Radiation sensitivity of transforming DNA.

Biologically active DNA isolated from Bacillus subtilis was exposed in vitro to X-rays at a concentration of 10 microgram/ml in 29 mM phosphate buffer. Radiation-induced damage to the DNA was quantitatively determined by measuring the decrease in its transforming activity (try2 locus) using B. subtilis 168M (try-) as recipient. In O2, which removes .H and eaq-, the radiation sensitivity of the DNA is less than that in N2-saturated water. In N2O, which has been shown to increase yields of .OH in irardiated aqueous solutions, the radiation sensitivity of Transforming DNA is twice that observed in O2 and 1.5 times that in N2. Addition of 5 X 10(-2) M ethanol or 1.7 X 10(-1) M t-butanol, both .OH scavengers, causes large (about tenfold) reduction in the radiation sensitivity in all three saturating gases. These results suggest the importance of the .OH radical in the loss of biological activity of DNA.


Transurethral electroresection of the diverticular neck: indications, technique, results and analysis of ten surgical cases.

In cases of bladder diverticulum it is not sufficient to deal with the obstruction to urinary passage at the neck of the bladder. The detrusor musculature enclosing the neck of the diverticulum functions in a sphincter-like fashion and maintains an intradiverticular urinary retention. If total extirpation of the diverticulum involves major surgical risks owing to poor general condition or advanced age, transurethral electroresection of the diverticular neck may be carried out with full success.


Astigmatism and acuity in two primate infants.

The development of grating acuity was followed in two astigmatic primate infants, one a human being and one a pigtail macaque monkey. Both infants showed variations of acuity with grating orientation, predictable from the orientation and type of astigmatism present. Optical correction of the human infant during testing virtually eliminated the variation of acuity with orientation, suggesting that a neurally based meridional amblyopia had not yet been established.


Effects of ascorbate and ATP upon amino acid transport in the toad's cornea.

We have examined the effects of ascorbate upon amino acid uptake by the in vitro toad cornea. Physiologic levels of ascorbate increase the uptake of leucine by approximately 35% but have no effect upon the uptake of alanine. Uncouplers of oxidative phosphorylation do not inhibit the stimulation by ascorbic acid of leucine accumulation, indicating the increased synthesis of ATP is not the mechanism; exogenous ATP, unlike ascorbate, stimulates the uptake of both alanine and leucine. Carbon monoxide blocks the effects of ascorbate, whereas 2-heptyl-4-hydroxyquinoline-N-oxide (HOQNO), which inhibits "reverse" electron transfer, enhances the accumulation of leucine. The evidence suggests that ascorbate serves as an energy source for the uptake of leucine.


Perfusate effects upon resistance to aqueous humor outflow in the rhesus monkey eye. A comparison of glutathione-bicarbonate Ringer's solution to pooled aqueous humor as perfusate.

In vivo perfusion of the anterior chamber of normal rhesus monkeys with pooled rhesus aqueous humor gives an initial total facility of 0.48 +/- 0.08 (+/-S.E.) microliter/min/mm Hg. With continued intermittent perfusion for 2 hr this value increased only slightly to 0.57 +/- 0.10 microliter/min/mm Hg. Perfusion of the paired eyes of the same monkeys with glutathionebicarbonate Ringer's solution gives an initial total facility of 0.55 +/- 0.08 microliter/min/mm Hg. This value increased to 1.21 +/- 0.15 microliter/min/mm Hg with continued intermittent perfusion. Thus aqueous is a satisfactory perfusate for experiments requiring prolonged stability of the eye, but glutathione-bicarbonate Ringer's solution is not a satisfactory substitute perfusate. Neither addition of physiologic amounts of ascorbic acid to the buffered salt solution nor careful modification of the pH of the solution to the physiologic level prevented the increase of total facility it produces when used as a perfusate. A reversible, fast-phased small-magnitude increase in total facility was noted in eyes perfused with either perfusate. It is speculated this is caused by neural mechanisms for intraocular pressure control.


The role of hemolysin in corneal infections with Pseudomonas aeruginosa.

Cultures of Pseudomonas aeruginosa considered to be of proven virulence were found to have higher titers of extracellular hemolysin than cultures of lesser virulence. Intracorneal injection of purified hemolysin produced extensive corneal opacification with extensive leukocytic infiltration of the tissue. It is suggested that the hemolysin plays a role in the pathogenesis of P. aeruginosa infections by effecting lysis of host cells and/or subcellular organelles, leading to the release of enzymes destructive to corneal tissue.


Experimental pyelonephritis. V. Functional characteristics of pyelonephritis.

Changes in renal and ureteral function were studied in monkeys with experimental pyelonephritis, and correlated with the findings of 131I Hippuran scintiphotos. During the acute phase, delayed excretion of radionuclide was found to be a combined result of prolonged intrarenal as well as ureteral transit times. During the chronic phase, scintiphoto studies revealed decreased renal uptake of radionuclide suggesting decreased renal blood flow. Subsequent individual renal function studies confirmed the decrease in renal function and provided data that strongly support the "intact nephron hypothesis" in chronic pyelonephritis.


Detection of antibodies to Neisseria gonorrhoeae by counterimmunoelectrophoresis.

Antigen was partially purified from Neisseria gonorrhoeae B370 saline wash and used to assay human sera for the presence of antibodies to N. gonorrhoeae. The antigen activity as monitored by counterimmunoelectrophoresis (CIE) is resistant to trypsin and papain but sensitive to heat and periodate oxidation. Of the sera from patients with bacteriologically confirmed cases of gonorrhea, 80% were positive by CIE using this antigen preparation. Of the sera in the negative control group 11% were reactive.


The selectivity of vancomycin and lincomycin in NYC medium for the recovery of N. gonorrhoeae from clinical specimens.

Varying concentrations of vancomycin and lincomycin were tested separately in NYC medium to determine the degree of their selectivity and sensitivity for isolation of N. gonorrhoeae from clinical specimens. Results indicate that 2 microgram/ml of vancomycin used in conjunction with colymycin, amphotericin B, and trimethoprim lactate provide adequate selectivity and reduce the possibility of losses of vancomycin-sensitive strains of gonococci seen with 3 microgram/ml of vancomycin. The same medium with concentrations of from 1 to 4 microgram/ml of lincomycin substituted for vancomycin permitted more contamination and fewer recoveries of gonococci as compared with 2 microgram/ml of vancomycin.


Pseudomonas aeruginosa in swimming pools related to the incidence of otitis externa infection.

A study is reported which demonstrates that four out of twenty-four people developed otitis externa as a result of swimming in a pool with a high incidence of Pseudomonas aeruginosa. Serotyping and phage typing were used to establish that P. aeruginosa was the etiolgoical event responsible for the outbreaks of the infection.


An efficient method to produce specific anti-actin.

The production of affinity column purified (specific) anti-actin is described. With the immunization scheme employed, all rabbits produced precipitating antibodies over several months, so that 30 mg specific anti-actin per rabbit could be isolated in 6 months. The antibodies against native and detergent denatured smooth muscle actin are characterized by immunodiffusion tests, staining of the I-band of isolated myofibrils and stress fibers in tissue culture cells, using indirect immunofluorescence.


Histochemical quantification of dopa-oxidase (tyrosinase) activity in epidermal melanocytes.

The graphical method of Lineweaver-Burk was applied to the histochemical system to obtain quantitative information on the dopa-oxidase activity in human epidermal melanocytes. In vitro experiment showed that the incubation time necessary for yielding a certain amount of dopa-melanin is related to the amount of enzyme present. In the case of histochemical experiment, the time required for the first appearance of dopa-melanin deposition in melanocytes at various substrate concentrations was plotted against the reciprocal of the substrate concentration. This technique made it possible to compare the dopa-oxidase activity at various sites of the tissue.


Static lung mechanics of intact and excised rhesus monkey lungs and lobes.

Subdivisions of lung volume and pressure-volume (PV) curves of the lung and chest wall (CW) were measured in 12 rhesus monkeys (Macacca mulatta) under pentobarbital anesthesia. In addition, volumes and PV curves were obtained on the excised lungs and lobes of 12 cynomolgus monkeys (M. fasicularis). Boyle's law was used to determine functional residual capacity (FRC) in the intact animals and water displacement to determine minimal volume (MV) in the excised lungs. Total lung capacity (TLC = lung volume at a transpulmonary pressure of 30 cmH2O) was similar in vivo and in vitro (90 + 83 ml/kg) but residual volume (RV = volume at airway pressure of -50 cmH2O) and MV differed markedly (16.5 + 5.9 ml/kg). In the intact animals a very stiff CW appeared to determine RV, whereas airway closure determined MV in excised lungs. PV curves of upper and lower lobes were not different when expressed as %TLC but when expressed as milliliters of gas per gram of lung, the upper lobes contained significantly more gas per unit weight.


Quantitation of polychlorinated biphenyl residues by electron capture gas-liquid chromatography: reference material characterization and preliminary study.

Weight per cent compositions of individual peaks of Aroclors 1016, 1242, 1248, 1254, and 1260 were determined under standard gas-liquid chromatographic (GLC) conditions. The GLC peak compositions were determined by using a Hall electrolytic conductivity detector for chlorine measurement and chemical ionization mass spectrometry with single ion monitoring for molecular weight characterization. The Aroclors used are available as reference materials for individual peak quantitation of polychlorinated biphenyl (PCB) residues by electron capture GLC. On the basis of a limited interlaboratory study and a collaborative study, the individual peak method shows improved interlaboratory precision and/or accuracy in PCB quantitation over existing methods.


Influence of growth rate and nutrient limitation on the gross cellular composition of Pseudomonas aeruginosa and its resistance to 3- and 4-chlorophenol.

Concentrations of 3-chlorophenol and 4-chlorophenol below their minimal inhibitory concentrations were found to increase the permeability of Pseudomonas aeruginosa cells to protons. Levels of such activity were assessed in suspensions of cells prepared from chemostat-grown cultures, limited by either magnesium (Mg-lim) or glucose (G-lim), with the use of five growth rates. Drug concentrations required to produce the same levels of proton translocation varied with the growth rate and the nutrient limiting growth. Fast-growing cultures were more sensitive than slower-growing ones, and G-lim cells were generally more sensitive than Mg-lim ones. 3-Chlorophenol had greater activity than 4-chlorophenol at slow growth rates, but at faster rates of growth their activity was similar. Variation in these iso-effective concentrations for different cells probably reflected an alteration in the ease of drug penetration of the outer envelope. Uptake of the compounds by cells in suspension varied, drug-sensitive bacteria absorbing more than resistant ones. This variation in uptake persisted when bacteria were solvent-extracted to remove readily extractable lipids (REL). Since no significant alteration in cell size was observed among the growth conditions studied, variation in absorption probably resulted from an altered affinity of the cells to the drug, with little involvement of REL. Overall REL content did not alter significantly with growth rate or nutrient limitation. However, total phospholipid content decreased and fatty acid content increased with increasing growth rate. For G-lim and Mg-lim cultures phosphatidylcholine content remained constant, yet phosphatidylethanolamine and phosphatidylglycerol content decreased with increasing growth rate. Diphosphatidylglycerol content decreased with increasing growth rate for Mg-lim cultures and remained relatively constant for G-lim cultures. Lipopolysaccharide content of the cells was higher in Mg-lim than in G-lim cultures and decreased with increasing growth rate in both cases. Lipopolysaccharide content correlated significantly with drug uptake and sensitivity, and it appeared to determine the degree of penetration of the cell envelope by these chlorinated phenols.


Isolation and characterization of an R' plasmid in Pseudomonas aeruginosa.

An R' plasmid, R'PA1, carrying a 3- to 4-min segment of the Pseudomonas aeruginosa chromosome has been derived from the incP-1 plasmid R68.45. The chromosomal segment includes the markers argA, argB, argH, and lys-12. The plasmid retains all the properties of R68.45, including chromosome mobilization ability and wide bacterial host range. R'PA1 reverts to R68.45 in rec+ strains of P. aeruginosa, but it can be maintained in a recA strain.


Chromosome mapping in Pseudomonas aeruginosa PAT.

A linkage map of Pseudomonas aeruginosa PAT has been derived from the results of conjugation experiments using the plasmids FP2-2, R68, R91-5, and R68.45. FP2-2 and R68 each mobilize the chromosome from single, distinct transfer origins. R91-5 appears to mobilize the chromosome from two such origins, and R68.45 utilizes a number of transfer origins. R68 and R91-5 have both been shown to mobilize the chromosome with a polarity opposite to that by FP2-2. The locations of the transfer origins of these plasmids are such that it has not been possible to demonstrate chromosomal circularity by means of interrupted mating experiments. However, the available time-of-entry data combined with linkage data from plate mating experiments support the conclusion that the chromosome of P. aeruginosa is circular.


Occurrence of glutathione in bacteria.

Glutathione and soluble thiol content were examined in a broad spectrum of bacteria. Significant soluble thiol was present in all cases. The thiol compound was glutathione in most of the gram-negative bacteria but not in most of the gram-positive bacteria studied. Glutathione was absent in four anerobes and one microaerophile but was present in a blue-green bacterium. The glutathione content of Escherichia coli increased significantly during transition from exponential to stationary phase.


Catabolite inhibition and sequential metabolism of sugars by Streptococcus lactis.

Growth of galactose-adapted cells of Streptococcus lactis ML(3) in a medium containing a mixture of glucose, galactose, and lactose was characterized initially by the simultaneous metabolism of glucose and lactose. Galactose was not significantly utilized until the latter sugars had been exhausted from the medium. The addition of glucose or lactose to a culture of S. lactis ML(3) growing exponentially on galactose caused immediate inhibition of galactose utilization and an increase in growth rate, concomitant with the preferential metabolism of the added sugar. Under nongrowing conditions, cells of S. lactis ML(3) grown previously on galactose metabolized the three separate sugars equally rapidly. However, cells suspended in buffer containing a mixture of glucose plus galactose or lactose plus galactose again consumed glucose or lactose preferentially. The rate of galactose metabolism was reduced by approximately 95% in the presence of the inhibitory sugar, but the maximum rate of metabolism was resumed upon exhaustion of glucose or lactose from the system. When presented with a mixture of glucose and lactose, the resting cells metabolized both sugars simultaneously. Lactose, glucose, and a non-metabolizable glucose analog (2-deoxy-d-glucose) prevented the phosphoenolpyruvate-dependent uptake of thiomethyl-beta-d-galactopyranoside (TMG), but the accumulation of TMG, like galactose metabolism, commenced immediately upon exhaustion of the metabolizable sugars from the medium. Growth of galactose-adapted cells of the lactose-defective variant S. lactis 7962 in the triple-sugar medium was characterized by the sequential metabolism of glucose, galactose, and lactose. Growth of S. lactis ML(3) and 7962 in the triple-sugar medium occurred without apparent diauxie, and for each strain the patterns of sequential sugar metabolism under growing and nongrowing conditions were identical. Fine control of the activities of preexisting enzyme systems by catabolite inhibition may afford a satisfactory explanation for the observed sequential utilization of sugars by these two organisms.


Binding and transport of thiamine by Lactobacillus casei.

The relationship between thiamine transport and a membrane-associated thiamine-binding activity has been investigated in Lactobacillus casei. Thiamine transport proceeds via a system whose general properties are typical of active uptake processes; entry of the vitamin into the cells requires energy, is temperature dependent, exhibits saturation kinetics, and is inhibited by substrate analogs. A considerable concentration gradient of unchanged thiamine can be achieved by the system, although the vitamin is slowly metabolized to thiamine pyrophosphate. Consistent with these results, L. casei also contains a high-affinity, thiamine-binding component which could be measured by incubation of intact cells with labeled substrate at 4 degrees C (conditions under which transport is negligible). Binding was insensitive to iodoacetate, occurred at a level (0.5 nmol per 10(10) cells) nearly 20-fold higher than could be accounted for by facilitated diffusion, and was found to reside in a component of the cell membrane. Participation of this binder in thiamine transport is supported by the observations that the processes of binding and transport showed similarities in their (i) regulation by the concentration of thiamine in the growth medium, (ii) binding affinities for thiamine, and (iii) susceptibility to inhibition by thiamine analogs.


Interspecies transformation in Bacillus: mechanism of heterologous intergenote transformation.

Bacillus subtilis-Bacillus globigii hybrids were made by integration of the B. globigii aromatic region (aroB to aroE) as an intergenote in the B. subtillis chromosome. Transformation of the heterologous intergenote by B. subtillis DNA (or vice versa) occurred at about 10% of the frequency of homologous transformation by hybrid donors into the same region. Heterologous intergenote crosses were unusually sensitive to shear fragmentations of donor DNA to sizes less than 30 X 10(6) to 40 X 10(6) daltons. In all cases, the entire intergenote was transferred en bloc. Homologous transformation of intergenote markers by B. globigii DNA was not unusually shear sensitive, and linkage was normal for markers in the intergenote. A model is proposed in which efficient heterologous intergenote transformation occurs by recognition and base pairing of homologous DNA sequences of both flanks of the intergenote.


Interspecies transformation in Bacillus: sequence heterology as the major barrier.

The relative contribution of DNA restriction and of sequence heterology as barriers to interspecies transfer of DNA was studied in the heterologous transformation of Bacillus subtilis recipients by DNA was studied in the heterologous transformation of Bacillus subtilis recipients by DNA isolated from B. globigii. Transformants were obtained at very low frequencies in the evolutionarily nonconserved aromatic region; high cotransfer of linked markers was observed. New mutations were introduced into the B. globigii intergenote sequence in the resulting hybrids; these markers could be transformed with high efficiency by both B. globigii and B. subtilis DNA, representing a 10(5)-fold increase in heterologous transforming efficiency. A restriction activity in B. globigii crude extracts inactivated the biological activity of B. subtilis and hybrid DNA but not B. globigii DNA in vitro, demonstrating different sites for restriction and modification between these species. In vivo, however, B. globigii and hybrid DNA transformed the B. globigii sequence in a hybrid recipient with the same efficiency. These results show that sequence heterology is the major barrier to interspecies transformation and that, in this system, enzymatic restriction does not prevent interspecies transformation.


D-alanine incorporation into macromolecules and effects of D-alanine deprivation on active transport in Bacillus subtilis.

An auxotroph of Bacillus subtilis 168 unable to synthesize D-alanine loses the ability to support endogenously energized transport when deprived of D-alanine. Revertants of the mutant retain transport activity. The loss of transport is specific for substrates taken up by active transport; substrates taken up by group translocation are transported at normal rates. The loss of transport can be retarded by pretreatment of the cells with inhibitors of protein synthesis. Since the loss of transport could be due to an alteration in a D-alanine-containing polymer, we investigated the incorporation of D-[14C]alanine into macromolecules. The major D-alanine-containing polymers in B. subtilis are peptidoglycan and teichoic acid, with 4 to 6% of the D-[14C]alanine label found in trypsin-soluble material. Whereas the peptidoglycan and teichoic acid undergo turnover, the trypsin-soluble material does not. Treatment of the trypsin-soluble material with Pronase releases free D-alanine. Analysis of acid-hydrolyzed trypsin-soluble material indicated that approximately 75% of the radioactivity is present as D-alanine, with the remainder present as L-alanine. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of partially purified D-[14C]alanine-labeled membranes indicated the presence of two peaks of radioactivity (molecular weights, 230,000 and 80,000) that could be digested by trypsin. The results suggest that D-alanine may be covalently bound to cellular proteins.


Nutritional studies with Pseudomonas aeruginosa grown on inorganic sulfur sources.

Pseudomonas aeruginosa was grown on a succinate-basal salts medium supplemented with various inorganic sulfur compounds as its sole source of sulfur. The organism was able to grow on the sodium salts of sulfide, thiosulfate, tetrathionate, dithionite, metabisulfite, sulfite, or sulfate, but not on those of dithionate. Analyses of the culture media after 24 h of growth indicated accumulation of sulfate from each inorganic sulfur source except sulfate. Manometric studies with resting cells obtained by growth on each of these sulfur sources yielded net oxygen uptake for all substrates except sulfite and dithionate. Similar results were obtained with extracts from these cells by spectrophotometric techniques. Thiosulfate oxidase activity appeared to be induced by growth on sulfide, thiosulfate, or tetrathionate, with little or no activity observed when cells were grown on inorganic sulfur sources of higher oxidative states. Metabisulfite oxidase appeared to be associated with growth on all inorganic sulfur compounds. Rhodanese activity appeared to be constitutively present, and its activity, observed only in soluble fraction, seemed independent of the growth medium employed. Thiosulfate and tetrathionate oxidase activities were studied in greater detail than some of the other sulfur oxidases, and both were found to be distributed between particulate and soluble fractions.


Physiological characterization of an Escherichia coli mutant altered in the structure of murein lipoprotein.

Studies using isogenic transductant strains mlpA+ and mlpA as well as reversion analysis suggested that the physiological consequences of a structural gene mutation in murein lipoprotein include (i) increased sensitivity toward chelating agents ethylenediaminetetraacetic acid and ethyleneglycol-bis (beta-aminoethyl ether)-N,N-tetraacetic acid, (ii) leakage of periplasmic enzyme ribonuclease, (iii) weakened association between the outer membrane and the rigid layer accentuated by Mg2+ starvation, resulting in the formation of outer membrane blebs, and (iv) decreased growth rate in media of low ionic strength or low osmolarity. It is suggested that the bound form of lipoprotein plays an important role in the maintenance of the structural integrity of the outer membrane of the Escherichia coli cell envelope. Other outer membrane components may also contribute to the anchorage of outer membrane to the rigid layer, probably through ionic interactions with divalent cations. Using the phenotype of ribonuclease leakage as an unselected marker in a three-factor cross with P1 transduction, we were able to establish the gene order of man mlpA aroD pps on the E. coli chromosome.


Turnover-synthesis of chloroplast DNA in developing chloroplasts.

The mechanism for the turnover-synthesis of chloroplast DNA in the absence of net synthesis during the chloroplast maturation in Euglena gracilis was determined. DNA synthesis was measured by incorporation of32Pi into chloroplast DNA. The density label, 15N, was incorporated to examine the mechanism of turnover-synthesis. The newly synthesized segments represent a replacement of segments in the DNA containing 1.5 X 10(3) to 6.1 X 10(3) nucleotides. Twenty-three fragments of chloroplast DNA, generated by digestion with the restriction endonuclease EcoRI, became labeled with 32Pi. Turnover-synthesis, therefore, replaces segments throughout the molecule of chloroplast DNA.


Double mutants of Bacillus subtilis growing as helices.

Double mutants of Bacillus subtilis, deficient in autolysin and rod in genotype, grow as helical filaments of unseparated cells when changed from the cocci to rods.


RSF1010 plasmid as a potentially useful vector in Pseudomonas species.

RSF1010 plasmid DNA was introduced into Pseudomonas putida and P. aeruginosa cells and maintained stably, suggesting the potential usefulness of this plasmid as a vector in Pseudomonas species. The number of copies of RSF1010 was 43 per chromosome equivalent in P. putida cells.


Ethionine-resistant mutants of the filamentous blue-green alga Plectonema boryanum.

Plectonema boryanum mutants that are resistant to ethionine are unable to incorporate ethionine into acid-precipitable material. Ethionine causes bleaching of chlorophyll in sensitive cells.


Acute cerebral symptomatology, a rare presentation of scleromyxedema.

A 65 year old male with the entity, scleromyxedema, experienced exacerbation of the disease in which the main clinical features involved the central nervous system. He presented with clouded sensorium, disorganized thinking, combative behavior, headache, unsteady gait and grand mal seizures. A few days after hospital admission the symptoms abated. After a 6 day hiatus, the symptoms suddenly recurred, continuing for another week. The symptomatology again suddenly ceased with complete clearance of mental status. During the full-blown delirium, the electroencephalogram had demonstrated diffuse slowing while lumbar puncture, brain scan, E.M.I. scan and cerebral arteriogram failed to contribute to the understanding of the clinical presentation. Scleromyxedema rarely involves the central nervous system. This case illustrates a very unusual manifestation of scleromyxedema, prominent central nervous system involvement presenting as an acute organic brain syndrome. It is the only case which includes formal mental status examination, cerebrospinal fluid findings and electroencephalogram results.


A compound possessing antitumor and interferon-inducing activities derived from the common antigen (OEP) of Pseudomonas aeruginosa.

OEP, a component consisting mainly of protein with small amounts of lipids and sugars, has been isolated from the autolysate of Pseudomonas aeruginosa and purified by physicochemical methods. It possesses remarkable biological properties, showing antitumor and interferon-inducing activities. As regards the antitumor activity of the sample, the ED50 value against ascites sarcoma-180 was 1 microgram/kg mouse/day, and its interferon-inducing activity amounted to 15 units at a concentration of 0.01 microgram/ml. Both activities increased after protease digestion, reaching about ten times those of the sample which had not undergone digestion. The protease-treated OEP contained 17% protein, 14.5% total sugars, 31% lipids, 12.5% hexosamine, 3.8% KDO, and 2.7% phosphorus. Neutral sugars consisted of 12.4% rhamnose, 2.7% mannose, 66.9% glucose, and other unidentified material. Total lipids derived from OEP consisted of 65% loosely-bound and 35% covalently-bound lipids; the former contained C14:10, C16:0, C16:1, C18:0, and C15:1 acids and the latter, beta-OH C10:0, C12:0, alpha-OH C12:0, beta-OH C12:0, C16:0, and C16:1 acids. The antitumor and interferon-inducing activities of OEP remained after the removal of loosely-bound lipids from OEP.


Chemical modification of ribonuclease T1 with ozone.

The single tryptophan residue in ribonuclease T1 [EC 3.1.4.8] was selectively oxidized by ozone to N'-formylkynurenine, which was then converted to kynurenine by acid-catalyzed deformylation in the frozen state. The two enzyme derivatives thus formed, NFK- and Kyn-RNase T1, lost enzymatic activity at pH 7.5, at which native RNase T1 most efficiently catalyzes the hydrolysis of RNA. At pH 4.75, the modified enzymes retained a decreased but distinct enzymatic activity toward RNA without alteration of substrate specificity, and Kyn-RNase T1 was four times more active than NFK-RNase T1. The binding of 3'-GMP to these modified enzymes decreased remarkably at pH 5.5, the optimum pH for binding to the intact enzyme. The gamma-carboxyl group of glutamic acid 58 was still reactive to iodoacetic acid after modification of tryptophan 59. The amounts of the carboxymethyl group introduced into NFK- and Kyn-RNase T1 were 0.36 and 0.59 mol, respectively, under conditions such that quantitative esterification of native RNase T1 takes place. CD spectroscopy indicated that the tertiary structure of the molecule was disordered in NFK-RNase T1, but not significantly in Kyn-RNase T1. It is concluded that tryptophan 59 functions in maintaining the active conformation of the protein structure, particularly in constructing the active environment for a functionally important set of groups involved in the binding of the substrate at the active site, although direct participation of in tryptophan the catalytic function of ribonuclease T1 is unlikely.


Improved preparation and cooperative calcium contraction of glycerinated Vorticella.

An improved method for the preparation of glycerinated Vorticella convallaria was investigated. The pretreatment of living vorticellas with a medium containing 0.1% saponins and subsequent treatment with an extraction medium containing 35% glycerol at about 0 degrees C was satisfactory. The equilibrium average length of contractile stalks of glycerinated vorticellas was measured at various free calcium concentrations in the reaction medium. It was found that the contractile element in the spasmoneme of the stalk is contracted by a cooperative interaction involving at least two calcium ions.


Synthesis and secretion of kidney beta-galactosidase in mutant le/le mice.

We have found that the pigmentation mutant light ear in the mouse has a striking effect on lysosomes in the kidney. Male mice homozygous for the le mutant allele have a 4-fold elevated concentration of kidney beta-galactosidase (EC 3.2.1.23). The abnormal elevation of kidney beta-galactosidase is the net result of two processes. First, beta-galactosidase is elevated due to the defective urinary secretion of lysosomal enzymes which is a specific effect of the le mutation. Secondly, this effect is most evident in males and testosterone-treated females because of the induction of beta-galactosidase synthesis by testosterone, which occurs in +/+ as well as in mutant mice. The pale-ear mutation (ep) which mimics the pigmentation phenotype of le also has a similar effect on kidney lysosomes.


Fractures of the neck of the talus. Long-term evaluation of seventy-one cases.

Seventy-one fractures through the neck of the talus were clinically evaluated and classified on the basis of roentgenographic appearance. The follow-up interval averaged 12.7 years. Good or excellent results were achieved in 59 per cent of the fractures. Accurate anatomical reduction of displaced fractures, if necessary by open reduction and internal fixation, is recommended. Avascular necrosis of the talar body occurred in 52 per cent of the fractures (in two of thirteen non-displaced fractures, in half of the fractures with subluxation or dislocation of the subtalar joint, and in sixteen of nineteen fractures with complete dislocation of the body of the talus). Many patients with avascular necrosis treated conservatively had satisfactory results. The complications of avascular necrosis, malunion, subtalar arthritis, and infection required twenty-five secondary procedures. Triple arthrodesis, tibiocalcaneal fusion, and dorsal beak resection of the talar neck all resulted in a high percentage of satisfactory results, but talectomy did not.


The spinal disorders in diastrophic dwarfism.

Of seven patients with diastrophic dwarfism, all had cervical spina bifida occulta. Two had cervical kyphosis, which was severe in one. Scoliosis was present in five patients and was always progressive. Lumbar lordosis was seen in all seven patients and was not progressive.


Fractures of the fibula proximal to the distal tibiofibular syndesmosis.

Study of thirty-six cases of fracture of the fibula at levels proximal to the distal tibiofibular syndesmosis established that there are three types, distinguished by the direction of the fracture line, which are produced by different mechanisms: supination-external rotation, pronation-abduction, and pronation-external rotation. Advanced lesions that were seen were severe injuries of the ankle which included rupture of the deltoid ligament or fracture of the medial malleolus and complete diastasis of the distal tibiofibular syndesmosis in addition to the fracture of the fibula. Surgical treatment is necessary in most advanced lesions.


Adaptation to cycloheximide of macromolecular synthesis in Tetrahymena.

Cycloheximide (CHI) at 10 ng/ml partially inhibited protein synthesis in exponential cultures of Tetrahymena Sp. At 20 ng/ml or greater, inhibition was complete. When protein synthesis was inhibited to any extent, cell division ceased immediately. In all instances where measured, synthesis of RNA and DNA also ceased. After a period of delay, cellular functions reinitiated in the order: (i) protein synthesis, (ii) DNA synthesis and, (iii) RNA synthesis and cell division. The delay in cell division was divided into three phases of: I, zero; II, low; and, III; fully recovered rates of exponential protein synthesis. The length of the three phases increased with increasing concentration of CHI. Prior growth of cells for one generation in the presence of 7.5 ng/ml CHI (facilitation) eliminated phase I and slightly decreased phases II and III following subsequent challenge with an inhibitory concentration of CHI. Facilitation for six generations further decreased phases II and III. Protein synthesis and cell division were not inhibited during facilitation. In the culture, succinate dehydrogenase activity did not increase during the delay but increased normally at the onset of division. In contrast, NADPH-cytochrome c reductase activity continued to increase for an hour after inhibition of protein synthesis, was constant for a period and did not increase again until an hour after reinitiation of cell division and RNA synthesis. Inhibition of division of all cells was immediate and reinitiation of synthesis and cell division was non-synchronous.


Heat shock dependent fluctuations of RNase activity during the cell cycle of synchronized Tetrahymena.

The total cellular acid RNase activity per milliliter of culture increases sharply following each heat shock in the cell cycle of Tetrahymena pyriformis ST synchronized with heat shocks spaced one generation time apart. Thus, the RNase activity per 10(5) cells is 24.5 units immediately after the end of the sixth heat shock, increases to 39.0 units during the following 55 minutes and decreases to 24.2 units at the start of the seventh heat shock. No change in the RNase activity occurs during the heat shock period. In logarithmically growing cells the RNase activity per 10(5) cells is 15.4 units. The heart shock stimulates the increase in the RNase activity, since no rapid increase occurs during the free running division cycle but a rapid increase occurs after an additional heat shock given at different times during the cell cycle. Inhibition of the increase in RNase activity by cycloheximide suggests that concurrent protein synthesis is required for the stimulation of the RNase activity by the heat shock treatment.


Separation of polychlorobiphenyls from chlorinated pesticides in sediment and oyster samples for analysis by gas chromatography.

Polychlorobiphenyls (PCBs) have been separated from DDT and its analogs and from the other common chlorinated pesticides by adsorption chromatography on columns of alumina and charcoal. Elution from alumina columns with increasing fractional amounts of hexane first isolates dieldrin and heptachlor epoxide from a mixture of chlorinated pesticides and PCBs. The remaining fraction, when added to a charcoal column, can be separated into two fractions, one containing the chlorinated pesticides, the other containing the PCBs, by eluting with acetone-diethyl ether (25:75) and benzene, respectively. The PCBs and the pesticides are then determined by gas chromatography on the separate column eluates without cross interference. The method is applicable to sample extracts prepared for gas chromatography. Recoveries of the PCBs (Aroclors) and the chlorinated pesticides are good and the method is applicable to sediment and marine biota samples.


Evaluation of the Microcult system for isolating and identifying Neisseria gonorrhoeae.

Specimens from 95 patients attending a venereal diseases clinic were examined for gonococci by three methods--a conventional culture technique using modified Thayer-Martin medium, microscopy of a Gram-stained direct smear, and the Microcult system. For 56% of the specimens the results by all three methods agreed. Assuming the results obtained by culture on Thayer-Martin medium to be correct, the largest source of error was due to false-positive results: microscopy gave 26 and Microcult gave 15 such results. False-negative results were less common: Microcult gave 14, microscopy six. Microcult gave positive results more quickly than the conventional Thayer-Martin cultural method, but the gonococci were difficult to isolate by subculture from the Microcult culture pads. The Microcult medium was not absolutely specific for Neisseria gonorrhoeae. Nevertheless, the Microcult test may well prove to be a useful adjunct to the diagnosis of gonorrhoea, especially when laboratory facilities are not readily available.


Effect of Tween 80 on incubation period of Lactobacillus casei assay of serum folate.

Contamination of folic acid assay medium with oleate led to a lag phase when Lactobacillus casei cultures were grown on folic acid but not when whole serum provided the folate source. This led to high assay values when using 20-hour incubation periods but satisfactory results were obtained after 48 hours' incubation. The addition of Tween 80 to the medium eliminated the lag phase and the assay results were consistent after 13, 24, and 48 hours' incubation.


IgM lambda cytoplasmic crystals in three cases of immunocytoma: a clinical, cytochemical, and ultrastructural study.

Endoplasmic reticulum-associated crystals were seen in 1-10% of the bone-marrow lymphocytes and in the lymphocytes of the peripheral blood in three cases of immunocytoma. Their crystalline nature and their location in the cisternae of the rough endoplasmic reticulum was proved by ultrastructural study. IgM lambda in the crystals was demonstrated by fluorescent and peroxidase-labelled antibody methods. The crystals did not stain with the PAS reaction, suggesting that the immunoglobulin was not bound to a carbohydrate group. A defect in glucosyltransferase activity with failure to modify the immunoglobulins could explain the absence of the PAS reaction and the accumulation of immunoglobulin in crystalline before reaching the Golgi region.


Cerebral involvement in multiple myeloma: case report.

Cerebral myeloma in a 49-year-old white man took the form of diffuse arachnoid infiltration, intracerebral perivascular cuffing, and frank intracerebral invasion.


Aberrant form of Pseudomonas aeruginosa in sputum and cerebrospinal fluid causing infection in a compromised patient.

A patient with non-Hodgkin's lymphoma developed meningitis due to an aberrant form of Pseudomonas aeruginosa observed on Gram stain. The organism was grown on primary isolation media without needing hypertonic media. The significance of aberrant forms in body fluids is discussed.


Comparison of susceptibility of Neisseria meningitidis to sodium sulphadiazine and sodium fusidate in vitro.

Out of 100 strains of meningococci examined 62 were resistant to 1 mg/l or more of sodium sulphadiazine, including 82% of group W135 strains and 69% of group B strains. All strains were sensitive in vitro to 0.5 mg/l of sodium fusidate. Sodium fusidate should be considered as a chemoprophylactic agent for those who may be at risk of meningococcal disease.


The representation of the body surface in somatosensory area I of the grey squirrel.

Microelectrode mapping methods were used to determine the organization of primary somatosensory cortex, SmI, in grey squirrels. A systematic representation of the contralateral body surface was found within somatic konicortex. This primary representation differs from maps of SmI in other mammals in at least two significant ways. The first way in which SmI of squirrels differs from the organization reported for other mammals is that SmI of squirrels contains a double representation of the hand and parts of the forearm. The glabrous skin of the digits is represented twice in a mirror image fashion joined at the finger tips. The hairy skin of the digits, wrist, and parts of the forearm are also represented twice, once on each side of the joined representations of the glabrous skin. A second unique feature of SmI of squirrels is that there is a small region of cortex completely surrounded by SmI that was unresponsive to light cutaneous stimuli under our recording conditions. This unresponsive zone is easily identified in brain sections by architectonic features that deviate from sensory koniocortex and approach motor cortex. A third significant finding was that the back is rostral to the belly in the representation of the trunk in SmI of squirrels. This is the reverse of the orientation reported elsewhere for SmI of mammals, but corresponds to the orientation of the trunk representation in Area 3b of owl monkeys (Kaas et al., '78; Merzenich et al., '78). This similarity supports an earlier contention that the representation of the body in Area 3b of primates is the homolog of SmI in other mammals (Merzenich et al., '78).


Differential effects of monocular deprivation seen in different layers of the lateral geniculate nucleus.

Recent investigations have suggested that the morphological effects of monocular deprivation can be explained by a developmental competitive interaction between the pathways from the two eyes. This study presents evidence in the tree shrew for binocular competition and for an unequal effect of such competition on the different layers of the lateral geniculate nucleus. The effects of monocular deprivation were evaluated by comparing cell size changes in the binocular and monocular segments of the lateral geniculate nucleus in three tree shrews raised with one eye sutured. In two of these animals the open eye was injected with 3H proline in order to identify accurately geniculate layers innervated by the non-deprived eye. Cell sizes in three normal animals and one monocularly enucleated animal were measured for comparison. The results show the following main effects: First, that monocular deprivation significantly changes cell size in the binocular but not the monocular segment of the geniculate nucleus. Comparisons with cell size in normal animals indicates that non-deprived cells may grow in response to deprivation. Second, that cell size in geniculate lamina 3 is not affected by monocular deprivation, suggesting that cells in this layer are morphologically or functionally secluded from competitive interactions affecting the other layers. Finally, that monocular enucleation in the adult tree shrew affects all parts of the geniculate nucleus including layer 3 and the monocular segment, demonstrating that these parts of the geniculate nucleus are responsive to lack of retinal innervation.


Transport of radioactivity from primary auditory neurons beyond the cochlear nuclei.

Transneuronal degeneration in secondary brainstem auditory nuclei has been described following cochlear lesions, and Marchi studies have revealed degeneration in the trapezoid body after such lesions. These findings support the view of some early neuroanatomists that primary auditory afferents project beyond the cochlear nuclei. Silver impregnation studies of degenerating cochlear afferents have failed to support this claim, leaving the question unresolved. Using [3H] amino acids auditory projections in the monkey were traced autoradiographically from labeled ganglion cells: (1) in all portions of the spiral ganglion, (2) in apical and middle turns of the cochlea and (3) primarily in the basal turn of the cochlea. Labeling of the entire spiral ganglion resulted in profuse transport of isotope to parts of all cochlear nuclei [anteroventral (AVCN), posteroventral (PVCN), and dorsal (DCN) cochlear nuclei]. Labeled axons entering the trapezoid body (TB) projected ipsilaterally to: (1) the lateral trapezoid nuclei (LTN), (2) the lateral superior olivary nucleus (LSO), (3) the dorsal dendritic zone of the medial superior olivary nucleus (MSO), and (4) the pericollicular or cortical nucleus of the inferior colliculus (IC). Auditory fibers crossing the midline in the TB projected contralaterally to: (1) the medial trapezoid nucleus (MTN), (2) the ventral dendritic zone of the MSO, (3) the ventral nucleus of the lateral lemniscus (VNLL), and (4) the central nucleus of the inferior colliculus (CNIC). Selective labeling of cells in the apical and middle ganglionic turns ofthe cochlea resulted in a similar pattern of centripetal transport. Selective [3H] uptake primarily by ganglion cells in the basal turn of the cochlea resulted in: (1) labeling of restricted parts of all cochlear nuclei, and (2) a considerable reduction of isotope transported beyond the cochlear nuclei. Labeled fibers in the TB were distributed sparsely in the ipsilateral LTN, LSO and dorsal dendritic zone of the MSO. Fibers in the TB were not labeled contralaterally in these animals. Interpretation of these data considers the possibility of transneuronal isotope transport. The pattern of isotope transported beyond the cochlear nuclei does not correspond to the secondary projections of any individual cochlear nucleus, although it bears some resemblance to that of the AVCN. The current study suggests that some primary auditory afferents project beyond the cochlear nuclei.


Echocardiographic evaluation of cardiac function and drug effects in acute myocardial infarction.

The hemodynamic evaluation of patients with acute myocardial infarction (AMI) usually is performed by invasive methods. A prospective echocardiographic study was conducted on 23 AMI patients to determine the feasibility of this technique in evaluating hemodynamics and in measuring the effect of drugs on left ventricular performance. The results showed that: 1) reproducible measurements of left ventricular end-diastolic and end-systolic dimensions can be obtained by echocardiography, and 2) echocardiography can be used in the assessment of the effect of drugs in AMI. As echocardiography is a simple noninvasive procedure, it is well suited for conducting longitudinal studies in patients outside the coronary care unit and in ambulatory AMI patients.


The distributional effects of national health insurance in Quebec.

In November of 1970 a major change in public health policy occurred in Quebec: the movement from a mixed private-public system to a completely public system of financing health care (known as Medicare). This policy change had important economic effects on the distribution of income, taxation, and health care costs. This paper analyzes these economic effects by focusing on the changes in financial burden of medical care costs between 1969-70 and 1971-72 for eight income classes. The key results that emerge are: the total cost of medical care increases sharply for all of the income groups, and the burden of the cost of medical care becomes more equitable across the income groups. Based on these results, policy considerations for the present debate on national health insurance in the United States are offered.


Pathogenesis of diphtheria carrier state from the immunological point of view.

Results of a comparative investigation of diphtheria antitoxin and type-specific antibacterial antibodes in 264 carriers of diphtherial bacteria, 41 diphtheria patients and 263 non-infected subjects are presented. A high level of antitoxin did not prevent the development of toxigenic-strain carrier state. A basically similar immunological antibacterial response was observed in patients with manifest forms of diphtheria and in carriers of toxigenic strains; such a response could not as yet be detected in carriers of non-toxigenic strains. It has been suggested that the infectious process in the toxigenic-strain carrier state is due to factors of the virulence responsible for infectivity and invasiveness of the diphtherial microbe. The toxin plays no pathogenic role in carrier state.


Viremia and serum antibodies in Macacus rhesus monkey after inapparent infection with European tick-borne encephalitis virus.

1. Inapparent infection was called forth in M. rhesus monkeys by means of subcutaneous inoculation of ETBE virus. 2. Viremia was found in 18 (86 per cent) of 21 monkeys. In all the 18 monkeys, specific virus-neutralizing antibodies were found; in 17 of them complement-fixing antibodies developed in addition. 3. Neutralizing antibodies (N greater than or equal to 1.7 log10) were first recorded on 10th day with a peak on 32nd day, retaining, after a small decrease, a relatively high level in all reacting animals. 4. Complement-fixing antibodies were first found on 18th day, showing a peak on 22nd day whereafter they dropped considerably or even disappeared so that on 150th day they were present in a low titre in only 35 per cent of the originally reacting monkeys. 5. The findings were compared with the situation in naturally infected humans and in hamsters infected inapparently (experimentally) with ETBE virus.


Latent expression of a Cgamma gene.

Rabbit 136 represented the first instance whereby more than two alleles for any immunoglobulin locus are detected phenotypically in a single animal. This was reported as the acquisition of the a2 and b6 markers in the animal nominally typed a1a3, b4b5 after intensive immunization. Follow-up studies indicate that another immunoglobulin marker, notably d11, also appeared in the postimmune serum. The d11 specificity was detected serologically by the hemagglutination-inhibition assay and chemically by analysis of the CNBr digestion products involving a strategic methionine.


Characterization of a soluble factor that specifically suppresses the in vitro generation of cells cytotoxic for syngeneic tumor cells in mice.

A tumor-specific soluble factor found in extracts of thymocytes from mice bearing small P815 tumors has been demonstrated. This factor is capable of significantly suppressing the in vitro generation of syngeneic cells cytotoxic for P815 targets if it is added to culture vessels within the first 30 hr of culture. The suppressive factor eluted from Sephadex G-100 after hemoglobin and was estimated to have a m.w. in the range of 40 to 60,000. Preparative isoelectric focusing of thymic extracts established that the suppressive material has an isoelectric point in the range of pH 4.6 to 4.9. The suppressive activity of extracts could be removed by passage of the material through immunoadsorbent columns prepared from membrane proteins of P815 cells but not by analogous columns prepared by using L1210 membrane proteins. The suppressive material was not removed by its passage through immunoadsorbent columns containing anti-mouse immunoglobulin.


Purification of human monocytes on microexudate-coated surfaces.

Human blood monocytes, but not other Ficoll-Hypaque cells, adhere to plastic surfaces from which confluent BHK cells have been removed. EDTA (3mM) rapidly and completely removes monocytes, providing a simple technique for preparation of human monocytes in suspension. The method should be valuable for studies of monocyte function where monocyte monolayers are not suitable.


Isolation and serial cultivation of rabbit skin epithelial cells.

A method to isolate and to serially cultivate rabbit skin epithelial cells from adult trunk skin has been developed. Using a collagen gel as substrate and trypsin and EDTA to dissociate cells, nonproliferative primary cultures of rabbit cells may be converted to proliferative populations, and at least 3 serial passages achieved. In the presence of large concentrations of methotrexate (up to 1000 microgram/ml), epithelial cells in primary culture show no decrease in their ability to attach, spread, or keratinize. Following conversion to proliferative populations by trypsin and EDTA low concentrations of methotrexate (1 microgram/ml) are strongly cytotoxic. When the incorporation of 32PO4(3-) and 3H-thymidine into DNA of proliferative and nonproliferative cells is compared, the incorporation of 32PO4(3-), but not that of 3H-thymidine, correlates with changes in cell number and DNA content. In both primary and serially cultivated cells, L-serine is required for optimal growth.


Malignant lymphoma of the faucial tonsil.

Ten cases of malignant lymphoma of the faucial tonsil treated in the R.U.H., Bath, during 1965--1975 are reviewed. Dysphagia and irritation in the throat are predominant symptoms. Enlarged tonsil is the commonest feature. Radiotherapy is the treatment of choice and the prognosis has improved considerably with modern supervoltage radiotherapy.


Procedure for a normalised thyroxine determination in small sephadex columns.

A rapid simple test for measuring normalised serum thyroxine is described in detail, using small Sephadex columns. A small portion of test serum is reintroduced into the test system at the competitive binding stage, so that corrected T4 values are obtained when the concentrations of thyroxine binding globulin are variable. Only 125 microliter serum is required for the whole test. Values obtained by the present method correlated well with the product of thyroxine concentration and radioactive T3 uptake (T4--RT3U index) and with a commercially available method for normalized thyroxine (T4N). Day-to-day variation was CV=6%.


Strain differences in the immune response of mice to homologous sperm-specific lactate dehydrogenase (LDH-C4).

The sperm-specific isozyme of murine lactate dehydrogenase (LDH-C4) was injected into female mice of various strains. Two regulatory phenotypes characterize the resultant immunity to LDH-C4: one is manifested by high, intermediate or low levels of response, the other by the immediate or delayed maturation of peak titer. The response of several strains can be classified as high (SWR, SJL, BABL/c, C3H/He) and intermediate to low (A, CBA, DBA/2, DBA/1, C57BL/6) according to the level of antibody production and cell mediated immunity. BALB/c, SJL and SWR strains are immediate responders while DBA/2 and C3H/He mice are clearly delayed responders. Maturation and magnitude of response do not appear to be related. Both the antibody and cell mediated responses are T-dependent, but are not obviously associated with Ig allotype or H-2 regulation.


A heat-sensitive lysis mutant of Bacillus subtilis 168 with a low activity of pyruvate carboxylase.

A mutant of Bacillus subtilis which grew in complex medium at 30 degrees C but lysed at 45 degrees C has been isolated. It could only grow on minimal medium at 45 degrees C with added aspartate (20 microgram ml-1) but lysed if lysine (20 microgram ml-1) was also present. The requirement for aspartate was due to a low activity of pyruvate carboxylase; the site of the mutation (pyc) was linked (16% cotransducible using phage PBSI) to the pyrD locus, and the order of markers deduced was: pyrD-cysC-pyc. This defect appeared to lead to decreased synthesis of mesodiaminopimelic acid (mesoA2pm), an amino acid unique to peptidoglycan and its precursors. At the restrictive temperature the mutant accumulated uridine-5'-diphosphate N-acetylmuramyl-L-alanyl-D-glutamate, since meso A2pm is the next amino acid to be added to the growing peptide chain of peptidoglycan. This resulted in an inhibition of peptidoglycan synthesis, determined as a reduced incorporation of N-acetyl[14C]glucosamine. Peptidoglycan synthesis was not decreased if the mutant was grown in media containing aspartate but lacking lysine. The sensitivity to lysine may arise because (i) at 45 degrees C the mutant was starved for aspartate and hence mesoA2pm even when aspartate was present, since aspartate utilization, as estimated by the incorporation of [3H]aspartate into trichloroacetic acid precipitable material, was relatively inefficient; and (ii) this diminished level of mesoA2pm synthesis from aspartate was further curtailed since lysine inhibits one of the aspartokinases in B. subtilis. Thus, addition of lysine allowed protein synthesis and hence autolysin production to proceed whilst peptidoglycan synthesis remained inhibited. When autolysis was blocked, either indirectly by stopping protein synthesis through starvation of aspartate and lysine, or directly by introducing a lyt mutation, then shifting the mutant to 45 degrees C did not result in lysis but growth still ceased.


Antibody-modification of measles "in vitro" infection.

While the involvement of measles-like virus with subacute sclerosing panencephalitis (SSPE) has been shown in many laboratories, the possible mechanisms by which a normal measles infection may lead to the chronic condition are unclear. The work reported here demonstrates that the growth and maintenance of Vero cells infected with the MV 30 strain of measles, in the presence of multivalent antibody, results in a redistribution of the viral antigens within the cells and an alteration in the properties of this attenuated virus which persists even after removal of the antiserum from the culture medium. It is suggested that these in vitro findings could be parallel to the situation that occurs in vivo with measles encephalitis in hamsters and human SSPE.


Single case study. Contact epilepsy: a rare form of reflex epilepsy.

An 80-year-old male is presented who had violent myoclonic seizures with occasional brief loss of consciousness, triggered by tactile stimuli directed to the upper extremities and upper part of the trunk which evolved over a 10-year period. Physical examination revealed very few neurological abnormalities. His resting electroencephalograms were normal, but generalized spikes, polyspikes, and slow wave discharges were precipitated by tactile stimuli with the patient sitting up. He showed no significant response to standard anticonvulsant therapy. The relevant literature is reviewed briefly.


Clinical evaluation of intravenous nitroglycerin for neurosurgery.

Moment-to-moment control of blood pressure is important in the management of the neurosurgical patient. The ideal agent to control blood pressure or induce hypotension should be non-toxic, maintain cerebrovascular autoregulation, and not alter cardiac output or change intracranial pressure. Intravenous nitroglycerin has been used to control blood pressure in 54 neurosurgical cases. This agent produces a rapid, controllable, but not precipitous fall in blood pressure without rebound, is non-toxic, may not alter cerebrovascular autoregulation, and does not raise intracranial pressure. Our clinical experience with intravenous nitroglycerin indicates that it has an important role as a hypotensive agent for the neurosurgical patient.


The relation of cerebral ischemia, hypoxia, and hypercarbia to the Cushing response.

A marked increase in intracranial pressure (ICP) produces a concomitant increase in systemic blood pressure (the Cushing response). In this study a comparison is made between this response of systemic blood pressure to increased ICP and the blood pressure responses produced by ischemia, hypoxia, and hypercarbia of the primate brain. A carotid-to-carotid cross-perfusion system was used to produce a purely cerebral hypoxia and hypercarbia. Each stimulus, except hypercarbia, produced a hypertensive response that was qualitatively and quantitatively similar. These responses were characterized by a short latent period, a rapid development, and an increase in mean arterial pressure of 60% or more. The similarity of the responses suggests that these stimuli act through a final common pathway independent of the purely mechanical effects of increased ICP upon the brain.


Re-evaluation of differential sacral rhizotomy for neurological bladder disease.

The authors describe long-term follow-up results (4 to 6 years) in 13 patients who underwent differential sacral rhizotomy for urgency incontinence. Six patients were originally presented in a preliminary report in 1973. In the last seven patients, a highly selective rhizotomy of sacral fascicles innervating only the urinary bladder was performed. Results in the original six patients appear to be superior to those in patients who underwent a more refined rhizotomy. Possible explanations for this as well as alternative approaches to the treatment of urgency incontinence are briefly discussed.


Labeling of platelets with oxine complexes of Tc-99m and In-111. Part 1. In vitro studies and survival in the rabbit.

We have used both Tc-99m oxine and In-111 oxine to study the effects in the rabbit of various parameters on platelet labeling and the in vivo survival of platelets harvested by four different methods. For In-111 oxine, platelet labeling in saline produces much higher efficiencies (90%) than labeling in the presence of plasma (20%), with no significant shortening of in vivo survival (1% survival at 5.9 days). For Tc-99m oxine, labeling efficiencies are considerably lower (30%) and survival is shorter (1% survival at 3.8 days). For both radioagents, a 30-min labeling incubation at room temperature is suggested.


Platelets labeled with oxine complexes of Tc-99m and In-111. Part 2. Localization of experimentally induced vascular lesions.

Using rabbit platelets harvested and labeled with either Tc-99m or In-111 oxine as described in Part 1, we have successfully imaged experimentally induced fresh venous thrombi and newly injured arterial intima. Visualization of lesions up to 6 hr old is striking. Thrombi and arterial damage 24 hr old, however, were usually not imaged successfully; nor were preformed platelet-poor arterial emboli. The varying rates of platelet deposition in vascular lesions of different ages and types account for these observations. Should human cells prove as effective, widespread clinical application is anticipated.


Effect of peroral administration of xylitol on exocrine secretions of monkeys.

The effects of the administration of xylitol on the biochemical properties of monkey parotid and submandibular saliva and lacrimal fluid were investigated. Monkeys (Macaca mulatta) were fed either a sucrose or xylitol diet for 3 days. Ingestion of xylitol was associated with a significant increase of the activity of the salivary lactoperoxidase. The concentration of protein was also increased. Higher lactoperoxidase activity was found in parotid than in submandibular saliva. The concentrations of inorganic phosphate, calcium and SCN ions were practically unaffected. The concentration of SCN ions in pilocarpine stimulated monkey saliva was low (less than 5.5 mg/liter). Peroral administration of 2.5 g of xylitol or sorbitol per day to M. fascicularis resulted in almost similar levels of salivary lactoperoxidase activity. The administration of xylitol orally or by gastric intubation was not found to affect the concentration of lactoperoxidase, protein, phosphate, and SCN and iodine ions in lacrimal fluid. The results suggest that specific dietary sugars have a selective effect on the biochemical properties of saliva.


Plasma zinc levels in premature infants receiving parenteral nutrition.

Plasma zinc levels in premature infants receiving parenteral nutrition without supplementation of trace elements were evaluated. The mean +/- SE for plasma zinc concentration prior to the start of parenteral nutrition  was 53 +/- 6 microgram/dl. During the first two weeks of parenteral nutrition the levels remained low, but did not change significantly. However, from day 14 through day 32 there was a statistically significant (P less than 0.05), progressive decline in plasma zinc values. Perhaps the shortened gestational periods were etiologic in producing the initial low plasma zinc concentration in these patients. Since low-birth-weight infants apparently have a high requirement for zinc, the reduced growth rates of these patients may be related to their apparent zinc deficiencies.


Meningococcus group A vaccine in children three months to five years of age. Adverse reactions and immunogenicity related to endotoxin content and molecular weight of the polysaccharide.

Vaccination of 21,007 children between the ages of three months and five years was completed with five different lots of the meningococcal group A capsular polysaccharide vaccine. A correlation was found between the frequency and severity of adverse reactions and the endotoxin content of the vaccine lots. All vaccine lots elicited a serum antibody response. The endotoxin content of the vaccines did not correlate with the serum antibody response.


Tetrapeltalonema (t.) mystaxi sp. n. (Nematoda: Filarioidea) from Brazilian moustached marmosets, Saguinus m. mystax.

Tetrapetalonema (T.) mystaxi sp. n. is described from the subscapular connective tissues of Saguinus mystax. The parasite is placed in the subgenus Tetrapetalonema and most closely resembles Tetrapetalonema atelensis, from which it can be differentiated by its long esophagus, size and shape of the spicules, and the size and arrangement of nuclei in the tail of the microfilaria.


Phenol oxidase activity: inductionin female schistosomes by in vitro incubation.

A biochemical methods has been developed for detecting phenol oxidase in female Schistosoma mansoni. Enzyme activity is observed only after incubation of the female schistosomes for an extended period of time in tissue culture media. Male S. mansoni do not contain detectable levels of phenol oxidase activity. The properties of this enzyme are similar to those identified for a phenol oxidase from Fasciola hepatica. L-DOPA, dopamine, and tyrosine were found to be good substrates for this enzyme. Vmax = 14.1, 8.1, and 6.1 mumoles O2/min/mg protein for each substrate, respectively. This enzyme appears to be associated with egg production and thus may be a useful marker for biochemical and immunological studies.


Cockroaches as vectors of Sarcocystis muris and of other coccidia in the laboratory.

To assess the roles of the German cockroach (Blatella germanica) and the American cockroach (Periplaneta americana) in the transmission of Sarcocystis muris and of 3 other coccidia of cats-Toxoplasma gondii, Isospora felis, and Isospora rivolta, cockroaches exposed to feces containing these coccidia were periodically fed to mice, as was a portion of the fecal matter. Sarcocystis muris sporocysts, which in feces remained infectious for at least 20 days, were also transmitted to mice by P. americana for at least 20 days and by B. germanica for 5 days after exposure to infectious feces. Toxoplasma gondii oocysts were transmitted by P. americana intermittently up to 10 days, but by B. germanica only immediately after exposure to feces. Oocysts of 2 species of Isospora, when associated with fecal matter, remained infectious for 20 days. Those of I. rivolta were transmitted by both cockroach species for 10 days, but I. felis was transmitted only by by B. germanica, and for only 2 days.


Fine structure of immature cysts of Sarcocystis cruzi.

Sarcocystis cruzi forms cysts in striated muscle of the bovine host following schizogony. The fine structure of the immature cyst within muscle fibers of the ventricular myocardium was studied in relation to its development and to the multiplication of parasites within it. The young cyst is enclosed by a cyst wall containing numerous small protuberances. Metrocytes within the cyst are irregular in shape and are separated from each other and the cyst wall by a thin layer of ground substance. The parasite multiplies by endodyogeny within the metrocyte. As the cyst enlarges, the host muscle fiber is disrupted and large protrusions are present in the cyst wall.


The opossum (Didelphis virginiana) as a host for Sarcocystis debonei from cowbirds (Molothrus ater) and grackles (Cassidix mexicanus, Quiscalus quiscula).

Sarcocystis-infected muscles from ducks, cowbirds, and grackles were fed to cats, opossums, rats, and a dog. Only the opossum (Didelphis virginiana) was a suitable definitive host. All opossums that were fed Sarcocystis-infected cowbirds (Molothrus ater) and grackles (Cassidix mexicanus and Quiscalus quiscula) passed sporocysts in their feces. Opossums that ate the cowbirds had prepatent periods of 5 and 10 days and remained patent for at least 105 days. Opossums that ate the grackles became patent on day 10 after the infective meal and remained patent for over 90 (Quiscalus) and 105 (Cassidix) days. A single opossum fed infected muscle from a pintail duck (Anas acuta) passed sporocysts in the feces from days 13 through 18 after infection. No sporocysts were passed by opossums fed infected muscle from the green-winged teal (Anas carolinensis) and shoveller (Spatula clypeata). Sporocysts of duck, cowbird, and grackle origin were structurally similar. Mean dimensions of sporocysts were: duck-origin, 11.2 by 8.2 micron; cowbird-origin, 11.4 by 7.8 micron; Cassidix-origin, 11.2 by 7.8 micron; and Quiscalus-origin, 11.6 by 7.7 micron. We designate the sporocysts of cowbird and grackle origin as Sarcoycstis debonei Vogelsang, 1929 (Syn. Isospora boughtoni Volk, 1938).


Differences in antibacterial activity of benzalkonium chloride.

Benzalkonium solutions obtained from different manufacturers were shown to have different activities. This difference in activity was related to the composition of the benzalkonium chloride. The potential seriousness of this situation is emphasized, and a recommendation is made that the official monographs on benzalkonium chloride be amended appropriately, noting the apparently superior antibacterial activity of the tetradecyl (C14) homolog.


Effect of acylated amino acids and acylated amino acid analogs on microbial antitumor screen.

A series of N-acetyl,-N-propionyl, and N-chloroacetyl derivatives of amino acids and amino acid analogs was tested for growth-inhibitory activity using a Lactobacillus casei system as a prescreen for possible antitumor activity. While none of the acetyl or propionyl derivatives of these amino acids and amino acid analogs caused any remarkable inhibition, certain chloroacetyl derivatives exhibited significant activity. The chloroacetyl derivatives, especially those of essential amino acids and of analogs of essential amino acids, showed modest, but pharmacologically significant, inhibition; those of nonessential amino acids exhibited no activity. When two such inhibitory acyl derivatives were combined in a single assay, the extent of inhibition was neither additive nor synergistic but was that of the more active of the two test components.


Improved GLC determination of plasma nitroglycerin concentrations.

A specific and quantitative assay for determining nanogram levels of nitroglycerin in plasma was developed. The method involves stabilization of the drug in plasma with silver nitrate, followed by multiple extraction using purified hexane. Isosorbide dinitrate is added as the internal standard. The hexane extract is subsequently concentrated and injected into a glass column packed with 3% SP-2401 on 100--120-mesh Supelcoport at 140 degrees. A 63Ni-electron-capture detector gives a linear response over the range of 0.1--50 ng of nitroglycerin/ml of rat plasma. From spiked samples, the procedure gave a recovery of about 90%. There was little or no interference from the isomeric glyceryl dinitrates and endogenous compounds in rat or human plasma.


Pharmacokinetics of nitroglycerin in rats.

The plasma nitroglycerin levels obtained after intracardial (0.7 mg/kg), oral (7 mg/kg), and topical (7--14 mg/kg) doses of nitroglycerin in rats are reported. Nitroglycerin followed essentially one-compartment kinetics after intracardial administration, showing a mean half-life of about 4 min and a mean apparent volume of distribution of about 3 liters/kg. After oral drug administration, "flip-flop" kinetics were evident. The mean oral bioavailability was determined to be 1.6%, firmly supporting the contention that nitroglycerin is extensively metabolized during first passage through the liver. Under the experimental conditions studied, no detectable levels of nitroglycerin were observed after topical application.


Improved stability of proteins immobilized in microparticles prepared by a modified emulsion polymerization technique.

Proteins can be immobilized in spherical microparticles of polyacrylamide gel (having a diameter of about 1 microgram) by an emulsion--polymerization technique. Higher cross-linked gels have a structure consisting of relatively large pores. This structure is advantageous when dealing with biologically active proteins acting on molecules dissolved in the surrounding medium. A rapid equilibrium is established between the interior of the particles and the medium, and rate-limiting diffusion is not observed. A suspension of carbonic anhydrase immobilized in microparticles will thus have kinetic properties very much like the free enzyme. In addition to the entrapment of the protein molecules in the three-dimensional network formed by the polyacrylamide threads, protein molecules are also fixed in the cross-linked threads of polyacrylamide. This fixation is probably responsible for the improved stability of the protein molecules against heat denaturation. Not even autoclaving at 110 degrees for 30 min denatured the immobilized enzyme completely (more than 25% of the enzyme activity was left). The higher resistance of molecules in microparticles against proteolytic degradation also is documented.


Discriminative effects of cyclazocine in the squirrel monkey.

In order to characterize the discriminative stimulus properties of cyclazocine squirrel monkeys were trained to discriminate between intramuscular injections of 0.1 mg/kg of cyclazocine and drug vehicle in a discrete-trial avoidance paradigm in which a response on one of two levers would prevent or terminate the delivery of a mild electric shock to the tail. Behavior was considered to be under stimulus control when the monkeys completed at least 22 trials of a 25-trial session on the appropriate choice lever after they received cyclazocine or vehicle. Stimulus generalization (i.e., dose-response) curves were then determined for a variety of drugs over a broad range of doses. The following analgesics with narcotic antagonist properties produced stimulus control of behavior comparable to that produced by 0.1 mg/kg of cyclazocine: ketocyclazocine (0.1 mg/kg), butorphanol (1.0 mg/kg), oxilorphan (3.0 mg/kg) and levallorphan (3.0 mg/kg). Time course experiments revealed that the duration of complete stimulus control was relatively short: 1 hour after 0.1 mg/kg of cyclazocine and 3.0 mg/kg of oxilorphan and 0.5 hour after 0.1 mg/kg of ketocyclazocine. Naloxone produced a dose-related antagonism of the stimulus control by cyclazocine and butorphanol which was complete at 1.0 mg/kg. In contrast, as much as 10 mg/kg of naloxone only partially blocked stimulus control by ketocyclazocine and failed to modify stimulus control by oxilorphan and levallorphan. The monkeys showed partial generalization to other drugs with activity as narcotic agonists, antagonists or both (e.g., morphine, naloxone, pentazocine, nalbuphine, nalmexone and nalorphine), but little or no generalization to the nonopioid psychoactive drugs, d-amphetamine, mescaline, pentobarbital and scopolamine. This discrimination paradigm appears to have potential as a model for the quantitative assessment of the discriminative stimulus properties of narcotic antagonist analgesics.


Should dentures be worn continuously?

Material has been presented to show the potential problem in continuous denture wearing. Commercial booklets for patient education have been reviewed and found to be in need of revision. Dental schools are not in agreement in the subject of continuous denture wear. The need for unanimity is evident, and if this is to be achieved, patient education publications must be revised. A maximum effort is needed to educate edentulous patients about oral tissue health, and especially the length of time that dentures should be worn.


[Voluminous tracheal diverticulum. One case (author's transl)].

A tracheal diverticulum, probably of congenital origin, was discovered accidentally during the course of a broncho-pulmonary affection. Diverticuli of the trachea are usually found during a simple systematic radiological examination, or when an established pulmonary condition is being investigated. Routine bronchography, alone, or associated with a tomograph, can be used to demonstrate its characteristics and precise location. Bronchoscopy may then be carried out in order to study the area surrounding the diverticular orifice more closely, and to establish the condition of its mucous lining. Several evolutive stages are involved in the pathogenesis of tracheal diverticuli, varying from a rudimentary bronchiole to megalotrachea, which, for many authors, is an autonomous condition because of its anatomical and pathological make-up, producing its own well-defined symptomatology.


[Arterial hypertension and horseshoe kidney during Von Recklinghausen's disease. Angiographic study and review of the literature (author's transl)].

Angiographic studies in a young girl aged 16 years who developed arterial hypertension during the course of Von Recklinghausen's disease, demonstrated the presence of an obliterated renal artery in a horseshoe kidney. The distal arterial segment was revascularized by two homolateral ureteral arteries. A full review of the literature revealed 30 cases of renal artery lesions for which angiography had been carried out in young people with neurofibromatosis. This demonstrates the low incidence of obliterative lesions (4 cases throughout the world) which are always associated with collateral vascularization. It was not possible to apply the usual surgical treatment in our case because of the associated horseshoe kidney.


Physical, hormonal and behavioural aspects of sexual development in the marmoset monkey, Callithrix jacchus.

Measurements of growth, plasma progesterone and testosterone levels, and copulatory behaviour were obtained from captive marmosets from birth until 600-800 days of age. Body weight and knee-to-heel length were similar for both sexes. Males exhibited a neonatal testosterone surge from 15-100 days and testosterone levels began to rise again, coincident with the growth of the testis, at about 250 days. The males were copulating by 400-500 days of age. Paired females were apparently ovulating and able to conceive from about 400 days. In peer groups, only the dominant female became pregnant, because subordinate females failed to ovulate.


The role of histamine in implantation in the rabbit.

When disodium cromoglycate, an inhibitor of histamine release, was instilled into the uterine lumen on Days 5 or 6 of pregnancy, the number of blastocysts implanting was significantly (P less than 0.002) reduced. Simultaneous instillation of histamine and disodium cromoglycate prevented the effect.


Electron microprobe analysis of the different epithelial cells of toad urinary bladder. Electrolyte concentrations at different functional states of transepithelial sodium transport.

The electrolyte composition of toad urinary bladder epithelial cells has been measured using the technique of electron microprobe analysis. Portions of hemibladders, which had been mounted in chambers and bathed with a variety of media, were layered with albumin solution on their mucosal surfaces and immediately shock-frozen in liquid propane at -180 degrees C. From the frozen material 1--2 micrometer thick cryosections were cut and promptly freeze-dried for 12 hr at-80 degrees C and 10(-6) Torr. Electron microprobe analysis using a scanning electron microscope, an energy dispersive X-ray detector, and a computer programme, to distinguish between characteristic and uncharacteristic radiations, allowed quantification of cellular ionic concentrations per kg tissue wet wt by comparison of the intensities of the emitted radiations from the cells and from the albumin layer. Granular, mitochondrial-rich, and basal cells, and the basal portions of goblet cells, showed a similar composition, being high in K (about 110 mM/kg wet wt) and low in Na (about 13 mM/kg wet wt). The apical portions of goblet cells were higher in Ca and S and lower in P and K, presumably reflecting the composition of the mucus within them. With Na-Ringer's as the mucosal medium, cells gained Na and lost K, when their serosal surfaces were exposed to ouabain, 10(-2) M. Replacement of mucosal Na by choline virtually prevented these ouabain-induced changes. Cellular ion contents were unchanged when Na in the serosal medium was replaced by choline. No differences in Na and K concentrations were detected between nuclei and cytoplasm. These results provide independent support for the hypothesis the the cellular Na transport pool in toad bladder epithelial cells derives exclusively from the mucosal medium and that no important recycling of Na occurs from the serosal medium to the cells.


Transients in toad skin: short circuit current and ionic fluxes related to inner sodium substitution by monovalent cations.

When the Na electrochemical potential difference across the skin (delta muNa) is altered by perturbing the transmembrane electrical potential difference or the external Na concentration, effects on transport and associated oxygen consumption can be described by the formalism of linear nonequilibrium thermodynamics (Vieira, Caplan & Essig, 1972, J. Gen. Physiol. 59:77; Danisi & Lacaz-Vieira, 1974, J. Gen. Physiol. 64:372; Procópio and Lacaz-Vieira, 1977, J. Membrane Biol. 35:219). We now show that with modifications of delta muNa by substitution of Li or choline for Na in the inner bathing solution, this formalism is no longer applicable. Inner Na by K substitution ((Na X K)i) causes profound alterations in short-circuit current (SCC), JinNa, K efflux (JeffK) and PD. SCC drops transiently after (Na X K)i in Cl and in SO4 media, increasing subsequently. In Cl medium, following the initial transient, there is a late decline in SCC toward a steady state. The rate of SCC decline in Cl medium is more pronounced than that observed in SO4 medium. (Na X K)i causes a transient increase in JinNa with a peak synchronous to the minimum in SCC, both in Cl and in SO4 media. This was interpreted as due to depolarization of the inner membrane. In SO4 medium, following the peak observed after (Na X K)i, JimNa drops, to increase again toward a steady state in which SCC and JinNa are not statistically different, resembling the control condition before (Na X K)i. In Cl medium, however, the JinNa steady state is approximately 100% higher than SCC. This difference is due to an important K efflux (JeffK), which builds up progressively after the substitution. The apparent K permeability [JeffK/(Ki)] is of comparable magnitude in Cl and in SO4 media before (Na X K)i and also in SO4 medium after (Na X K)i. However, in Cl medium, after (Na X K)i, the apparent K permeability increases one order of magnitude as compared to the control condition before the ionic substitution. In Cl medium, the high levels of JinNa and of Jeff(K) observed in the steady state after (Na X K)i were interpreted as being a consequence of cell swelling. SCC and PD follow very different temporal patterns after (Na X K)i which are characterized by transients in SCC and a simple fall in PD. Reasons for these differences are discussed.


Low temperature microspectrofluorometry: design of a 'cold chamber'.

Low temperature microspectrofluorometry allows an improvement of spectral resolution and an increase of fluorescence intensity. Suppression of fluorescence fading, or at least a marked reduction, is also obtained. A cooling chamber for microspectrofluorometric measurement is described which allows the cooling, under a microscope, of a biological sample down to liquid nitrogen temperature. Objectives with numerical apertures better than 1.0 and a magnification power up to 100X can be used. Low temperature measurements on a histological sample are presented and discussed.


Effect of fixation on cell membrane of early embryonic material as observed on freeze-fracture replicas.

Some cell membranes of chemically fixed, cryoprotected and freeze-fractured chick embryonic material are characterized by 150-250 nm diameter circular smooth blebs. No such blebs are observed, however, on cryoprotected, rapidly frozen but not chemically fixed samples. It is concluded, therefore, that fixation with buffered glutaraldehyde and not cryoprotection with glycerol is mainly responsible for the appearance of the blebs. The suggestion that blebs represent a budding virus is not tenable, since blebs are present in material obtained from virus free embryos.


Tumor cell threshold required for suppression of macrophage inflammation.

In DBA/2 mice bearing transplanted, syngeneic P815 mastocytoma, macrophage accumulation was impaired in the tumor when the cancer grew intraperitoneally. By varying the number of transplanted mastocytoma cells and quantitating the macrophage response to a standardized stimulus of proteose peptone, we determined that 4-16x10(6) mastocytoma cells were required to inhibit monocyte inflammation. That interference with monocyte inflammation required a threshold number of tumor cells was consistent with an increase in tumor-associated macrophages proportional to tumor growth during early cancer. It was also consonant with a greater number of macrophages in tumors initiated with small rather than large tumor inocula. Impairment of monocyte inflammation could be passively transferred with ascitic fluid.


Effect of ethynodiol diacetate with ethinyl estradiol on the mammary glands of rhesus monkeys: a preliminary report.

The oral contraceptive combination of ethynodiol diacetate with ethinyl estradiol (Demulen) was given cyclically to 48 female rhesus monkeys for 5 years. Doses employed were 1, 10, and 50 times the human dose. Treatment did not induce palpable breast nodules, and there were no deaths from mammary gland cancer.


Ionized calcium and magnesium: the effect of septic shock in the baboon.

Ionized calcium (Ca2+) and ionized magnesium (Mg2+) are important intracellular "second messengers" and control exictation-contraction coupling, excitation-secretion, oxidative phosphorylation, and mitochondrial acid-base balance. The present study examines the effect of septic shock on serum (Ca2+) and (Mg2+). Five adult female baboons were subjected to live E. coli septic shock and then resuscitated. Three baboons served as controls. Ca2+ was measured by the Orion SS-20 flow-through calcium electrode and Mg2+ calculated by the method of Killen. Other measurements included: total calcium, bound calcium, total magnesium, bound magnesium, phosphate, albumin, globulin, hemotocrit, and total protein. This study shows that there are significant disturbances of Ca2+ and Mg2+ during septic shock in the baboon. These disturbances may in part explain cellular dysfunction during shock including: decreased myocardial contractility, inappropriate secretion of endocrine cells, decrease in oxidative phosphorylation, and mitochondrial acidosis.


A comparative trial of co-trimoxazole and chloramphenicol in thyphoid and paratyphoid fever.

A comparative trial of co-trimoxazole and chloramphenicol was carried out on 91 patients, 57 having typhoid fever and 34 cases having paratyphoid fever. Co-trimoxazole is an effective drug in the treatment of enteric fevers with respect to clinical cure, absence of relapses and the mild nature of short term toxic drug effects. Unlike some of the earlier reports, treatment failure or non-responsiveness to the drug occurred in just under 10 per cent of the cases and would constitute a drawback of therapy with co-trimoxazole. This feature was not observed in the patients receiving chloramphenicol. The excretion of Salmonellae after drug therapy was more common with chloramphenicol than with co-trimoxazole, again indicating the value of the latter drug in the treatment of enteric fevers.


Membrane-free scrapie activity.

Determinations of scrapie activity in subcellular fractions from infected hamster brains through the asymptomatic and symptomatic course of infection revealed the presence of substantial amounts of scrapie infectivity in the 100,000 X g supernatant fractions, indicating that association with physically discernible membrane structures is not necessary for the transmission of the scrapie agent. An increase of scrapie infectivity in the 100,000 X g supernatant fractions after vigorous homogenization of infected membrane-rich fractions suggests that the agent is identical in membrane-rich and 100,000 X g supernatant fractions.


The effect of oral potassium supplements on plasma potassium in normokalaemic and hypokalaemic patients.

Thirteen out of 44 patients taking bendrofluazide 10 mg daily became hypokalaemic over a period of three months. Oral potassium supplements of 3.6 grams daily (48 mmol) given in addition to bendrofluazide for a further period of 3 months raised plasma potassium level significantly in hypokalaemic patients only. We conclude that where patients on diuretic therapy are followed up with plasma potassium measurements, it is generally necessary to prescribe oral potassium in the presence of hypokalaemia only.


A survey of blood groups.

A survey was conducted to investigate into the frequency of different blood groups in Punjab. A total of 1415 persons were included in this survey. The slide method was used for determination of ABO and AB blood groups as well as Rh factor. The frequency of blood group A was 21.20%; B, 36.16%; AB, 9.05% and O, 34.14%. Distribution of blood groups among various castes revealed the incidence of blood group A, 13.57% to 30%; B, 28.125% to 50%; O, 16.67% to 40%; and AB, zero to 25%. Only 2.76% cases were found to be Rh negative. Rh negative frequency was much higher in Baluchs, Awans and Gujjars than Rajputs, Jats and Arains.


Effect of environments on human functions: studies on water metabolism.

The purpose of this review is to study general behaviour of human systems with respect to the environmental conditions. This type of work will be of profound significance to record the effect of medical treatment in various climatic zones of the world (Arayne and Saify, 1975). We attempted to discuss various facts which would be helpful for tackling the health problems of the people residing in these areas. The statistical data is avoided at the moment and a descriptive pattern is adapted in order to express views, about one of the important aspects of medical science.


[Serum-concentrations of the immunoglobulins iga, ige and igm in children with different age and diseases with different aetiologies (author's transl)].

Normal values of the immunoglobulins, G, A and M in the serum were measured with the immunodiffusion-method by Mancini et al., (1965) (immunodiffusion-plates: Hyland-Travenol) for children in the age between 0-15 years. Moreover, we measured the course of the immunoglobulin development of some babies during hospitalisation. Here we found a wide individual range in synthesis of immunoglobulins.


[Oculoauriculovertebral dysplasia (author's transl)].

A case of okulo-aurikulo-vertebral syndrome in a three year old girl is described. The similarities between the maxillary arch syndromes are emphasized on the one hand and on the other the relatively frequent occurrence of congenital unilateral facil palsy with congenital cardiac defects is outlined. Aetiological hypotheses are discussed.


The prevalence of Hepatocystis kochi in African green monkeys.

The prevalence of Hepatocystis kochi was studied in 178 African green monkeys from Kenya and 61 from Ethiopia. Examinations of blood smears for gametocytes and examinations of the livers for merocysts were performed to determine the presence of infection in these animals. The overall prevalence of infection was 29%. No significant difference in infection rate was found between monkeys from the different geographic areas or between males and females.


A primate model for prolonged endotoxin shock. Blood-vascular reactions and effects of glucocorticoid treatment.

A primate model was developed to study sequential blood-vascular responses, primarily of the lung and liver, and hematologic changes during prolonged endotoxemia with or without glucocorticoid treatment. In this model, pairs of animals, one with intermittent glucocorticoid regimen, were continuously infused with endotoxin throughout the experimental period. The duration of the experiment and the onset of progressive shock could be adjusted by changing the rate of endotoxin infusion. Endotoxemia at a rate of 10 mg. per kg. per hour resulted in progressive shick which was significantly delayed with glucocorticoid treatment. Endotoxin-induced hematologic alterations included early leukopenia and gradual development of disseminated intravascular coagulation. Morphologic studies revealed margination of neutrophils and mononuclear cells in the microcirculation of lung and liver. These changes were associated with sustained phagocytosis of endotoxin by the sequestered leukocytes and Kupffer cells, degranulation of the hepatic sinusoids and spaces of Disse contained extensive fibrinous deposits which in advanced stages of shock were accompanied by midzonal and centrilobular necrosis. Pulmonary lesions included margination, degranulation and fragmentation of leukocytes, early appearance of fibrin in hepatic sinusoids, and rapid development of disseminated intravascular coagulation, endothelial damage and associated lesions of lung and liver. The results indicate that events relating to sustained phagocytosis of endotoxin by the marginating leukocytes initiate a state of intravascular inflammation with disseminated intravascular coagulation and play a vasic role in the pathogenesis of pulmonary and hepatic lesions during prolonged endotoxemia leading to shock. The findings also suggest that glucocorticoid treatment attenuates endotoxin-induced blood-vascular reactions thereby providing an early protection against the development of shock and structural damage to the lung and liver.


The identification of amyloid P-component (protein AP) in normal cultured human fibroblasts.

The amyloid protein, AP, has not previously been detected in normal or nonamyloidotic tissues. In this study, human fibroblasts were examined for the presence of AP by immunofluorescence technique. Normal human skin fibroblasts were cultured in Eagle's minimum essential medium for varying periods of time. Antiserum was prepared in rabbits using AP isolated from amyloid-rich tissues. Using indirect immunofluorescence and anti-AP, fluorescent material was found to be distributed in a punctate pattern throughout the cytoplasm with sparing of the nucleus. The fluorescent reaction was speicifically inhibited by absorption of anti-AP with AP-positive serum but not by addition of AP-negative human cord serum. Thus, AP may have a fibroblast origin and a relationship to normal connective tissue.


Comparative studies of pulsatile and nonpulsatile flow during cardiopulmonary bypass. III. Response of anterior pituitary gland to thyrotropin-releasing hormone.

Previous studies have indicated that, during nonpulsatile cardiopulmonary bypass, the anterior pituitary gland fails to respond to the tropic stimulus of thyrotropin-releasing hormone (TRH). This is in contrast to the normal response seen during closed cardiac and general surgical procedures. The Stöckert pulsatile pump system described in Part I has been employed in a comparative study of TRH responses in 20 patients subjected to pulsatile or nonpulsatile perfusion during open-heart surgery. In the nonpulsatile group, a consistently subnormal response to TRH injection was again found. In the pulsatile group, however, the pituitary response to TRH was normal in nine patients out of 10. The quantitative difference between the groups was statistically highly significant (p less than 0.005). These results indicate that the subnormal pituitary function seen with nonpulsatile bypass may be prevented by the use of pulsatile perfusion.