Genetic control of alcohol dehydrogenase levels in Drosophila. Among the progeny of Drosophila flies heterozygous for two noncomplementing Adh-negative alleles, two individuals were found that had recovered appreciable alcohol dehydrogenase activity, thereby surviving the ethanol medium used as a screen. The most likely explanation is that these Adh-positive flies are the product of intracistronic recombination within the Adh locus. Judging by the distribution of outside markers, one of the crossovers would have been a conventional reciprocal exchange while the other appears to have been an instance of nonreciprocal recombination. The enzymes produced in strains derived from the original survivors can be easily distinguished from wild-type enzymes ADH-S and ADH-F on the basis of their sensitivity to denaturing agents. None of various physical and catalytic properties tested revealed differences between the enzymes of the survivor strains except that in one of them the level of activity is 55--65% of the other. Quantitative immunological determinations of ADH gave estimates of enzyme protein which are proportional to the measured activity levels. These results are interpreted to indicate that different amounts of ADH protein are being accumulated in the two strains.


Alcohol dehydrogenase polymorphism in populations of Drosophila melanogaster. II. Relation between ADH activity and adult mortality. Eight Drosophila melanogaster strains, seven homozygous for AdhF alleles and one for an Adh-null mutant, were compared for ADH activity in males and adult mortality on ethanol-supplemented food. The strains differed considerably in these qualities. A positive correlation was found between ADH activity and LD50. The relevance of this finding is discussed in relation to the differential selection acting on Adh genotypes kept on ethanol-supplemented food.


The phospholipid-dependence of uridine diphosphate glucuronyltransferase. Temperature-dependence of microsomal enzyme activity and thermotropic changes in membrane structure. Arrhenius plots of the non-latent UDP-glucuronyltransferase (p-nitrophenol acceptor) activity of guinea-pig microsomal membranes prepared with 154 mM-KCl were linear from 5 to 40 degrees C. Arrhenius plots for other microsomal preparations from guinea pig and rat liver that show various degrees of transferase latency, exhibited two linear regions intersecting at a sharp transition point near 20-25 degrees C. This discontinuity was abolished or greatly decreased when transferase latency was removed by treating the membranes with perturbants of phospholipid bilayer strucutre. The fluorescent probe N-phenyl-1-naphthyl-amine detected a thermotropic change in the fluidity of the phospholipid acyl chains of all the microsomal membrane preparations studied, at temperatures close to those of the Arrhenius-plot transitions. It is concluded that the thermotropic change in the structure of the membrane bilayer probably is a 'phase separation' or clustering of phospholipids, which affects a permeability barrier that restricts access of substrate to the transferase molecules.


Characterization of purified human liver acid beta-D-galactosidases A2 and A3. 1. Human liver acid beta-galactosidase A2 and A3 were isolated by chromatography on concanavalin A-Sepharose 4B, Sepharose 6B, and Sepharose 4B-6-aminohexyl 1-thio-beta-D-galactopyranoside. beta-Galactosidase A2 and A3 were purified to final specific activities of 45.5 and 20.6 mumol/min per mg respectively with 4-methylumbelliferyl beta-D-galactopyranoside as substrate. 2. Form A2 had a mol.wt. of 150000 +/- 15000 (gel filtration) and appeared as a single band of protein (mol.wt 65000 +/- 1000) on electrophoresis in the presence of sodium dodecyl sulphate. 3. Form A3 had a mol.wt. (gel filtration) of 660000 +/- 66000. On electrophoresis in the presence of sodium dodecyl sulphate, form A3 appeared as a major band of protein (72% of total) of mol.wt. 65000 +/- 1000 and minor protein bands of mol.wt. 44000 +/- 1000 and 26,000 +/- 1000 and 22000 +/- 1000. 4. Gel-filtration chromatography of purified beta-galactosidase A3 generated approximately equal amounts of forms A3 and A2. beta-Galactosidase A1 was not detected by gel-filtration chromatography of partially or highly purified preparations of forms A2 and A3. 5. Both forms A2 and A3 had identical isoelectric points of 4.42 +/- 0.02. The data suggest that forms A2 and A3 are dimeric and multimeric forms of beta-galactosidase A1. 6. Amino acid analysis of beta-galactosidase A2 gave a ratio of acidic to basic amino acids of 2.6:1. 7. beta-Galactosidase A2 contained 7.5% carbohydrate by weight and sialic acid, D-galactose, D-glucosamine and D-mannose were present in the molar proportions 1.1:1.0:1.7:2.7.


Purification and properties of nitrogenase from Rhodospirillum rubrum, and evidence for phosphate, ribose and an adenine-like unit covalently bound to the iron protein. 1. The molybdenum-iron (Mo-Fe) protein, iron (Fe) protein and the activating factor of nitrogenase from Rhodospirillum rubrum were purified. 2. The Mo-Fe protein has properties similar to those of the Mo-Fe proteins of other nitrogen-fixing organisms. 3. The Fe protein is similar to other Fe proteins with respect to its molecular weight, metal composition and e.p.r. signal. 4. The Fe protein is different from other Fe proteins in that it apparently has two types of subunits rather than one, its u.v. spectrum has an extra peak, and phosphate, ribose and an adenine-like unit are covalently bound to the protein. The presence of these non-protein groups on the protein may explain the requirement for activation of R. rubrum Fe protein.


The immobilization of adenine nucleotides on polysaccharides by using glutaraldehyde coupling and borohydride reduction. Adenine nucleotides were immobilized on modified Sepharose 4B or Dextran T40 with glutaraldehyde and reduced with KBH4. Binding was dependent on pH and the nature of the amino group on the modified polysaccharide. ATP bound to soluble dextran retained coenzyme activity with glycerol kinase. Binding is proposed to occur via a Schiff base.


The effect of sodium 2-mercapto-ethane sulphonate and hypertonic saline aerosols on bronchial clearance in chronic bronchitis. 1  The efficacy of a mucolytic agent, 2-mercapto-ethane sulphonate, administered in the form of an aerosol was evaluated in a group of eleven patients with chronic bronchitis in a controlled, double-blind, crossover study. 2  Saline aerosol isotonic (1.21M, 7.1%) to the drug was used as a placebo. 3  Approximately 1 ml drug/placebo was inhaled by the patients twice a day for 3 days and a final dose was given on the mornings of the drug/placebo trial runs. 4  There was no improvement in this group of patients in lung function or subjective well being attributable to the drug. 5  The viscosity of sputum, dry macromolecular weight and N-acetyl neuraminic acid/fucose ratio remained unaltered throughout the study. 6  An enhancement of tracheobronchial clearance was obtained following the administration of either placebo (31%) or drug aerosols (24%) Statistical significance (P less than 0.01) was only achieved for the placebo and was attributed to an increase in sputum volume.


Detection of antibodies after immune complex splitting in serum of patients with bullous pemphigoid and systemic lupus erythematosus. No free anti-basement membrane antibodies were found in the sera of four patients with bullous pemphigoid, and no free anti-DNA antibodies in the sera of two patients with systemic lupus erythematosus. The sera treated with 3 mol/l urea and by gel chromatography to separate these antibodies from any circulating complexes, and antibodies to basement membrane were detected by immunofluorescence and to DNA by the Farr technique. The appropriate antibodies were found in all the sera, indicating that failure to detect antibodies by routine procedures may be due to binding of the antibodies to soluble antigens forming complexes in the sera.


Ribosomal proteins in growing and starved Tetrahymena pyriformis. Starvation-induced phosphorylation of ribosomal proteins. The complements of ribosomal proteins in growing and starved cells of Tetrahymena pyriformis strain GL were examined by two-dimensional gel electrophoresis. In growing cells, the 40-S ribosomal subunit contained 30 proteins, 4 of which migrated toward the anode at pH 8.6, while the 60-S ribosomal subunit contained 46 proteins, 9 of which migrated toward the anode at pH 8.6. When exponentially growing cells were transferred into a non-nutrient medium pronounced phosphorylation of a single 40-S ribosomal subunit protein, S6, was induced. The phosphorylation was very specific; more than 99.5% of the [32P]phosphate incorporated into ribosomal proteins was associated with S6. Phosphate was incorporated into S6 as O-phosphoserine and O-phosphothreonine. Two-dimensional gel electrophoresis indicated that the complement of proteins associated with the ribosomes isolated from starved cells differed from that of growing cells. Careful examination, however, suggested that except for the phosphorylation of certain ribosomal proteins in starved cells, the observed differences did not reflect starvation-induced changes in vivo, but most probably different levels of artifactual modifications (limited proteolysis) during the preparation of the ribosomes.


Transformation in Bacillus subtilis with nitrogen mustard crosslinked DNA. Effect on cotransformation and mutation frequencies. Bacillus subtilis DNA was treated in vitro with nitrogen mustard and the crosslinked molecules were purified, after alkali denaturation, by hydroxyapatite chromatography. When tested for the ability to transform the trpC2-hisB2 segment, these molecules exhibited a decrease in the cotransformation index (r) as compared to native or renatured DNA. The decrease in r was not accompanied by an increase in mutagenicity.


The role of ATP in the transport of rapidly-labeled RNA from isolated nuclei of rat liver in vitro. To understand the mechanism of the action of ATP on the in vitro transport of the rapidly-labeled RNA from isolated nuclei, the fate of ATP during the incubation as well as the effect of ATP, its analogues and other ribonucleoside triphosphates on the transport was examined and the following results were obtained. (1) More than 97% of added ATP remained acid soluble. No polyadenylation of the rapidly-labeled RNA in the released fraction by added ATP occurred although new polyadenylate segments smaller than 10 S were synthesized. (2) The addition of an ATP-generating system to the reaction mixture restored the initial rate of the release of the rapidly-labeled RNA from isolated nuclei. (3) Among the ribonucleoside triphosphates tested, ATP was most effective in stimulating the release. GTP was about 2/3 as effective as ATP. UTP showed some effect, but CTP showed no effect. EDTA was also non-effective. (4) When no ATP-generating system was added to the reaction mixture, AMP failed to mimic the effect of ATP. However, the combination of AMP and pyrophosphate could take the place of ATP. (5) Both AMP-CPP and AMP-PCP, the ATP analogues, showed the equal degree of their effect on the release, regardless of the position of the methylene bond. From these results, the principal role of ATP in the in vitro transport systems seemed to be its interaction with isolated nuclei to dissociate a structure which retains the rapidly-labeled RNA in the nucleus.


Asymmetric transcription during post-germinative development of Bacillus subtilis spores. The relative transcription from L and H strands of Bacillus subtilis DNA during consecutive stages of spore outgrowth was determined and compared to the transcription pattern during log-phase growth of vegetative cells. Pulses of [3H] uridine were administered during early, middle and late outgrowth phases of germination and the RNAs isolated. The asymmetry ratio of H/L as determined by hybridization at saturating RNA/DNA inputs showed a gradual decrease. During the period studied (10-90 and 90-160 min post-induction), about 50 and 35%, respectively, of the radioactive RNA consisted of ribosomal RNA transcripts. The decrease in the H/L asymmetry ratio was due predominantly to the appearance and accumulation of L strand transcripts and not to either changes in the quantity of H strand transcripts nor to fluctuation in the rate of rRNA synthesis.


Asymmetric transcription during post-germinative development of Bacillus subtilis spores. II. Hybrid competition analyses. Hybrid-competition analyses were done to estimate the relatedness of 3H-labeled mRNA species synthesized during spore germination and log-phase growth. The competitions showed that early in the germination process 10--15 and 1--3% of the RNA transcribed from the H and from the L strand, respectively, were unique and absent during log-phase growth. At later stages, the amounts of the germination-specific H transcripts decreased more rapidly than the L transcripts. The competitions with pulse-labeled log-phase RNAs showed that vegetative genes were transcribed more rapidly from the H strand than from the L strand. Most of the results could be correlated with the observed decrease in the H/L asymmetry ration during spore germination.


Evaluation of the rate of basal oxygen consumption in the isolated frog skin and toad bladder. In the study of active transport it is important to distinguish between oxygen consumption sustaining transepithelial transport and that responsible for other tissue functions (basal metabolism). Since amiloride blocks transepithelial active sodium transport and the associated oxygen consumption in the frog skin and toad bladder, we and others have employed this agent to evaluate the rate of basal metabolism. This technique has recently been criticized in a report that amiloride (and ouabain) increased oxygen consumption when no sodium was available for transport. We have been unable to corroborate these observations. With magnesium-Ringer as external bathing solutions, amiloride and ouabain failed to stimulate oxygen consumption. With sodium-Ringer as external bathing solution amiloride reduced oxygen consumption about 30%, to a level indistinguishable from that found on external substitution of magnesium-Ringer for sodium-Ringer. We conclude that the use of amiloride permits evaluation of the rate of basal metabolism with acceptable accuracy; a possible slight depressant effect of ouabain on basal metabolism remains to be investigated.


Further evidence for changes in the level of palmitoyl-CoA desaturase during thermal adaptation in Tetrahymena pyriformis. Palmitoyl-CoA desaturase activity in microsomes was increased up to about 4-fold within 2 h after temperature shift from 39.5 to 15 degrees C. Compared with control cells, cycloheximide-treated cells indicated no induction of palmitoyl-CoA desaturase by a decrease in temperature. The results suggest that temperature acclimation requires an increase in the level of the desaturase enzyme content.


Effect of growth temperature on lipid and fatty acid compositions in the blue-green algae, Anabaena variabilis and Anacystis nidulans. The lipid composition was affected by growth temperature in Anacystis nidulans, but was not in Anabaena variabilis. A. variabilis contained fatty acids of 18 and 16 carbon atoms, which were localized at 1- and 2-positions, respectively, of the glycerol moiety of lipids. Desaturation of C18 acids was affected by the growth temperature. A. nidulans contained fatty acids of 14, 16 and 18 carbon atoms. Monounsaturated and saturated acids were esterified mainly to 1- and 2-position, respectively. Desaturation and chain length of fatty acids were influenced by the growth temperature. The variations in lipid and fatty acid compositions with the growth temperature are discussed in relation to the growth temperature-dependent shift of thermotropic phase transition temperature of the membrane lipids in the blue-green algae.


On the haemoprotein character of prostaglandin endoperoxide synthetase. Prostaglandin endoperoxide synthetase is a membrane-bound glycoprotein isolated as a dimer of molecular weight of approximately 129 000 consisting of two identical polypeptide chains. Several research workers have reported that haemin (ferri-protoporphyrin-IX) is required to restore the full enzymic activity of the pure apoprotein. Difference spectroscopy shows association of haemin up to two molecules per polypeptide chain of molecular weight 70 000. Both the cyclooxygenase and the peroxidase activity displayed by the enzyme can be optimally stimulated by similar quantities of haemin. The restored haemin-enzyme complex has a millimolar absorption coefficient at 408 nm of 61 mM-1 . cm-1 per haem. Using this value, the presence of non-haem iron in the enzyme is virtually excluded. These findings and the spectra of the reassociated enzyme-haemin complex point to a haemoprotein character. The availability of haemin to the enzyme might play a regulating rôle in its action.


Studies on human gastric mucosal immunoglobulin A. Immunoglobulin A (IgA) was found in mucus scraped from the surface of the human antrum. Fresh human gastric mucosa removed at operation was washed free of loosely adhering material and the gelatinous mucus lining the tissue scraped. The scrapings were separated by gel filtration on Sephadex G-200 and on Sepharose 4B into two carbohydrate-containing fractions. One of these fractions was shown by immunodiffusion to contain IgA which differs from human colostral secretory IgA by being devoid of secretory component activity. Moreover, secretory component was not detected in our unfractionated gastric mucosal scrapings. It is concluded that, contrary to the general belief, the predominant immunoglobulin A of human gastric mucus is not associated with the secretory component. Our results do not exclude the possibility that, as in serum, small amounts of secretory IgA and of the secretory component may be present in gastric secretions, however if so, the levels of these compounds would fall below the level of sensitivity of our methods.


Isolation and partial characterization of a guinea pig serum apolipoprotein comigrating with apo-E on sodium dodecyl sulfate-polyacrylamide electropherograms. Study of guinea pig plasma lipoproteins has shown that they contain a polypeptide that comigrates with the arginine-rich polypeptide (apo-E) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This comigrating polypeptide differs from apo-E in its amino acid composition, immunological cross-reactivities, electrophoretic mobility in urea polyacrylamide gel, and elution volume from Sephadex gel columns. It is present in very low density lipoproteins and low density lipoproteins from both control and cholesterol-fed guinea pigs.


Studies on calcium ion-induced conformation changes in the actin-tropomyosin-troponin system by fluorimetry. IV. Conformational changes in the region containing fluorescence-labeled sulfhydryl group(s) of troponin. Conformational changes associated with the functional states of the molecule of troponin were studied using SH-direct fluorogenic reagents, N-(p-(2-benzimidazolyl)phenyl) maleimide (BIPM) and N-(1-anilinonaphthyl-4) maleimide (ANM). 1. The fluorescence parameters of ANM-troponin, intensity, and polarization, did not change on combining it with tropomyosin alone, but markedly changed when F-actin was further added to the system. 2. The conformation around the dye-labeled sulfhydryl group(s) was shown to be susceptible to Ca2+ in terms of fluorescence intensity of the label, thermal transition of the conformation, and the microenvironment near the label. 3. On addition of Ca2+, the fluorescence characteristics of the two systems, ANM-troponin . tropomyosin and ANM-troponin . tropomyosin . F-actin complexes, were altered in opposite directions. When BIPM was used in place of ANM, similar changes were observed: a simple decrease in the intensity when pCa was decreased from 7.4 to 5.5 in the system without F-actin and a sigmoidal increase in the range from pCa 7 to 6 in the system with F-actin. Heavy meromyosin, when added to the latter complex (the reconstituted thin filaments), made the profile of its Ca2+ concentration dependence of fluorescence similar to that of the former complex. When tropomyosin was labeled in place of troponin, similar results were obtained. The data obtained imply that the Ca2+-induced conformational changes of troponin are markedly modified when detached from actin, and that heavy meromyosin weakens the interaction of the troponin . tropomyosin complex with F-actin.


Development of ocularity domains and growth behaviour of axon terminals. Ontogenetic development of ocularity domains--stripes, patches and layers in cortex, colliculus superior and lateral geniculate nucleus--is the result of organization that may either be intrinsic to the postsynaptic structure or induced to it by the afferents. A specific type of axonal growth behaviour that was recently proposed as a basis for ontogenetic development of retinotopy is sufficient to account also for ocularity domains. No intrinsic organization in the postsynaptic structure is required. The latter merely serves as a propagating medium for markers carried by the presynaptic terminals. Computer simulations demonstrate the mechanism to be complete and consistent.


Prematurity and perinatal mortality in the Rhesus (Macaca mulatta): relationship to birth weight and gestational age. While the relative influence of birth weight and gestational age in determining perinatal mortality has not been definitively established, it has been assumed that birth weight makes the predominant contribution to perinatal mortality. The joint effects of birth weight and gestational age were examined by analyzing approximately 2,500 births from timed pregnancies in two rhesus (Macaca mulatta) breeding colonies. Perinatal events in the rhesus are described and shown to be similar to the human. The results demonstrate that gestational age is as important as birth weight in determining perinatal mortality. Since the degree of accuracy in the estimation of rhesus gestational age was much greater than is usually attained in human studies, the estimation of gestational age from the last menses may be too crude to determine the importance of this variable in human perinatal mortality.


Measurements of Euglena motion parameters by laser light scattering. Measurements of Euglena gracilis motion parameters have been performed by the spectral analysis of the scattered laser light. Samples were oriented by a radiofrequency field to obtain easily interpretable spectra. Cell rotation frequency and flagellar beating frequency distributions were obtained from the homodyne spectra, whereas the Doppler lines obtained at small observation angles by heterodyne detection yielded the swimming speed distributions. We discuss the broadening of the heterodyne spectra at large angles of observation. An application of this method to the study of the photo-kinetic effect is also described.


Effects of electromagnetic fields on the motion of Euglena gracilis. The orientation behavior of Euglena gracilis cultures in electromagnetic fields is shown to agree with the predictions of a model involving only a passive mechanism. The increase in Euglena motor activity with increasing field intensity is demonstrated by measuring various motion parameters by the laser scattering technique. The effect of electric field on the speed of Euglenas is compared with that of temperature. We conclude that the electric field warms up the culture, thus inducing an increase in cell motility.


[Characteristics of DNA during binding with polycyclic aromatic hydrocarbons in vitro]. Polycyclic aromatic hydrocarbons (PAH) were covalently bound to DNA by means of various activating systems. The following systems were used: the microsomal fraction of the rat liver, the system with I2, the system with ascorbic acid and FeSO4. Breaks in DNA due to the activating systems action appeared in all of these systems. Plateau of the PAH binding system curve in the microsomal system cannot be attributed either to the fall of the PAH metabolism rate to zero, or to the PAH binding sites in DNA. This plateau is the result of equalization of the rates of the two contrary-directed processes: the binding of metabolites and their removal due to DNA degradation. Because of the breaks in DNA caused by the activating systems, the authors failed to discover the changes in sedimentation data of DNA due to the covalently bound PAH.


Familial occurrence of monoclonal gammapathies. The purpose of this work was to evaluate the genetic propensity importance in the monoclonal gammapathies occurrence. Systematic serum-electrophoreses were performed on 172 relatives of 37 reported patients and on 10,784 controls over 30. The 4 families including one or more "paraproteinemia" other than the proband's were investigated. Experimental, epidemiologic, immunologic and genetic arguments are discussed.


Effect of hexachlorobenzene (HCB) on the activity of some enzymes from Tetrahymena pyriformis. Tetrahymena pyriformis Wh 14 was grown in Erlenmeyer flasks under continuous stirring at 30 degrees C for three days . After the culture had produced dry matter of about 100 mg HCB was added in acetone at a dose level of 0, 0.001, 0.1 and 1.0 ppm to the culture and incubated for another 7 days. At a dose level of 0.001 ppm the activity of delta-aminolevulinate dehydratase, hexokinase, and pyruvate kinase remained unaffected but was increased for glutamic-oxaloacetic transaminase, glutamic dehydrogenase, isocitrate dehydrogenase, and malate dehydrogenase while 0.1 ppm HCB increased the activity of all enzymes studied, the only exception being glutamic-pyruvic transaminase, the activity of which was depressed by HCB exposure. A concentration of 1.0 ppm HCB depressed the activity of most of the enzymes below control values with the exception of the two mitochondrial enzymes, MDH and ICDH, studied here.


Toxicity of carbofuran to blue-green alga Nostoc muscorum. Effect of commercial grade pesticide furadan (3% a.i. as carbofuran) was studied on the survival, growth and nitrogen fixation of blue-green alga Nostoc muscorum. The lower concentration of furadan i.e. 25 microgram/ml enhanced survival, growth and nitrogen fixation in the alga whereas these were gradually inhibited in higher concentrations (50--1000 microgram/ml) and the presence of more than 1200 microgram/ml was algicidal. The preliminary observations revelaed that pesticide is biodegraded by the alga.


Venereal syphilis in tropical Africa.

Venereal syphilis in tropical Africa. A steady decline in the incidence of positive results to the Kahn test is reported in Malawian patients during the period 1968-75. Other studies have shown that the incidence of early and late syphilis in sub-Saharan Africa has dropped considerably over the past few decades. The number of reported cases of early syphilis in certain urban areas, however, appears to be high. It is suggested that the downward trend in the incidence of syphilis in Africa is related to the increased and often indiscriminate use of penicillin.


Method for studying the role of indigenous cervical flora in colonisation by Neisseria gonorrhoeae. A method for quantitating cervical flora has been evaluated statistically and used to study the bacterial flora of the cervix in 14 women sexually exposed to men with gonococcal urethritis. A comparison was made between those women who subsequently became colonised with Neisseria gonorrhoeae and those who did not to determine whether either total microbial populations or the different species present could be related to colonisation by N. gonorrhoeae. Two control groups of healthy women, one of patients from a public clinic and the other of patients from a private practice, were studied in the same way. Normal flora isolates were tested in vitro for antagonism or synergism toward N. gonorrhoeae or both. Cervical flora was characterised in all patient groups by wide variations between individuals, both in type and numbers of organisms. No significant differences were found in total bacterial populations or in the number of species isolated from the cervix between patient groups. Populations of N. gonorrhoeae ranged from less than 10 bacteria to log104.36. Only one normal flora isolate, a strain of Streptococcus viridans isolated from a woman exposed to but not infected by N. gonorrhoeae, demonstrated inhibition of growth towards N. gonorrhoeae.


Bulk growth of Neisseria gonorrhoeae type 1 in a biphasic system. A biphasic system for the bulk growth of Neisseria gonorrhoeae is described. It appears to combine the convenience of liquid media with the growth qualities of solid media. By using the agar in dialysis tubes rather than as slabs the surface-to-volume ratio was improved and harvesting made easier. The system is also useful in isolating gonococci from blood and joint fluids in patients with disseminated infection.


Isolation of Chlamydia trachomatis from Bartholin's ducts. Exudate from Bartholin's ducts from 30 selected patients was investigated for Chlamydia trachomatis and Neisseria gonorrhoeae. N. gonorrhoeae was isolated from the duct exudate in 24 patients and C. trachomatis in nine. Concurrent infection of the ducts was present in seven (29.2%); the remaining two patients were sexual contacts of men with non-specific urethritis. The duct exudate was mucopus in seven patients, cloudy mucus in one, and clear mucus in the other. Although contamination of the vulva by C. trachomatis derived from cervical or urethral infection cannot be excluded, three cases are described which suggest that a true infection of the duct occurs and may persist after gonococcal infection has been cured.


The role of frontal and parietal cortex in cognitive processing: tests of spatial and sequence functions. Normal monkeys and monkeys with resection of anterior frontal or posterior parietal cortex were trained to press a panel next to a green panel as a test of extrapersonal spatial orientation and to press a panel next to their own prior press as a test of personal spatial orientation. All monkeys also learned two sets of sequence problems in which the solutions were made independent of spatial location by randomly shifting the locations of the stimuli after each response within a trial. The Parietal Group was significantly impaired on the extrapersonal 'next-to' task but not the more difficult personal 'next-to' task. The Frontal Group was impaired on both the personal and the extrapersonal 'next-to' tasks but only when the relevant cues shifted spatial locations from trial to trial. The performance of the Parietal Group completely overlapped that of the Normal Group on the sequence problems regardless of the level of testing sophistication the monkeys had attained. In contrast, the Frontal Group demonstrated a significant impairment in learning sequences but only when the monkeys were naive. Once they became sophisticated they learned each sequence at a normal rate. Their poor performance was attributed to the lack of stability in the spatial location of the stimuli. The data support the view that a distinction between personal and extrapersonal spatial orientation is relevant to posterior parietal function but indicate that neither sequencing per se nor personal spatial orientation or spatial memory per se is dependent on intact frontal functioning. Rather, the frontal cortex is involved with a higher-order control essential to allow the monkey to perceive the reliable aspects of stimuli contained in a stimulus context full of unreliable noise and to further allow for flexible response pattern appropriate to the demands of a variable context.


Effect of ethanol on neuronal activity in the parietal association cortex of alert monkeys. The effect of alcohol was studied in alert monkeys on the cellular mechanisms of the posterior parietal association cortex, a region that normally participates in visuo-spatial co-ordination of hand movements. In thirty-two experiments, the effects of intracardiac administration of ethanol were monitored by the intracortical multiple-unit recording technique. Alcohol produced rhythmic groupings of the spontaneous impulse activity; the rhythm was accentuated by closing the eyes. The dominant frequency of this rhythm (3.5 to 1 Hz) correlated inversely with the blood alcohol level. Three groups of response types were studied in Brodmann's area 7. At 8 of 12 recording sites, a close correlation was observed between the monkey's reaching accuracy and the magnitude of integrate multineuronal responses to reaching with the contralateral arm under visual guidance, or to grasping an object. Half of the 10 recording sites which were activated by complex visual stimulation also showed a close correlation with the behavioural action of alcohol. Least sensitive to alcohol were somatosensory responses; only 3 of 10 of such recording sites were influenced by moderate doses of alcohol. Larger doses producing coma increased the proportion of responses blocked by alcohol, whereas no effects were observed in the adjacent primary somatosensory cortex. Our results show that the posterior parietal association cortex is very sensitive to the action of alcohol. Moreover, these findings support the theory that the action of alcohol in various parts of the central nervous system depends on the complexity of synaptic contacts to the location under study.


Interaction of LSD and other hallucinogens with dopamine-sensitive adenylate cyclase in primate brain: regional differences. The influence of D-lysergic acid diethylamide (LSD) and mescaline on adenylate cyclase activity was studied in homogenates of Cebus and rhesus monkey anterior limbic cortex (ALC), frontal cortex (FC), caudate nucleus and retina. Previous studies have shown these tissues to contain dopamine-stimulated adenylate cyclase (AC). In addition, we are now reporting the presence of a dopamine-sensitive adenylate cyclase in the auditory cortex. AC of ALC and auditory cortex was stimulated by LSD and mescaline, whereas activity of FC, caudate nucleus and retina was not stimulated by the same agents. In contrast to regional specificity for stimulation, LSD was capable of antagonizing dopamine-stimulated activity in all brain regions examined. LSD and mescaline produced similar maximal stimulation (about 70%) of AC of ALC homogenates, but the EC50 for LSD (0.43 micrometer) was about one-tenth that for mescaline (4.5 micrometer). Similar relative potencies were also observed for the auditory cortex enzyme. Although much weaker than LSD, methamphetamine also produced a dose-dependent stimulation of ALC AC. Both agonist and antagonist effects of the hallucinogens appear to involve interaction with dopamine receptors; LSD- or methamphetamine-stimulated activity in ALC was blocked by haloperidol and fluphenazine, which are dopamine antagonists, but not by phentolamine, an alpha-receptor blocker. Antagonism of dopamine by LSD in both ALC and FC was found to be competitive and mescaline was an effective but weaker antagonist than was LSD. In addition, neither histamine--nor Gpp(NH)p--stimulated activity of FC was inhibited by LSD. It is proposed that the occurrence of dopamine agonistic action of hallucinogens in only certain regions of primate brain may provide a basis for at least some of the behavioral effects of LSD, mescaline and methamphetamine in primates.


Columnar cortico-cortical interconnections within the visual system of the squirrel and macaque monkeys. Cortico-cortical interconnections within the visual cortex of squirrel monkeys (Saimiri sciureus) were studied by means of single or multiple injections of [3H]leucine or combined [3H]leucine and horseradish peroxidase into the dorsolateral striate and prestriate cortices. Injections of [3H]leucine were also made into the dorsolateral striate cortex of a Macaca speciosa for comparison. The results indicated that in Saimiri the dorsolateral prestriate cortex is precisely and reciprocally connected with the striate and peristriate cortex, and with the posterior bank of the superior temporal sulcus, including the middle temporal area (MT). The dorsolateral striate area is precisely and reciprocally connected with the prestriate and MT area, but does not project to the perstriate cortex as in the case of the macaque. At each target site, the radioactively labelled terminal fields are distributed in a distinctly columnar fashion, with labelled columns (120-480 microm in diameter, commonly 240 microm) interdigitating with sparsely labelled or unlabelled columns of lesser widths. The HRP-labelled neurons invariably exist within the radioactively labelled columns. For all of the cortical areas examined except area 17, lamina IV is the principal 'receptive' layer for associational fibers, while layers III and II, as well as V and VI within the same column, receive progressively less input. As for area 17, associational fibers from the prestriate cortex terminate mainly within lamina I, with laminae II, III, V and VI receiving decreasing amounts of input. The present results indicate that the major visual cortical areas are interconnected in precise, topographical and reciprocal fashion. The columnar arrangement is found to be the basis of both extra- and intercortical connections.


Scanning electron microscope study of separated calcospherites from the matrices of different mineralizing systems. Mineral particle clusters, corresponding to calcospherites or matrix vesicle-initiated clusters in calcifying cartilage and dentin and to collagen bundle-related mineralization in lamellar bone, have been isolated from NaOCl solutions used to dissolve the organic matrix in preparation of anorganic mineralizing fronts for scanning electron microscopy.


Symposium on nutritional requirements of the surgical patient. 1. Nutrition and body composition. Body composition measurements were determined by a multiple isotope dilution technique to assess nutritional status of patients and to determine the efficacy of nutritional support. The body composition of 75 patients with severe malnutrition was characterized by a contracted body cell mass with a relatively expanded extracellular mass. An elective operation of moderate severity resulted in a 14% decrease in the body cell mass while the extracellular mass increased by 10%. The 4% postoperative decrease in body weight did not accurately reflect the change in the body cell mass. The efficacy of total parenteral nutrition (TPN) with lipid as the major caloric source was compared with TPN with hypertonic dextrose. With lipid a daily infusion of 44.2 Cal/kg (185 kJ/kg) was required to maintain the body cell mass while with the solution containing hypertonic dextrose 34.7 Cal/kg (155 kJ/kg) was required--a 27% difference. Total parenteral nutrition with hypertonic dextrose is therefore more efficacious than TPN with lipid as the major caloric source.


Symposium on nutritional requirements of the surgical patient. 2. Peripheral parenteral nutrition. During total parenteral nutrition hypertonic (25%) dextrose combined with 5% amino acid solutions must be used to achieve the necessary non-protein calorie/nitrogen ratio of 150:1. The resultant hyperosmolarity prohibits utilization of peripheral veins and makes cannulation of the subclavian vein mandatory. This exposes the patient to the risks of infection and technical complications, but these are uncommon and less important than the deleterious effects of chronic starvation. However, under certain clinical conditions it is possible to supply partial parenteral nutrition through peripheral veins, thereby avoiding the dangers of subclavian catheterization. Three such techniques--the intralipid system, protein sparing and infusion of the "P-900" solution--have been used with moderate success. The composition of the solutions and the techniques used are described.


Case report: Macroglobulinemia in a dog. This report describes a case of macroglobulinemia in a six year old castrate male Collie cross dog with clinical signs of epistaxis, anemia, retinopathy and high serum viscosity. The highest total serum protein was 12 g/dl with approximately 60% monoclonal beta globulin. Proteinuria, Bence Jones protein and osteolytic lesions were not detected.Chemotherapy and partial removal of the plasma protein by withdrawal of whole blood and transfusion with packed red cells from a DEA negative donor resulted in transient clinical remission.


Cerebellar medulloblastoma: results of a new method of radiation treatment. Nine patients with medulloblastoma were referred to the Radiation Oncology Section at the University of Chicago from 1966 to 1976. In all patients, the tumor was situated in the posterior cranial fossa, projecting from the cerebellum into the fourth ventricle. After partial tumor resection and histological diagnosis, radiation treatment was instituted: a localized dose of 1000 rad to the posterior fossa through lateral opposing ports and a total dose of 4000-5000 rad through the "hockey-stick" port to the entire CNS. With this treatment, 9 patients yielded actuarial 3- and 5-year survival rates of 88% and 73%, respectively. Five of the patients possessed no history of neurologic or spinal growth deficits after treatment. Two patients had a slight retardation of spinal growth. The remaining patients had presented symptoms of a tumor mass in the posterior fossa for a period of over 8 months prior to treatment. They were found at craniectomy to have diffuse intracranial tumor involvement, and their survival times deteriorated rapidly. The "hockey-stick" port provided a uniform distribution of radiation exposure to the entire brain and spine. It was simple to use and posed little inconvenience to patients in the pediatric age group.


Computerized body tomography in breast cancer. I. Internal mammary nodes and radiation treatment planning. The internal mammary area has been reviewed on CBT scans from 46 postmastectomy patients, and chest wall thicknesses computed there from the scan. Thicknesses ranged from 10 to 43 mm and 16 to 70 mm on the operated and nonoperated sides, and were weight-related in 38 modified mastectomy patients. Direct Cobalt and 15 MeV electron portals delivered 97-98% of the dose prescribed at 3 cm to a depth of 35 mm, the maximum average thickness on the operated side, while 12 and 10 MeV electrons gave 10 and 20% less at that depth. At 70 mm, underdosage with Cobalt and 15 MeV was 22% and 72%; insignificant doses were delivered with 10 and 12 MeV electrons. Routine determination of chest wall thickness is recommended in patients planned for electron beam treatment, in obese patients, and in patients treated with tangential photon techniques, to avoid underdosage to the internal mammary area. Internal mammary nodes were not routinely visualized, but abnormalities consistent with enlarged nodes were seen in six patients and gross recurrence in another.


Anticoagulation and high dose liver radiation: a preliminary report. Two groups of patients were observed for evidence of acute radiation hepatitis during "high dose" radiation to the liver. The first group of 18 patients with metastatic liver disease received an average of 4,050 rad to the whole liver. Half received anticoagulation with warfarin. One patient on anticoagulation developed evidence of acute radiation hepatitis while 2 patients did so without anticoagulation. Eleven patients with Hodgkin's disease received 4,000 rad to the left lobe of the liver during extended field radiation. Four of these 11 patients were anticoagulated to therapeutic range. Only one of the fully anticoagulated patients showed changes on liver scan consistent with radiation hepatitis whereas three did so without anticoagulation. No serious sequelae from anticoagulation occurred in either group. These preliminary data suggest that anticoagulation may be safely administered with high dose hepatic radiation and that further trials with anticoagulation are warranted.


Nodular lymphocytic lymphoma eventuating into diffuse histiocytic lymphoma: immunoperoxidase demonstration of monoclonality. The patient described here had a nodular, poorly differentiated lymphocytic lymphoma associated with a serum monoclonal protein, IgG lambda. Following a three year period of radiation-induced clinical remission she developed generalized diffuse histiocytic lymphoma. Direct immunoperoxidase staining of the tissue sections demonstrated that the neoplastic cells of each biopsy only contained IgG lambda immunoglobulin, identical to the serum monoclonal protein. This is presumptive evidence that these two histopathologically distinctive malignant lymphomas, occurring consecutively in the same patient, were responsible for the synthesis and secretion of the same serum M component. This strongly suggests that both lymphoid neoplasms arose from the same malignant clone. The results 1) confirm the light microscopic observation that nodular lymphocytic lymphoma may progress to diffuse histiocytic lymphoma and 2) offer further evidence that histiocytic lymphomas arising in patients with previous B cell malignancies are most probably related to the original B cell proliferation and do not represent the emergence of a second, separate malignant clone.


Promotion by dietary phenobarbital of hepatocarcinogenesis by 2-methyl-N,N-dimethyl-4-aminoazobenzene in the rat. The hepatocarcinogenicity of 2-methyl-N,N-dimethyl-4-aminoazobenzene, previously shown to be noncarcinogenic in adult rats in the absence of further treatment, was observed by following a 1- to 6-week period of feeding this dye to weanling rats with the dietary administration of 0.05% phenobarbital for up to 70 weeks. Many large hepatocellular carcinomas developed in the phenobarbital-treated animals by 72 weeks, whereas a very small number of tiny neoplastic nodules, including one carcinoma, were seen in the rats not given this drug. This study suggests that the use of promoting agents, following the short-term administration of weak carcinogens for the liver, can be useful in demonstrating the initiating activity of such compounds. This system may be useful in the identification of such agents in the environment.


Role of membrane permeabilities (calcium, chloride, and potassium) in the genesis of the notch observed on simian and prosimian cardiac action potentials. The effect of temperature reduction on monkey ventricular action potentials has been studied. Under this condition the genesis of a notch separating the AP spike from the AP plateau has been related either to a conduction phenomenon or to a delay in the activation of the slow inward current. It is observed that the development of a notch at the beginning of the plateau depends both on the presence of a large outward, repolarising current, carried by chloride and/or potassium ions, and on the presence of a slow inward calcium current large enough to depolarise the membrane as the chloride current deactivates.


Relief of coronary artery spasm by nitroglycerin: time-dependent variability in drug action. The arteriographic distinction between a fixed atheromatous obstruction and localized vasospasm in the coronary artery is often decided by the response of the lesion to nitroglycerin. We studied the time course of nitroglycerin in four patients with coronary artery spasm as revealed by selective angiography. Following complete dissolution of a 0.6 mg tablet of nitroglycerin sublingually a slight increase in heart rate occurred as early as two minutes, variable changes in overall vessel diameter were observed within four minutes, but the localized spasm remained fixed. It was not until six minutes had elasped that reinjection showed disappearance of spasm and uniform patency of the vessel in all cases. These observations stress the importance of waiting an appropriate period of time (at least six minutes) following complete absorption of sublingual nitroglycerin before any conclusion can be rationally drawn regarding the nature of a stenotic lesion as seen angiographically.


Determination of meningococcal antibodies by microassay. A modified microassay procedure, using triphenyltetrazolium chloride as a germination indicator, was compared with a macroassay method proposed by the World Health Organization for determining the level of antibodies before and after immunization with Group A meningococcal polysaccharide vaccine. There was excellent agreement between the results obtained by the two methods. The vaccine used appeared to be safe and immunogenic.


[Identification of GABA accumulating neurons in the dorsal raphe nucleus]. A possible GABAergic innervation of the nucleus raphe dorsalis (NRD) was investigated by measuring glutamate decarboxylase activity in the NRD after lesioning the afferents of this nucleus. The slight decrease found in the enzymatic activity suggests that these afferents have a minor participation in the GABA innervation of the NRD and implies the existence of an intrinsic GABAergic system in this nucleus. This local innervation was demonstrated by radio-autography and shows fibers, axonal varicosities and cell bodies which accumulate 3H GABA in the caudal part of this nucleus.


[Inhibition of LH-RH induced release of gonadotropins by substance P in cultured rat anterior pituitary cells]. Using anterior pituitary cells cultured for 7 days and then incubated for 4 hrs, substance P, an undecapeptide, inhibited the stimulatory effect of LH-RH on the release of LH-RH on the release of LH and FSH. This inhibitory effect, which was similar for both gonadotropins was only observed when the adenopituitary cells were put in culture at DI and Proestrus stages of the oestrous cycle. Furthermore substance P partly inhibited the basal release of FSH at DI and DII stages but did never affected that of LH.


[Prediction of glycan structures of human N-glycoproteins]. By adding the sequence beta-(1 leads to 4)-GlcNAc-beta-(1 leads to)-Asn or alpha Fuc-(1 leads to 6 or 3)-beta-(1 leads to 4)-GlcNAc-beta-(1 leads to)-Asn to the oligosaccharides isolated from human urines of mannosidosis, fucosidosis and sialidosis, we are able to reconstitute numerous structures of asparaginyl-glycans. We postulate i) that these structures which have not yet been characterized pre-exist in glycans of human glycoproteins, probably in the cytoplasm or/and the cell membrane; ii) that they are products of the action of endo-beta-N-acetyl-glucosaminidases which are protected because of the lack of exoglycosidases and accumulate in the cells, and then in the urine.


[Short term tests of carcinogenesis. Evaluation, predictive values, and diverse strategies]. The concepts of validation, evaluation and predictive values of short term tests for carcinogenicity are rigorously defined. The relationships between the parameters measuring these concepts are established. This allows and estimation of the practical efficiency of Ames Salmonella test (1). A new strategy for the evaluation of tests is proposed.


Long-term changes in mitral valve area after successful mitral commissurotomy. We examined the long-term effects of closed instrumental mitral commissurotomy on mitral valve area (MVA) in 18 patients, followed for as long as 14 years after successful operation. Each patient had preoperative and early postoperative cardiac catheterization; late postoperative determination of MVA was obtained 10-14 years (mean 12.2 years) after commissurotomy. In 17 patients, the MVA was determined by cross-sectional echocardiography and in one patient by repeat cardiac catheterization. Thirteen of 18 patients had no change in MVA between early postoperative study (mean MVA = 2.7 cm2) and late postoperative study (mean MVA = 2.9 CM2). MVA in five patients decreased 0.7-2.2 cm2 (mean 1.4 cm2) during the follow-up period. In these five patients, the mean MVA at early postoperative study was 2.7 cm2 and at late postoperative study was 1.3 cm2 (p less than 0.001). At late postoperative evaluation, cardiac symptoms were associated with severity of mitral stenosis but did not predict restenosis. A successful, closed, instrumental mitral commisurotomy can provide substantial long-term improvement in MVA.


Blood levels after sublingual nitroglycerin. Pharmacokinetic analysis of nitroglycerin (GTN) has been hampered by the lack of a sensitive and specific method for measuring GTN in blood. Therefore, we examined the appearance of GTN in blood after administering 0.6 mg sublingually in 10 studies of normal volunteers. We used a gas-liquid chromatographic method with electron-capture detection and isosorbide dinitrate as the internal standard. GTN appeared in blood at 0.5 minutes, reached a peak of 2.3 +/- 0.36 ng/ml at 2 minutes, fell to 50% of peak value at 7.5 minutes and was barely detectable at 20 minutes. These blood levels paralleled the changes in heart rate and systolic blood pressure. These data show rapid appearance and disappearance of GTN from blood after sublingual administration, a large volume of distribution, and a rapid rate of total body clearance that precludes the liver from being the sole elimination site. This method for analysis of GTN and isosorbide dinitrate should be helpful in defining the role of chronic nitrate therapy.


Quantitative determination of trinitroglycerin in human plasma. We developed a simplified method for quantitative measurement of trinitroglycerin in human plasma using hexane extraction and analysis by gas-liquid chromatography with electron-capture detection. This assay was linear from 0.5-60 ng/ml. Sensitivity and reproducibility were +/- 0.5 ng/ml. We used this assay to evaluate the pharmacodynamics of trinitroglycerin in 14 patients. Maximum plasma levels were similar with trinitroglycerin given by constant intravenous infusion (1.6 +/- 0.4 ng/ml (SEM)), transcutaneously (2.3 +/- 0.6 ng/ml), or sublingually (1.6 +/- 0.6 ng/ml). Despite similar levels and hemodynamic responses after intravenous trinitroglycerin, the dose range was wide (37.5-175 microg/min, n = 5), emphasizing the need to individualize therapy. In normal volunteers on no other drugs, the plasma level time course followed changes in heart rate better than blood pressure changes. Use of the trinitroglycerin assay may enhance optimization of trinitroglycerin therapy when administered by different methods.


An assessment under routine conditions of an immunoelectrophoretic assay for thyroxine-binding globulin. The correct clinical interpretation of serum total thyroxine requires a knowledge of the thyroxine binding globulin (TBG) concentration. An immunoelectrophoretic method for TBG assay has been assessed under routine conditions for precision, sensitivity and recovery. TBG has been compared with T3 Resin Uptake for euthyroid subjects, and patients with myxoedema and thyrotoxicosis. The relationship between TBG and age has also been studied. The method proved to be reliable, sensitive and a technically simple method for the routine determination of TBG and an excellent replacement for the indirect T3 Resin Uptake Test.


Effects of Ca, Mg, and EDTA on creatine kinase activity in cerebrospinal fluid. For one to obtain a precise estimate of creatine kinase (CK) activity in cerebrospinal fluid, the sample fraction is increased by about 10-fold over that used for serum. This increases the concentration of interfering substances, Ca being especially important. Therefore, the relationship between Ca, Mg, and EDTA was examined. Enzyme activity was maximal with 15 mmol of Mg per liter in the presence of 3 mmol of EDTA per liter, otherwise according to the (Scandinavian) recommended conditions for determination of CK activity in serum. These modifications increased the activity of CK by 35% for CK-MM and by 60% for CK-BB. Counteraction of Ca-induced inhibition was the main reason to this increase. We describe a practical and sensitive method for determining CK in cerebrospinal fluid.


Evaluation of two commercially available laser nephelometers and their recommended methods for measurement of serum immunoglobulin G. The Hyland and Behring laser nephelometer systems for assay of specific proteins are described. Immunoglobulin G was measured to assess the overall performance of the two systems. Intra-batch precision figures were comparable to those for the radial immunodiffusion method run routinely in our laboratory. There was no significant interference from turbid or lipemic specimens. Accuracy, ease of instrument operation, standard curve stability, linearity, and accessory equipment are discussed. Immunoglobulin G is measured rapidly, accurately, and precisely by either system.


Double light-chain disease: a case report. A patient with massive proteinuria was discovered to have double light-chain disease. Immunological studies demonstrated monoclonal light chains of both the lambda and kappa type in urine. The light chains were separate and distinct and were not found to be a part of any of the whole molecule immunoglobulins such as IgG, IgM, IgA, IgD, or IgE. Uniqueness of the proteins was confirmed by column chromatography. Clinical studies showed that the patient had multiple myeloma.


Enzyme immunoassay for human ferritin.

Enzyme immunoassay for human ferritin. We describe an enzyme immunoassay with use of beta-D-galactosidase for quantitation of ferritin in human serum. The minimum detectable ferritin concentration is 0.25 microgram/L of serum, which is comparable to results obtained by radioimmunoassay. The correlation coefficient between values determined by enzyme immunoassay and radioimmunoassay was 0.95 (n - 1 = 85, p less than 0.001).


Urinary lysosomal enzyme excretion after renal allotransplantation. Three urinary lysosomal enzymes, beta-glucuronidase (beta-Gluc), beta-galactosidase (beta-Gal) and N-acetyl-beta-D-glucosaminidase (NAG), were measured in twenty-one renal allograft recipients to evaluate their role in the diagnosis and prediction of rejection episodes, and in the prediction of eventual graft outcome. A fluorometric assay using methylumbelliferone substrates was used to measure the three enzymes in morning urine samples and enzyme activity was defined in terms of urine creatinine concentration. Urinary NAG levels increased significantly in 13/16 first rejection episodes and 4/4 instances of acute tubular necrosis and graft infarction. In 5 of the 16 first rejection episodes the NAG was predictive of the rejection. NAG was not useful in diagnosing second or subsequent rejections and beta-Gluc and beta-Gal were of little value in assessing any component of renal transplant pathology. As a prognostic index of eventual graft outcome, the peak urinary NAG was particularly encouraging. It correlated strongly with deterioration in graft function as time passed such that only 2/10 patients with peak NAG greater than 1400 Units had normal serum creatinines at 6 months post transplantation. Conversely 4/4 patients with peak NAG levels less than 700 Units had normal serum creatinine at that time. In our series the measurement of urinary NAG was a useful adjunct to the diagnosis of first rejections but appears to be more valuable in predicting graft outcome.


Variable expression in a dominantly inherited skeletal dysplasia with similarities to brachydactyly E and spondyloepiphyseal-spondyloperipheral dysplasia. Variable expression and penetrance of dominantly inherited disorders present problems in diagnosis and counseling. The variation in clinical findings within a family with an autosomal dominant skeletal dysplasia is presented. In some members only shortened metacarpals were found, as seen in classic Brachydactyly E. Others presented with more severe and generalized skeletal involvement, such as is found in some of the spondyloepiphyseal dysplasias. This family may represent the true spectrum of Brachydactyly E; they may be affected with a specific spondyloepiphyseal dysplasia; or they may represent a new syndrome. The authors favor the first possibility and feel that this family serves to emphasize the importance of examining all affected members in a kindred with an autosomal dominant disease.


Immunological control of fertility: measurement of affinity of antibodies to human chorionic gonadotrophin. Four baboons were primed with diazotized beta human chorionic gonadotrophin and boosted with diazotized C-terminal beta human chorionic gonadotrophin peptide, and the changes in antibody amount and affinity determined using a double isotope modified Farr assay, using labelled human chorionic gonadotrophin as the antigen. The degree of cross-reaction with human luteinizing hormone was also determined. Although appreciable reactivity with luteinizing hormone was observed soon after immunization, this declined rapidly during the response. At the time intervals studied, there was a progressive increase in affinity of antibodies to human chorionic gonadotrophin until day 248 after priming. At day 313, in two of the animals, there was a decrease in affinity from 1.04 X 10(11) to 6.80 X 10(10) and 1.05 X 10(11) to 4.93 X 10(10) l/mol, whereas in the other two baboons there was a further increase in antibody affinity. At corresponding time intervals, there was a steady decrease in values of total antibody binding sites. To determine the overall effect of the maturation of affinity with a decrease in antibody amount on biological efficacy, the theoretical amount of chorionic gonadotrophin that would be neutralized was calculated. We computed that in all instances, over 99% of a peak concentration of chorionic gonadotrophin that could be in circulation in a pregnant baboon would be neutralized. This was in excellent agreement with results of mating experiments in these baboons. In over forty cycles studied, none of the matings resulted in a sustained pregnancy.


Identification of nephritic factor as an immunoglobulin. C3 nephritic factor (C3NeF) activity in sera from three patients with mesangiocapillary glomerulonephritis, one of whom had partial lipodystrophy, was found on chromatography to be associated with fractions containing IgG and no other detectable proteins. Immunoadsorption of IgG from these fractions with a highly purified anti-IgG removed the C3NeF, and the IgG, eluted after combination with the anti-IgG, retained C3NeF activity. In each case the isolated IgG with C3NeF activity was found to contain more than one subclass of IgG and both kappa and lambda chains, indicating that the immunoglobulin comprising C3NeF in these patients is heterogeneous and not monoclonal. The identification of C3NeF as an immunoglobulin suggests that it may be an autoantibody against antigenic determinants of complement components present in the C3 convertase of the alternative pathway.


Stimulation of human B lymphocytes by Listeria cell wall fraction. Cell wall fraction of Listeria monocytogenes (LCWF), a B cell mitogen for mouse spleen cells, is also mitogenic for human adult and cord peripheral blood lymphocytes. Purified B-cell suspensions responded to LCWF in vitro proliferation, to a similar extent as the unfractionated suspensions. Furthermore, LCWF-induced B cell differentiation into IgM-containing cells and their percentage correlated significantly with the extent of lymphocyte proliferation.


Free immunoglobulin light chain synthesis by lymphocytes from patients with hypogammaglobulinaemia. Lymphocytes from six individuals with reduced or deficient serum immunoglobulins of one or more class were assessed for immunoglobulin production in vitro. There was no clinical evidence of a secondary cause for hypogammaglobulinaemia and three of the cases were receiving immunoglobulin therapy. The predominant immunoglobulin product in the culture supernatants form four cases was free light chain. In contrast, peripheral lymphocytes from two cases with partial IgA deficiency and from normal individuals exhibited a balanced synthesis of heavy and light chains. These findings are discussed with particular reference to free light chain synthesis by immature neoplastic B lymphocytes and to normal B lymphocyte differentiation.


Effect of indomethacin on salt and water homeostasis. The effects of indomethacin-induced prostaglandin inhibition on sodium and chloride homeostasis in normal man were assessed. Seven normal subjects were on a 150-mEq sodium diet for 3 days prior to receiving indomethacin or no drug. Indomethacin decreased fractional excretions of sodium and chloride without affecting fractional excretion of potassium, creatinine clearance, or percent fractional reabsorption of free water. Cumulative sodium excretion at 8 hr fell from 49.8 +/- 7.2 to 16.1 +/- 4.8 mEq (p less than 0.005) after indomethacin. Chloride fell at 8 hr from 49.7 +/- 6.4 to 21.3 +/- 5.1 mEq (p less than 0.005). Urinary volume and osmolal clearance decreased in similar magnitudes such that free water reabsorption was not changed by indomethacin. This study showed that indomethacin decreased renal sodium and chloride excretion, implying that endogenous prostaglandins may be modulators of renal sodium excretion.


A computer program for Wiener filtering of evoked potential data. We have developed a computer program for Wiener filtering of evoked potential data. The basic algorithm involves computation of the difference berween the power spectrum of the sweep sum and the sum of power spectra of individual sweeps. Power spectra are computed by means of the discrete Fourier transform. The program is now being run on a LSI-11 computer in a neurophysiology research laboratory to analyze somatic evoked potential data from monkeys.


Lateralized preferences and right-left discrimination in the monkey: choice of mirror-image shape, position of recovered food and hand usage. Rhesus monkeys were tested for lateral preferences during mirror-image shape discrimination and food recovery from a row of pellets. Position of recovered food was unrelated to hand preference or mirror-image preference. There was no significant difference in the number of individuals preferring right and left lateral mirror-image shapes. Individuals tended to retain the same mirror-image preference to the same degree upon repeated testing. Animals of greater weight had stronger preferences. In all these respects, the features of mirror-image preference resembled those previously described for hand preference during a simple reaching task. The strength of different lateral preferences expressed by each animal were not significantly related thus failing to support the concept that asymmetric bodily responses can serve as cues for right-left discrimination in the environment. However, when the direction as well as strength of preference was considered, there appeared to be a tendency for animals to prefer the mirror-image shape whose reward bias was opposite to that of the preferred hand. This finding might have been due to a positional bias though there was evidence against this possibility.


Linear discriminant function analysis in neuropsychological research: some uses and abuses. The present paper addressed the continued misinterpretation and misapplication of linear discriminant function analysis in neuropsychological research. Methodological problems concerning the influence of shrinkage and stepwise selection procedures on LDFA are virtually ignored and affect both the classification and inferential application of LDFA. Throughout the paper examples of potential abuses of LDFA were cited and data from a familiar research problem was employed to demonstrate procedures which enable more accurate interpretation of LDFA results. Linear discriminant function analysis and its multivariate equivalents are powerful and flexible tools for exploring group differences provided appropriate applications and interpretations of results are made.


The inverse relationship between cost and survival in the critically ill cancer patient. The enormous cost of intensive multiple organ system support is apparent from patient or third party charges of $1500--$2000 per day exclusive of physician fees sampled during a retrospective review of 700 consecutive recent admissions to the Critical Care Facility of Memorial Cancer Center. Mortality rates of 49% for general medical, 54% for lymphoma or leukemia, and 20% for surgery patients suggest the need for a selective admission and discharge policy which concentrates financial and personnel resources on those for whom there remains a reasonable chance of worthwhile palliation, if not cure, of their malignancy. An informal policy of this kind may have contributed to a 10% increase in hospital discharges and a reduction of in-unit mortality from 22--18% when compared to 1035 earlier unselected admissions. A modified version of the classification suggested by the Critical Care Committee of the Massachusetts General Hospital has been adopted for use at this institution. A similar approach by other cancer centers is urged so that predictive indices based on prognosis of the underlying disease as well as physiological status may be developed. Otherwise, cost-benefit analysis by third party payers or government will become an unavoidable, and less satisfactory, alternative.


Experience with a sustained-release formulation of oxprenolol in the management of angina pectoris in hospital out-patient departments. One hundred and two patients with angina pectoris under treatment with beta-receptor antagonists prescribed on a multi-dose basis were openly switched to treatment with once-daily sustained-release oxprenolol (160 mg per tablet). Eighty-eight patients were successfully managed on once-daily oxprenolol and 70% achieved significant benefit with a single morning dose of 160 mg. The mean number of anginal attacks and the mean glyceryl trinitrate consumption were both significantly reduced. It is concluded that once-daily treatment with oxprenolol in sustained-release form offers the advantage of reduced tablet ingestion without symptomatic detriment in the management of angina pectoris.


Inhibition of growth and cell wall morphogenesis of Bacillus subtilis by extracellular slime produced by Physarum flavicomum. Slime secreted by microplasmodia of the myxomycete Physarum flavicomum inhibited the uptake of glucose and amino acids, as well as growth and cell division of the bacterium Bacillus subtilis. Morphological changes such as production of chains, swollen cells, and/or cell lysis, occurred coincident with these physiological inhibitory events. These phenomena were all dependent on the concentration of slime present in the growth medium. Electron microscopy revealed that the cell walls of slime-inhibited cells were undergoing degradation and the process was most pronounced in the swollen cells. Isolated cell walls of B. subtilis were also found to undergo degradation upon incubation with slime. Boiled slime did not exhibit lytic activity on native cell walls, but boiled cell walls were degraded by native slime. The inhibitory effect of slime seemed to be, at least in part, due to an inherent peptidase (protease) activity. B. subtilis eventually overcomes the inhibition exhibited by slime due to the production of an antagonist of slime.


Activity of thymidine kinase during the cell cycle in Tetrahymena pyriformis. The presence of thymidine kinase has recently been reported in Tetrahymena pyriformis. The activity pattern for this enzyme was investigated during the cell cycle in both the one heat-shock per cell generation and the starvation-refeed system. Thymidine kinase was found to be a peak enzyme during S-phase in both situations. Nucleoside phosphotransferase was a continuous enzyme in the one heat-shock per cycle system, however, it closely paralleled the thymidine kinase curve during starvation and refeeding.


Patterns of pulmonary involvement in systemic amyloidosis. The clinical and histopathologic features of pulmonary amyloidosis were reviewed in 22 patients with systemic amyloidosis who came to autopsy. Eleven of 12 patients (92 percent) with primary amyloidosis had prominent interalveolar amyloid deposits. Symptoms attributable to these deposits were found in four cases (33 percent), while severe lung involvement was the apparent cause of death in one. Extensive deposition was noted in all three cases of amyloidosis associated with multiple myeloma or Waldenstrom's macroglobulinemia. Five of seven patients (71 percent) with secondary amyloidosis showed histologic lung involvement, which was perivascular or tracheobronchial in location, but not associated with symptoms. Histologic lung involvement is frequent in all forms of amyloidosis and lung tissue obtained from any patient with unexplained interstitial or reticular-alveolar pulmonary disease should be stained with Congo-red and viewed for green birefringence under polarizing microscopy for the presence of amyloid.


Pulmonary function and morbidity in 40 adult patients with cystic fibrosis. Pulmonary function and cardiopulmonary complications were studied in a group of 40 patients with cystic fibrosis who reached the age of 25 years. Mean values for vital capacity (VC), functional residual capacity, residual volume (RV), the ratio of RV over total lung capacity (RV/TLC), conductance, and the ratio of the forced expiratory volume in one second over VC were abnormal. There was a variable pattern of progression from patient to patient. The men differed from the women only in that they had a significantly larger TLC and inspiratory capacity than the women. The resultant preservation of VC may have an advantage for survival in those patients in whom it is observed. Pseudomonas aeruginosa was encountered with increasing frequency with age. Massive hemoptysis did not result in early death. The occurrence of rightsided heart failure secondary to cor pulmonale, with or without respiratory failure, was a poor prognostic sign.


Free genes for rRNAs in the macronuclear genome of the ciliate Stylonychia mytilus. When separated on an agarose gel, macronuclear DNA of the hypotrichous ciliate Stylonychia mytilus gives rise to many well-defined bands ranging in molecular weight from 0.3 x 10(6) to 14 x 10(6) dalton. Hybridization of 25 S rRNA, 17S rRNA or 5 S RNA to such a gel revealed sharp hybridization bands. This suggests that this banding pattern is not an artefact due to nonspecific degradation of macronuclear DNA but that the DNA in the macronucleus of Stylonychia occurs in discrete fragments, each coding for at least one gene. The size of the DNA fragment coding for rRNA was found to be 4.5 x 10(6) dalton, the fragment coding for 5 S RNA has a molecular weight of 150,000-250,000 dalton.


Reiterated genes with varying location in intercalary heterochromatin regions of Drosophila melanogaster polytene chromosomes. The localization of two cloned D. melanogaster DNA fragments in polytene chromosomes was determined by means of in situ hybridization. These different fragments (Dm 225 and Dm 234B) are present in the genome in hundreds copies and contain genes whose transcription yields two different classes in abundant mRNA (Ilyin et al., 1976, 1977; Tchurikov et al., 1978). About 20--30 sites of these genes are demonstrable in the polytene chromosomes of a given stock. There are small but significant variations in the number and localization of these sites among individuals of the same stock. On the other hand, different stocks of D. melanogaster have an utterly different distribution of revealed hybridization sites in the polytene chromosomes. The location of both fragments (Dm 225 and Dm 234) was found to be virtually identical within any given stock of D. melanogaster. 69 sites for localization of Dm 225 or Dm 234 genes were detected in the chromosomes of 11 individuals studied. At least 50 (and up to 62) of them coincide with intercalary heterochromatin regions which are known to be characterized by ectopic pairing, late replication and the presence of "weak spots" in the chromosome. The ability of Dm225 and Dm 234 to code for the "abundant" classes of messenger RNA (Ilyin et al., 1976) and the fact that their location may coincide with the histone and ribosomal genes suggest that intercalary heterochromatin regions are "nests" containing various types of actively transcribable tandem-repeated genes coding for common "household" cell functions.


The location of highly repetitious DNA in the somatic chromosomes of Drosophila melanogaster. In situ hybridization of Drosophila melanogaster somatic chromosomes has been used to demonstrate the near exact correspondence between the location of highly repetitious DNA and classically defined constitutive heterochromatin. The Y chromosome, in particular, is heavily labeled even by cRNA transcribed from female (XX) DNA templates (i.e., DNA from female Drosophila with 2 Xs and 2 sets of autosomes). This observation confirmes earlier reports that the Y chromosome contains repeated DNA sequences that are shared by other chromosomes. In grain counting experiments the Y chromosome shows significantly heavier label than any other chromosome when hybridized with cRNA from XY DNA templates (i.e., DNA from male Drosophila with 1 X and 1 Y plus 2 sets of autosomes). However, the preferential labeling of the Y is abolished if the cRNA is derived from XX DNA. We interpret these results as indicating the presence of a class of Y chromosome specific repeated DNA in D. melanogaster. The relative inefficiency of the X chromosome in binding cRNA from XY and XYY DNA templates, coupled with its ability to bind XX derived cRNA, may also indicate the presence of an X chromosome specific repeated DNA.


Total parenteral nutrition as primary therapy for inflammatory disease of the bowel. Of the series of 21 patients with Crohn's disease who were treated with TPN as primary therapy, there were only four (19 per cent) who did not eventually need surgical intervention. The mean follow-up period for this group of patients was 27.25 months. The remaining 14 patients were operated on an average of 9.9 months after their course of TPN. Of the five patients with mucosal ulcerative colitis who were treated with primary TPN, three are now doing well in response to medical therapy after a mean follow-up period of 27.3 months.


Protein-calorie malnutrition in patients with colorectal cancer. Protein-calorie malnutrition, as determined by anthropometric measures and laboratory tests, was assessed in 17 preoperative patients with colorectal cancer and 47 control patients. The cancer patients had significant deficits in visceral protein and skeletal muscle and no deficit in fat stores. Greater attention should be given to preoperative nutritional assessment and to the correction of protein deficits.


[Age dependence of the P2 latency of visually evoked cortical responses to checkerboard pattern reversal (author's transl)]. The age dependence of the P2 latency of visually evoked cortical responses to checkerboard pattern reversal was examined in 60 healthy individuals of between 10 and 69 years of age. Separate examination of the right and left eye yielded no statistically significant difference in P2 latency. A certain age dependence of P2 latency was discovered inasmuch as healthy individuals under 15 years and over 65 are--with high statistically significance--apt to show longer P2 latency than healthy individuals in the remaining life span.


[Reactions in the brainactivity during increased carbondioxyde concentration (author's transl)]. A comparative study of two kinds of respiration (normal air and mixed with 4% CO2) was carried out in 8 healthy students. During the three experiments, each one lasting over 120 min, CO2 or air was inhaled using a mask. Blood samples were taken from the fingers, an average increase of pCO2 of 1.9 mm (p less than 0.01) and pO2 of 7.3 mm (p less than 0.01) was found during CO2-inhalation. The ECG and EEG were recorded and reaction times to tone stimuli in a foreperiod reaction time experiment were measured. During CO2-inhalation a clear reduction of the power in the alpha-band was found in frontal, central and occipital region in the order of 23% (p less than 0.05) and 12% (p less than 0.05) and 22% (p less than 0.01). The heart rate interval decreased significantly by 2.3% (p less than 0.05). No significant changes were found in CNV, reaction time and percentage event-related alpha-desynchronization.


[Effect of hypnosis and suggestion on the EEG-powerspectrum in the preparatory interval (author's transl)]. Fourier-analysis of the EEG (P4 02, P3 O1, CZ A1) in the stimulation period (1 sec) before acoustic stimulation showed significant differences between hypnosis and waking. Diminished power was found in the slower spectrum (0-3 and 4-7 c/sec) over the right hemisphere (P4O2) during hypnosis. Increased power was found in the alpha-spectrum (8-13 c/sec) over the Vertex (CZA1) during suggestion. We interpreted this effect as inhibition of exteroceptive perception during suggestion. Powerspectrum was averaged over 30 stimulation periods before acoustic stimulation with identic tones (sinus of 500 c/sec, 70 dB, duration 40 msec, stimulus interval 3--10 sec). The combination of experimental conditions (Hypnosis/Waking and Suggestions) were given in a balanced order to control seriel effects. We examined 12 persons in a repeated measurement design.


On the correlation between FSH, LH and prolactin serum levels. In 188 males FSH, LH, and prolactin serum levels determined from a single blood sample were found to be closely correlated. No correlation appeared to testosterone levels. The same correlation is observed, if serum levels of FSH, LH, and prolactin are measured after stimulation with LH-RH and TRH. In order to explain the close correlation, in five young men hormone levels were measured at 2-min-intervals over a period of 2 hours. Peaks of prolactin often correspond to those of FSH and LH, and a statistical correlation was found in two cases between FSH and prolactin. Results suggest a common releasing mechanism, which is superposed to the main mediating mechanism.


[Steroid metabolism in  primates. XX. Excretion of C21-steroids in urine of women and baboons (Papio hamadryas) during pregnancy]. Urinary excretion of 10 C21 steroids was investigated in women and baboons (Papio hamadryas) in various stages of pregnancy, in comparison to controls. In pregnant women, excretion of total C21 steroids is slightly increased, whereas in pregnant baboons it is slightly decreased. In women, excretion of tetrahydrocortisol and tetrahydrocortisone is diminished, that of 20 beta-OH-F (11-beta,17alpha,20beta,21-tetrahydroxy-4-pregnen-3,20-dione) and of 11-deoxycortisol is increased. In pregnant baboons no significant alterations in corticosteroid metabolism were established.


Ethosuximide pharmacokinetics in a pregnant patient and her newborn. Ethosuximide concentration in serum was monitored during the last trimester of pregnancy in a patient. After delivery, the decline in serum concentration of ethosuximide was observed in the nonnursing neonate. The half-life of elimination of transplacentally acquired ethosuximide in this neonate was 41.3 hr. The ratio of breast milk to maternal serum concentration of ethosuximide was approximately 1. A total daily exposure to ethosuximide of 12.8 to 38.4 mg (3.6 to 11.0 mg/kg) as a result of nursing was predicted.


Effects of chronic epileptic foci on control of pyramidal tract neurons in monkeys. Five Macaca mulatta monkeys were operantly conditioned to control the firing patterns of single precentral pyramidal tract neurons. The accuracy with which the monkeys could control normal PTNs from within the focus was significantly poorer than PTNs from contralateral, homotopic cortex. In comparison to nonepileptic monkeys, there was no significant difference in the accuracy with which PTNs from cortex contralateral to interictal foci were controlled. By contrast, comparison of the time necessary to gain accurate control over individual PTNs from contralateral cortex showed the epileptic monkeys to be significantly encumbered when compared to nonepileptic monkeys. These data suggest that interictal foci produce "noise" in remote regions of brain that are involved in an operant task requiring a high degree of discrimination.


Identification of metabolites of valproic acid in serum of humans, dog, rat, and mouse. In kinetic studies of VPA in humans, dogs, rats, and mice, as well as in clinical routine analysis of serum concentrations of VPA in epileptic patients, 2--4 peaks (depending on the species examined) were regularly found in the gas chromatograms in addition to VPA. Comparison with control serum indicated that these peaks resulted from metabolism of VPA. By GC--MS, two of these metabolites could be identified as 5-hydroxy-2-propyl-pentanoic acid (5-OH-VPA) and 4-hydroxy-2-propyl-pentanoic acid (4-OH-VPA), using synthesized reference substances. Both metabolites results from omega (omega1, omega2) oxidation of VPA, 5-OH-VPA only occurring in serum of mice, and 4-OH-VPA in serum of mice and humans. With the aid of low- and high-resolution mass spectra, likely structures of the two remaining metabolites, both of which were found in serum of all the species examined, were proposed. One of these, 3-hydroxy-2-propyl-pentanoic acid (3-OH-VPA) confirms the involvement of beta-oxidation in the metabolism of VPA. The fourth metabolite, whose identity is uncertain, indicates a substance not described previously as a metabolite of VPA.


Pesticide use in agriculture.

Pesticide use in agriculture. During the last three decades, the use of modern organic synthetic pesticides has increased about 40-fold. Total U.S. production, for domestic and expert use, in 1976 was about 1.4 million pounds. Crops receiving the most intensive application of various pesticides were cotton for insecticides, corn for herbicides, and fruits and vegetables for fungicides. Examination of use trends of pesticides indicates that the volume in pounds of herbicides used on crops is increasing, whereas the quantities of insecticides and fungicides remain stable. New chemical classes of compounds such as the synthetic pyrethroid insecticides are being introduced, but are not yet significant in terms of their share of the market. The increased usage of pesticides, together with knowledge of some of their adverse effects, has alerted the public to the need for regulation. To assist in the regulatory decision-making process, emphasis is being placed on benefit-cost analyses. Additional and improved biological inputs and methodologies are needed to provide accurate analyses.


Comparison of the effect of various doses of thyroxine on jejunal disaccharidases in intact and adrenalectomized rats during the first 3 weeks of life. Administration of D,L-thyroxine (T4) daily (25 or 250 nmol/100 g body weight/24 h) for 4 days increased jejunal activity in 15-day-old rats; no effect was seen in 8-day-old rats. Maltase activity was increased in 15-day-old rats only when a 250-nmol dose was used. Similar results were obtained in unoperated and adrenalectomized rats. Specific activity of lactase was not influenced in unoperated 8- and 15-day-old rats; it was decreased in adrenalectomized 8- and 15-day-old rats when treated with a 250-nmol dose of T4; in 15-day-old rats, it also responded to 25-nmol doses. The lowest dose used (2.5 nmol/100 g body weight) had no effect at all.


Inbreeding effect: embryonic development and fecundity of Drosophila melanogaster offspring. Inbreeding depression observed on fecundity of adult Drosophila depends on the effect observed during development of the eggs laid by their parents. This depression does not then depend on the homozygosity per se of the adult genome. It is mainly due to the deleterious effect observed primarily during embryogenesis.


Species-dependent stereospecific serum protein binding of the oral anticoagulant drug phenprocoumon. 13 mammalian species are classified into 3 clearcut groups with respect to the stereospecific serum protein-binding of phenprocoumon: 2 groups showing opposed stereospecific binding characteristics and a 3rd group exhibiting no stereospecific binding. Structural differences in the albumin molecule account for these stereospecific differences in serum protein-binding.


Bronchial mucosal permeability.

Bronchial mucosal permeability. The tracheobronchial epithelium has well-developed tight junctions which on a morphologic basis should be markedly resistant to penetration by protein molecules. Despite this, antigen inhalation in monkeys allergic to Ascaris suum results in the rapid onset of pulmonary physiologic changes. Recent studies in man and animals have shown that a substantial number of mast cells exist in the bronchial lumen and epithelium. We suggest that antigen-antibody interaction initially occurs on these superficial mast cells leading to mediator release and the stimulation of airway irritant receptors. Antigen challenge also results in increased epithelial permeability to protein in the Ascaris-allergic monkey, and from studies on guinea pigs we suggest that this is due to alterations in the tight junctions. Antigen challenge in the monkey also produces increased permeability to labeled histamine and hyperresponsiveness to low concentrations of histamine. We suggest that the apparent airway hyperreactivity to inhaled histamine seen after inhalation of ozone, and NO2, or after upper respiratory infections could be due to damage to epithelial tight junctions. The resultant increase in mucosal permeability would result in an increased amount of histamine reaching airway smooth muscle for a given inhaled concentration.


Induced varicoceles in rhesus monkeys.

Induced varicoceles in rhesus monkeys. Varicoceles were surgically induced unilaterally in seveh rhesus monkeys. Effects of the varicoceles were documented by quantitative and qualitative changes in the semen analysis and testicular biopsies. Testicular temperatures appeared to be higher bilaterally in animals with varicoceles. Testosterone and estradiol levels in the testicular vein were somewhat higher on the experimental side. We found no evidence for adrenal retrograde flow.


Effects of immunization with the beta-subunit of ovine luteinizing hormone on corpus luteum function in the rhesus monkey. Rhesus monkeys immunized with the beta-subunit of ovine luteinizing hormone (oLHbeta) developed circulating antibodies which cross-reacted strongly with rhesus monkey chorionic gonadotropin. Normal ovulatory cycles continued, but the fertility of immunized monkeys as compared with that of controls was significantly reduced. Thus, the rhesus monkey represented a useful animal model for the study of certain aspects of an "antifertility vaccine." We investigated the effects of circulating antibodies to oLHbeta on corpus luteum function by measuring production rates (PRs) and peripheral concentrations of progesterone during the luteal phase of the menstrual cycle. Both parameters were significantly lower in immunized animals than in control animals. The length of the menstrual cycle was also significantly reduced. Progesterone PRs were also determined on days 10 and 15 after mating to test the assumption that the antifertility vaccine prevents pregnancy by interfering with "corpus luteum rescue" (the increase in PRs of progesterone usually occurring on day 15 after mating in fertilized animals). PRs increased from days 10 to 15 in pregnant controls, were unchanged in nonpregnant controls, and were significantly lower on day 15 in immunized monkeys as compared with nonpregnant and pregnant controls. These results suggest that "corpus luteum rescue" is suppressed in immunized animals.


Non-immunological regression of dimethylbenz(A) anthracene-induced experimental keratoacanthomas in the rabbit. In 9 rabbits, with a total of 17 experimental keratoacanthomas, a search has been made for immune-mediated mechanisms which could possibly be involved in the spontaneous regression of these tumours. Immunofluorescence studies did not reveal significant staining patterns. With skin tests, using autologous extracts prepared in three different ways, no delayed cutaneous hypersensitivity reactions were observed.


Modulation of gastrin release by acute changes in plasma calcium. Gastrin release was studied in 5 hypergastrinemic patients, both during calcium infusion and EDTA infusion. In each patient, gastrin decreased in conjunction with the fall in plasma calcium, and increased during calcium infusion. Plasma gastrin and calcium levels were strongly correlated.


Radiographic findings in patients with esophageal involvement by mediastinal granuloma. Of 97 patients with mediastinal granuloma, 13 had involvement of the esophagus by extension from adjacent lymph nodes or pleura. A knowledge of the anatomic relationships of these structures is important in understanding the distribution and radiologic features of these lesions. The most common manifestation was extrinsic compression, being present in 7 (54%) of the 13 patients. Three patients (31%) had either a fistula or a sinus tract. Esophageal stricture and diverticulum formation also occurred. Mediastinal granuloma should be considered in the differential diagnosis in patients with any of these findings.


[Rule of antibody structure: the primary structure of a human monoclonal IgA1-immunoglobulin (myeloma protein Tro), I. Purification and characterization of the protein and its L- and H-chains (author's transl)]. Myeloma protein Tro was prepared from the serum of a myeloma patient by ammonium sulfate precipitation. It was purified by gel filtration and ion exchange chromatography or by Pevikon block electrophoresis. The purity of the preparation was tested by several electrophoretic or immunoelectrophoretic methods. L- and H-chains of the purified protein after reduction and alkylation were separated by gel chromatography. The protein and its L- and H-chains were characterized by amino acid analyses and end-group determinations.


[Rule of antibody structure: the primary structure of a human monoclonal IgA1-immunoglobulin (myeloma protein Tro), II. Cleavage of the monomer IgA-molecule and the reduced and alkylated H- and L-chains by cyanogen bromide (author's transl)]. The monomer of myeloma protein Tro as well as the reduced and alkylated H- and L-chains were cleaved by cyanogen bromide. All cyanogen-bromide fragments were isolated and characterized by amino acid analyses, end-group and molecular weight determinations. The 4 smaller fragments of the 5 H-chain fragments were split with trypsin. The peptides were isolated and their primary structure was determined.


[Rule of antibody structure: the primary structure of a human monoclonal IgA1-immunoglobulin (myeloma protein Tro), III. Isolation and characterization of the tryptic peptides of the H-chain (author's transl)]. The reduced and either aminothylated or carboxymethylated H-chain of the monoclonal IgA1 immunoglobulin Tro was digested with trypsin. The tryptic peptides were isolated by gel and ion-exchange chromatography. Because of different methods of alkylation, the cysteine-containing peptides could be obtained in two forms and showed additional overlaps. Sequence studies performed with these fragments elucidated the primary structure of the protein.


[Rule of antibody structure: the primary structure of a human monoclonal IgA1-immunoglobulin (Myeloma protein Tro). IV. Isolation and characterization of the chymotryptic peptides of the H-chain (author's transl)]. The preceeding papers dealth with the purification and characterization of IgA immunoglobulin Tro and its H- and L-chains, the separation and characterization of the cyanogen bromide fragments and the isolation of the tryptic splitting products of the H-chain. In this paper the chymotryptic peptides of the H-chain are presented. All chymotryptic peptides were isolated and purified parallel to the isolation of tryptic peptides. On the basis of these overlapping splitting products the arrangement of the tryptic peptides in the protein could be determined. These and other splitting products listed in this paper contributed to the complete sequence determination of of the H-chain.


[Rule of antibody structure: the primary structure of a human monoclonal IgA1-immunoglobulin (myeloma protein Tro), V. The arrangement of the tryptic peptides and a discussion of the complete primary structure of the H-chain (author's transl)]. This communication deals with the sequence work done with tryptic and chymotryptic peptides and some cyanogen bromide splitting products. With these peptides, and if necessary with their splitting peptides, the whole primary structure of the alpha1-H-chain of myeloma protein Tro is established. The position of the amides is determined by electrophoresis and digestion with aminopeptidase M. The alpha1-chain Tro comprises 475 amino acid residues. Because of its specific exchanges and deletions the variable part of alpha1-chain Tro belongs to subgroup III of variable parts of H-chains. The switch from the variable to the constant part occurs at position 119/120 and is analogous to other chains which have been sequenced up to now. The large number of cysteine residues in the alpha-chain which may influence the tertiary structure, especially in the hinge and the subsequent CH2-region, is noteworthy. Furthermore, myeloma protein Tro is compared with the other alpha1-chain Bur[5] sequenced in the meantime, and protein But[6], which is an IgA2 molecule of the allotype A2m(2).


Geriatric complex offers options from housing to skilled nursing. A not-for-profit geriatric complex offers comprehensive services and care ranging from independent living, with limited supportive services, in apartment units, to an intermediate level of care in a health-related facility, to skilled nursing and intensive care in an accredited long-term care facility. Thus, the elderly residents and patients are provided with ready access to progressive patient care in either direction whenever needed. The complex includes newly constructed and recycled apartment and medical care buildings.


Identity of euchromatic bands from man to cercopithecidae (Cercopithecus aethiops, Cercopithecus sabaeus, Erythrocebus patas, and Miopithecus talapoin). The karyotypes of four species of Cercopithecidae: Cercopithecus aethiops tantalus, C. sabaeus, Erythrocebus patas, and Miopithecus talapoin are analysed with nearly all the banding techniques. They are compared with each other, and with the karyotypes of the Baboon P. papio and with that of man. It can be concluded that the quasi-totality or the totality of the euchromatin is common to all, but has undergone structural rearrangements, generally detectable. The heterochromatin, defined by C-band staining, and late-replicating DNA, in contrast, appears very variable: In particular, E. patas has acquired very large heterochromatic segments. The significance of these modifications is discussed.