Photo-incuced cross-linkage of gene-5 protein and bacteriophage fd DNA+. The gene 5 protein, coded for by the bacteriophage fd, forms a complex with single stranded fd-DNA such that one gene 5 protein monomer interacts with four bases. Exposure of this complex to ultraviolet light results in the formation of covalent bonds between 25-30% of the gene 5 protein monomers which are bound to the DNA. In contrast, when the intact fd virion, which is a complex of coat protein and DNA, was exposed to ultraviolet irradiation, no detectable protein DNA cross-links were found.


The secondary structure of E. coli ribosomes and ribosomal RNA's: a spectrophotometric approach. The thermal denaturation spectra of E. coli 50s and 30s ribosomal sub units and of their isolated RNA's were studied over the wavelength range of 2300-3000 Angstrom. It was possible to fit the experimental denaturation spectra with super positions of the reference spectra for denaturation of A - U and G - C base pairs derived from model polyribonucleotides. The coefficients of these linear combinations were used to calculate the fractions of A - U and G - C base pairs in the samples. It was found that the helical content of the RNA's inside the subunits is smaller than that of the isolated RNA's, thus suggesting that proteins may affect the secondary structure of RNA in the ribosome.


(dA-dT) dependent inactivation of the DNA template properties by interaction with netropsin and distamycin A. The inhibitory effect of the polypeptide antibiotics netropsin and distamycin A on DNA dependent nucleic acid synthesis has been shown to be related to the base composition of the template DNA. A number of natural DNA's of quite different dA-dT content as well as poly (dI-dC)-poly (dI-dC), poly (dA-dT)-poly (dA-dT), poly (dA) - poly (dT) and poly (dG) - poly (dC) has been studied as templates in DNA and in part in RNA polymerase reaction. The highest binding efficiency of netropsin existing for (dA-dT) - containing DNA polymers and the less pronounced interaction with the (dI-dC)-containing polymer shown by the melting and CD spectrral behaviour of the complexes are entirely reflected in the template inactivation. The same is evident for distamycin A. However, in contrast to netropsin the antibiotic distamycin A exhibits some binding tendency to poly (dG) - poly (dC). Binding effects of a netropsin derivative to DNA and (dA-dT) -containing polymers suggest the importance of hydrogen bonds of the peptide groups in the complex formation.


Accessibility of chromatin to DNA polymerase I and location of the F1 histone. The effect of prebound poly-L-lysine upon the template activity of DNA, chromatin and F1 histone-depleted chromatin for E. coli DNA polymerase I has been investigated. Measurements have been made in the absence and presence of 0.1M NaCl. From the results we conclude that only ca 60% of the polylysine-accessible DNA, i.e. 22% of the total DNA of the chromatin, is accessible to the DNA polymerase I and that ca. 30% of the polylysine-accessible DNA, i.e. 11% of the total DNA, is associated with the F1 histone.


Enzymatic multiplication of a chemically synthesized DNA fragment. A synthetic DNA fragment of 19 residues was enlarged by the enzymatic addition of deoxyadenylate residues to its 3'-end with calf thymus terminal deoxynucleotidyl transferase. The 3'-terminus of this elongated DNA strand was blocked with 2', 3'-dideoxyadenylate to prevent hydrolysis by the 3'-exonuclease function of E. coli DNA polymerase I. This elongated and 3'-blocked fragment was annealed to an oligomeric primer and used as a template for the synthesis of a complementary copy of the synthetic 19-mer. The product of such a repair synthesis was separated by gel filtration and analyzed by nearest neighbor techniques. All template strands were copied with complete repair in over 90% of the chains. Facile recovery of the elongated template by virtue of its size permitted repetition of the copy process, thus allowing accumulation of the desired strand.


Formylatable methionine transfer RNA from Mycoplasma: purification and comparison of partial nucleotide sequences with those of other prokaryotic initiator tRNAs. The major species of the formylatable methionine tRNA from Mycoplasma mycoides var capri has been purified. The 5'- and 3'-terminal sequences of the purified tRNA are pC-G- and C-A-A-C-C-AOH, respectively. Thus, this tRNA also contains the unique structural feature found in two other prokaryotic initiator tRNAs in that the first nucleotide at the 5'-end cannot form a Watson-Crick type of base-pair to the fifth nucleotide from the 3'-end. The Mycoplasma tRNA does not contain ribothymidine; however, a specific uridine residue in the sequence G-U-psi-C-G- can be enzymatically methylated by E. coli extracts to yield G-T-psi-C-G. Since ribothymidine is absent in crude tRNA from this strain of  Mycoplasma, the absence of T is probably due to the lack of a U yields T modifying enzyme.


Replication of colicin E1 plasmid DNA added to cell extracts. Closed-circular DNA of colicin E1 plasmid can undergo a round of semiconservative replication when added to an extract of Escherichia coli. Extracts of cells that do not carry the plasmid are able to perform complete replication of the plasmid. Replication requires de novo RNA synthesis but not protein synthesis.


[The effect of sympatholytics and adrenergic receptor blockade on the histophysiology of the insular apparatus of the pancreas and insulin sensitivity of white rats]. Experiments were conducted on 200 male albino rats.  It was shown that prolonged administration of sympatholytics (ornide or actadine) and also of a blocker of the alpha-adrenorecptors with phentholamine or of beta-adrenoreceptors with inderal led to the accumulation of zinc in the cytoplasm of beta-cells, reduction of the content in them of specific aldehyde-fuchsinophilic granularity, neoformation of the islands of Langerhans and to increase in the animal sensitivity to the exogenous insulin.


N-formylmethionyl peptides as chemoattractants for leucocytes. Leucocytes such as neutrophils are attracted by N-formylmethionine, but not by methionine. Di- and tripeptides containing formylmethionine are strong attractants for both neutrophils and macrophages, whereas the corresponding nonacylated compounds are not chemotactic. The formylated peptides may be related to an incompletely characterized chemotactic material normally produced by bacteria which attract the same animal cells.


[Alterations in the histostructure of the pancreas in experimental diabetes caused by quinoline derivatives]. Administration of chinoline derivatives, with a capacity to form stable complexes with metals (zinc?), was accompanied by a selective damage of the pancreatic islands with development of diabetes mellitus. Changes in the histostructure of the tissue caused by chinoline compounds of various chemical structure were unitypical. Their severity chiefly depended on the severity and duration of diabetes. Diabetes under study arising after the administration of chinoline derivatives were good models for detailed ascertaining of histostructure of the islet tissue and of the pancreatic duct in diabetes.


Separation of transfer ribonucleic acid by sepharose chromatography using reverse salt gradients. The transfer ribonucleic acids of Escherichia coli bind to unsubstituted Sepharose in the presence of high concentrations of ammonium sulfate at pH 4.5. Transfer RNA species are eluted individually from the Sepharose by a gradient from high to low concentrations of ammonium sulfate; leucine tRNA is fractionated into five isoaccepting species. The order of elution of these isoaccepting species differs from that seen with reverse phase chromatography. By means of only these two procedures, one isoaccepting species of leucine tRNA can be purified to apparent homogeneity. Isoaccepting tRNA species for 9 amino acids have been resolved. This established the general utility of this chromatographic system for the separation and purification of specific isoaccepting transfer RNAs.


Chromatin directed transcription of 5S and tRNA genes. Chromatin prepared by gentle methods from mouse myeloma cells retained its ability to synthesize RNA using bound endogenous RNA polymerase (RNA nucleotidyltransferase; nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6). The transcription resembles that observed in vivo in several respects. The low-molecular-weight RNA species 5S RNA and the 4.5S precursor to 4S RNA, are transcribed accurately and transcription is reinitiated continually in vitro. Their synthesis was not inhibited by alpha-amanitin (1 mug/ml) as was found previously for these species in isolated nuclei.


Biogenesis of membrane lipids: mutants of Escherichia coli with temperature-sensitive phosphatidylserine decarboxylase. Phosphatidylserine decarboxylase catalyzes the last step in the pathway leading to phosphatidylethanolamine, the principal membrane lipid of E. coli. Mutants of E. coli have now been isolated in which this enzyme is theramolabile. The structural gene for phosphatidylserine decarboxylase (psd gene) is closely linked to the pur A locus at about 83 min on the standard map of the E. coli chromosome. When a mutant with thermolabile decarboxylase is incubated at 42 degrees, growth ceases, but only after a substantial fraction (20-40%) of the total phospholipid of the cell has been replaced by phosphatidylserine. Examination of such mutants with altered content of phospholipids may shed light on the role of specific phospholipids in membrane function.


Cell cycle-dependent induction of mutations along a yeast chromosome. The relation between DNA replication and the action of the mutagen N-methyl-N'-nitro-N-nitroso-guanidine has been studied in Saccharomyces cerevisiae. The frequenceis of reversion to prototrophy of six auxotrophic markers located along one arm of chromosome VII were examined as a function of the vegetative cell cycle. Exponentially growing cells were treated with nitrosoguanidine and then separated by zonal rotor centrifugation into fractions equivalent to stages in the cell cycle. The frequency of reversion for five of the six markers is greatest during the period of DNA replication. Each marker has a single point of maximum reversion, approximately 10-fold greater than the frequency observed at other points in the cell cycle. For any one marker the effect of nitrosoguanidine is restricted to an interval shorter than the period of DNA replication. The two markers most distant from each other, ade5 and leul, both have their highest reversion frequency early during DNA replication. The peak reversion frequency for lys5 is somewhat later, while the peaks for tyr3 and trp5 occur near the end of DNA replication. The results indicate that nitrosoguanidine acts primarily during DNA replication and that different markers appear to be affected at different intervals during the DNA biosynthetic period. If nitrosoguanidine does act at the growing point of DNA replication, these observations indicate that the initiation of DNA replication occurs at specific times during the period of DNA synthesis and at specific initiation sites. Further, there must be more than one point of initiation of DNA replication on one arm of chromosome VII.


Nucleotide sequence of an RNA polymerase binding site at an early T7 promoter. Escherichia coli RNA polymerase (EC 2.7.7.6), bound in a tight complex at an early T7 promoter, protects 41 to 43 base pairs of DNA from digestion by DNase. I. The protected DNA fragment contains both the binding site for RNA polymerase and the mRNA initiation point for the promoter. The sequence of the DNA fragment and the sequence of the mRNA that it codes for are presented here. A seven-base-pair sequence, apparently common to all promoters, is implicated in the formation of a tight binary complex with RNA polymerase.


The relationship between enzyme activity, cell geometry, and fitness in Saccharomyces cerevisiae. The relationship between enzyme activity, cell geometry, and the ploidy levels has been investigated in Saccharomyces cerevisiae. Diploid cells have 1.57 times the volume of haploid cells under nonlimiting growth conditions (minimal medium). However, when diploid cells are grown under conditions of carbon limitation, they have the same volume as haploid cells. Thus, by altering the environmental conditions, cell size can be varied independently of the degree of ploidy. The results indicate that the basic biochemical parameters of the cell are primarily determined by cell geometry rather than ploidy level. RNA content, protein content, and ornithine transcarbamylase (carbamoylphosphate: L-ornithine carbamoyltransferase, EC 2.1.3.3), tryptophan synthetase [L-serine hydro-lyase (adding indole), EC 4.2.1.20], and invertase (alpha-D-glucoside glucohydrolase, Ec 3.2.1.20) activity are related to cell volume, whereas acid phosphatase (orthophosphoric-monoester phosphohydrolase, EC 3.1.3.2) activity, a cell surface enzyme, is related to the surface area of the cells. Fitness is determined by the activity of certain cell surface enzymes, such as acid phosphatase, diploids would be expected to have a lower fitness than haploids because of the lower surface area/volume ratio. However, when fitness is determined by the activity of an internal enzyme, diploids would be expected to have the same fitness as haploids. Results from competition experiments between haploids and diploids are consistent with these predictions. The significance of these results to the evolution of diploidy as the predominant phase of the life cycle of higher plants and animals is discussed.


Reversible redistribution of phytochrome within the cell upon conversion to its physiologically active form. The intracellular localization of phytochrome was seen in dark-grown oat (Avena sativa L., cv. Garry) and rice (Oryza sativa L., cv. unknown) shoots after various light treatments using an indirect peroxidase-antiperoxidase antibody labeling method. Phytochrome is generally distributed throughout the cytoplasm in cells of tissue that had not been exposed to light prior to fixation. Within, at most, 8 min after the onset of saturating red irradiation, phytochrome, now present in the far-red-absorbing form, becomes associated with discrete regions of the cell. These regions do not appear to be nuclei, plastids, or mitochondria. After phototransformation back to the red-absorbing form originally present, phytochrome slowly resumes its general distribution. It is possible that this discrete localization of the far-red-absorbing form of phytochrome represents a physiologically significant binding with a receptor site in the cell.


Fusion of the Escherichia coli lac genes to the ara promoter: a general technique using bacteriophage Mu-1 insertions. The lac genes were fused to the ara promoter by means of phage phi 80 translocations of the lac and ara genes to att80. Homology for a crossover between the nonhomologous ara and lac operons was provided by mu insertions. Selection for recombinants within the mu insertions generated strains that had the ara promoter on one side of a mu insertion and the lac genes on the other side. ara-lac fusions were obtained from these strains by deleting the mu insertion. These fusions extend the techniques available for studies on the lac operon to studies on the ara operon. It should be possible to fuse other operons by this method.


Replicative intermediates of colicin E1 plasmid DNA in minicells. Pulse-labeled colicin E1 plasmid (Col E1) DNA in minicells was examined to characterize replicating molecules. Replication of Col E1 DNA principally occurred in covalently closed molecules and involved the synthesis of variable length single-stranded DNA fragments that were dissociable from the template DNA and ultimately incorporated into the completely replicated molecules. RNA was found to be associated with some of these newly synthesized fragments. Replicating molecules containing different size displacement loops were observed by electron microscopy.


Regulation of RNA polymerase synthesis in Escherichia coli: a mutant unable to synthesize the enzyme at 43 degrees. We report the isolation of a mutant of E. coli in which the capacity to synthesize RNA polymerase (EC 2.7.7.6) (the beta and beta' subunits) is rapidly lost at 43 degrees. The mutation has no effect on the stability or activity of the polymerase itself. The mutation is recessive and is closely linked to the rif locus (the structural gene for the beta subunit). Using strains carrying the mutation, we have shown that polymerase is present in excess in rapidly growing E. coli cells.


Interaction of Escherichia coli dnaB and dnaC(D) gene products in vitro. Purified E. coli dnaB and dnaC(D) gene products interact physically and functionally in vitro. This interaction was demonstrated as follows: (a) A complex of dnaB and dnaC(D) gene products was isolated by gel filtration; ATP specifically was required for isolation of the complex. (b) The DNA-independent ribonucleoside triphosphatase activity associated with dnaB gene product was inhibited by dnaC(D) gene product. (c) The dnaC(D) gene product was protected from inactivation by N-ethyl-maleimide by the combination of dnaB gene product and ATP; this protection required ATP specifically.


Molecular basis of beta-galactosidase alpha-complementation. In previous studies, a cyanogen bromide peptide derived from amino-acid residues 3-92 of beta-galactosidase (EC 3.2.1.23; beta-D-galactoside galactohydrolase) was shown to have alpha-donor activity in intracistronic alpha-complementation. We have now isolated the defective beta-galactosidase alpha-acceptor protein from the deletion mutant strain M15 of Escherichia coli and find that it lacks residues 11-41 of betal-galactosidase. This is demonstrated by the isolation and sequence determination of a cyanogen bromide peptide from the M15 protein, which is identical to the corresponding peptide from beta-galactosidase except for the missing amino acids. We conclude that the alpha-donor peptide restores the region missing in the M15 protein.


New cell surface antigens in rat defined by tumors of the nervous system. Tumors of the central and peripheral nervous system were induced in rats with ethylnitrosourea. Many of these tumors were transplanted in syngeneic recipients, and several cell lines were derived from them. An antiserum raised against one such cell line in C3H mice defined two cell surface antigens in cytotoxicity tests. One, the common antigen, was present on rat brain and embryonic tissues and was present in large amounts on most tumors or cell lines from the nervous system. Fibroblastic cell lines had smaller amounts of this antigen, which also could be detected by immunofluorescence. The other, restricted antigen was not detected on normal or other, restricted antigen was not detected on normal or embryonic tissues. It was present on six tumors from the nervous system, on one glial cell line, and on a Schwann-cell line RN22. In addition, it was present on four out of eleven cloned cell lines isolated from rat tumors at the Salk Institute. Two of the positive clonal lines had been shown to have properties unique to neuronal cells. The restricted antigen was therefore expressed on the cell surface of some, but not all, glial, Schwann, and neuronal neoplastic cells.


Immunoreactive somatostatin is present in discrete cells of the endocrine pancreas. A discrete population of cells of the endocrine pancreas contains immunoreactive somatostatin as shown by immunofluorescence. These cells are different from those containing glucagon or insulin. This unexpected observation may be of physiopathological significance in the regulatory mechanisms involved in the secretion of glucagon and insulin.


Mapping of late adenovirus genes by cell-free translation of RNA selected by hybridization to specific DNA fragments. Cytoplasmic RNA, isolated from cells late after infection by adenovirus type 2 and fractionated by hybridization to specific fragments of adenovirus DNA produced by cleavage with the endonuclease R-EcoRI, was used as template for protein synthesis in cell-free mammalian extracts. Each of the R-EcoRI fragments of DNA selects RNA that encodes specific subsets of the viral polypeptides. From the known order of the R-EcoRI fragments, the following partial map is deduced: (III, IIIa, IVa2, V, P-VII, IX), (II, P-VI), 100K, IV-where the relative order of the components enclosed in parentheses has not yet been determined.


Proposal concerning mechanism of evolution of the genome of Escherichia coli. Many pairs of genes whose gene products are functionally related lie either 90 degrees or 180 degrees apart on the circular map of the E. coli chromosome. A mechanism of evolution is proposed that involves two sequential duplications of an ancestral genome, followed by mutation and divergence of function of replicate genes.


Site specific recA--independent recombination between bacterial plasmids: involvement of palindromes at the recombinational loci. A recA-independent recombinational event is described which results in insertion of an entire plasmid genome at a unique site of another plasmid, and coincident excision of a precisely defined DNA segment originally present at the point of the insertion. The resulting recombinant molecules subsequently can undergo site-specific translocation of their component segments or inversion of their original DNA sequence orientation. The events observed entail nonreciprocal exchange of genetic material, and involve a discrete nucleotide sequences that is duplicated in rotationally symmetrical reverse orientation on plasmid DNA (i.e., inverted repeat; palindrome).


Phenylalanyl-tRNA synthetase from baker's yeast: role of 3'-terminal adenosine of tRNA-Phe in enzyme-substrate interaction studied with 3'-modified tRNA-Phe species. TRNA-Phe species from baker's yeast modified at the 3'-terminus in many cases are phenylalanylatable substrates. Out of several tRNA-Phe species possessing a modified 3'-end that cannot be phenylalanylated, only two, tRNA-Phe-C-C-2'dA and the tRNA-Phe-C-C-formycin-oxi-red, are strong competitive inhibitors for tRNA-Phe-C-C-A during phenylalanylation. In the ATP/PPi exchange, both these inhibitors reduce Vmax to about 25%; but whereas tRNA-Phe-C-C-2dA has no influence on KmATP and Km Phe during ATP/PPi exchange, tRNA-Phe-C-C-formycin-oxi-red reduces KmATP from 1430 muM, found in the absence of tRNA-Phe, to 230 muM, and Km-Phe, from 38 to 14 muM. The values found in the presence of tRNA-Phe-C-C-formycin-oxi-red during ATP/PPi exchange are identical with those determined in the phenylalanylation of tRNA-Phe-C-C-A. All other tRNA-Phe species carrying a modified 3'end that cannot be phenylalanylated exhibit a mixed competitive-noncompetitive inhibition in the phenylalanylation reaction. In the ATP/PPi exchange, they do not influence KmATP and KmPHE  and only weakly, if at all, Vmax. The results show that the 3'adenosine of tRNA-Phe cannot solely be a passive acceptor for phenylalanine, but must in addition play an active role during enzyme-substrate interaction. The data can be consistently explained by the hypothesis that the 3'-adenosine of tRNA-Phe triggers a conformational change of the enzyme.


Three steps in conversion of large precursor RNA into serine and proline transfer RNAs. Bacteriophage T4 serine and proline transfer RNAs are derived from a common precursor RNA. This precusor RNA lacks -C-C-A sequences which could provide 3' termini for the mature transfer RNAs. We have deduced part of the pathway leading to the formation of the C-C-A sequences in the transfer RNAs by characterizing incompletely matured precursor molecules which accumulate during infection of mutant hosts that lack specific enzymes associated with transfer RNA metabolism. Maturation is initiated by the addition of -C-C-AOH to the 3' terminus of the precusor RNA through the combined actionof an unidentified nuclease and tRNA nucleotidyltransferase (EC 2.7.7.25). Precursor RNA molecules terminating in -C-C-AOH is serine transfer RNA and the second product is immature proline transfer RNA. The terminal steps leading to proline transfer RNA have not been fully delineated, but are known to involve the replacement of a -C-UOH sequence by -C-C-AOH.


Affinity labeling of the ribosomal decoding site with an AUG-substrate analog. The trinucleotide AUG was condensed at the 5'-end with N-bromoacetyl-p-aminophenylphosphate. This bromoactylated AUG analog reacted irreversibly with the mRNA binding site of Escherichia coli 70S ribosomes. After reaction of 70S ribosomes with the AUG analog, labeled 30S subunits could be isolated that were programmed for initiation-factor-dependent binding of fMet-tRNAfMet. This shows that this AUG-affinity label reacted in the decoding site for fMet-tRNAfMet. By combination of sodium dodecyl sulfate-, Sarkosyl-, and ureapolyacrylamide gel electrophoresis the AUG-affinity label was found to be irreversibly bound to ribosomal proteins S4, the ram gene product, and S18.


A ribonucleoprotein precursor of both the 30S and 50S ribosomal sunbunits of Escherichia coli. A ribonucleoprotein particle (46S) has been isolated from [3H]uridine pulse-labeled cultures of E. Coli AB301/105. Evidence from pulse chase experiments and from protein analysis suggested that this particle may give rise to both the 30S and 50S ribosomal subunits. Direct deproteinization of the particle yielded 30S RNA, while deproteinization after treatment with a crude RNase III preparation yielded products similar to 23S and 16S RNA. This result is consistent with the idea that the 46S ribonucleoprotein is the in vivo counterpart of 30S RNA, which is the in vitro product obtained after phenol extraction.


Cell surface alterations induced by vaccinia and Newcastle disease viruses (38486). A comparison was made of HEp-2 cell surface changes induced by NDV or vaccinia virus infection. Three parameters were examined as a function of time after infection: the kinetics of hemadosorption and the appearance of concanavalin (con A) binding sites, and alterations in electrophoretic mobility of single cells. The kinetics of appearance of con A binding sites was strikingly similar for both virus infections, whereas hemadsorption preceded NDA synthesis and followed vaccinia synthesis. These data suggest that in the vaccinia-infected cell the hemadsorption and con A binding sites are different. NDV infection or exposure of sham-infected cells to bacterial neuraminidase significantly reduced their anodal mobilities. This also occurred after enzyme treatment of vaccinia-infected cells. Measurements of the sialic acid content of NDV or sham-infected cells before and after neuraminidase treatment indicated the exposure to the enzyme or NDV materially reduced the sialic acid content of cells. Vaccinia-infected cells contained considerably more sialic acid than did normal cells. For  the vaccinia-infected cell a change in surface properties as detected by hemadsorption or increased con A binding was not reflected in a change in electrophoretic mobility.


Ultrastructral effects of in virto experimentation on right ventricular papillary muscle from cats in hypovolemic shock (38487). The present data demonstrate for the first time that repeated stimulation (2-3 hr in an oxygenated perfusate) of right ventricular papillary muscles from cats subjected to hypovolemic shock does not alter the ultrastructure of the shock lesions. Neither does the in vitro experimentation cause functional impairment as determined by the measured isometric twitch tension. The data also indicate that electron microscopy is important to the evaluation of papillary muscles from cats subjected to shock.


A mode of the growth of Mycobacterium lepraemurium in a cell-free liquid medium (38501). The first report regarding in vitro growth patterns of M. lepraemurium was presented. Evidence is indicated that a growth mode of a single cell of M.lepraemurium in vitro is similar to that of culturable mycobacterium, especially atypical mycobacterium. This finding has added one property to characteristics of M. lepraemurium which have been already known.


Development of response to glucose of fetal rat islet in organ culture (38479). Pancreases of 18-day fetal and 3-day neonatal rat were grown in organ culture in both standard glucose (150 mg/100 ml) and high glucose (500 mg/100 ml) media. Insulin content of medium was measured by radioimmunoassay at time of transfer. In fetal cultures, standard and high glucose media contained a similar level of insulin through 6 days of culture. In neonatal cultures, high glucose medium contained 40-60% more insulin than did standard medium. However, after 8 days of organ culture fetal pancreas developed responsiveness to high glucose; a greater amount of insulin was present in the high glucose medium (50% by 10 days and 70% by 12 days) than in standard glucose medium. The time at which this responsiveness develops in vitro approximates the chronologic age which corresponds to 3-5 days postnatal period. The maturation of this responsiveness appears to be inherent to the pancreas and is independent of other organ systems. When neonatal explants, grown in standard medium for 8 days, were transferred to high glucose medium, 80-160% more insulin was detected in the high glucose medium than in standard medium during the next 4 days of culture. These results indicate that once glucose responsiveness had developed, it is maintained in organ culture for at least 12 days.


The effect of magnesium deficiency in mice on serum immunoglobulin concentrations and antibody plaque-forming cells. Magnesium-deficient mice immunized with SRBC showed a significant decrease (P less than 0.001) in the number of PFC in their spleens compared with mice on a control diet. Serum immunoglobulin concentrations (IgG1, IgG2, IgA and IgM) were determined after 3, 6, 9 and 12 days on the respective diets. The serum IgG2 and IgM concentrations of magnesium- deficient mice were decreased (P less than 0.005) by 6 days and remained at these concentrations until 12 days. The serum IgG1 and IgA concentrations of magnesium deficient animals also decreased (P less than 0.01) by 6 days but returned toward control concentrations at 12 days. Serum magnesium concentrations confirmed the magnesium deficiency of the experimental animals. Therefore, magnesium deficiency has profound immunosuppressive capabilities in mice by significantly reducing the number of antibody synthesizing cells and serum immunoglobulin concentrations.


Effect of synthetic luteinizing hormone--releasing hormone in newborn rats. Administration of synthetic LH-RH to male and female rats on the first day of life reduced pituitary content of FSH and LH and increased serum concentrations of LH.


Mechanisms of endotoxin tolerance. IX. Effect of exchange transfusion. Healthy New Zealand rabbits were injected iv with an LD-80 dose of E. coli endotoxin.  Twenty minutes later, after removal of over 50% of the endotoxin by the RES, exchange transfusion was performed, accomplishing a rapid and sustained reduction in the level of endotoxemia simulating that seen in animals rendered highly tolerant by seven prior sublethal injections of toxin.  Depite such reduction in endotoxemia, 96-hr mortality was only slightly, and not significantly reduced compared to sham exchanged controls (70 vs 83% respectively).  Additional control studies indicated that exchange tranfusion per se did not enhance endotoxin mortality.  The findings directly support the concept that endotoxin tolerance is based primarily upon enhanced RES resistance to endotoxin toxicity rather than upon enhanced RES clearance of circulating endotoxin.


Immunosuppressive effects of experimental infection with Plasmodium gallinaceum. Experimental infection of chickens with P. gallinaceum mardedly suppressed the splenic PFC response to SRBC.  Suppression was most pronounced when birds were immunized at the time of peak parasitemia.  The PFC response to E. coli LPS was of low magnitiude in both normal and infected chickens; however, it, too, was suppressed in infected birds, but not to the same degree as observed in response to SRBC.  Cellular immunity as evidenced by allograft rejection was not influenced by infection.


Failure of peritoneal exudate macrophages to reverse immunologic impairment by Friend leukemia virus. Transfer experiments with peritoneal exudate macrophages from normal donor mice were performed to determine if a defect of normal macrophage function or activity was a major or contributing factor to the immunosuppression characterizing leukemia virus infection of mice. Challenge immunization of Friend leukemia virus-infected mice with sheep erythrocytes resulted in markedly depressed hemolytic antibody responses, as compared to responses of normal noninfected mice. When PE cell suspensions rich in macrophages were transferred from normal donor mice to leukemia virus infected recipients there was no affect on the FLV-induced impairment of the immune response. Similar transfer of PE cells to normal uninfected mice generally resulted in a moderate depression of the expected immune response. In no case did the PE cells enhance the immune responses in normal or virus-infected mice.


Inhibition of LH release as influenced by LRF infusion. Four ovariectomized ewes were infused with LRF (10 mug/hr for 20 hr.  Jugular vein blood samples were taken at 30 min intervals.  After 16 hr of LRF infusion each animal was given a 1 mg iv injection of LRF.  At the end of the 20 hr infusion period, the animals were sacrificed and the pituitary removed.  Pituitary and plasma samples were analyzed for LH.  Plasma LH concentration reached a peak level of 73 ng/ml, 1.5 hr after starting the LRF infusion.  A rapid decline in LH concentration occured for the next 3 hr.  The plasma LH concentration declined slowly to preinfusion levels over the next 15.5 hr.  A small insigificant rise in plasma LH concentration occured when the animals were given 1 mg of LRF after 16 hr of LRF infusion.  At the end of the treatment period pituitary LH concentration varied from 369 to 1360 ng/mg.  Two of the four ewes had pituitary LH concentrations similar to untreated ovariectomized ewes.  The pituitarys' refractoriness to LRF apparently is not due to depletion of pituitary LH.


Effect of intermittent infusion of LH-releasing hormone of serum LH and FSH levels in immature male rats. The effect of intermittent intravenous infusions of LH-RH on serum LH and FSH levels was studied in immature male rats. At the end of the infusion, serum LH and FSH levels were higher than those after saline infusion. One hr after the end of infusion of LH-RH, serum LH levels fell, reaching saline control values, but FSH levels remained higher. Moreover, a pulsative pattern of LH release but not of FSH, was obtained during the intermittent infusion with LH-RH. These findings indicate that under appropriate conditions after administration of LH-RH, it is possible to find high GSH levels without a concomitant rise of LH levels. The continued elevation of FSH may be explained by the longer biological half-life of FSH. Estradiol benzoate depressed the basal serum GSH level and augmented the basal serum GSH level and augmented LH release after intermittent infusion with LH-RH, indicating that estrogen modified FSH/LH ratio. The results suggest that discordance of plasma LH and FSH levels which is occasionally observed in some physiological conditions does not necessarily indicate the presence of another FSH-RH which is distinct from LH-RH decapeptide.


Alteration of bone marrow-thymus cell synergism in hereditary asplenic and adult splenctomiced mice. The cooperation betweeen bone marrow (B) and thymus (T) cells was markedly impaired in mice with congenital asplenia.  The deficiency of IgM producers could not be corrected by neotal transplantation of spleen cells.  The use of T and B cells from splenectomized donors resulted in a marked shift from 19S to 7S antibody forming cells.


The effect of oral and vaginal administration of synthetic LH-RH and [D-ALA-6, DES GLY-10-NH2]-LH-RH ethylamide on serum LH levels in ovariectomized, steroid blocked rats. Effects of oral and vaginal administration of LH-RH and [D-ALa-6, DesGly-10-NH2i1-LH-RH ethylamide (D-Ala-6-LH-RH-EA) on serum LH levels in ovariectomized, estrogen, progesterone treated rats were investigated. Oral administration of synthetic LH-RH induced a quick rise of serum LH levels with the greatest elevation at 15 min at any dose levels tested. On the other hand, oral administration of D-Ala-6-LH-RH-EA resulted in a slow but progressive rise of LH during 120 min of observation. The total amount of LH released by 10 mug of the analog was much greater than the total released by 1000 mug of LH-RH. Vaginal administration of 100 mug of LH-RH mixed with Carbowax induced a progressive rise of LHwhich was indistinguishable from that following 10 mug of the analogue, suggesting that the potency of the analogue is 10 times greater than that of LH-RH for vaginal administration. Ten mug of LH-RH given through the vagina induced a rapid rise of LH with the peak at 15 min, whereas 1 mug of the analog induced a slow but progressive rise. Greater resistance of D-Ala-6-LH-RH-EA than LH-RH against in vivo breakdown is postulated as one of the causes of greater and prolonged LH release by the former.


Electrocardiographic recordings for assessing survival of cardiac allografts in the hamster cheek pouch. Techniques for the recording of electrical events associated with contraction of allografted myocardium in the cheek pouch of inbred hamsters have been developed. The results of such recordings have been useful in assessing contractility and viability of the graft. The degree of tolerance to cardiac allografts in cheek pouches of inbred hamsters appears to be a function of histocompatibility and not "immunological privilege" of the cheek pouch.


A23187: a calcium ionophore that directly increases cardiac contractility (38704). The effect of the calcium ionophore A23187 on contractility in guinea pig left atria was studied. This ionophore increased both the force of contraction and the rate of tension development in a concentration dependent manner. The positive inotropic effect of A23187 is not mediated by activation of beta-receptors or by the release of endogenous catecholamines since neither propranolol nor pretreatment with reserpine altered the inotropic effect of this agent. Our studies of the dependence of contractile force on external calcium indicate that A23187 enhances the response of atrial muscle to external calcium ions. Since A23187 is known to facilitate the movement of calcium across biological membranes, we believe the ionophore may be acting either by increasing calcium influx across the myocardial cell membrane or by facilitating calcium release from sarcoplasmic reticulum.


Method for differentiation of nonspecific from specfic toxoplasma IgM fluorescent antibodies in patients with rheumatoid factor. In a study performed to define the prevalence of false positive toxoplasma IgM-IFA test results in sera containing RF, 8 (19.5%) of 41 sera which were positive for RF were positive in the toxoplasma DT and conventional toxoplasma IFA test. Three of these eight were also positive in the toxoplasma IgM-IFA test and in two, the results were considered to be false positives. Of the 33 sera remaining which were positive for RF but negative in both the DT and conventional IFA test, three were positive in the toxoplasma IgM-IFA test. Of 51 sera from patients with suspected rheumatoid arthritis or other collagen vascular disorders, all of which were negative when tested for RF, none was positive for toxoplasma IgM antibodies in the IgM-IFA test. Sera from 15 adults with the acute lymphadenopathic form of toxoplasmosis and 13 infants with congenital toxoplasmosis were tested for the presence of RF. Whereas none of the sera from the acquired cases had demonstrable RF, two of the congenital cases had RF, and their titers were both 1:320. False positive IgM-IFA test results became negative after treatment of sera with heat-aggregated IgG. In contrast, IgM-IFA test titers in cases of acute congenital or acquired toxoplasmosis were unaffected by this treatment. Thus, treatment with heat-aggregated IgG can be used to differentiate false positive IgM-IFA test titers due to RF from those due to specific IgM toxoplasma antibody.


Ovulation and gonadotropin-releasing activity of [p-LEU-6, DES-GLY NH2-10, pro-ethylamide-9] -GNRH. The ovulation-inducing and gonadotropin-releasing activities of [d-Leu-6, des-Gly NH2-10,  Pro-ethylamide-9]-GnRH (II), were evaluated in rats, rabbits, and sheep. A sc dose of 3.4 ng/100 g body wt of the analog was equal to 160 ng/100 g body wt of GnRH in causing ovulation in the diestrous rat. At these dose levels, the integrated LH release was 1.9 times greater for the analog. Both the time of increase and maximum serum concentrations of LH were delayed after injection of the analog. Oral administration of II and GnRH to the proestrous rat resulted in an ED50 for ovulation of 0.92 and 54 mug/100 g body wt,respectively. Serum levels of LH and FSH were highly variable for the various treatment groups when both releasing substances were administered orally. The intense ovulating activity of II was also evident in the estrous rabbit as indicated by an activity 31 times greater than that of GnRH. Additionally, the analog was at least 50 times more active than GnRH in releasing LH in both the mid-luteal and anestrous ewe. From our experiments with the cycling rat it appears that the intense ovulation-inducing activity of II can be accounted for by the intrinsic LH-releasing activity of the nonapeptide, rather than by a prolonged release stimulus.


Immunoglobulin levels and antibody-coated bacteria in urines from patients with urinary tract infections. The presence of antibody-coated bacteria in urines from patients with urinary tract infections has previously been reported to correlate with renal infection as opposed to bladder infection. Urine specimens from 12 patients with pyelonephritis and 12 patients with cystitis were studied to determine whether the antibody coating the bacteria is associated with elevated urine levels of total protein or of particular classes of immunoglobulins. The classes of antibody bound to the infecting bacteria in urines from the patients with pyelonephritis were compared to the levels of unbound antibody in the urine. Each specimen was found to contain antibody-coated bacteria, but not all of the specimens had elevated levels of total protein or immunoglobulins. Thus, the occurrence of antibody-coated bacteria in pyelonephritis did not depend on marked elevations of total urinary protein or immunoglobulins. Studies of patients with cystitis showed that immunoglobulins and protein present in the urines, even in elevated quantities, did not react with the infecting bacteria in patients with bladder infections, as each of these patients had negative FA tests for antibody-coated bacteria.


Survival of osteocompetent marrow cells in vitro and the effect of PHA-stimulation on osteoinduction in composite bone grafts. The osteoinductive capacities of bone-marrow autografts, washed marrow-free bone allografts, and composite grafts of washed allogeneic bone impregnated with viable or killed autologous marrow cells have been compared in a heterotopic site in rabbits. Composite grafts (similar to 40 mg allogeneic bone) with viable marrow performed equally well as autografts, providing that these implants contained at least 50,000 marrow cells. Composite grafts with dead marrow were noninductive, and grafts with 10,000 viable marrow cells produced much less new bone than grafts with 50,000 cells. Postoperative treatment of host rabbits with PHA-P increased the osteoinductive capacity of composite grafts with initially subcritical numbers of marrow cells to control levels. These results indicate that the osteoinductive cells in composite grafts are mobilized from the marrow elements rather than from the undifferentiated cells in the host bed.


Plasma scalpel excision of burns. An experimental study. We used a plasma scalpel to excise experimental full-thickness burns in 12 pigs, followed by immediate skin autografting. The results were as follows: (1) The skin autograft takes were excellent following the plasma scalpel excisions, and they healed on essentially the same time scale as similar autografts following steel scalpel excisions, producing scars of similar sizes. (2) Pigs in which burn wounds were excised with a steel scalpel lost an average of approximately 5 gm of blood for every one gm lost in the animals which had excisions with the plasma scalpel. (3) The time required for a plasma scalpel burn excision was essentially the same as that required for a standard steel scalpel.


Basal cell carcinoma of the medial canthal area. We advise an aggressive approach in ablating basal cell carcinomas which have originated in the region of the medial canthus. Extirpation of the entire tumor under accurate histological control, whether it includes skin only or the entire orbital contents and ethmoid air cells--and reconstruction with one of the described procedures--gives the surgeon an effective armamentarium to successfully treat these potentially lethal lesions.


A simplified technique for free transfer of groin flaps, by use of a Doppler Probe. Our application of the Doppler probe to microvascular surgery is discussed, including the monitoring of the superficial circumflex iliac artery in free groin flaps. Our technique of free groin flap transplantation is compared to that of others. Three of our cases are discussed.


Four V-flap repair of preputial stenosis (phimosis). The 4 V-flap technique for repair of preputial stenosis meets a need for an alternative to circumcision in the repair of phimosis. It is especially useful in cases where the penis is small and all available tissue should be retained. we have used the method for 3 years and have had no complications. On occasion, we have used 6 or 8 V-flaps, but we find the 4 V-flap repair is usually simpler and equally effective.


Arteriovenous malformations of the mandible. Graduated surgical management. Two cases of arteriovenous malformation in the mandible are described, in which muscle embolization was used. The success in one patient and the failure in the second correlate with the caliber of the vessels in the two malformations. A scheme of graduated surgical management for mandibular arteriovenous malformations is proposed.


The deltoscapular flap.

The deltoscapular flap. We present a young patient in whom a large soft tissue defect of the neck was repaired with a deltoscapular flap.


Anterior extrapleural line: superior extension. Anatomic sections of the superior aspect of the anterior mediastinum reveal that normal structures can cause indentations upon the adjacent lung. On lateral chest films, the soft-tissue density of the anterior superior mediastinal structures contrasts with that of the normal lung, revealing a normal, undulating configuration of the anterior superior mediastinum. We have termed this the "vascular incisura," analogous to the cardiac incisura of the left lung seen inferiorly. An appreciation of normal variations within this space is essential when evaluating pathologic alterations.


Transpyloric extension to duodenal bulb in gastric lymphoma. Gastric lymphoma may present in a spectrum of morphologic patterns which may mimic a variety of diseases clinically, endoscopically, radiologically and surgically. From its common location within the gastric antrum, transpyloric submucosal spread frequently occurs to involve the duodenal bulb and occasionally the proximal descending duodenum. This distinctive pathologic characteristic results in contour deformities, filling defects, and ulcerations of the duodenum which can be traced in continuity from the gastric lesions. These radiological observations are significant in the preoperative diagnosis of primary malignant lymphoma of the stomach and in the evaluation of disseminated lymphoma.


Angiographic features of peripancreatic malignant lymphoma. Angiographic features are described in 5 patients with peripancreatic lymphomas who initially presented with clinical features of primary pancreatic disease. Each patient demonstrated a large hypovascular mass with considerable displacement of pancreatic and peripancreatic arteries and associated compression of adjacent veins. Smooth arterial encasement was present in 2 cases. Signs of mass out of proportion to signs of invasion mitigated against the diagnosis of carcinoma in each case. Other differential diagnostic considerations are pancreatic pseudocyst and cystadenoma.


Graf/Pen computer for rapid neuroangiographic measurements: Sylvian loops and venous angle. The Graf/Pen sonic digitilizer facilitates routine application of neuroradiologic measurements during film interpretation. The Vlahovitch and Probst measurements were performed 23 times faster with this device than manually. The Graf/Pen computer combination shows great potential in the rapid quantitative analysis of both carotid and vertebral angiograms.


Distribution of various labeled thioglucoses in rodents. Gold, silver and lead thioglucose were evaluated in rodents to determine the value of organo-metallic compounds in the study of metabolic abnormalities. Increased radioactivity concentration was noted in the hypothalamus with all compounds. Gold thioglucose concentrated in the kidneys and thymus, and 203Pb-thioglucose concentrated in the pancreas and thymus.


The immune response of hens to multiple Escherichia coli injections and transfer of immunoglobulins to the egg and hatched chick. Four spaced E coli antigen injections were given to laying hens in order to cause an extended period of antibody production. Antibody could be detected as early as four days after the first antigen injection reaching a peak at the 20th day. IgM was the first antibody to be detected. From the eighth day IgG could be detected replacing the IgM fraction gradually. Antibody to E coli produced by the hen could be detected in yolk of eggs and in chicks from the 15th day but not after the 87th day post treatment. Fluctuation or antibody transmitted by the individual hen was observed. Yolk and chick antibody titres were slightly lower than those found in the serum of the hens on the same day. Only IgG antibodies were found in yolks and serum of day-old chicks.


Experimental infection of cockerels with Salmonella typhimurium. Six-month-old SPF Brown Leghorn cockerels were experimentally infected per os with S typhimurium (1 times 1010) and slaughtered at intervals up to 42 days following infection. Observations were made on the clinical pathology, bacteriology and serology during the course of infection and extensive bacteriological examinations were undertaken after post mortem examination.


Immune response of sheep to Fasciola hepatica infection. The IgG immunoglobulin levels and the immune response to Fasciola hepatica digestive tract antigens were studied in experimentally infected lambs. A synchronic increase and decrease of IgG-1 serum levels and indirect fluorescent antibody titres were observed during the course of the infection. Antibody activities were demonstrated in IgG-1, but not in IgG-2 isolates. The antibody activity was partly sensitive to reduction with mercaptoethanol.


Immunoglobulin classes of antibodies produced against Toxoplasma gondii by ovine fetuses. Sera from aborted or newborn lambs with congenital toxoplasmosis were fractionated on Sephadex G-200. Sera and fractions were tested for Toxoplasma antibodies using the indirect fluorescent antibody test. Most of the antibody was found to reside in the IgG fraction.


Megakaryocytes in agar cultures of mouse bone marrow. Cytologic and immunofluorescent data demonstrate that cells morphologically resembling megakaryocytes appear in thin layer agar cultures of cellular fractions of mouse bone marrow and increase in number from zero to a maximum of approxiamately 60 per culture on day 6. It would appear that these "candidate" megakaryocytes are derived from a morphologically unidentified precursor(s) since they are not present in the original cell suspension cultured but begin to appear 24 hours later. Similarities between the ultrastructure of "candidate" megakaryocytes and that of femoral marrow megakaryocytes support morphological similarities at the light microscopic level. Pretreatment of mice with either vinblastine and nitrogen mustard or antiplatelet serum has no effect on the number of "candidate" megakaryocytes appearing in cultures of their marrow. Preliminary data suggest that the rate of appearance of these cells in culture is responsive to serum from thrombocytopenic donors.


Use of blood and blood components.

Use of blood and blood components. The indications for transfusions are anemia compromising delivery of oxygen, acute blood loss, cardiopulmonary bypass, exchange transfusion, maintenance of hemostasis, and sepsis associated with granulocytopenia. When transfusion therapy is indicated, only that component of whole blood which is needed for correction of the problem should be given. The options for use each component have been discussed.


Pancreatic pseudocysts.

Pancreatic pseudocysts. Pseudocysts are fascinating lesions of the pancreas which present as upper abdominal masses in about 80 per cent of cases, but also as obstructive jaundice, intrasplenic and intra-left-renal masses, mediastinal masses, flank abscess, pleural effusions, and ascites rich in amylase. They are diagnosed by urine amylase with greater sensitivity than by serum amylase. Cysts must be differentiated from pancreatic abscesses, indolent phlegmonous pancreatitis, cystadenomas, and carcinomas of the pancreas, as well as lymphomas and other rare tumors. They may be satisfactorily treated by large sump tube drains to the outside but about one third will require a further operation. Internal drainage by cystogastrostomy is the simplest and best current procedure, but not applicable to all cases. A good alternative is Roux-en-y cyst-jejunostomy. Caution is needed in the preoperative workup since all procedures are accompanied by an operative mortality approaching 10 per cent, mostly due to hepatic disease, portal hypertension, stress ulcerations, and hemorrhage. The follow-up shows 85 per cent good results from proper drainage but 40 per cent are diabetics and in many patients the ravages of alcoholism continue unabated.


Donor heart resuscitation and storage.

Donor heart resuscitation and storage. At the present time, simple hypothermia or regional or total body perfusion probably afford the best means of myocardial protection of the donor heart. However, the potential of either technique is extremely limited, and a combination of hypothermia with some form of perfusion system will probably enable considerably longer periods of storage of the donor organ. Such a perfusion system has not yet been conclusively developed, though considerable advances have been made. It is doubtful whether or not the addition of hyperbaric oxygen to hypothermia greatly prolongs the storage period. Metabolic inhibition by a chemical agent is an attractive method of preservation, possibly associated with hypothermia, but the search for the perfect agent continues. Actual freezing of the organ may prove feasible in the future, but recent work in the field of cryobiology has proved almost uniformly disappointing. The use of the autoperfusing heart-lung preparation as a short term storage system deserves further study, but its value as a really long term system of storage of the heart seems unlikely at the present time. Xenobanking has been encouragingly successful in experimental situations, but its clinical application will prove to be expensive and difficult.


Re-evaluation of the biomechanics of blunt impact injury of the head. With blunt impacts, there may be bruising or tearing of scalp, elastic deformation of the skull with or without linear fracture, mass motions or relative movements of the brain mass--inertial stress propagation--as well as pressure gradients. Mass motions of the brain may cause concussion, vascular tears with extravasation and contusions of the cerebral surface as well as lesions in the deeper portions of the cerebral mass. Coup contusion is caused by the inbending bone at the impact site striking the immobile head. Contrecoup contusiions result from injury to the brain surface in the frontotemporal area as the moving brain impacts the rough and irregular bony interior. In the experimental laboratory, a contusion is easily produced by a moving object striking the relatively immobile head. During impact if the head is on a solid stand, such as the metal table, a contrecoup lesion is seen at the opposite end from the impact site. This contrecoup lesion is produced by the brain impacting the skull, as well as the flattening of the skull against the brain at the antipole, from the presence of the solid table. Intermediate contusions develop between the impact site and the antipole in the brain interior as a result of inertial stress propagation.


Direct influence of endotoxin on cellular respiration. Hepatocyte oxygen consumption was evaluated in vitro in 70 rabbits. In selected instances, Escherichia coli endotoxin was added to a chamber containing either rabbit hepatocytes or hepatocyte homogenates. Endotoxin directly depressed the respiration of intact rabbit hepatocytes. Endotoxin also decreased the oxygen consumption of hepatocyte homogenates. The intact cell membrane is not an effective barrier to the deleterious effect of endotoxin. A patient in a state of endotoxic shock, in addition to having a hemodynamic derangement, probably has circulating toxins that directly render cellular oxidative phsophorylation less efficient.


Trends in surgical treatment of calculous disease of the biliary tract. From the data presented, there are five distinct trends in operations for calculous biliary tract disease. There is less delay in operation following diagnosis than ever before. Diagnosis is being made early in those with symptoms. Asymptomatic calculi are being revealed more frequently by complete over-all medical evaluations including cholecystography. Acute obstructive cholecystitis, a complication of cholelithiasis, is becoming less frequent in proportion to the total patients admitted to hsopitals. The operative mortality is concentrated among those in the elderly group, 65 years old and older. The limited capacity of many patients in this category to tolerate the burden of any surgical procedure is being met by palliative, temporary procedures such as cholecystostomy and ductal decompression rather than definitive cholecystectomy and choledochotomy. Roentgenologic facilities are becoming available to provide visualization and critical evaluation of the entire ductal system at the beginning of an operation. This provides a more realistic basis for common duct exploration, an increment associated with morbidity. More important is the assurance against overlooking calculi, retained ductal stones.


[A clinico-morphologico-functional study of the kidneys in glomerulonephritis]. The article deals with the results of a clinico-functional-morphological study of the kidneys in glomerulonephritis (50 observations) which was carried out with the use of the method of puncture biopsy of the kidneys. It was shown that clinical forms of glomerulonephritis, accompanied with hematuria, were characterized by the absence of fixation of immune complexes in the basal membrane of the glomeruli. According to the electron microscopy data, this corresponds to the dissappearance of deposits from the subendothelial parts of the basal membrane. The extramembranous glomerulonephritis, revealed with the help of electron microscopy technique, was characterized by the nephrotic syndrome. An increased tension of immunological processes in the glomeruli was accompanied by a more grave clinical course of glomerulonephritis, by impairment of not only glomerulous but tubular functions as well. A greater dicrease in the function of osmotic concentration of the urine in fibroplastic types of glomerulonephritis, as compared with non-firboplastic ones, was apparently connected not only with lesiones of tubules but rather with more expressed sclerotic changes in the interstitial tissue of the kidney.


Improved HL-A typing of cadaveric renal donors. I. Quantitation of HL-A gene dosage. A quantitative microabsorption technique has been used to determine a gene dosage effect on HL-A. This allows homozygosity or heterozygosity of HL-A antigens to be determined prospectively in cadaver donors of renal allografts where less than four antigens were detected by standard lymphocytotoxicity. This in turn provides more precise matching of donor and recipient.


Reactions of kidney cells with cytotoxic antisera: possible evidence of kidney-specific antigens. HL-A typing of cadaver kidney cell suspension by fluorochromasia cytotoxicity was successful in 76 out of 124 cases. In the 44 cases with confirmed phenotypes, 24 had identical results for lymphocytes and kidney cells. Twenty kidney cells had HL-A antigens not detected on that donor's lymphocytes, most commonly HL-A7 and HL-A8. In eight of these 20 cases, the additional kidney antigens brought the total to more than two per segregant sereis, in disagreement with an earlier report from this laboratory. The discrepancy was traced to a change in the method of complement preparation. The complement was successfully deprived of the resulting non-specific cytotoxicity for kidney cells by absorption with human red blood cells. Prior to absorption, the complement had rendered kidney cells susceptible to the lytic effect of anti-A and B red cell antibodies. Using the absorbed complement, a patient who had hyperacutely rejected two cadaver kidneys provided sera with an antibody reacting with, and absorbed by, the kidney cells but not the lymphocytes of the donors.


Mycoplasma in synovial fluid from the patients with rheumatoid arthritis. Mycoplasma colonies were found on culture of synovial fluid in 14 of 18 cases of rheumatoid arthritis. It was possible to demonstrate the colonies in primary culture medium only by the method of hot water fixation and Giemsa staining. The organisms grown on solid medium were also observed electron-microscopically.


Amino acid metabolism in Wegener's granulomatosis. The urinary excretion of amino acids and their derivatives in cases of Wegener's granulomatosis have been examined, and the excretion of urinary amino acids in such cases was different from normal and reticulum cell sarcoma. In Wegener's cases, the amino acids which were always found in readily detectable amounts totaled 33; urinary phenylalanine was 4-5 times higher than in normal subjects. From these experimental results, we believe that the observation of amino acid excretion into urine is an important indicator for the diagnosis of Wegener's granulomatosis. In addition, the results of quantitative examination on the urinary amino acid excretion were compared with normal and reticulum cell sarcoma. Comparison of the analytical data on urinary amino acids of the normal and patient groups indicated significant metabolic abnormalities of some amino acids at the earliest stage of Wegener's granulomatosis.


Instrument to facilitate nephrostomy.

Instrument to facilitate nephrostomy. An instrument to facilitate the placement of a nephrostomy tube is described. The techniques for performing nephrostomies are historically reviewed.


Kidney cooling in partial nephrectomy. Evaluation of a technique. A technique of cooling the isolated human kidney by immersing it in a plastic bag filled with iced saline slush is described. This technique is simple, swift to perform, requires no specialized equipment, and is inexpensive; it has proved to be effective and safe.


Small-Carrion penile prosthesis. New implant for management of impotence. The etiology of impotence and a review of various techniques in treatment are discussed. A perineal surgical approach with a new type of paired sponge-filled silicone prostheses is described. The prostheses are inserted into previously dilated corpora cavernosa. Of the initial 31 patients, excellent results were obtained 27, and a good result in 1. Of the 3 patients with initial serious complications, adequate functional results were attained in 2. The distinct advantages and potential complications using the Small-Carrion penile prosthesis and surgical technique are discussed.


Blood urea nitrogen and serum creatinine.  Physiology and interpretations. Any elevations in levels of blood urea nitrogen and/or serum creatinine do not necessarily indicate structural renal disease.  Conversely, blood urea nitrogen or serum creatinine values, which appear to be within the range of normal, do not by themselves rule out significant reduction in glomerular filtration rate.  Any interpretation of the blood levels of these two substances must be done with the awareness that a variety of extrarenal factors can affect them.  The blood urea nitrogen to serum creatinine ratio can be a valuable tool in the determination or renal functional and structural integrity.


Hematologic problems in urology. Basic mechanisms and clinical approach. Baxic clotting mechanisms are reviewed. The clinical and laboratory aspects of disseminated intravascular coagulation and fibrinolysis are discussed, and an approach is suggested to those problems encountered by the urologist.


Urinary tract disorders.  Clinical comparison of flavoxate and phenazopyridine. In nine separate clinical trials, 382 patients having symptoms of either prostatitis, acute cystitis, urethritis, and/or trigonitis were randomly assigned to treatment with flavoxate or phenazopyridine.  Over-all response was evaluated in 384 patients after five days of therapy.  In patients having prostatitis, response was satisfactory in 66 per cent treated with flavoxate and 31 per cent treated with phenazopyridine.  In all other patients, satisfactory responses were reported in 80 per cent on flavoxate compared with 56 per cent on phenazopyridine.  Similarly, symptom-severity evaluations at two and five days of therapy showed most symptoms improved in more of the patients on flavoxate therapy than on phenazopyridine therapy.  Although more adverse effects were reported in patients treated with phenazopyridine than with flavoxate, the difference between medications was not statistically significant.


Treatment of chronic prostatitis.  Comparison of Minocycline and Doxycycline. The results of minocycline and doxycycline therapy in 41 patients with chronic prostatitis and minocycline therapy in 6 patients with acute prostatitis were evaluated.  In the comparative study of chronic prostatitis, minocycline and doxycycline were given on the same dosage schedule, milligram for milligram: a loading dose of 200 mg. followed by 100 mg. twicd daily.  Over-all clinical responses to therapy with either agent were generally satisfactory, and no statistically significant difference was demonstrable in this regard.  In the group with chronic prostatitis treated wtih minocycline, however, all symptoms manifested before therapy had disappeared after therapy even where over-all results had been judged unsatisfactory.  This was not true of the group with chronic prostatitis treated with doxycycline.  Symptoms in 6 patients persisted after therapy had been terminated.  Here the difference in results between the two groups was found to be statistically significant.  A review of symptoms two to eight weeks after therapy revealed no significant difference between the two groups. After two years only 6 patients in the entire group with chronic prostatitis had returned with recurrent problems: 3 of these patients had been treated with minocycline and 3 had been treated with doxycycline.  Results of therapy in the small series of patients with acute prostatitis treated with minocycline were generally satisfactory.


Bacterial effect on sperm motility.

Bacterial effect on sperm motility. Human semen containing normal number of sperm was exposed to concentrations of Escherichia coli varying from 500 to 10-8 colonies per cubic centimeter.  A significant decrease in motility was abserved at 10-6 colonies per cubic centimeter.


[Use of ftorafur for the treatment of 3d-4th stage]. To treat ovarian cancer of stage III-IV the authors have used an antimetabolite-fluorafur. A total dosage of 17-23 g. "marked improvement" was noted in 15 patients, "insignificant improvement" - in 9, there was no improvement in one case. It was found that the level of FSH excretion was reduced twice under the influence of fluorafur, the greater decrease corresponding to a better clinical effect. The drug used in doses applied by the authors, proved to be nontoxic.


Orthopedic applications of liquid crystal thermography. Liquid crystal thermography can assist the clinician in evaluating inflammatory conditions or delineating viability of tissues by the differences in coloration that occur with the use of these unique substances. The technique has proved useful in studying hemophilia, tumors of the extremities, arthritis and vascular conditions, including the complications of diabetes.


[The action of a tropic acid ester on bronchospasm: a double-blind study (author's transl)]. 12 patients with chronic bronchitis were treated with two different doses (0.02 and 0.08 mg) of Sch 1000 (Atrovent) administered by metered dose inhalation and the results compared with those following administration of a placebo in a cross-over double-blind study. The airway resistance and thoracic gas volume fell significantly after treatment with the drug, with no appreciable difference in effect between the dosages. The bronchodilatory action of the drug lasted about 4 hours and differed markedly from that of the placebo. No anticholinergic side effects or specific effects on the circulation were encountered at the administered dosage.


[Chromosome studies on human fibroblast cultures following exposure to cyproheptadin]. Cyproheptadin was tested on chromosomes in fibroblast cultures of children for its possible mutagenic efficacy. Neither 24-hour exposure to Cyproheptadin at concentrations of 8-16 mg/l medium nor a chronic exposure for 8-11 weeks at a concentration of 8 mg/l caused any discernable chromosomal mutations. At concentrations between 8-16 mg/l reversible cytomorphological and cytochemical changes occured; 32 mg/l suppressed cell division and higher concentrations (64-128 mg/l) brought about irreversible changes leading to cell death. These reactions were rather in vitro cytotoxic effects of unspecific nature.


An in vivo and in vitro phosphorylation of yeast ribosomal proteins. Phosphorylation of yeast ribosomal proteins has been demonstrated in vivo and in vitro. 32-P-labelled product represents an ester-linked class of phosphoprotein. Acrylamide-gel electrophoresis has shown that in both types of experiments radioactive proteins migrate similarly; this might indicate that closely related groups of proteins become phosphorylated in vivo and in vitro. In the presence of [32-P] ATP the amount of covalently bound phosphate was 1.0 - 1.2 moles/mole of ribosome. The phosphorylation of ribosomal proteins did not appreciably affect the activity of ribosomes in a cell-free protein-synthesizing system containing poly(U) and elongation factors.


Preparative enzymic synthesis of nucleoside-5'-phosphates. 1. Wheat shoot phosphotransferase has been employed, with p-nitrophenylphosphate as a phosphate donor, to specifically phosphorylate the 5'-position of a variety of nucleosides and nucleoside analogues. The specificity of the enzyme towards the 5'-position of pentose nucleosides is testified to by the complete resistance to phosphorylation of 5'-O-methylcytidine. 2. With the use of ion-exchange chromatography, the foregoing procedure has been applied to the large-scale preparation of nucleoside-5'-phosphates with overall yields of the order of 80-90%. Quantitative recovery of unreacted nucleoside makes it possible to use this method without risk of losses either on a small or large scale with rare nucleosides. It is also applicable to acid- and alkali-labile nucleosides which cannot readily be phosphorylated by chemical procedures. 3. The wheat shoot phosphotransferase also phosphorylated a galactopyranosyl nucleoside, as well as such derivatives as 1-(beta-hydroxyethyl)cytosine and 5-(beta-hydroxyethyl)uracil, showing that the enzyme does not have an absolute requirement for a 5-membered sugar ring, but rather for the presence of a primary hydroxyl group. 4. The phosphorylated derivatives of galactopyranosyluracil, and of both hydroxyethyl pyrimidines, were resistant to 5'-nucleotidase. E. coli alkaline phosphatase converted all three nucleotides quantitatively to the starting compounds. 5. A synthesis of 1-(beta-hydroxyethyl)cytosine is described.


Effects of dihydrotestosterone on LH release induced by LH-RH in men. In order to determine the effect of dihydrotestosterone on the feed back mechanisim of the hypothalamo-pituitary-testis axis, nine healthy subjects were subjected to LH-RH tests before and after treatment with 5alpha-DHT. A double antibody radio-immunoassay technique was used to measure the concentration of LH and FSH in the plasma. Our results clearly show that the pituitary LH release by LH-RH after pre-treatment with 5alpha-DHT is more prononeced. In the light of actual findings from several laboratories it is not possible to interpret clearly the results of our own experiments, and hence we advance only some hypotheses.


Accumulation of alprenolol in some polypeptide hormone producing cells and in melanin-containing tissues. The distribution of the beta-adrenergic-receptor blocking drug alprenolol labelled with 3H was studied in mice by whole body autoradiography. The most characteristic feature in the distribution pattern was the accumulation in endocrine cells within the pancreatic islets, the adrnal medulla, the pituitary gland and some cells of the thyroid, presumably representing the parafollicular cells. A hgih accumulation was also observed in melanin-containing tissues.


Further studies on enzymic inactivation of luteinizing hormone- releasing hormone (LH-RH) by peptidases in the rat hypothalamus. Luteinizing hormone-releasing hormone (LH-RH) is known to be inactivated by peptidases in the rat hypothalamus with consequent loss of LH-releasing ability. To make a further study of the peptidases' action on the decapeptide, synthetic LH-RH and its [1-9NH2] analogue were incubated with the supernatant hypothalamic fraction containing the enzyme activity. Using an assay system measuring gonadotrophin release in ovariectomized/steroid-primed rats, both LH-RH and the [1-9NH2] analogue were found to be inactivated to different extents after incubation with the fraction, the analogue completely losing both LH- and FSH-releasing activity, and the releasing hormone almost completely losing its LH- and totally losing its FSH-releasing activity. The findings extend the initial studies by showing that the peptidases can remove both the decapeptide's intrinsic LH- and FSH-releasing activity and that these enzymes act on LH-RH at a site other than the C-terminal glycinamide, since they are able to inactivate the [1-9NH2] analogue lacking this residue.


Circadian rhythms of the endocrine pancreas.  A quantitative biochemical and immumocytochemical study. Cellular hormone levels of insulin and glucagon in the endocrine pancreas of the rat have been observed and quantified over the 24-hours period, at 3-hourly intervals, by T.V. image conversion analysis on immunocytochemical preparations.  Parallel estimations of blood sugar were carried out.  Glucagon levels were at their lowest when the blood sugar levels were at their highest.  Quantitative cytochemistry is regarded as a valuable tool for the investigation of changes in intracellular hormone levels under physiological and pathological conditions.


Level diagnosis of symptomatic urinary tract infections in childhood. As no method for localization of urinary tract infection has been shown to be absolutely reliable, six procedures have been carried out simultaneously in 25 girls with acute symptomatic infections and the reliability of each method assessed. While clinical diagnosis of pyelonephritis or cystitis correlated well with the overall results of the battery of tests, the reliability of individual tests varied. Highest reliability was obtained with CRP determinations followed by antibody titration, sedimentation rate, and renal concentrating capacity. In the bladder washout test only 8 of the 14 patients with pyelonephritis had findings clearly indicating high infection. Intermittent or inadequate discharge of bacteria from the renal parenchyma is suggested as the major source for this inaccuracy. In fact, half of the 42 final washout specimens from girls with acute pyelonephritis contained less than 1000 bacteria per ml, indicating that low numbers of organisms in ureteric urine is common in childhood pyelonephritis.


Betamethasone 17-valerate in childhood asthma. A double-blind crossover trial in children not taking other corticosteroid therapy. A double-blind crossover trial of Betamethasone 17-Valerate steroid aerosol compared with placebo was carried out on 18 children with severe intermittent or chronic asthma. Seventeen of the 18 children showed a clinically obvious improvement on the active drug. The remaining child was unable to use the inhaler properly. In 14 children the response was dramatic. Improvement was shown at home by a reduction in the number of asthmatic symptoms, improvement in twice daily peak flow rates and by a lowered intake of sympathomimetic tablets. At monthly clinic visits, improvement was shown by chest examination, weight gain and by detailed respiratory function tests. By each of these criteria for improvement the benefit of Betamethasone 17-Valerate over the placebo was highly significant. There were no side effects attributable to the therapy and no evidence, as judged by short tetracosactrin tests, of adrenal suppression resulting from the drug. Betamethasone 17-Valerate appears to be a safe and effective therapy in children with severe asthma.


Escherichia coli serogroups in breast-fed and bottle-fed infants. 1) Eighty-seven breast-fed and 95 bottle-fed infants were examined for differences in Escherichia coli serogroup pattern. 2) The serogroup composition was less complex in breast-fed infants. Fewer serogroups were found in the individual breast-fed child. However, with few exceptions, the same O groups were found in the two groups of infants. The prevalent O groups were among those also found most frequently in faeces from adults. 06 strains were more common in the breast-fed group, while 07 and 016 were not at all found in that group. 3) A special search for E. coli strains with Kl antigen showed that this antigen predominated in the bottle-fed infants. 4) Klebsiella and other Enterobacteriaceae were more frequently found among bottle-fed infants. 5) It is concluded that the intestinal milieu exerts a selective pressure which may result in a selection of different serotypes in two different intestinal milieus such as those examined.


The establishment of K99, a thermolabile, transmissible escherichia coli K antigen, previously called "Kco", possessed by calf and lamb enteropathogenic strains. The transmissible antigen in enteropathogenic E. coli strains from calf and lamb, previously called Kco, is established as the E. coli K99 antigen. It is probably of protein nature since it is destroyed by heating. It is pointed out that other antigens present, growth medium and unknown factors are of great importance for the demonstration of this antigen.


Influence of methylprednisolone on complement activity in germfree rats and on antibody activity to Escherichia coli in monocontaminated rats. By means of radio-isotope technique, the influence of methylprednisolone treatment on opsonic and bactericidal serum activities against E. coli was studied on germfree and monocontaminated rats. Based on the present results it seems unlikely that methylprednisolone impairs the production of complement components. A slight suppression of antibody activity was only found in markedly wasted monocontaminated rats treated with very high doses of methylprednisolone from the day before contamination.


Occurrence of K88-negative escherichia coli serotypes in pigs with post weaning diarrhoea. Faecal swabs from pigs with post weaning E. coli diarrhoea in 43 different herds were bacteriologically examined. A survey of the isolated haemolytic E. coli strains showed that only 1 of the examined strains possessed the K88 antigens and that E. coli strains belonging to serogroup O149:K91 were most frequently isolated. The results suggest that the K88 antigen is of minor significance in the development of post weaning diarrhoea associated with E. coli serotype O149:K91.


Comparison of defensive behavior evoked by chemical and electrical stimulation of the hypothalamus in cats. Comparison of defensive behavior evoked by chemical anf electrical stimulation of the hypothalamus in cats. Acta Physiol. Pol. 1975, 26 (1) 23--31. An injection of 5 mug of carbachol, as well as electrostimulation of the same hypothalamic area evoked in cats the same type of defensive behavior -- rage reaction. Experiments with carbachol injection and electrostimulation after blockade of the hypothalamic muscarinic receptors (10 mug of atropine) indicate that rage reaction is evoked in a different way by the two methods. Controversial data regarding localization of the hypothalamic "centres" responsible for particular type of defensive reactions are discussed.


Breast reconstruction after radical mastectomy. The loss of the female breast by mastectomy for treatment of carcinoma is frequently a depressing psychologic experience. While some women learn to cope with the loss, others do not despite the use of specially constructed brassieres. Adaptations of implantation materials and basic plastic surgical techniques are now available for selected postmastectomy patients. These can be useful in modifying the altered body image of the patient who has lost her breast.


Avulsion injuries in patients receiving corticosteroids. Minor trauma often produces avulsion injuries to the skin and soft tissue of patients who are receiving corticosteroid therapy on a continuing basis. Effective emergency management of these wounds reduces the duration of disability for the patient. Early grafting is a more conservative course in terms of predictable patient recovery than watchful waiting. The most important aspects of this treatment are immediate grafting and sufficient immobilization of the graft by the dressing.


A new method for automated detection of the R-on-T phenomenon. The detection of premature ectopic beats coinciding with the T-wave of the antecedent beat is important for patient monitoring. In the method described here, the difficulties of direct measurement of QT time are avoided by evaluating the changes of QT time according to heart rate by use of a diode function generator. An analog circuit is used for comparing the computed QT time with the coupling interval of successive beats. In case of a R-on-T-phenomenon an alarm is given. The frequency of alarms is registered on a trend recorder. The methods is based on empirical equations which all contain a constant factor. Our investigations showed that the variability of this factor during longer periods of monitoring was small enough to allow sufficient exactness of the evaluation procedure.


Nonparoxysmal junctional tachycardia in acute myocardial infarction: computer-assisted detection. Thirty consecutive patients with acture myocardial infarction had continuous magnetic tape recording of their stay in the coronary care unit. Analysis of the 24 hour tape recordings was implemented on a Honeywell model 316 digital computer. In the first 24 hours after admission to the coronary care unit, 12 of the 30 patients (40 percent) exhibited nonparoxysmal junctional tachycardia; in 5 the arrhythmia was not recognized by conventional monitoring techniques. For the subsequent 3 days, the incidence rate of the arrhythmia was 13 percent for the first 48 hours and 3 percent for 72 hours. Although the mortality rate in patients with nonparoxysmal junctional tachycardia was greater than in patients not demonstrating the arrhythmia (33 versus 6 percent), there was a greater percentage of patients with anterior infarction in the former group; therefore, mortality may have been related to site of infarction rather than being reflective of the arrhythmia or its associated pathophysiologic state. Of possible significance is the association of a greater degree of sinus arrhythmia with nonparoxysmal junctional tachycardia. The incidence of nonparoxysmal junctional tachycardia in this group of patients was greater than previously reported. It is possible that computer tape analysis may have provided more accurate recognition of the arrhythmia and, thus, more realistic incidence data. The association of nonparoxysmal junctional tachycardia with sinus arrhythmia could only have been recognized by computer technique. The computer system is not a diagnostic system but rather a tape review method.


Diagnosis and management of complications of prosthetic heart valves. Complications after heart valve replacement remain a substantial source of morbidity and mortality despite continuing advances in surgical care and prosthetic design. Infectious endocarditis occurs in about 4 percent of patients and may appear early (within 60 days) or late after operation. Endocarditis of early onset is commonly due to staphylococcal, fungal or gram-negative organisms and is fatal in 70 percent or more of cases. Infection of late onset is more often of streptococcal origin and the mortality rate is lower, about 35 percent. With either type, prompt recognition, vigorous and appropriate antimicrobial therapy and early consideration of surgical intervention are crucial. The postperfusion and postpericardiotomy syndromes are relatively common and relatively benign syndromes associated with postoperative fever. Their recognition is important to prevent confusion with endocarditis or sepsis and thus to reassure the patient and physician. Treatment is primarily symptomatic. Intravascular hemolysis occurs with most prosthetic heart valves but is more common with certain prostheses and with paraprosthetic valve regurgitation, with significant hemolytic anemia in 5 to 15 percent. Oral iron replacement therapy is effective in the majority of patients, but occasionally blood transfusion or reoperation for leak around the prosthesis is necessary. Prosthesis dysfunction due to thrombus may be recognized clinically by recurrence of heart failure, syncope, cardiomegaly and altered prosthetic valve sounds or new murmurs. Hemodynamic studies verify the diagnosis, and prompt reoperation is indicated for this potentially lethal problem. Systemic embolization has decreased markedly with the introduction of cloth-covered prostheses and is frequently related to erratic or ineffective anticoagulant therapy. We continue to recommend anticoagulant therapy for all patients with prosthetic heart valves unless there is a major contraindication.


Renal consequences of valvular heart disease. Three aspects of potential renal involvement in patients with valvular heart disease are discussed. These include (1) disturbances in renal salt and water handling and their implications with respect to diuretic management; (2) the hemodynamic effects of angiographic contrast agents with identification of potentially dangerous effects on the kidneys; and (3) the histologic patterns of bacterial endocarditis in the kidney and their similarity to those of immunologically mediated disease.


Oral contraceptives and ascorbic acid.

Oral contraceptives and ascorbic acid. Plasma, leukocyte, and platelet ascorbic acid levels are decreased in women ingesting oral contraceptive steroids. Studies have shown that it is the estrogenic component of the oral contraceptive agents that is associated with the decresased ascorbic acid concentrations. Urinary excretion of ascorbic acid does not appear to be increased by the steroids. Although serum levels of copper are increased by estrogens and oral contraceptives, ascorbic acid catabolism does not appear to be increased (unpublished). Our preliminary data on tissue uptake of ascorbic acid suggest that changes in tissue distribution are one possible answer for the observed effects of the steroids on blood levels of ascorbic acid.


Control of brain monoamine synthesis by diet and plasma amino acids. The rates at which monoaminergic neurons in rat brains synthesize their neurotransmitters depend on the availability of the amino acid precursors tryptophan (for serotonin) and tyrosine (for dopamine and norepinephrine). The administration of tryptophan, the injection of insulin, or the consumption of a single protein-free high-carbohydrate meal all elevate brain tryptophan levels and, soon thereafter, the levels of serotonin and its major metabolite 5-hydroxyindole acetic acid. The addition of protein to the meal suppresses the increases in brain tryptophan and serotonin, because protein contributes to plasma considerably larger amounts of the other neutral amino acids (e.g., leucine, phenylalanine) than of tryptophan, and these other amino acids compete with tryptophan for uptake into the brain. The elevation of brain tyrosine (by injection of the amino acid or consumption of a single 40% protein meal) accelerates brain catecholamine synthesis, as estimated by measuring brain dopa accumulation after decarboxylase inhibition, or brain catecholamine accumulation after inhibition of monoamine oxidase. These observations suggest that serotonin- and catecholamine-containing brain neurons are normally under specific dietary control.


Lymphocyte surface receptors and leukemia virus-induced immunosuppression. The number and distribution patterns of lymphocytes in the spleens and lymph nodes of Balb/c mice which express immunoglobulin surface receptors were studied in terms of the effects of a murine leukemia virus on the immune-response mechanism. Friend leukemia virus induces a prompt, marked depression of the immune response of mice to antigens such as sheep erythrocytes and E. coli LPS. A functioning T- and B-lymphocyte system is necessary for the response to the SRBC's whereas E. coli LPS, a T cell-independent antigen, stimulates B cells alone. Although the responses to both classes of antigen were markedly depressed in FLV-infected mice, the major defect appeared to be impairment of B-cell function, at least early in the course of infection. In order to examine in more detail the mechanism of interaction between FLV and lymphoid cells with Ig surface receptors, presumably B cells, immmunofluorescent analyses were performed with spleen, and lymph node cells from FLV-infected mice. Within a few days after infection there was a marked decrease in the percentage of spleen cells with Ig surface molecules, although the absolute number of these cells was either unchanged or increased due to marked splenomegaly caused by the virus. A marked decrease in the percentage of splenocytes with theta antigen, considered a marker for mature T cells, also was evident in infected mice. The number of spleen cells showing evidence of FLV infection (i.e., positive for FLV-associated antigens) increased rapidly during the first few days after infection, and within 2 to 2 1/2 weeks nearly all of the nucleated splenocytes were positive for the tumor antigen. In contrast to the results for spleen cells, there were increases rather than decreases in the percentages of Ig-positive and theta-positive cells in the lymph nodes after infection. The number of lymph-node cells that showed the presence of FLV antigen was much lower than in the spleen, and their appearance was also much slower as the leukemic process progressed. Despite these differences between spleen and lymph-node cells in terms of relative percentages of Ig- and theta-positive lymphocytes, relatively similar depressions were evident for the percentages of lymphoid cells that could redistribute their surface Ig receptors into polar caps when incubated with anti-Ig serum at 37 C. Marked impairment of the Ig-capping responses for both spleen and lymph-node cells paralleled the course of infection and development of immunosuppression. These observations indicate that murine leukemia virus infection can both alter the responsiveness of immunocompetent cells to T-dependent and independent antigens and depress the number and normal functional activity of these cells, as reflected by altered surface Ig receptors and antigens.


The effects of consultation. A review of empirical studies. Although consultation, as an activity for intervention, has achieved considerable popularity among human service professionals and figures prominently in current federal mental health legislation, a basic question still unanswerable is, "Does it work?" This paper reviews 35 consultation outcome studies reported between 1958 and 1972 in an attempt to provide some answers to this question. Although their quality varies greatly, the evidence seems to lend some support to the effectiveness of consultation as a change method. In 69% of the studies reviewed, positive change was demonstrated on the consultee, client, or system level or at some combination of these. The review also suggests that, despite a need for studies which build cumulatively on earlier ones so as to provide comparable data instead of a conglomerate of isolated findings, progress has been made in the evaluation of consultation.


Early secondary prevention with disadvantaged preschool children. A body of research data is reviewed pointing to considerable intellectual lag and nonstandard linguistic abilities among the disadvantaged. While "difference" and "deficit" theorists interpret these findings differently, many observers agree that early educational intervention may be a useful approach to such problems. A series of early intervention programs is reviewed for three young disadvantaged groups: infants, toddlers, and preschoolers. Findings from these programs suggest that early intervention helps materially to reduce the intellectual and linguistic problems of the young disadvantaged.


Immunization of children with attenuated measles-rubella bivalent vaccine. The effects of simultaneous administration of Schwarz-strain measles virus vaccine and Cendehill-strain rubella virus vaccine as a single bivalent injection was evaluated in 346 children susceptible to both diseases. With placebo and monovalent controls, four bivalent preparations were used in a double-blind protocol to determine the effects of variations in the concentration of one or both components. No unusual reactions occurred and simultaneous administration did not enhance clinical reactivity. For measles, the seroconversion rate was 97% for monovalent vaccine and 97% to 100% (average 98%) for bivalent vaccines. For rubella, the rate was 100% for monovalent vaccine and 94% to 100% (average 99%) for bivalent vaccines. Thus, the vaccines were as safe and effective when given together as when given separately.


Autoimmune phenomena in alcholic cirrhosis. Serum immunoglobulins usually are increased impressively in alcoholic cirrhosis, particularly IgA and IgM. The basis for these changes has not been clarified. Previous studies with sera of cirrhotic subjects failed to show autoantibody reactions found in other hepatocellular diseases. Two autoantibody reactions were demonstrated by immunofluorescent techniques, using IgG, IgM, and IgA of cirrhotic sera. Purification was achieved by starch block electrophoresis, gel filtration of Sephadex G-200, chromatography on DEAE-Sephadex, and affinity chromatography on columns of Sepharose 4B, in that sequence. IgM appeared as a nonspecific antinuclear antibody, IgA bound to alcoholic hyaline (Mallory bodies). IgG failed to stain any of the examined tissues. It may be the blocking agent which prevents the above-mentioned autoimmune phenomena in whole serum.


Computer-aided diagnosis of "dyspepsia". Experience with computer-aided diagnosis of "dyspepsia" in a consecutive prospective series of 212 patients coming to surgery is described. Analysis is concentrated upon 122 patients who presented to an outpatient clinic de novo for diagnosis. During their first (outpatient) hospital contact, a firm diagnosis was made in just over half of these patients (though where made, it was usually correct). After full investigation, the diagnostic accuracy (prior to operation) was 92.6%. Using data elicited solely from the house surgeon's interview at the time of admission, the computer's overall diagnostic accuracy was 87.7%. The cost of each new computer diagnosis was around 25 new pence ($0.60). and the time taken was about 5 minutes. In a further small series designed to discriminate between organic and functional dyspepsia, the computer correctly assigned all but 1 of 23 patients with organic disease to the correct disease category. However, almost half of 33 patients with x-ray negative dyspepsia were predicted by the computer to have organic lesions. Time alone will tell whether the computer is a better early predictor of eventual organic disease than currently available radiologic methods.