunity, presumably caused by chronic uraemia or long-term haemodialysis.


The formation of dihydrodiols by the chemical or enzymic oxidation of 7-hydroxymethyl-12-methylbenz[alpha]anthracene and the possible role of hydroxymethyl dihydrodiols in the metabolic activation of 7,12-dimethylbenz[alpha]anthracene.

The formation of dihydrodiols from 7-hydroxymethyl-12-methylbenz[alpha]anthracene by rat-liver microsomal fractions, by mouse skin in short-term organ culture and by chemical oxidation in an ascorbic acid/ferrous sulphate/EDTA system has been studied using a combination of thin-layer chromatography and high pressure liquie chromatography. The 3,4-, 8,9- and 10,11-dihydrodiols were formed in all three systems. The 5,6-dihydrodiol was formed in rat-liver microsomal fractions and in chemical oxidation but was not detected as a metabolite of [7-3H]hydroxymethyl-12-methylbenz[alpha]anthracene when this compound was incubated with mouse skin in short-term organ culture. The possible role of hydroxymethyl dihydrodiols in the in vivo metabolic activation of 7,12-dimethylbenz[alpha]anthracene in mouse skin has been studied using Sephadex LH-20 column chromatography. The results show that the hydrocarbon-nucleic acid products formed following the treatment of mouse skin in vivo with [7,12-3H]dimethylbenz[alpha]anthracene are not the same as those that are formed following the treatment of mouse skin under the same conditions with either 7-hydroxymethyl-12-methylbenz[alpha]anthracene or 7-methyl-12-hydroxymethylbenz[alpha]anthracene.


The formation of dihydrodiols from benzo[alpha]pyrene by oxidation with an ascorbic acid/ferrous sulphate/EDTA system.

In the oxidation of benzo[alpha]pyrene in an abscorbic acid-ferrous sulphate-EDTA system, four dihydrodiols were detected. Three, trans-4,5-dihydro-4,5-dihydroxybenzo[alpha]pyrene, trans-7,8-dihydro-7,8-dihydroxybenzo[alpha]pyrene and trans-9,10-dihydro-9,10-dihydroxybenzo[alpha]pyrene were identified by their UV spectra and by direct comparisons of their chromatographic properties, using HPLC, with those of the authentic compounds. The fourth compound appeared to be trans-11,12-dihydro-11,12-dihydroxybenzo[alpha]pyrene since its ultraviolet spectrum was identical to that of the cis-dihydrodiol. Time-course experiments showed that the maximum amounts of products were obtained after 8 h of oxidation. A re-examination of the dihydrodiols formed from benzo[alpha]pyrene by rat-liver microsomal fractions failed to show the formation of the trans-11,12-dihydrodiol.


The association of bacterial mutagenicity of hydrocarbon-derived 'bay-region' dihydrodiols with the Iball indices for carcinogenicity and with the extents of DNA-binding on mouse skin of the parent hydrocarbons.

The mutagenic activities of benz[alpha]anthracene, 7-methylbenz[alpha]anthracene, 7,12-dimethylbenz[alpha]anthracene, 3-methylcholanthrene and benzo[alpha]pyrene, together with those of the trans-dihydrodiols derived from these hydrocarbons that would be expected to yield 'bay-region' vicinal diolepoxides on further metabolism have been examined in assays with S. typhimurium TA100 using post-mitochondrial supernatant fractions prepared from the livers of 3-methylcholanthrene-treated rats. Mutagenic activities obtained have been compared with: (a) the extents of reaction with DNA that occur in mouse skin following treatment with these hydrocarbons; (b) the carcinogenicities of the hydrocarbons expressed as Iball indices; (c) their activities as tumour-initiating agents on mouse skin. Close positive associations were found between the microsome-mediated mutagenicities of the dihydrodiols that could yield "bay-region" diol-epoxides and: (a) the extents of reaction with DNA in hydrocarbon-treated mouse skin; (b) the carcinogenic potencies of the parent hydrocarbons; although these correlations are not perfect, the mutagenic activities of the hydrocarbons themselves in microsome-mediated assays with S. typhimurium show no correlation with their extents of DNA binding on mouse skin and a poor correlation with their activities as initiating agents. These comparisons also indicated a statistically-significant positive correlation between carcinogenicity and the in vivo DNA binding on mouse skin treated with the hydrocarbons. Differences in the metabolic pathways by which polycyclic hydrocarbons are activated in vivo and in vitro are discussed in relation to the improved correlations found with the dihydrodiols.


Chemical and ultrastructural examination of lead-induced morphological convertants of Bacillus subtilis.

Actively-growing Bacillus subtilis 168 cells, exposed to lead nitrate, had only slightly decreased ability to bind the divalent cation magnesium. The nature and quantity of the major cell wall metal binding components, teichoic and teichuronic acids, and the carbohydrate constituents of the peptidoglycan remained relatively constant. Purified cell walls, isolated from cells exposed to lead for 6 and 13 days, retained 9.9 micrograms Pb+2 and 3.5 micrograns Pb+2/mg cell wall, respectively. The occurrence of this lead in the isolated cell wall did not interfere with its Mg2+-binding capacity. While cationic binding properties, growth rate and cell yield indicated non-interference from lead, light and electron microscopic studies clearly demonstrated morphological alterations in approx. 30--50% of the lead treated cells. These alterations included the conversion to irregular spherical forms, some of which contained thickened cell walls. These anomalies are virtually identical to those reported for mutants of this bacterium derived via the introduction of classical mutagens. Protoplasts, similar to those produced by antibiotic and enzymatic treatments, were also present in the lead-treated cells. Although the most tenable explanation appeared to be cellular mutations, the morphological convertants appear to be derived from lead's interference with cell wall biosynthesis process and/or the assemblage of cell wall subunits.


[Topography of the tecto-tectal component of the main ipsilateral visual pathway of the frog (Rana esculenta L.)].

The detailed topography of the tecto-tectal component of the Frog's ipsilateral visual pathway is electrophysiologically obtained by mapping the optic lobes. This linkage transfers the visual information explored along a transversal tectal row on to an homologous line oriented at 130 degrees on the opposite tectum. The ipsilateral projection of the temporo-nasal axis of the retina, but not of the antero-posterior axis of the visual field, is reversed compared to its contralateral projection. Finally, the majority of the homologous tectal points are asymmetrical with respect to the animal's sagittal axis.


[Immunohistochemical identification, in an anuran amphibian (Xenopus laevis Daud.) of infundibular neurons reacting with antigastrin serum].

Neurons containing peptides immunocytologically related to gastrin have been revealed by immuno-cytology in the post-chiasmatic hypothalamus of Xenopus laevis. Their pericarya are localized in the postero-dorsal zone of the pars ventralis of the tuber cinereum; their axons end on the capillaries of the external zone of the median eminence.


[Cytolysis through cells dependent on immunization against cellular antigens: identification and enumeration of cytotoxic cells].

In this report we show how to identify and enumerate alloantigen-dependent killer cells. Individual effector cells are associated by micromanipulation to target cells and the doublets are incubated at 37 degrees C. Killers are identified by the lysis of the associated target. Killer cells can be subdivided into two subpopulations: cell responsible for the lysis of the specific target cells which bear the immunizing H-2 antigens and cells which kill only lectin pretreated targets.


[A model for determination of the expected numbers of chromosome alterations and break points].

The assumption that the expected number of chromosome break points is simple and directly proportional to the length of chromosomes is criticized. Translocations and inversions imply two dependent break points in relation to their distribution on the whole karyotype, that is why, this assumption should be modified. A model is presented which takes the dependence into account and which provides the formulas for the calculations of probabilities of binary rearrangements and of their respectives break points. We apply the model to the human karyotype.


[Demonstration and evolution of chorionic gonadotropin in ewes].

Occurrence of ovine Chorionic Gonadotropin (oCG) is demonstrated in placenta and amniotic fluid with the use of a radioreceptor assay (corpus luteum membranes) in ewes. Identification of oCG is possible as early as 15th day of pregnancy. It should be secreted at a constant rate, and its maximum concentration is recorded on the 130th day. This hormonal factor might be one of the major components accountable for high progesteronemia observed during the 100 last days of pregnancy.


[Effects of feeding corn infested by Fusarium to sows].

The effects of feeding Gilts with mouldy Corn containing 3,61 mg/kg zearalenone were tested. Ingestion of this mycotoxin by puberous Gilts blocked the sexual cycles in more than half of the animals. Uterine horns were enlarged and corpora lutea didn't regress into corpora albicantia. The presence of zearalenone in the diet of pregnant Gilts had no effect on embryonic mortality at 80 days of pregnancy, but reduced foetal weight by 26%.


[Fourier transform analysis of glycolipid depots in Fabry's disease].

An application of the Fourier Transform Process to the Fabry inclusion study has been made. The study, which rests upon five tissues and eight persons, brings out a new low frequency stratification. Various degrees of freedom exist for the basic molecule association. The periods are given for the three fundamental directions of the inclusion.


Uptake and distribution of daunorubicin and daunorubicin-DNA complex in mice as studied by whole-body autoradiography and liquid chromatography.

The tissue distribution of daunorubicin (D) and daunorubicin-DNA complex (D-DNA) was studied in mice by means of whole-body autoradiography (WBA) and high-performance liquid chromatography (HPLC). A higher accumulation of radioactivity in the blood after 1 min and a lower initial accumulation in the cardiac muscle were found after administration of 3H-D-DNA than after the infection of free drug. Comparative studies of plasma levels of daunorubicin and daunorubicinol (DOH) in D- and D-DNA-treated animals by HPLC showed that the initial differences were negligible from 2 h onward. A rapid accumulation of D in bone marrow occurred in both D- and D-DNA-treated mice. D reached its maximum level after 1 h and was almost constant for 12 h. A new WBA finding was a rapid and specific accumulation of radioactivity in the pituitary gland, in the thyroid, and in the pancreatic islets, which might be of some interest in consideration of possible late endocrine side effects of anthraquinone glycoside therapy.


Microvascular architecture of anthropoid primate intestine.

Microvascular architecture of the small intestine of New World monkey, ape, and man was examined with the silicone rubber injection technique and the results compared to previous observations in dogs and Old World monkeys. In man, chimpanzee, and New World monkey the small intestine villus contains a single centrally located vein draining a subepithelial capillary plexus converging at the apex of the villus. These villi also contain a single eccentrically located artery rising to the midlevel of the villus, where it branches into subepithelial capillaries over the rest of its length. This vascular architecture most closely resembles that observed in the gut of Old World monkeys in which the villus artery is absent altogether. This observation contrasts the microvascular architecture of canine intestinal villi in which marginal arteries surround a centrally located vein. These patterns of microvascular anatomy are analyzed in terms of the role of the gut in the pathogenesis of experimental shock. The differences observed may account for the known species variations in canine and primate experimental shock.


Prolonged shock in the baboon subjected to infusion of E. coli endotoxin.

This study was designed to examine the response of the baboon during a 24-hour period following Escherichia coli endotoxin infusion. Experiments were conducted on young adult baboons, unrestrained and maintained at a light plane of anesthesia induced with pentobarbital sodium. Light and electron microscopic studies on lung, heart, liver, and kidney were conducted; hematologic changes and physiologic responses were measured. The efficacy of heparin to prevent the coagulopathy and increase survivability was assayed. Hepatic sinusoidal fibrin thrombi with underlying hepatocyte cellular damage was seen in the endotoxin-treated group. In contrast, the experimental group receiving heparin showed no sinusoidal fibrin thrombi but demonstrated hepatocellular damage. Liver dysfunction was indicated by elevation of blood levels of enzymes. Glomerular fibrin thrombi were not present. Although heparin prevented the formation of hepatic thrombi in endotoxin-treated baboons, it did not increase survival. Platelet and complement levels decreased in both experimental groups, while wide variations in white blood cell and fibrinogen levels were observed. Polymorphonuclear leukocyte-platelet aggregations previously reported in the pulmonary vasculature during acute shock were not observed in the present study, and their absence may have been related to the longer time of survival.


Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat.

We studied the pulmonary vascular effects of prostacylin, PGI2, in the cat with intact chest under conditions of controlled blood flow. Intralobar injections of PGI2, 0.03--1 microgram, decreased arterial pressure in the perfused lobe in a dose-dependent manner. Inasmuch as lobar blood flow was held constant and left artrial pressure was unchanged, the fall in lobar arterial pressure reflects a decrease in lobar vascular resistance. Prostaglandin E1 (PGE1) and nitroglycerin also decreased lobar arterial pressure; however, PGI2 had greater vasodilator activity than did these substances. Vasodilator responses to PGI2, PGE1, and nitroglycerin in absolute terms were dependent on the baseline level of tone in the pulmonary vascular bed. Prostacyclin reversed the hypertensive and platelet aggregating effects of ADP in the lobar vascular bed. These data indicate that PGI2 has significant vasodilator activity in the feline pulmonary lobar vascular bed.


Valve replacement for aortic regurgitation: long-term follow-up with factors influencing the results.

One hundred consecutive cases of valve replacement for aortic regurgitation performed between 1967--1971 were analyzed to identify and quantitate factors related to a favorable result. Of 83 perioperative survivors, 78% (n = 65) became asymptomatic and 58% (n = 48) were alive 5--9 years postoperatively. The cause of aortic regurgitation affected both the speed of progression of symptoms and the postoperative result. Death due to myocardial failure may be prevented by optimal timing of operation. Accordingly, we identified variables that discriminated between patients who had an excellent postoperative result and those who died of myocardial failure. The most important discriminators were the severity (p = 0.03) and duration (p = 0.04) of dyspnea, the extent of therapy for heart failure (p = 0.001), physical findings of left ventricular failure (p = 0.002), the cardiothoracic ratio (p = 0.007), the resting pulmonary capillary wedge pressure (p = 0.01), and a cardiac index less than 2.2 1/min/m2 (p = 0.03). The data suggest that evidence of left ventricular failure, even of mild degree, is an indication for operation in patients with severe aortic regurgitation.


The T3/TBG ratio and the biochemical investigation of thyrotoxicosis.

The relationship between serum tri-iodothyronine (T3) and thyroxine-binding globulin (TBG) has been studied in euthyroid subjects. This relationship is similar to that previously described for thyroxine (T4) and TBG. Serum T3, TBG and T4 data are presented for euthyroid subjects of all ages and the T4:T3 and T3:TBG ratios calculated. Similar data has been derived for patients with clinically proven thyrotoxicosis and for patients in which the diagnosis was in doubt. The results suggest the T3:TBG ratio enhances the use of the T3 assay to confirm thyrotoxicosis. The fact that 25% of our patients suffering from thyrotoxicosis had apparently normal serum T4 levels reinforces the contention that a serum TBG assay must be carried out as part of a basic thyroid function screen.


Variation in values for iodothyronine hormones, thyrotropin, and thyroxine-binding globulin in normal umbilical-cord serum with season and duration of storage.

We measured concentrations of thyroxine, triiodothyronine, reverse triiodothyronine, thyroxine-binding globulin, and thyrotropin in pooled samples of cord sera from normal newborns. Sera collected in winter contain significantly (p less than 0.05) higher concentrations of the first tour--14.9, 13.4, 9k9, and 7.5%, respectively--than do sera collected in summer; thyrotropin concentrations are similar in samples collected during winter and summer (p greater than 0.05). With storage, the values for the thyronines and thyrotropin decreased progressively at rates between 0.9 and 5.3% per year; those for thyroxine-binding globulin did not change significantly.


Radial and linear thin-layer chromatographic prodedures compared for screening urines to detect oligosaccharidoses.

We describe a circular (radial) thin-layer chromatographic procedure for separating urinary oligosaccharides. Results were better than those obtained by a single linear development. Bands and specific patterns were finely resolved for various known oligosaccharidoses. The procedure provides a simple means of screening for these disorders.


Evaluation of a solid-phase enzyme immunoassay for insulin in human serum.

We describe a "sandwich-type" enzyme immunoassay for insulin in serum, in which antibody Fab'-beta-D-galactosidase conjugate and an antibody-immobilized silicone rubber solid-phase are used. The interference by serum factors with the solid-phase enzyme immunoassay can now be removed by using a buffer containing gelatin. Serum samples of 50 microL can be analyzed by the enzyme immunoassay, which is as sensitive as radioimmunoassay for human insulin. Our results correlate well with those for radioimmunoassay (r = 0.97, slope = 0.92, y-intercept = 4.6 milli-int. units /L for 181 samples). Between-assay and within-assay coefficients of variation are less than 15% over the useful ranges of the assay (5--160 milli-int. units/L).


Human amylase isoenzymes separated on concanavalin A--Sepharose.

Human salivary amylase and pancreatic amylase were purified and characterized. These amylases gave two bands and one band, respectively, each staining for both protein and sugar, after electrophoresis on sodium dodecyl sulfate--polyacrylamide gel. The relative molecular mass (Mr) or pancreatic amylase was calculated to be 60 000; for the two components (A and B) of salivary amylase the Mr were 61 000 and 64 000. The two salivary amylases were separated by chromatography on concanavalin A--Sepharose; only component B bound to concanavalin A. The carbohydrate content of pancreatic amylase was 1.61 +/- 1.02% (SD), and of salivary amylases A and B 2. 18 +/- 0.71% and 8.77 +/- 2.28%, respectively. The salivary and pancreatic amylases had completely identical antigenicities against antibody to either. On isoelectric focusing, pancreatic amylase showed one peak at pH 7.0, salivary amylase A showed a major peak at pH 6.4 WITH A TRACE OF MATERIAL At pH 5.9, and salivary amylase B a major peak at pH 5.9 and one minor peak at pH 6.4. Serum amylase was separated into two major peaks with isoelectric points (pl) of 6.4 and 7.0, respectively, and one minor peak, with a pl of 5.9. Only a small part of the serum amylase with a pl of 5.9 combined with concanavalin A; the two other serum amylases did not.


Improved double-antibody enzyme immunoassay for methotrexate.

We report an enzyme immunoassay procedure for methotrexate measurement that takes less than 3 h to perform. beta-D-Galactosidase (EC 3.2.1.23) from Escherichia coli was conjugated to methotrexate by means of the mixed anhydride reaction. Bound and free labeled drug were separated by a preincubated cubic complex of first and second antibody. The enzyme activity of the bound fraction was measured with o-nitrophenyl-beta-D-galactopyranoside as substrate. The standard curve covered the range 1 to 10 micrograms of methotrexate per liter. One microgram of methotrexate per liter inhibited binding of the tracer by 17%. The assay is specific for methotrexate in the presence of folinic acid (citrovorum factor), folic acid, tetrahydrofolic acid, and other methotrexate metabolities. Intra- and inter-assay CVs were less than 5 and 10%, respectively. Results obtained with this enzyme immunoassay method agreed well with those obtained with an established radioimmunoassay method.


Induction of craniofacial malformations in rhesus monkeys (Macaca mulatta) with cyclophosphamide.

Administration of cyclophosphamide to pregnant rhesus monkeys induces two syndromes of craniofacial malformations characterized by underdevelopment of the face of different pattern depending on the timing of treatment. The first is cleft lip with cleft palate and exophthalmos. The second is a craniofacial dysmorphia with marked underdevelopment of the midfacial bones, highly arched closed palate, and either meningoencephalocele or persistent anterior fontanel. Since cleft lip and palate are among the most common malformations in man, and several human syndromes involving abnormal craniofacial development have features in common with the dysmorphic monkeys, these induced anomalies may prove valuable in investigations on the pathogenesis of such malformations and as surgical models.


Glycosidases in serum of cystic fibrosis patients.

In a study of eight glycosidases in serum samples from 72 cystic fibrosis patients, 85 cystic fibrosis parents and 34 healthy and diseased controls, significant elevations of mean alpha-glucosidase levels were found in cystic fibrosis patients. All other glycosidases did not show any significant change. Mean alpha-glucosidase levels in obligate heterozygotes were the same as in control individuals. Moreover, alpha-glucosidase levels in cystic fibrosis patients correlated with the degree of clinical impairment as measured by the Schwachman score.


Myoclonus and the electroencephalogram, a review.

Myoclonus is a phenomenon which cuts through a considerable number of neurological conditions. It occurs in a variety of epileptic conditions (Primary generalized epilepsy, hypsarrhythmia, Lennox-Gastaut syndrome, also known as "petit mal variant"), in inborn errors of metabolism (Tay-Sachs disease, forms of ceroid lipofuscinosis), in neurobiochemically still poorly understood forms of degenerative processes such as Essential hereditary myoclonus epilepsy (Lafora-Unverricht-Lundborg), in benign heredo-degenerative disorders (Hartung's syndrome), in CNS infections (SSPE, Jakob-Creutzfeldt disease), in metabolic encephalopathies (renal failure, hypoglycemia), in CNS poisoning, in acute cerebral anoxia and in post-anoxic states. The EEG plays a crucial role in the differential diagnosis of these conditions by the demonstration of a) presence or absence of typical inter-ictal abnormalities, and b) various correlates of the myoclonic ictal event.


Thyrotrophin-releasing hormone inhibits the pentagastrin stimulated gastric secretion in man. A dose response study.

Actions of thyrotrophin-releasing hormone (TRH) have generally been confined to the central nervous system (CNS). We have studied the effect of increasing doses of TRH i.v. (8, 40, 200 and 1000 microgram/h) on pentagastrin-stimulated gastric secretion in ten normal individuals. All doses caused stepwise inhibition of gastric juice (volume), acid and pepsin output. When employing the largest dose of i.v. TRH (1000 microgram/h) the inhibition was 44% for gastric volume, 51% for acid output and 57% for pepsin output. This study shows that TRH inhibits gastric secretion, and indicates that TRH has actions outside the CNS in man.


Characterization of 'e' antigen associated with hepatitis B.

Hepatitis B 'e' antigen (HBe) from the serum of a chronic carrier of HBsAg has been partially purified and characterized. It behaves as an acidic protein, pI 4.5--5.0, which is thermolabile and sulphydryl-sensitive. In serum it usually has a flotation density 1.3 g/cm3, but is sometimes found at density 1.15 g/cm3 because of its association with lipid. HBe from serum is polydisperse on gel filtration although most antigen is recovered with a nominal molecular weight of 3 x 10(5) Daltons. In contrast, in the presence of chaotropic ions, the bulk of serum HBe is found as a species of 3 X 10(4) Daltons previously detected in small amounts under non-dissociating conditions. This suggests that the larger material is formed by non-covalent association of the 3 X 10(4) Dalton species either with itself or other serum components. This would include IgG, although there is no evidence that HBe itself bears immunoglobulin determinants. Analysis of HBe precipitins by polyacrylamide gel electrophoresis under reducing and dissociating conditions suggests that its component polypeptide chains are about 1.7 X 10(4) Daltons.


Value of operating auxiliary personnel for caries diagnosis in dental epidemiology.

The ability of a suitably trained operating auxiliary to obtain similar diagnostic results to those of a dentist was tested on 200 11--12 year-old boys and girls selected from a larger sample taking part in a 3-year caries prophylactic clinical trial. A clinical and radiographic examinati-n of all children was performed by both examiners at the beginning of the study and at three subsequent yearly examinations. The reliability of the caries prevalence and incremental data was high for both the dentist and hygienist. Differences between mean caries scores were consistently found between the examiners at the initial lesion level for clinical and radiographic diagnosis. Over the incremental periods of the study neither examiner revealed a significant difference between control and test groups until the end of the 3rd year when both measured a significant difference in mean DMFS at the clinical cavitation level, 26.2% for the dentist and 25.2% for the hygienist.


Forearm pseudarthrosis--neurofibromatosis: case report.

A 3 1/2-year-old white girl with neurofibromatosis sustained left radius and ulna fractures. The radius was sclerotic with no medullary canal at the fracture site, and the ulna was hypoplastic distal to the fracture. The fractures failed to unite when immobilized in a long arm plaster cast for 5 months and pseudarthrosis developed. Three subsequent operative attempts to obtain union of the pseudarthrosis by means of internal fixation and bone grafting over the next 30 months were also unsuccessful, and the pseudarthrosis persisted. The forearm was supported in a custom molded leather brace until the child was 13 1/2 years old and had reached skeletal maturity. Osseous union was then operatively obtained using dual onlay tibial cortical and cancellous bone grafts. There has been no recurrence of the pseudarthrosis 3 years and 2 months after bone grafting. The author recommends postponing surgical attempts to achieve union of the forearm bone pseudarthrosis associated with neurofibromatosis until the patient reaches skeletal maturity.


A new principle of injectable depot contraceptives. I Drug selection and studies in monkeys.

The aim of the investigations was to develop a long-acting depot contraceptive on the basis of norethisterone or levonorgestrel. Disappointing results with levonorgestrel nonanoate and levonorgestrel undecylate showed that elongation of the fatty acid, esterified with the steroid, decreased the bioavailability of the latter due to incomplete hydrolysis of the ester. Therefore, several new compounds were synthesized which contained a bifunctional molecule between the steroid and the fatty acid. In vivo studies showed an increase in hydrolysis when glycolic acid was taken as the "bridge", compared to the hitherto known esters. Due to the new principle of the steroid-fatty acid connection, in the case of norethisterone, it was possible to introduce tridecanoic acid as lipophilic release controlling substituent without a loss of bioavailability in the baboon. This compound (called: "norethisterone glycotridecanoate") and the corresponding levonorgestral derivative were chosen for a pharmacokinetic-clinical study in women.


Epididymitis in rams: effect of vaccination and culling on the clinical incidence of the disease.

Ram epidiymitis caused by Brucella ovis can be effective controlled by an annual program combining rigorous culling clinically affected animals and appropriate vaccination of the remaining animals. Yearling rams purchased or saved as replacement breeders should be immunized at 4-5 months of age by two injections of Br. ovis bacterin spaced 3-6 weeks apart. Annually, approximately one month prior to the breeding season, all rams, replacements and older breeders as well, should be carefully examined by palpation of the scrotal contents. Every ram evidencing an abnormality should be culled as a breeder. All the remaining rams should receive a "booster" injection of Br. ovis bacterin.


Epididymitis in rams: studies on vaccine efficacy.

Simultaneous inoculation with Br. ovis bacterin plus Br. abortus strain 19 produced the greatest immunity. This procedure was not permitted, however, as widespread use of Br. abortus in sheep might pose a hazard to the brucellosis eradication program in cattle. Subsequent work demonstrated that an aluminum hydroxide adsorbed bacterin, administered as two injections spaced 3-6 weeks apart, conferred a significant and acceptable level of immunity.


Biochemical and serological studies on Pasteurella multocida isolated from cattle in the Sudan.

Of 42 strains of Pasteurella meltocida isolated from different outbreaks of hemorrhagic septicaemia and from healthy cattle in various parts of the Suden, 38 belonged to Carters' type B and four to type E. The strain used for vaccine production was type E. With respect to somatic antigen determination, there was some correlation between the results of the gel diffusion and the agglutination tests as most strains reacted with 0 groups 6 antisera in both tests. However, some antigens cross-reacted with antisera of different 0 groups in the gel diffusion test. No correlation was observed between the pattern of biochemical reactions and the serological types.


Avian mite dermatitis.

A case of dermatitis caused by the Northern fowl mite is presented. Fowl mites and their clinical significance are discussed.


The comparative efficacy of minocycline and penicillin-V in Staphylococcus aureus skin and soft tissue infections.

The antistaphylococcal properties of orally administered minocycline and penicillin-V were compared for one hundred and fifteen patients receiving minocycline and one hundred and twenty-eight receiving penicillin-V for various types of cutaneous infections. The majority of bacterial isolates were staphylococcal organisms. Of these 82 percent showed initial in vitro sensitivity to minocycline while only 20 percent did to penicillin-V. The percentage of clinical cures was higher with minocycline (74 percent) than with penicillin-V (54 percent), however, most patients, in both groups, showed clinical improvement. The rate of clinical improvement appeared to be significantly faster with minocycline. There was a higher percentage of adverse, chiefly vestibular, effects in the minocycline group (16 percent vs 7 percent). The study clearly demonstrates the superior antistaphylococcal properties of minocycline as compared with penicillin-V.


Tuberculosis in Oriental immigrants: a study in military dependents.

Tuberculosis in Oriental immigrants is likely to be resistant to therapy with certain drugs. In 73 military dependents with positive cultures for tuberculosis who immigrated from six Asian countries, the tuberculosis was found to be resistant to isoniazid in 58 percent (42 patients), to streptomycin in 36 percent (26 patients), to p-amino-salicylic acid in 14 percent (ten patients), to rifampin in 7 percent (five patients), and to ethambutol in 7 percent (five patients). Despite the presence of drug-resistant organisms and often extensive disease, negative cultures were attained in all but one patient. Consideration of the high incidence of drug-resistant tuberculosis should be made in planning a program of treatment for these patients. Recognition of cultural differences may also be of value in the successful treatment of this difficult group of patients.


Diagnosis of tuberculosis: routine cultures of bronchial washings are not indicated.

During a five-year period, cultures of bronchial washings for Mycobacterium tuberculosis were obtained almost routinely (859 of 1,012 bronchoscopic examinations.). This practice proved costly, and the diagnostic yield was extremely low. Only three cases were diagnosed solely by this method (0.35 percent). Five other cases were false-positive. Additionally, 39 patients with known active pulmonary tuberculosis had false-negative cultures of bronchial washings; 13 of these 39 patients were receiving antituberculosis drugs at the time of their bronchoscopic examinations. The inhibitory effect of local anesthetics upon the growth of M tuberculosis is the possible cause for the remaining 26 false-negative cultures. We conclude that bronchoscopic examination and culture of bronchial washings are not the best sources for diagnosis of pulmonary tuberculosis and that cultures of sputum and/or gastric washings are usually sufficient. The practice of obtaining routine cultures of bronchial washings in known pulmonary tuberculosis is of questionable value, when nearly two-thirds may be false-negative.


Studies with cefuroxime: a new beta-lactamase resistant cephalosporin.

28 patients suffering from a variety of bacterial infections have been treated with cefuroxime. 18 were cured and 6 improved during treatment. Side effects were minimal and intramuscular injection was well tolerated. Serum and urine levels well in excess of the MICs of sensitive organisms were obtained using dosages of 750 mg 8 hourly. Biliary excretion was impaired in the presence of obstruction, but adequate bile levels of cefuroxime were observed following relief of the obstruction. Cefuroxime was widely active against gram-negative bacilli and against Streptococcus faecalis, but less active against Bacteroides spp.


Schizontocidal activity of antibiotics against blood-induced Plasmodium gallinaceum infection.

Comparative studies on the blood schizontocidal activity of antibiotics against Plasmodium gallinaceum infection of chicks have shown that doxycycline, minocycline, demeclocycline, tetracycline and oxytetracycline possess high antimalarial activity as judged by suppression of parasitaemia and extension of survival period. Of these, demeclocycline, tetracycline and oxytetracycline were effective only at high dose level. Chloramphenicol, erythromycin and gentamicin were relatively inactive. Treatment in 5- to 6-day-old established infection of chicks has shown that doxycycline and minocycline are relatively more effective than oxytetracycline and tetracycline in controlling acute infection.


[The effect of parenteral nutrition on cellular immune status in patients with gastrointestinal cancer].

In a pilot study, the distribution of lymphocyte subpopulations in the peripheral blood and skin tests with recall antigens have been examined in 42 patients with gastrointestinal cancer before and during a perioperative parenteral hyperalimentation. Concerning the calories and the concentrations of amino acids and carbohydrates, two different solution regimens were applied. During parenteral nutrition with 2400 and 2200 kcal especially the absolute numbers of lymphocyte subpopulations increase reflecting the changes of total lymphocyte count. There was no marked difference between the 2 groups. Both solutions are qualified to balance the preoperative catabolic situation indicated by preoperative lymphopenia. This kind of parenteral nutrition did not influence the patient's cellular immunological status which was tested by 3 recall antigens. It must, however, be considered that the physical i.e. nutritional situation of the patients was not reduced to an extent where the immunological status was impaired. Our results suggest that in the perioperative period cancer patients should be supported by hypercaloric parenteral nutrition. On the other hand more sensitive immunological tests such as DNCB for skin testing and functional assays for in vitro tests are necessary to assess the effects of this kind of therapy.


[Surface changes of the pulmonary valve following pulmonary valve xenotransplantation in the descending aorta. An experimental study in dogs].

Upon implantation in the descending aorta, glutaraldehyde-conditioned pulmonary valves (n = 46) are immediately covered by a protein layer, followed by a fibrinous layer. Two to thirty minutes later platelets, WBCs, macrophages, and microthrombi are incorporated into the valve's surface. After 3 weeks the first collagen fibers appear on the surface and slowly build a collagen layer that grows toward the free edge. These changes are very similar to the surface changes of bioprostheses implanted in humans.


[Studies on the modification of wound healing by a lack of essential fatty acids].

A fat-free diet produces a deficiency of essential fatty acids in Wistar rats. This is associated with disturbances of wound healing in the colon and skin due to an impaired collagen metabolism, since hydroxyproline content in the wound area is decreased. The results are of clinical significance with regard to total parenteral nutrition in surgical patients.


[The effect of exocrine glandular tissue on the transplantation results of isolated islands of Langerhans].

Islet cells were transplanted into isologous rat strains with exocrine pancreatic tissue as contaminant. The relationship of transplant function to the degree of contamination was tested. No influence on transplant success was found despite a five fold amount of exocrine tissue in one group after transplantation into livers of diabetic animals. But a 12-fold contamination of the 2000 isolated islets of Langerhans did not allow a normalization of blood sugar content. The glucose assimilation coefficient was constantly below 1.0. Purification of islet cell transplants was estimated by determination of amylase activity per islet according to SUTHERLAND.


[Nitrogen-saving effect of a 3% solution of amino acid infusion in the postoperative period].

Infusion of a 3% amino acid solution after moderate abdominal surgery for 4 - 6 days postoperatively results in a nitrogen-saving effect as compared with an infusion of carbohydrates or a combination of carbohydrates and amino acids. Patients who received only amino acids showed the lowest blood glucose levels, but a significant increase of ketone bodies and triglycerides in serum, which is an indication of lipolysis.


[Therapy of hepatic encephalopathy. Modification of the plasma aminogram using amino acid infusions].

When amino acid solutions with high concentrations of branched chained amino acids and low concentrations of aromatic amino acids were administered to patients with cirrhosis of the liver 1. the serum levels of tyrosine and phenylalanine were significantly reduced, 2. the molar ratio of the branched chained amino acids to the aromatic amino acids substantially increased, and 3. as therapeutic response in all cases treated, a marked improvement of hepatic encephalopathy was achieved.


[Predictive value of metabolic profiles in multiple trauma].

An increase in the lactate:pyruvate ratio as well as in serum gluocse levels and a decrease in base excess values permit an early prediction of vital outcome in severely traumatized patients. Further laboratory data such as enzymes, bilirubin, and amino-acid concentrations, however, demonstrate significant differences between survivors and nonsurvivros at a later stage, i.e., from the 6th day on.


Crohn's disease with spontaneous ileoumbilical and ileovesical fistulae.

A 17-year-old male with Crohn's disease involving the terminal ileum and cecum developed an umbilical fistula in the absence of previous surgery. While on intravenous hyperalimentation he developed an enterovesical fistula and was successfully treated by surgical resection. This combination of an enterovesical and umbilical fistula has not been previously reported. An aggressive approach to treatment is suggested.


Effects of vasoactive intestinal polypeptide (VIP) on lower esophageal sphincter in awake baboons: comparison with glucagon and secretin.

The effects of vasoactive intestinal polypeptide (VIP), glucagon, and secretin on lower esophageal sphincter pressure were investigated in awake baboons. The three hormones were compared with respect to effect on (1) resting lower esophageal sphincter pressure and (2) maximal stimulatory response to pentagastrin. VIP was shown to reduce resting and pentagastrin-stimulated lower esophageal sphincter pressure with significantly greater potency than either secretin or glucagon. For reduction of resting lower esophageal sphincter pressure, the potency ratio of VIP to secretin was 16:1 and of VIP to glucagon was 32:1 (P less than 0.05). For inhibition of pentagastrin-stimulated sphincter pressure, the potency ratio of VIP to secretin was 32:1 and of VIP to glucagon was 64:1 (P less than 0.02). This demonstration of significantly increased potency of VIP over known inhibitory hormones strengthens the suggestion that VIP may have a physiologic role in the control of lower esophageal sphincter function.


Choleresis and cholestasis produced by infusion of taurocholic acid or taurodehydrocholic acid combined with BSP in the rhesus monkey.

To study the determinants of BSP Tm in rhesus monkeys, animals with indwelling silastic catheters were infused with sufficient BSP to produce a rising plasma concentration and normal saline or taurocholic acid 3.5 mumol/min, 7.0 mumol/min, or 10.5 mumol/min. BSP Tm was 3.84 +/- 0.11 mg/kg/10 min during normal saline infusion, 5.52 +/- 0.53 mg/kg/10 min during taurocholic acid 3.5 mumol/min, despite greater bile flow with the latter compound. Higher infusion rates of taurocholic acid inhibited BSP Tm and the proportion of conjugated BSP secreted into bile, as well as bile flow and bile acid secretion. Taurodehydrocholic acid 7.0 mumol/min produced similar but less marked effects. These results indicate that bile flow does not explain the effects of bile acids on BSP Tm and suggests that bile acids exert varying effects on BSP transport or binding in micelles. The cholestasis observed with combined BSP and higher bile acid infusion rates is probably due to inhibition of liver cell intermediary metabolism or to liver cell toxicity.


Resonance Raman spectroscopy of chlorophyll-protein complexes.

Resonance Raman spectra of chlorophyll a (Chl a) and of Chl b were selectively obtained, at low temperature, from chlorophyll-protein complexes prepared from green and blue-green algae and from higher plants. Antenna Chl a in the Chl a-P700-protein complexes (CP I) and in the light-harvesting Chl a/b-protein complexes (CP ii gives resonance Raman spectra extremely close in all their features to those previously obtained from intact cells and chloroplasts. In particular, the same multiplicity of binding sites for the ketone carbonyl groups of Chl a is observed in both CP I and CP II as in intact membranes. These bindings sites are probably the same types as those observed in the intact membranes and are not the magnesium atoms of other chlorophylls. The magnesium atoms of most Chl a molecules in both CP I and CP II bind a single external ligand. Resonance Raman spectra of Chl b in CP II preparations, although very similar to those from intact membranes, show partial rearrangement of one of the two environmental subspecies of Chl b previously found in intact membranes. These results provide evidence that chlorophyll-protein complexes closely represent the state of the bulk of antenna chlorophyll in vivo.


The preparation and characterization of different types of light-harvesting pigment-protein complexes from some purple bacteria.

A general strategy, with some specific examples, is given for the isolation and purification of detergent-soluble, antenna pigment-protein complexes from the photosynthetic membranes. Absorption, fluorescence and circular dichroism spectra, and the pigment and protein composition of B800-B850-protein and B890-protein complexes of some purple bacteria (Rhodospirillum rubrum, Rhodopseudomonas sphaeroides and Rps. capsulata and Chromatium vinosum) are discussed. We conclude that there are probably two major classes of antenna carotenochlorophyll-proteins in purple bacteria containing bacteriochlorophyll a: a B890 complex which has one carotenoid and two bacteriochlorophyll molecules in the minimal unit (probable molecular weight around 20,000), and a B800 + B850 complex which has one carotenoid and three bacteriochlorophyll molecules in a similar-sized minimal unit. The whole cell spectrum of any purple bacterium can be reconstituted by combining different proportions of the spectra of these two complexes with that of the photochemical reaction centre.


[Antibacterial in-vitro activity of pipemidic acid and nalidixic acid (author's transl)].

The in-vitro activity of nalidixic acid and pipemidic acid was investigated in a combined study in 450 freshly isolated bacterial strains using the agar dilution test. Gram-positive cocci were resistant to both substances except for a few pipemidic acid sensitive staphylococci. Both substances had good antibacterial activity in the gram-negative spectrum. However, the MIC values of pipemidic acid were generally clearly lower than those of nalidixic acid. Only pipemidic acid showed activity against Pseudomonas aeruginosa. Thus the in-vitro results showed that pipemidic acid has clear-cut and valuable advantages for the treatment of urinary tract infections when compared with nalidixic acid.


[Diagnosis of systemic lupus erythematosus (author's transl)].

The positive demonstration of ds-DNA in a particular concentration is a diagnostic criterium for systemic lupus erythematosus. The most commonly used test at present has the disadvantage that radioactively marked substances are required. Thus a test method was developed for the laser nephelometer which is simple and which detects the antigen-antibody complex directly. First measurements on sera from SLE patients showed a good correlation with radioimmuno assay.


[Development of ossification in children with chronic digestive insufficiency (author's transl)].

In 84 children suffering from chronic insufficiency of digestion, ossification of both hands was observed by means of fluoroscopic controls for several years. In 48 of 71 patients there was a retarded ossification; in 23 it was normal, or respectively more advanced. 18 boys and girls succeeded in making up for there retardation by means of consequent diet so that it might be regarded as a "spurt of growth". But in 10 of them retardation was constant, and in 14 children it increased. The causes of insufficient improvement were: late diagnosis and therapy, failures of diet, but also additional diseases--different from digestive insufficiency--, and long-term use of corticosteroides. In 30 of 84 children ossification was always normal or advanced. They had received early and consequent diet for years. Only in few cases, slight or moderate diseases were diagnosed. Development of ossification was parallel to body height, but not to weight gain.