Cardiac syncope secondary to glossopharyngeal neuralgia--effectively treated with carbamazepine. A 64-year-old male with glossopharyngeal neuralgia, cardiac asystole and grand mal seizures has been relieved of his attacks by intake of 400 mg of Carbamazepine per day over a 4-year period. Simultaneous EEG-EKG recordings before and after drinking water document the diagnosis.


Monkey pepsinogens and pepsins. III. Carbohydrate moiety of Japanese monkey pepsinogens and the amino acid sequence around the site of its attachment to protein. Purified Japanese monkey pepsinogens I and II contain carbohydrate as a part of the enzyme molecule. By gel filtration on Sephadex G-100, chromatography on DE-32 cellulose, and polyacrylamide disc gel electrophoresis, the carbohydrate moiety could not be separated from the enzyme protein, and the content did not decrease on repeated chromatography. Glycopeptides were obtained by successive digestion of pepsinogens with thermolysin and aminopeptidases and isolated by chromatography on Sephadex G-25 and G-50. Identification and determination of carbohydrate components was performed by paper and gas-liquid chromatographies. The presence of 4 glucosamines, 6 galactoses, 6--8 mannoses, and 8--11 fucoses per molecule of the glycopeptide of both pepsinogens was observed, of which the high content of fucose is especially unique. The molecular weight of the carbohydrate chains should be around 4,000--5,000. The amino acid sequence of a major glycopeptide was deduced to be Ile-Gly-Ile-Gly-Thr-Pro-Gln-Ala-Asn, in which the asparagine residue is the site of attachment of the carbohydrate chain.


Crystallization and a 5 A X-ray diffraction study of Aphanothece sacrum ferredoxin. A chloroplast-type ferredoxin containing two non-heme iron and two labile sulfur atoms per molecule was prepared from Aphanothece sacrum. Crystals were obtained by dialysis against 75% saturated a-monium sulfate solution, and belong to the tetragonal system with cell dimensions a = b = 92.2 A and c = 47.6 A, containing four molecules in an asymmetric unit. The electron density map at 5 A resolution was calculated by using the best phase angles determined by the single isomorphous replacement method coupled with the anomalous dispersion effect. An anomalous dispersion difference Fourier map for the native crystal clearly showed four humps corresponding to the iron atoms in an asymmetric unit. The electron densis surface.


Detection of intermediates in protein folding of carbonic anhydrase with fluorescence emission and polarization. The three-dimensional structure of carbonic anhydrase is a result of specific folding of the protein chain to form a compact, globular molecule. Fluorescence measurements on the nature of the rate-limiting steps in folding from the random coil to the native structure show that each step involves an actual folding reaction of the protein chain. Emission intensity and polarization of the intrinsic fluorescence due to tryptophan residues reach a maximum during the early period of the folding process. The changes occur in at least three kinetic phases (tau1 less than 3 S, tau2 = 1 min, tau3 = 10 min, 1 M guanidinium chloride, 2 M NaC1, pH 7, 20 degrees C). None of these phases are explained by configurational changes in the fully unfolded chain. The results are consistent with a kinetic scheme that involves stepwise acquisition of the specific folded structure of the native enzyme.


Cyanobacterial phycobilisomes. Characterization of the phycobilisomes of Synechococcus sp. 6301. A procedure is described for the preparation of stable phycobilisomes from the unicellular cyanobacterium Synechococcus sp. 6301 (also known as Anacystis nidulans). Excitation of the phycocyanin in these particles at 580 nm leads to maximum fluorescence emission, from allophycocyanin and allophycocyanin B, at 673 nm. Electron microscopy shows that the phycobilisomes are clusters of rods. The rods are made up of stacks of discs which exhibit the dimensions of short stacks made up primarily of phycocyanin (Eiserling, F. A., and Glazer, A. N. (1974) J. Ultrastruct. Res. 47, 16-25). Loss of the clusters, by dissociation into rods under suitable conditions, is associated with loss of energy transfer as shown by a shift in fluorescence emission maximum to 652 nm. Synechococcus sp. 6301 phycobilisomes were shown to contain five nonpigmented polypeptides in addition to the colored subunits (which carry the covalently bound tetrapyrrole prosthetic groups) of the phycobiliproteins. Evidence is presented to demonstrate that these colorless polypeptides are genuine components of the phycobilisome. The nonpigmented polypeptides represent approximately 12% of the protein of the phycobilisomes; phycocyanin, approximately 75%, and allophycocyanin, approximately 12%. Spectroscopic studies that phycocyanin is in the hexamer form, (alpha beta)6, in intact phycobilisomes, and that the circular dichroism and absorbance of this aggregate are little affected by incorporation into the phycobilisome structure.


Characterization of the Bacillus subtilis bacteriophage PBS2-induced DNA polymerase and its associated exonuclease activity. The DNA polymerase induced by Bacillus subtilis bacteriophage PBS2 has a Stokes radius of 7.2 in buffers of high ioninc strength, suggesting a molecular weight in the range 145,000 to 195,000. The polypeptide bands observed on gel electrophoresis in dodecyl sulfate have apparent molecular weights of 78,000 and 69,000 (and possibly another 27,000) in equimolar amounts. In buffers of low ionic strength, the enzyme appears to form large aggregates and even precipitates, with about 90% loss of activity. A nuclease activity co-purifies with the PBS2 DNA polymerase and shows similar responses to changes in pH, MgCl2, N-ethylmaleimide, temperature, and dextran sulfate levels. The nuclease produces deoxyribonucleoside 5'monophosphates from denatured DNA containing thymine or uracil. No endonuclease activity is detectable on supercoiled DNA. The inhibition of nuclease activity by added deoxyribonucleoside triphosphates, the DNA-dependent turnover of triphosphates, to free monophosphates during DNA polymerization, the inhibition of nuclease activity by 3'-phosphates on the DNA template-primer, and the pattern of digestion of 5'-[32P]phosphate-labeled DNA all indicate that the PBS2 DNA polymerase-associated hydrolytic activity is a 3' leads to 5'-exonuclease.


Sequence and location of large RNase T1 oligonucleotides in bacteriophage Qbeta RNA. Twenty-nine oligonucleotides, 11 to 26 nucleotides in length, arising by complete RNase T1 digestion of bacteriophage Qbeta RNA and isolated by two-dimensional polyacrylamide gel electrophoresis, were sequenced. Their location within the genome was established with two methods. (a) In vitro synthesis of Qbeta RNA plus strands was started synchronously, using minus strands as template and nucleoside [alpha-32P]triphosphates as substrate; after various times, the reaction was stopped and the length of the products formed was correlated with their content of T1 oligonucleotides. (b) Qbeta [32P]RNA was elongated with poly(A) using terminal riboadenylate transferase; after mild treatment with alkali the fragments were fractionated by size and the poly(A)-containing molecules of each size class were isolated by chromatography on poly(U)-Sephadex and assayed for T1 oligonucleotides. The oligonucleotides in the 5' region were localized more precisely with method a, those near the 3' end with method b; in the middle region, the results of the two sets of analyses confirmed each other. The use of these oligonucleotides in the sequence determination of Qbeta RNA is discussed.


A hybridization procedure for the isolation of specific RNA segments applied to the analysis of bacteriophage Qbeta RNA. A method for the isolation of RNA fragments originating from defined regions of bacteriophage Qbeta RNA minus strands is described. Large RNase T1 oligonucleotides were isolated on a preparative scale from Qbeta RNA. The nucleotide sequences (13 to 26 nucleotides) and map positions of these oligonucleotides were known from previous work (Billeter, M. A. (1978) J. Biol. Chem. 253, 8381-8389). After addition of AMP residues (50 in the average) using terminal adenylate transferase, these pure oligonucleotides were hybridized to 32P-labeled Qbeta RNA minus strands synthesized in vitro. Fragments in the size range of 100 to 500 nucleotides were then generated by partial digestion with RNase T1. Fragments hybridized to such oligonucleotides were recovered by chromatography on poly(U)-Sephadex and then resolved according to their size by polyacrylamide gel electrophoresis. The specificity and reproducibility of the method as well as its suitability for the sequence analysis of Qbeta RNA was verified by using in particular a linker oligonucleotide derived from a Qbeta RNA region near the 3' end. The sequence catalogues of the RNase T1 and RNase A oligonucleotides of two fragments isolated in this way, 202 and 310 nucleotides in length, were established and all fragments isolated were shown to contain a sequence complementary to the linker oligonucleotide.


Reaction of the microsomal heme oxygenase with cobaltic protoporphyrin IX, and extremely poor substrate. A reconstituted heme oxygenase system which was  composed of a purified heme oxygenase from pig spleen microsomes and a partially purified NADPH-cytochrome c reductase from pig liver microsomes could not catalyze the conversion of cobaltic protoporphyrin IX (Co-heme) to biliverdin, although Co-heme could bind with the heme oxygenase protein to form a complex. The heme oxygenase system in the microsomes from pig spleen, rat spleen, and rat kidney also failed to oxidize Co-heme to biliverdin. Properties of the complex of Co-heme and heme oxygenase closely resembled those of cobalt myoglobin and cobalt hemoglobin; the Co-heme bound to the heme oxygenase protein did not react with cyanide and azide, the Co-heme moiety was reduced but only slowly with sodium dithionite, and the reduced form of the Co-heme did not appear to bind carbon monoxide. The co-heme bound to heme oxygenase was not reduced with the NADPH-cytochrome c reductase system in air. These findings further support the views that heme oxygenase may have a heme-binding crevice similar to those of myoglobin and hemoglobin and that reduction of heme is the prerequisite for the oxidative degradation of heme in the heme oxygenase reaction.


Bacillus subtilis bacteriophage PBS2-induced DNA polymerase. Its purification and assay characteristics. The DNA polymerase induced by Bacillus subtilis bacteriophage PBS2 (whose DNA contains uracil instead of thymine) has been purified and characterized for its specificity. The enzyme requires a high ionic strength for optimal stability and activity and is sensitive to various anions and to sulfhdryl reagents. Both dUTP and dTTP are incorporated efficiently as substrates and are competitive inhibitors at the same active site. The apparent Km and Ki values are about 6 micrometers for dTTP and 15 micrometers for dUTP, when denatured, uracil-containing B. subtilis or salmon sperm DNA (3.9 micrometers for dUTP and 2.6 micrometers for dTTP). The PBS2 enzyme works best on denatured DNA, on double-stranded DNA activated by DNase to produce gaps, or on primed homopolymeric DNA. Using denatured DNA preparations of average molecular weight 6.2 million, the apparent Km values are 270 micrograms/ml for B. subtilis DNA and 360 micrograms/ml for PBS2 DNA; the Vmax value for denatured PBS2 DNA containing uracil is 7-fold greater than that for denatured B. subtilis DNA containing thymine. However, lower molecular weight DNAs have 10-fold lower apparent Km values and show similar Vmax values for both B. subtilis and PBS2 DNAs. Thus, the PBS2 phage-induced DNA polymerase (which likely replicates only uracil-containing phage DNA using dUTP in vivo) has little selectivity for uracil- versus thymine-containing deoxyribonucleotides or DNA in vitro.


Purification and properties of a Bacillus subtilis endonuclease specific for apurinic sites in DNA. An endonuclease which hydrolyzes depurinated DNA has been purified from extracts of Bacillus subtilis cells. The endonuclease is a monomeric protein and has a molecular weight of around 56,000. The enzyme is specific for apurinic sites in double-stranded DNA, has a pH optimum at 8.0, and is slightly stimulated with 50 mM NaCl but completely inhibited with 500 mM NaCl. It requires no divalent cations and is insensitive to EDTA; it has no associated exonuclease. These properties are very similar to those of Escherichia coli endonuclease IV, which is also insensitive to EDTA and has no exonuclease activity, and very different from those of the main endonuclease for apurinic sites (endonuclease IV) of the same bacterium.


Isolation and characterization of a high molecular weight glycoprotein from human blood platelets. A high molecular weight glycoprotein consisting of three disulfide-linked 142,000 molecular weight chains has been isolated from human blood platelets. The glycoprotein, designated thrombospondin, is released by platelets in response to thrombin treatment and is proteolyzed when left in the presence of platelets after liberation. It is relatively insensitive to degradation by thrombin. Thrombospondin is a filamentous protein of dimensions approximately 7 X 70 nm and contains 1.9% neutral sugars, 1.4% amino sugars, 0.7% sialic acid, and no hexuronic acid. Amino acid analysis reveals that the level of cysteine is approximately 260 residues per molecule. Thrombospondin binds to immobilized heparin but is released by 0.45 M sodium chloride. A single band is obtained by isoelectric focusing, indicating a pI of 4.7 as well as a relatively high degree of purity. Degradation of the intact molecule with trypsin yields a stable core particle of molecular weight 210,000 comprised of three 70,000 chains.


Isolation of Staphylococcus aureus from sputum in cystic fibrosis. The success in the isolation of Staphylococcus aureus of different methods of sputum processing was investigated in 60 specimens collected from 14 patients with cystic fibrosis during a seven-month period. Fifty specimens (83%) from 11 patients yielded Staph. aureus by one or more methods. Direct plating of purulent portions of sputum on to media designed for general use in respiratory infections gave unsatisfactory results (35% yield of Staph. aureus). Some increase in isolations was obtained with preliminary liquefaction of sputum; but the best results were given by the addition of a medium selective for staphylococci (mannitol salt agar, BBL) or by initial sonication of sputum (each 83% yield). Seven of the 11 strains of Staph. aureus were thymidine-dependent and otherwise atypical in laboratory characteristics; these were isolated from patients who had received co-trimoxazole.


A test for 'hygienic' hand disinfection. A standardised test procedure is described in which finger-tips are inoculated with broth cultures of organisms (Staphylococcus aureus, Staphyloccocus saprophyticus, Escherichia coli, and Pseudomonas aeruginosa): counts are made from washings of hands after disinfection with various antiseptic-detergents, alcoholic solutions, or unmedicated soap. 70% alcohol, with or without chlorhexidine, was the most effective preparation. The two antiseptic detergents showed variable results, but against Gram-negative bacilli neither was significantly more effective than plain soap. Some tests were also made on the death rate of organisms dried on the skin without disinfection.


A simple manganous chloride and Congo red disc method for differentiating Neisseria gonorrhoeae from Neisseria meningitidis. Manganous chloride and Congo red incorporated into blotting paper discs have been used to differentiate gonococci from meningococci. The new technique is simple and reliable; the materials for the test are inexpensive. The method will increase the efficiency of distinguishing between the pathogenic Neisseria in any clinical bacteriology laboratory and especially in those in the tropical areas.


Astrovirus-associated gastroenteritis in children. In a small astrovirus-associated outbreak of gastroenteritis in a ward of a local children's hospital two out of five children with symptoms excreted astrovirus particles. No astrovirus particles were found in faeces from the remaining asymptomatic child, and no other viral or bacterial pathogens were found in any of the children. Virus excretion persisted for only a few days. Rising antibody titres to the astrovirus particles were demonstrated in one child, and IgM was also demonstrated in this patient's serum.


Design considerations for a positron emission transverse tomograph (PETT V) for imaging of the brain. Imaging of the brain by positron emission tomography can be optimized for sensitivity by dedicating the design of the tomograph to this application. We have designed a multislice positron emission tomograph (PETT V) for imaging the human brain and the whole body of small experimental animals. The detector system of PETT V consists of a circular array of 48 NaI(Tl) scintillation detectors, each fitted with two photomultiplier tubes, with one dimensional positioning capability. Suitable sampling is achieved by rotation of the circular array of detectors and by a wobbling motion of the detector circle. The proposed system is capable of providing seven slices simultaneously, with a spatial resolution in the plane of the slice from 7 to 15 mm and with slice thicknesses of 7 and 14 mm. The minimum scanning time is 1 sec. The estimated overall sensitivity of PETT V is 350,000 counts/sec/mCi in a 20 cm diameter phantom for a resolution of approximately 1.5 x 1.5 cm. The system is under construction.


Peptide hydrolases of Lactobacillus casei: isolation and general properties of various peptidase activities. Discovery of an endopeptidase by gel chromatography and separation of 3 exopeptidases (a dipeptidase, an aminopeptidase and a specific carboxypeptidase) from Lactobacillus casei NCDO 151 by affinity chromatography is described. The 3 exopeptidases were strongly inhibited by the metal chelators EDTA and 1,10-phenanthroline but were reactivated with Co2+ and Mn2+. The pH optima for aminopeptidase, dipeptidase and carboxypeptidase activities were 6.5, 7.6 and 7.2, respectively. Maximum activity was obtained at 45 degrees C for the aminopeptidase, at 30 degrees C for the dipeptidase and at 40 degrees C for the carboxypeptidase. The substrate specificities of the 3 enzymes were also studied. The properties of these 3 enzymes are compared with those of other bacteria.


Influence of heat treatment on antigenicity of bovine serum albumin in milk and model systems. Electroimmunodiffusion on a cellulose acetate support medium was used to study the effect of heat treatment on the antigenic activity of bovine serum albumin suspended in water, simulated milk ultrafiltrate (J & K buffer), or saline (.85%) and of bovine serum albumin in milk per se. Heat treatments were at 70, 73, and 75 C for 0 to 30 min. The suspending medium influenced the loss of antigenicity of bovine serum albumin upon heat treatment. The loss in increasing order was J & K buffer, saline, and water. In milk, the loss of antigenicity of bovine serum albumin was 70 C for 30 min, none; 73 C for 30 min, 24.6%; and 75 C for 20 min, almost complete with no characteristic cone formation upon electroimmunodiffusion.


Incorporation of amino acids by isolated submitochondrial fractions of lactating goat mammary gland in vitro. Incorporation of amino acids by mitochondria and its subfractions from mammary gland of the goat during lactation was studied in vitro. Assessment of distribution of radioactivity incorporated by intact mitochondria into its subfractions revealed maximum specific activity in the inner membrane. During lactation the inner membrane of mitochondria exhibited further stimulation in such incorporation. Matrix was the next active fraction whereas outer membrane and peripheral space had negligible radioactivity. In isolated submitochondrial fractions from mammary gland incubated with radioactive amino acids under similar conditions of assay, the inner membrane was the most potent subfraction in incorporation. In mammary tissue during lactation this fraction was the most active site. The relative sequence of the subfractions appeared to remain unaltered in lactation and was in the order of inner membrane greater than matrix greater than outer membrane greater than peripheral space. The ratio of specific activity in inner to outer membrane appears to increase significantly during lactation.


Immunotherapy of chemically-induced tumors in the hamster cheek pouch with dinitrochlorobenzene. Immune stimulation with an agent such as dinitrochlorobenzene (DNCB) may delay chemical carcinogenesis. Dimethylbenzanthracene (DMBA) was used to chemically induce tumors in the hamster buccal pouch. Hamsters were studied for the effect of DNCB sensitization in the buccal pouch prior to or after DMBA tumor induction. At appropriate time intervals the hamsters were sacrificed and each cheek pouch was examined histologically for the development of DMBA-induced tumors and for the presence of lymphoid cells infiltrating the tumor site. The results show that DNCB immunotherapy or immunoprophylaxis prior to or following DMBA tumor induction can alter the type of tumor produced and stimulate an infiltration of lymphoid cells into the tumor area probably invoking immune defense mechanisms.


The determination of antibody to Streptococcus mutans serotypes in saliva for children ages 3 to 7 years. The saliva of 29 children ages 3 to 7 years was followed by indirect immunoflourescence to determine the antibody reacting with the 5 different serotypes of S mutans. Fluorescent antisera specific for alpha chain and gamma chain were used. Statistical analysis of the data demonstrated a significant negative correlation between antibody of immunoglobin class (IgA) to S mutans type b and the decayed, extracted and filled surfaces of deciduous teeth.


Replantation of mature teeth without endodontics in monkeys. The purpose of this study was to evaluate the histologic response after replantation of mature, developed teeth without endodontic treatment in monkeys. To serve as experimental controls, the other replanted teeth received endodontic treatment. No significant differences were noted in the rate and quality of periodontal tissues healing between the endodontically and the nonendodontically treated teeth in monkeys sacrificed at 5, 7, and 14 days, and at 1, 2, and 3 months after replantation. However, specimens obtained at 4, 6, 9, and 12 months showed that teeth replanted without endodontics developed periapical complications, whereas endodontically treated teeth did not.


Choice of screening tests.

Choice of screening tests. In this paper, we consider one of the decisions that have to be made about a screening programme: which type of test to use. Our study shows that knowledge of the sensitivities, specificities, and costs of alternative tests is an inadequate basis for the choice of test. The monetary values of the different possible results of the test must also be estimated, or judgements made about the likely magnitude of these values. If judgements have to be made, they should be explicit, because different individuals are likely to judge differently, and their opinions will critically affect the choice of test.


Screening for mild hypertension: costs and benefits. It is important to understand the full implications of introducing a new screening and treatment programme into the National Health Service. In this paper, we calculate, for mild hypertension, the cost of community-based screening and the cost of case-finding in general practice. We show that case-finding in general practice is both less expensive and more efficient. We calculate the cost of running a programme in general practice for five years and divide that cost by an estimate of the number of deaths that might be prevented as a result of introducing such a programme. This calculation give a minimum cost for extending a life by the programme.


Admission and adjustment of residents in homes for the elderly. This paper discusses the relationship between psychological variables, a brief cognitive measure and a behavioural rating scale, and the subsequent adjustment of a group of elderly people newly admitted to a social services home for the elderly. It shows that, in this sample, three groups can be identified: a fairly independent group of people who show no apparent deterioration in functioning during the first year of admission; a more dependent group who show loss of functioning during the same period; and a third group who show an immediate negative effect from admission, and who have a poor outcome. We comment on the lack of evidence in support of a general negative relocation effect, and on the value of the procedures used.


Some observations on cochlear mechanics. A set of experiments was conducted using the Mössbauer effect to determine the vibratory characteristics of the basilar membrane, Reissner's membrane, the malleus, incus, and oval window in squirrel monkey. A few measurements were also made in guinea pig in the basal cochlear region. The nonlinear vibration properties of the basilar membrane are described in detail for the midfrequency region in the squirrel monkey. Only in this region have nonlinear effects been observed. A comparison of mechanical and neural data indicates good qualitative agreement.


Squirrel monkey temporary threshold shift from 48-h exposures to low-frequency noise. Five squirrel monkeys were exposed for 1, 2, 4, 8, 16, 24, and 48 h to a 375--750-Hz band noise at an overall SPL of 95 dB. The TTS4.5 growth pattern for the 750-Hz test frequency was biphasic and did not reach an asymptote after 48 h of exposure. For all exposures, the mean thresholds of the five monkeys returned to within 5 dB of the preexposure mean 20 h after exposure. Recovery curves from all exposures at the 750-Hz test frequency appeared biphasic. Increasing SPL from 95 to 105 dB increased TTS4.5 by 4 dB at 750 Hz for a 1-h exposure. Recovery from the  105-dB exposure followed the same pattern as recovery from the 95-DB exposure. When compared with data collected from human subjects under similar conditions, these experiments indicate that the growth and recovery of TTS in squirrel monkeys are sufficiently similar to growth and recovery in man to justify further comparative investigation.


A study of the effect of slow-reacting substances of anaphylaxis on the rhesus monkey airway. Slow-reacting substance of anaphylaxis (SRS-A) generated from rat peritoneal mast cells was aerosolized to the airways of a group of rhesus monkeys with established airway responses to ascaris antigen. A selective effect of SRS-A on pulmonary resistance and a lesser but significant effect on compliance was observed which differed from antigen, histamine, carbocholine, or prostaglandin (PG) F2alpha responses. The airway recovery from the PR change is slower than that from histamine and simulated PGF2alpha and some antigen experiments. The cutaneous reactions in rhesus monkeys due to SRS-A could be blocked in a dose response pattern by FPL55712 which did not affect histamine responses in rhesus skin.


Review of laxative utilization in a skilled nursing facility. Laxatives are the most frequently prescribed drugs in long-term care facilities. Of all nursing home patients, 58 percent receive laxatives--often more than one, and usually on a "prn" basis. This pattern of dosage is probably used in an effort to prevent constipation. Selection of a laxative should be based on careful evaluation of the cause of constipation, with due consideration being given to differences in drug effectiveness and the incidence of side effects. A review of laxative utilization among 73 elderly patients in a large metropolitan skilled nursing facility showed a rational use of these drugs. However, more attention should have been paid to the dietary management of constipation.


Macrophage sensitivity to endotoxin: genetic control by a single codominant gene. The effects of LPS on macrophages in vitro have been examined. LPS triggers macrophages to produce LAF and PGE2 in vitro. LPS is also cytotoxic for macrophages derived from LPS-sensitive mice and will significantly inhibit their phagocytic ability. Both LAF production and cytotoxicity are due to the direct effects of LPS on the macrophage and do not require the particpation of lymphocytes. Each of these functions is abnormal in C3H/HeJ mice. The nature of the gene(s) controlling these macrophage responses to LPS has been determined. The response of (C3H/HeJ X C3H/HeN)F1 macrophages was intermediate when compared to the parental responses and no sex linkage was found. Backcross linkage analysis suggested that the same autosomal codominant gene controls both macrophage and B lymphocyte-LPS sensitivity.


Localization of hepatitis A antigen in liver tissue by peroxidase-conjugated antibody method: light and electron microscopic studies. Hepatitis A antigen (HAAG) was localized in liver tissue from marmosets inoculated with human hepatitis A virus (HAV) by light and electron microscopy by using a peroxidase-conjugated antibody method. The fine granular peroxidase staining was scattered throughout the cytoplasm of liver cells when viewed with the light microscope. The distribution of HAAg-positive cells was focal. Virus-like particles, 24 to 27 nm in diameter, were observed in the cytoplasm of hepatocytes and smaller cells, resembling Kupffer cells, by standard thin-section electron microscopy (thin section EM). By immunoperoxidase electron microscopy (immunoperoxidase EM), HAAg was detected on the particles, which were aggregated within cytoplasmic vesicles of the hepatocyte. The surrounding membrane of the vesicles was also HAAg- positive. Similar HAAg particles were observed in the cytoplasm of smaller cells adjacent to hepatocytes as well. Thus, immunoperoxidase EM revealed that the 24- to 27-nm virus-like particles in the cytoplasm of liver cells obtained from marmosets were infected with HAV contained HAAg.


Regulation of immunoglobulin biosynthesis in the murine plasmacytoma MOPC 315. We have examined certain aspects of IgG biosynthesis by constructing hybrids between MPC11 (gamma2b, kappa) and MOPC 315 (alpha,lambda2) that have lost the ability to synthesize one or the other heavy chain. Cells express the three chains in a stable fashion, and both autologous (parental) and heterologous (nonparental) H and L chain pairs form and are secreted. The alpha H chain was found in polymeric form when associated with the heterologous kappa L chain. The lambda2 L chain covalently assembled to the heterologous gamma2b H chain. Surprisingly, autologous pairing was always favored over heterologous pairing in vivo by 5 to 10:1 in terms of rate of assembly. Similar ratios were maintained in the secreted protein. These results suggest that co-expression of particular H and L chain pairs is predetermined. Evolution presumably operates to improve antigen recognition as well as rate of assembly of active molecules.


Preparation of an alloantiserum to murine C3 and demonstration of multiple alleles. An antiserum was produced in C3H/He mice that can recognize the antigenic variations of murine C3. The alloantiserum is directed to the gene product of one of the alleles (C3-1a allele) of the C3-1 locus that controls genetic variations of murine C3 and is linked to H-2. The antiserum formed a single precipitin line in the Ouchterlony test with sera obtained from mice that carry the C3-1a/a or C3-1a/b genotype, but it did not react with sera from mice that do not have C3 coded for by the C3-1a allele. By the use of the alloantiserum, we detected a new C3 allotype (C3-1 CC) in SWR/J mice. The C3-1 CC is distinct from the other two allotypes on the basis of antigenicity and isoelectric point (pI). Therefore, at least three alleles have been identified for the C3-1 locus.


Pelage color cycles and hair follicle tyrosinase activity in the Siberian hamster. Hair follicle tyrosinase levels and melanin content, together with serum tyrosine levels have been studied in relation to annual pelage color changes in the Siberian hamster. Tyrosinase levels were found to peak not only at the spring moult when pigmented hair is produced but also at the autumn moult when the hair produced is unpigmented. The melanin content of hair follicles was high in summer and low in winter but serum tyrosine levels did not differ at the spring and autumn moults. These results suggest that some factor must exist to prevent the raised tyrosinase levels of the autumn moult being expressed as melanogenesis and that this factor must be photoperiodically modifiable, being controlled through a neuroendocrine mechanism.


Demonstration of fibronectin in human cerebrospinal fluid. Fibronectin is a glycoprotein found in plasma (cold-insoluble globulin), connective tissues, and cultures of fibroblasts and astroglial cells. This paper describes the identification of fibronectin in human CSF. Fibronectin in CSF was immunologically indistinguishable from the plasma form, as shown by double-diffusion analysis and by radioimmunoassay specific for fibronectin. Fibronectin was isolated from human CSF by affinity chromatography on Sepharose-coupled gelatin and was further analyzed by SDS-polyacrylamide gel electrophoresis. It showed a polypeptide band similar to that of plasma fibronectin. The fibronectin concentration in CSF of 17 neurological outpatients without demonstrable organic lesion in the CNS was 3.0 +/- 1.6 microgram/ml (mean +/- S.D.) which is about 0.6% of total CSF protein. In CSF of 11 MS patients, the concentration was significantly (p less than 0.005) lower (1.6 +/- 0.2 microgram/ml). Of patients with brain tumors, seven had very low levels, three were normal, and two had very high levels. The cause for the low levels in MS and tumor patients is not known.


Specific change in the direction of prostaglandin synthesis by intra-uterine tissues of the rhesus monkey (Macaca mulatta) during late pregnancy. The rates of production of prostaglandin E (PGE), prostaglandin F (PGF) and 13, 14-dihydro-15-oxo-prostaglandin F (PGFM) by intra-uterine tissues from pregnant monkeys in vitro have been determined using a method of tissue superfusion. The amnion, chorion, placenta, decidua basalis, decidua parietalis and myometrium were obtained at Caesarean section during late pregnancy. Production of PGE by all tissues was significantly lower at term than during late pregnancy, whereas production of PGF by the amnion, chorion, decidua parietalis and myometrium was significantly greater. All tissues produced significantly more PGE than PGF and also, excepting the decidua basalis and decidua parietalis, more PGFM than PGF. Close to parturition the amnion was quantitatively (per unit weight) the major source of prostaglandins. It is suggested that a specific change in the direction of prostaglandin synthesis by intra-uterine tissues occurs near parturition in the rhesus monkey.


Concentrations of oestradiol-17beta and progesterone in the peripheral plasma of the cynomolgus monkey (Macaca fascicularis) in relation to the length of the menstrual cycle and its component phases. Ninety-three female cynomolgus monkeys were monitored throughout 647 menstrual cycles; 93.2% of these cycles were 22--37 days long and were normally distributed, with a mean of 29.2 days. Menstrual bleeding generally lasted for 3--5 days and was not related to the length of the cycle. The levels of progesterone and oestradiol-17beta in the plasma were measured during the menstrual cycle in 30 monkeys. The concentration of oestradiol-17beta reached a mid-cycle peak on day 11 or 12 of the cycle. The interval between the beginning of the cycle and the oestrogen peak was constant; the interval between the oestrogen peak and the end of the cycle increased or decreased with the cycle length. The level of progesterone began to rise at about the time of the oestrogen peak and remained raised for longer periods as the length of the cycle increased. The length of the menstrual cycle, therefore, appeared to be determined by the duration of the increase in the level of progesterone or by the life of the corpus luteum in the luteal phase. The relationship between the lengths of the cycle and the luteal phase can be defined by the expression: cycle length = 12.6 + 0.96 X length of luteal phase (correlation coefficient = 0.875).


Production of thromboxane B2 by the intra-uterine tissues from late pregnant Rhesus monkeys (Macaca mulatta) in vitro. The rates of production of thromboxane B2 in vitro by intra-uterine tissues obtained from late pregnant monkeys by Caesarean section have been determined. The general quantitative order of rates of production was decidua basalis = decidua parietalis greater than placenta greater than chorion greater than amnion = myometrium. Myometrial production of thromboxane B2 was greater at term than during late pregnancy; no other tissue showed a significant trend with advancing gestation. These data demonstrate that the production of thromboxane B2 by intra-uterine tissues from late pregnant monkeys is both qualitatively and quantitatively different from the production of prostaglandins described previously. It is suggested that prostaglandins rather than thromboxanes are more intimately involved in the onset of labour in the rhesus monkey.


Genetic control of enzyme expression in Drosophila: a locus influencing tissue specificity of aldehyde oxidase. A natural genetic variant in Drosophila melanogaster with a highly tissue specific effect on the level of an enzyme (aldehyde oxidase) is described. This variant causes overproduction of the enzyme by a factor of 2- to 3-fold in paragonia (male accessory sex glands) while having no significant effect on the enzyme level in other tissues. This difference is controlled by a single genetic element in the vicinity of the aldehyde oxidase structural gene that operates in a strictly cis-active mode. It is not associated with any change in enzyme primary structure detectable by a variety of physical, chemical and immunochemical tests. The most likely explanation for all of these observations is that the variant defines a cis-active regulatory element adjacent to the structural site.


[Lesion of the lateral dorsal thalamic nucleus and alcoholic Korsakoff syndrome]. The authors report a clinico-pathological study dealing with the limbic nuclei of the thalamus in 11 cases of Korsakoff syndrome of alcoholic aetiology. There is no parallelism between the involvement of the latero-dorsal nucleus (L.D.), the medio-dorsal nucleus, the pulvinar and the importance of the retrograde amnesia. The mamillary bodies are always affected. The latero-dorsal nucleus was modified in 9 cases out of 11, the medio-dorsal in 7 cases and the pulvinar in 6 cases. In contrast, the anterior nucleus is normal. The frequency of the involvement of the L.D. is an argument to relate this nucleus with the limbic system. But the lesion of this nucleus is inconstant whereas that of the mamillary bodies is always observed.


Anti-riboflavin activity of 8N-alkyl analogues of roseoflavin in some Gram-positive bacteria. Three new 8N-alkyl analogues of roseoflavin (MM), i.e., 8-ethylamino- (EH), 8-methylethylamino- (ME), 8-diethylamino-8-demethyl-D-riboflavin (EE), their tetraacetates, and 8-amino-8-demethyl-D-riboflavin (HH) tetraacetate, were synthesized. A relation between the anti-riboflavin activity and the chemical structure of 8N-alkyl analogues (8N-methyl, ethyl) was studied by a restoration by riboflavin (RF) of inhibitory effect of the analogues on a growth of Gram-positive bacteria, i.e., Sarcina lutea, Bacillus cereus, and Staphylococcus aureus. The inhibitory effect of most of the analogues was restored by RF. But in some cases, i.e., 8-methylamino-8-demethyl-D-riboflavin (MH) in Sar. lutea and MM in Staph. aureus, the effect was not completely restored. Apparently, the inhibition in early phase of growth was restored, but the maximum growth was still suppressed. The non-alkylated amino analogue (HH) showed only unrestorable suppression of maximum growth in Sar. lutea. Of restorable effect by RF of N-alkyl analogues, approximate decreasing orders of anti-RF activity were as follows. Dialkylated analogue greater than monoalkylated. HH showed insignificant anti-RF activity. In each group, methylated analogue greater than ethylated. In B. cereus monoalkylated analogues, and in Staph. aureus monoalkylated and EE showed no significant inhibitory effect. Redox potentials of the N-alkyl analogues were measured, and a definite relation between the chemical structure and the potential was found (RF = EE greater than ME greater than MM greater than HH greater than EH greater than MH). But the anti-RF activity of the analogues was not completely explained by the difference of the redox potential from RF.


Trauma from occlusion in monkeys.

Trauma from occlusion in monkeys. Traumatic occlusion was induced in monkeys by insertion of bridges raising the bite. Both incisors and molars were used as abutments. Observation periods ranged from 7 to 24 months. No appreciable effect of the trauma on the apical proliferation of the crevicular epithelium was found. The results were the same in monkeys with or without marginal gingival inflammation before the trauma was induced.


Behavioral and dermatologic changes and low serum zinc and copper concentrations in two premature infants after parenteral alimentation. Two premature infants were observed to develop behavioral and dermatologic changes and low serum zinc and copper concentrations following cessation of prolonged parenteral alimentation, while being fed exclusively with human milk. Following treatment with exogenous oral zinc supplementation, prompt relief of symptoms and increases of serum zinc and copper concentrations were observed in both infants. These patients comprise about 5% of our premature infants who are treated with parenteral alimentation for more than two weeks. We recommend that premature infants on prolonged parenteral alimentation should be monitored for changes in serum zinc and copper concentrations and, if a marked fall is observed, supplementation should be considered.


Neutropenia associated with chrysotherapy for juvenile rheumatoid arthritis. Severe neutropenia, in the absence of generalized bone marrow depression, is a rare complication in adults receiving chrysotherapy for rheumatoid arthritis and has not been described in children. Isolated, severe neutropenia developed in five children with systemic onset JRA while they were receiving gold injections. This potentially fatal complication occurred within eight weeks of beginning therapy in four patients, and after 24 weeks of well-tolerated therapy in the fifth. Leukopenia preceded neutropenia in two children. Localized infection was successfully treated in one child; septicemia was fatal to a second child. Neutropenia resolved within eight to 14 days of its onset in the four survivors; chelation with dimercaprol in one child did not appear to alter the recovery time. It is suggested that a systemic onset of JRA in children less than 6 years of age identifies a higher risk group developing severe neutropenia during chrysotherapy. Cessation of gold therapy upon recognition of a decreasing neutrophil count may prevent or ameliorate a developing neutropenia; careful observation for, and early treatment of, infection may alter its outcome.


Effects of some psychotropic drugs on M-wave and operant behavior in the squirrel monkey. The effects of low doses of nabilone, chlorpromazine, pentobarbital, meprobamate, diazepam, chlordiazepoxiOde and d-amphetamine on behavioral responding to cues signalling the availability of food rewards, and on the M-wave, an evoked cortical potential previously reported to reflect the conditioned incentive value of the cues were determined in the squirrel monkey. Nabilone and chlorpromazine simultaneously depressed both the M-wave and behavior. Pentobarbital, meprobamate, diazepam and chlordiazepoxide could depress the M-wave without depressing behavior. This effect was most marked with diazepam. The only augmentation of the M-wave observed was the d-amphetamine, and this occurred in only one of five animals. The benzodiazepines were the only drugs to augment behavioral output. However, diazepam occasionally increased the number of cures responded to while concomitantly decreasing both total behavioral output and the amplitude of the M-wave. It is concluded that the M-wave cannot directly reflect the incentive value of the cue, but must rather reflect something that tends to parallel this value.


Selective modification of the renal and the hepatic toxicities of chloroform by induction of drug-metabolizing enzyme systems in kidney and liver. Renal and hepatic microsomal enzyme activities were measured in ICR male mice treated with phenobarbital (PB), 3-methylcholanthrene (3MC), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or polychlorinated biphenyls (PCB). The effect of these agents on subsequently administered single doses of chloroform (CHCI3) were also determined. 3MC, TCDD and PCB increased renal as well as hepatic microsomal enzyme activities. PB increased hepatic but not renal microsomal enzyme activities. The hepatotoxicity of CHCI3 was increased by pretreatment with PB but decreased by pretreatment with TCDD. 3MC and PCB were without effect on CHCI3-induced liver damage. Pretreatment with 3MC, TCDD or PCB reduced the renal toxicity of CHCI3, but PB had no effect on CHCI3-induced kidney damage. Since at least one product of enzymatic metabolism of CHCI3 is believed to be a toxic, reactive intermediate the differential effects of inducers of microsomal drug-metabolizing enzyme activities on the renal and hepatic toxicities of CHCI3 strongly suggest that the CHCI3 metabolite(s) ultimately responsible for renal and hepatic damage are not generated at a common site. That is the metabolite responsible for hepatic is probably generated in the liver and the metabolite responsible for renal damage is probably generated in the kidney.


Influences of season and age on maturation in vitro of rhesus monkey oocytes. Oocytes obtained from antral follicles of adult and adolescent rhesus monkeys during the annual breeding season extruded polar bodies in vitro at significantly higher rates (50--60%) than oocytes from animals of similar age during the non-breeding season ((20--30%) or from infant and prepubertal females at any time of the year (20--30%). The proportion of oocytes degenerating in culture was greatest in groups where maturation was highest.


Inhibition of human seminal fluid DNA polymerase by an IgG fraction of seminal plasma from vasectomized men. Immunoglobulin G (IgG) was isolated from ejaculates of intact and vasectomized men by precipitation with ammonium sulphate and DEAE-cellulose ionexchange chromatography. Velocity centrifugation revealed that all of the IgG from intact males was 7S protein while less than 40% of the seminal IgG of vasectomized men cosedimented with the 7S marker; the remaining, immunologically unidentifiable, protein was considerably smaller and heterogeneous in size. Only the 7S IgG from the post-vasectomy ejaculates inhibited the activity of a DNA polymerase from the seminal fluid of an intact male. These results suggest that formation of antibody reactive with the seminal fluid DNA polymerase is one manifestation of a vasectomy-associated autoimmune response in man.


[Ossification of the transverse ligament. Two observations (author's transl)]. The first two cases of ossification of the transverse ligament are reported. This abnormality is rare, but it is important to know of its existence to avoid confusion with lesions of the posterior surface of the tooth of the axis.


Unilateral forelimb deafferentation in the monkey: purposive movement. Monkeys with unilateral dorsal rhizotomy C2-T3 used their denervated limbs to retrieve unseen food pellets when movements of the intact contralateral limb were rendered ineffective by enclosure of the hand within a container. Even after protracted use in this condition, however, the deafferented limb ceased to be used in the test situation when the intact arm was released. These findings cast doubt on interpretations of lack of use of a unilaterally dorsal rhizotomized limb as being due to cross-spinal inhibition or to learned disuse.


Transmission of hepatitis B to the rhesus monkey. Studies on the humoral and cell-mediated immune response. The susceptibility of the rhesus monkey (Macaca mulatta) to hepatitis B virus was enhanced by the induction of chronic infection with Plasmodium inuei.


Chromosome banding patterns and nucleolar organizing regions in three species of Callithricidae (Saguinus oedipus, Saguinus fuscicollis, and Callithrix jacchus). Chromosome complements of three species of Callithricidae, Saguinus oedipus, Saguinus fuscicollis and Callithrix jacchus, were analyzed by various banding techniques. Morphometric data are presented. A diploid chromosome number of 2n = 46 is reconfirmed for all three species. Several interesting interspecies chromosomal variations were demonstrated by G- and C-band patterns. Active nucleolar organizing regions (NORs) were revealed by the Ag-AS silver histochemical stain.


Perception of sounds used in species-specific communication: the auditory cortex and beyond. The auditory cortex, located in the superior temporal gyrus, has been studied in squirrel monkeys with respect to its role in detecting species-specific vocalizations. Single neurons tested with selected vocalizations from the species' repertoire have been grouped into seven functional categories. Each category reflects a different level of processing with regard to vocalizations and artificial sounds. It is argued that, while the auditory cortex has the capability to detect and distinguish species-specific vocalizations, the interpretation of their biological significance likely takes place elsewhere.


Possible errors in identification of squirrel monkeys (Saimiri sciureus) from different South American points of export. We conducted karyological studies on one colony consisting of 12 Colombian and 34 Bolivian squirrel monkeys and a second colony of 47 monkeys imported into the United States between 1968 and 1974 through six importers. All animals in the first colony showed six acrocentric pairs of chromosomes. Bolivian monkeys were phenotypically distinguishable by their large size and coloration. In the second colony, 19 Peruvian, seven Colombian, five Bolivian and six Guyanan monkeys were correctly identified phenotypically and had five, six, six, and seven acrocentric pairs of chromosomes, respectively. Among Peruvian monkeys, 34.5% of the phenotypic classifications were in error.


Blood groups of macaques:a comparative study. Distribution of the human-type and of the simian-type blood groups in rhesus, crab-eating, bonnet, pig-tailed and stump-tailed macaques revealed significant similarities and differences among these species. Human-type A--B-O blood groups cut across taxonomic lines and seem less value for taxonomic purposes than the simian-type blood groups detected by cross-reacting isoimmune rhesus monkey sera.


Banding patterns of the chromosomes of two new karyotypes of the owl monkey, Aotus, captured in Panama. Two new chromosome complements of Aotus trivirgatus griseimembra are described making a total of five different karyotypes observed in this subspecies inhabiting Panama and the northwestern part of Colombia, South America. Detailed comparisons of the G-banded chromosomes of these five karyotypes suggest that the polymorphism of chromosome numbers 56 and 55 in Panamanian Aotus and 54, 53, and 52 in Colombian Aotus stems primarily from a Robertsonian translocation mechanism involving pairs B13 and B14 (or A1). A second Robertsonian translocation mechanism involving pairs B28 and B29 (or A2) constitutes the karyotypic differences between the two chromosomal races.


Growth and hematologic development of the patas monkey (Erythrocebus patas) to one year of age. Data from 338 blood samples of 31 patas monkeys is presented to show the normal hematolgoic development from birth to one year of age, and is compared to 120 samples from normal adults. Marked changes in hematocrit, hemoglobin, red cell numbers, and leukocyte distribution which occurred during the first month were followed by a slow progression to adult values. Body weight  data is also presented which shows a linear growth rate during the first year of life.


The course of development of glucose intolerance in the monkey (Macaca mulatta). Longitudinal studies of the rhesus monkey reveal a syndrome of diabetes mellitus in those that become middle-aged and obese. The sequence of events in the development of the disease progresses from normoinsulinemia with normoglycemia through stages of hyperinsulinemia followed by below normal insulin levels with hyperglycemia and glycosuria. We believe the rhesus to be an excellent nonhuman primate model for maturity-onset diabetes in humans.


An antigen resembling HL-A7 on the leukocytes of vervet monkeys. Human leukocyte typing sera of known specificities were used to test the leukocyte antigens of vervet monkeys. The results suggest that these leukocytes contained an antigen resembling the HL-A7 antigen of human leukocytes. This is similar to a previous observation with leukocytes from baboons. These findings are consistent with the suggestion that the 4a/4b complex is the precursor substance from which the other specificities have evolved.


Reduction of respiratory tract binding of benzo[a]pyrene in mice by immunization. Male inbred A/J mice immunized by combined ip and intranasal administration of a bovine serum albumin conjugate of 5-fluoro-12-methylbenzanthryl-7-acetic acid developed tracheal antibodies capable of binding the carcinogen benzo[a]pyrene (BP). Immunized mice administered 92 ng of [3H]BP intranasally exhibited a one-third reduction in BP content in respiratory tract tissues (nose and trachea) when compared with control mice 20 hours after BP administration.


Preventing necrotizing enterocolitis in neonates. Necrotizing enterocolitis of newborn infants virtually vanished from our nurseries during the four years since the introduction of a slowly progressive feeding regimen. This cautions approach to feeding has been applied to selected infants whose condition during labor and delivery or whose neonatal problems indicate that they are at risk.


Recognition of impending ketoacidosis delayed by ketone reagent strip failure. During a one-year period, six patients were admitted to the hospital in diabetic ketoacidosis following 12 to 24 hours of illness at home. Urine testing with strips impregnated with sodium nitroprusside had indicated that no ketone bodies were present. Nine of 11 bottles of reagent strips in use for less than three months by these and other patients contained totally unreactive strips. Nitroprusside tablets exposed more than three months continued to give accurate readings.


Effectiveness of immunization with single and multi-component vaccines prepared from a common antigen (OEP), protease and elastase toxoids of Pseudomonas aeruginosa on protection against hemorrhagic pneumonia in mink due to P. aeruginosa. Toxoids of protease and elastase of Pseudomonas aeruginosa were successfully prepared by treatment with 8% formalin plus 0.2 m lysine and by 4% formalin respectively. The two toxoids proved sufficiently potent to elicit high antibody titers as estimated by both the enzyme-neutralizing and passive hemagglutination tests. The effectiveness of immunizing minks with a single component-vaccine consisting of the common antigen (OEP) of P. aeruginosa or the protease toxoid (PT) or the elastase toxoid (ET) and with the two (PT and ET) or the three (OEP, PT and ET) component-mixed vaccines, on hemorrhagic pneumonia in minks due to the bacteria was investigated. Female Sapphire minks, 3.5 months old, were used in two experiments performed in 1975 and 1976. Minks were immunized three times in one month with a total of 1 mg of each of the three antigens in the case of a single component vaccine and with a total of 2 or 3 mg (equal amounts of each component) in the case of the two or three component vaccines. Two or three weeks after the last immunization, challenge exposure with strain No. 5 was carried out by intranasally inoculating an inoculum containing serial dilutions of 10(3) -10(10) of live bacteria. Summarizing the results of the two experiments, in the case of controls, nonimmunized minks and minks immunized with potassium aluminum sulfate (potash alum) alone, the LD50 values were approximately 10(3) -10(4) with no significant difference between the two. In the case of OEP-vaccinated minks, the LD50 value was about 10(6) and thus clearly differed from those of the controls. In minks immunized with the three-component-vaccine, however, the LD50 value was about 10(8) -10(9), which indicated that the three-component-mixed vaccine was remarkably more effective than the single OEP vaccine component. In minks immunized with either PT or ET or both, the LD50 values were about 10(8) -10(9). The effectiveness of the vaccine made with ET or PT alone is discussed in the text. The pathological findings of the minks which died or survived are described.


The role of OEP-antibodies in Pseudomonas aeruginosa infection. When mice were challenged intraperitoneally with 2.2 X 10(4) Pseudomonas aeruginosa in 0.5 ml of 2.7% mucin solution, the bacteria markedly increased in the peritoneal cavity, rapidly entered the blood stream, and the mice died, probably of bacteremia, within a short time. However, when mice were injected subcutaneously 4 hours prior to the challenge with 0.2 ml of 0.75% IgG (OEP-HA = 12.8) or IgM (OEP-HA = 64) separated from human plasma or 3% S-IgA EP-HA = 19.2) from fresh human milk, the bacteria were inhibited from propagating and were eliminated from the cavity so that they could not enter the blood stream. As a result, the mice tolerated the challenge and survived. When 3% IgA (OEP-HA less than 0.8) from human plasma was given, a complete cure was not effected in a few mice despite a general tendency of healing. Determination of the number of viable intra- and extracellular bacteria in the peritoneal cavity revealed that the infecting bacteria were rapidly phagocytized and killed by the peritoneal phagocytes in the presence of OEP-antibodies. These findings indicate that the effect of bacterial clearance from the cavity results from the cooperative action of OEP-antibodies and peritoneal phagocytes. Marked enhancement of phagocytosis by the antibodies was observed in an in vitro study in the presence of a heat-labile, complement-like substance(s). This finding is interpreted as evidence of the cooperative activity.


Weight and size of the placenta in cynomolgus monkeys (Macaca fascicularis). A gross anatomical survey of the placental development was carried out in 24 cynomolgus monkeys (Macaca fascicularis) of 4, 5, 6, 7, 8, 9, 10, 15 and 20 weeks of gestational age. Eight of the 24 placentas examined were found to be single discoidal and the remaining 16 bidiscoidal. The weight and size of placentas of each animal were measured. The average weight of the 20th week placentas was about 94 times heavier than that of the 4th week ones; the average diameter of the former was about 5 times larger than that of the latter.


Pharmacological mechanisms of analgesic nephropathy. The situation in the experimental field is unresolved; too many factors require clarification before the critical experiment can be conducted to settle the matter once and for all. However, as there is now plentiful evidence to convince any reasonable physician that commonly available analgesics, when abused, carry a significant health risk, one may resonably ask whether any further experimental evidence is needed? The object of this review is in no sense divisive, i.e., by pointing out discrepancies in the available data to thereby cloud the issue rather than resolve them. The problem of abuse lies properly in the field of public health education, and the first step to this would surely be an appropriate worning on the packaging of all commonly used analgesics. For future research, however, government health authorities should be guided in their preclinical testing requirements for mild antiinflammatory analgesics, and enough is now known to draw up guidelines for good laboratory practice in this field.


Experimental renal infection: acute and chronic studies of histology and function. Experimental renal infections have resulted in histologic lesions of acute and chronic pyelonephritis, but in most studies the urinary tract has been "traumatized" to induce persistent infection. Sequential functional alterations have been measured infrequently. The present studies were designed to separate the functional and histological changes caused by high pressure sterile reflux from reflux with pathogenic organisms. Reproducible disruption of the pelvic epithelium with extravasation of solution into the parenchyma and vasculature occurred with reflux of 2.0 ml of solution but not with 1.0 ml. Reflux with 2.0 ml of sterile broth failed to cause permanent histologic changes, but reflux with broth containing organisms resulted in minor inflammatory changes. There was no decrease in renal function in either group. In long-term studies, no histologic changes in the cortex or medulla were noted 21 weeks after reflux of 1.0 ml of broth containing organisms; however, there was failure of functional maturation in the infected animals commensurate with their growth, as compared to the shams and controls (P = 0.03). Sterile reflux did not cause cortical scars or changes in renal function, but persistent parenchymal infection was associated with arrest of functional growth.


[Isolated arterial blood vessel dysplasia in Sturge-Weber-Syndrome (author's transl)]. An 18 year old patient is reported who suffered from cerebral convulsions, originating in the right hemisphere, beginning at age fourteen. Explorative trepanation of the scull was carried out after confirmation of (1) discreet neurologic disturbances on neurologic examination in the right hemisphere, (2) focal sign on the right side in the EEG (focal slowing and focal sharp wave), and (3) a right-parietal increase of radioactive activity in the scintigram. Cerebral angiographia, insufflation encephalographia, skull x-rays and the ophthalmologic examinations were without pathologic findings. During trepanation a macroscopically typical finding of Sturge-Weber-syndrome could be demonstrated (angioma capillare et venosum) covering almost the entire right posterior hemisphere.


[Muscle blood flow and capillary diffusion capacity in patients with rheumatoid arthritis (author's transl)]. Capillary blood flow (Xenon-133) and diffusion capacity for Chrom-51-EDTA (PS-Product of Renkin) of striated muscle tissue were examined by double isotope method in patients with rheumatoid arthritis. Xenon-Clearance and PS-Product were studied under normal conditions and following hyperemisation. There existed no significant difference between rheumatoid patients and normal subjects and there was no evidence of increased capillary permeability. Apparently, derangement of muscle capillaries is rare in rheumatoid arthritis.


Experimental acetaminophen-induced hepatic necrosis: biochemical and electron microscopic study of cysteamine protection. In an attempt to elucidate the biochemical mechanism of acetaminophen-induced hepatic necrosis, the present study in hamsters was undertaken to evaluate the possible changes in lipid peroxidation and microsomal enzyme activities. The protective action of cysteamine was likewise assessed in the light of these biochemical variables and the fine structural features of the liver were seen by electron microscopy. One group of golden Syrian hamsters was administered a toxic dosage of acetaminophen (600 mg . per kg . intraperitoneally) while another group was treated with the same dosage of acetaminophen, followed 1 hour later by cysteamine (200 mg . per kg . intraperitoneally). The animals were sacrificed at 6, 12, 18, and 24 hours. Microsomal fractions were isolated for biochemical assays, and liver sections were prepared for electron microscopy. Results showed that significant enhancement of lipid peroxidation occurred in the untreated acetaminophen-poisoned group, as compared to the cysteamine-treated group. Glucose 6-phosphatase activity was markedly suppressed at 6, 12, and 18 hours after acetaminophen administration. Cysteamine treatment completely prevented the curtailment of NADPH-cytochrome c reductase and glucose 6-phosphatase activities in the protected group, and partially maintained aniline hydroxylase activity. Cytochrome P-450 level was unaffected in both the cysteamine-treated and the untreated groups at the respective time intervals. Electron microscopic examination showed progressive loss of the structural integrity of the endoplasmic reticulum, lipid infiltration, and vacuolation in the untreated acetaminophen-poisoned group. At 18 and 24 hours, sinusoidal congestion and myeloid figure formation were prominent. In the cysteamine-protected group, polysomes reassembled around the granular endoplasmic reticulum at 18 hours. It is postulated that lipid peroxide formed in vivo may facilitate the microsomal oxidation of acetaminophen to the toxic metabolite. NADPH-cytochrome c reductase is likely to be the locus within the NADPH-cytochrome P-450 electron transport chain susceptible to lipoperoxidation. The free radical-related lipoperoxidation may mediate the impairment of in vitro drug metabolism, as reflected by the depressed aniline hydroxylase activity. The abnormal phospholipid metabolism is manifested at the fine structural level by the myeloid body formation. The protective effects of cysteamine as seen in the attenuated lipid peroxidation and the consequent derangement of microsomal enzymes correlate well with the morphologic observations. Cysteamine protection is discussed in terms of its role as an inhibitor of the toxic metabolite formation.


3. The laboratory investigation of monoclonal gammopathies. The monoclonal gammopathies are a group of disorders characterized by proliferation of a single clone of plasma cells that produce a homogeneous, monoclonal (M) protein. The structure of immunoglobulins, relationship of normal (polyclonal) immunoglobulins to myeloma and macroglobulin (monoclonal) immunoglobulins, pattern of monoclonal immunoglobulin overproduction, and laboratory methods for the recognition and study of monoclonal proteins in the serum and urine are reviewed. Interpretation of these laboratory tests is emphasized. The demonstration of a monoclonal protein in the serum or urine of a patient suggests multiple myeloma or one of its variants (solitary plasmacytoma of bone, extramedullary plasmacytoma, or plasma cell leukemia); Waldenström's macroglobulinemia or, occasionally, lymphoma; heavy-chain diseases (gamma, alpha, and mu); primary amyloidosis; and monoclonal gammopathies of undertermined significance. The electrophoretic and immunoelectrophoretic patterns found in the monoclonal gammopathies are discussed. Periodic electrophoresis of the serum and urine is essential in the follow-up and management of patients with a monoclonal gammopathy.


Priority setting in quality assurance: reliability of staff judgments in medical institutions. A structured procedure using the judgments of a representative group of local providers for establishing priorities for quality assurance activity in diverse medical institutions was tested for reliability. Two independent matched teams of phy sicians, nurses, administrators, and other staff in eight separate medical facilities generated 320 topics which encompassed areas where quality assurance efforts would have either considerable or little impact in terms of improving health outcomes within reasonable costs. Concordance of judgment between teams in each facility was determined by analyzing the similarity of topics content, the agreement in scaling the health impact of similar topics generated by both teams independently, and the agreement by one team in scaling the health impact of topics generated by the other team. The findings revealed 44 per cent content agreement on topics independently generated, 93 per cent agreement on dichotomous scaling of similar topics, and 87 per cent agreement on five-point scaling of similar topics. Concordance of judgment by one team in scaling the other team's topics was highly significant (p less than .001). Preliminary analysis of topic content and scaling agreement among different facilities indicated low agreement both on the content areas and on the health impact of similar topics. It is concluded that the judgments of local providers in identifying cost-effective quality assurance priorities is highly relaible in the medical institutions studied.


Quality assurance through automated monitoring and concurrent feedback using a computer-based medical information system. A computer-based medical information system (COSTAR) has been used to support a quality assurance program where the data collection is an integral part of the patient care recording activity and, therefore, does not require a separate abstracting or encoding process. This program utilizes concurrent audit to detect deficiencies in patient care, and automatic rapid feedback to the responsible provider in time to allow the provider to correct the deficiency. This system has been demonstrated to improve follow-up of throat cultures, positive for Group A Beta hemolytic streptococcus. It is well accepted by the medical staff whose practice is being audited. Because the data are collected as part of the routine operation of COSTAR, the computer monitoring and feedback have only a small incremental cost.


Isolation and characterization of the monounsaturated long chain fatty acids of Mycobacterium tuberculosis. The positions of double bond in the monounsaturated C15-C32 fatty acids of Mycobacterium tuberculosis H37Ra were established by gas chromatography/mass spectrometry of the ozonized esters and their pyrrolidide derivatives. The monounsaturated C15-C21 fatty acids had the double bond primarily at the delta 9 position while the monounsaturated longer chain fatty acids (C22-C32) had the double bond in several positions. Many of the latter acids, especially the odd-numbered series, were very complex isomeric mixtures. Quantitation showed the most abundant even-numbered long chain fatty acid isomers to be as follows: C22, delta 4; C24, delta 5; C26, delta 7 and delta 9; C28, delta 9; C30, delta 11 and delta 13; C32, delta 13 and delta 15.


Effect of certain sulphydryl compounds and dimethyl sulphoxide on potassium release by certain amines and proteins from Pseudomonas aeruginosa. Dithiothreitol, cysteine, and mercapto-ethanol inhibit K+ release from cells of Pseudomonas aeruginosa by amines and NH4Cl incubated at pH 8.5. The inhibitions are competitive for the monamines and NH4Cl but non-competitive for the diamines and spermidine. The percent inhibition is largest for tryptamine, least for spermidine and ethylene diamine. DMSO inhibits K+ release by monamines and certain proteins but not significantly by diamines and histamine. The inhibitions are competitive.


Growth response of the marine blue-green alga, Gomphosphaeria aponina, to inorganic nutrients and significance to management of Florida red tide. A bioactive isolate from the blue-green alga Gomphosphaeria aponina is cytolytic towards the dinoflagellate, Gymnodinium breve, Florida's red tide organism. Batch and continuous cultures of G. aponina were used to determine nutrient limitation and to optimize mass-culture conditions. Iron and inorganic carbon were growth limiting; first-order saturation kinetics were observed for both substrates. For Fe3+, kinetic parameters were: Ks = 62 +/- 9 microgram 1(-1), and Ke max = 2.14 days-1. Maximum growth was observed at 150 micrograms Fe3+1(-1), with minimal growth below 10 microgram 1(-1). Cells colonized with increasing Fe3+ supplements, and time to reach maximum culture populations was inversely related to the concentration. For HCO3-,Ks = 62 +/- 4 mg1(-1) and Ke max = 1.3 day-1. Additions of NH4+ up to 200 micrograms 1(-1) were not stimulatory, whereas at 1.0 mg 1(-1) levels, Ke was 50% greater than for NO3- enriched medium. Concentrations greater than 25 micrograms PO4(3-) 1(-1) were stimulatory. However, at 1 mg1(-1), growth was less than in controls. Comparison of similar data available for G. breve would suggest that the inorganic nutrient requirements of G. aponina were minimal. Potential for natural control of G. breve by G. aponina is perhaps related to the efficiency of contact of the two organisms.


Penicillin resistance in Neisseria gonorrhoeae due to beta-lactamase production. Two isolates of Neisseria gonorrhoeae from two patients who did not respond to repeated treatment with penicillin were found to contain an active beta-lactamase. This enzyme has not been previously found in other gonococci isolated in the United States. Compared to other gonococci, these isolates had higher penicillin minimal inhibitory concentrations, and gave very small or no zones of inhibition in the disc agar diffusion test. The enzyme was demonstrated with three different rapid tests for beta-lactamase, by disc diffusion assay methods, and by gas-liquid chromatography-mass spectrometry determination of penicilloic acid--the enzymatic end product from penicillin.


[Sulfobacillus, a new genus of thermophilic sporulating bacteria]. An aerobic facultative thermophilic bacterium was isolated from the ore of the Nikolaev copper-zinc-pyrite deposit in the Eastern Kazakhstan. The bacterium is similar to Thiobacillus ferooxidans in the ability to use various energy subsrates (Fe2+, sulphide minerals and So) and in the acidophilic properties, but differs from it in the thermophilic nature, the structure of a cell wall, the ability to produce spores, and a lower GC content in DNA. Consequently, the organism has been identified as a new species of a new genus, Sulfobacillus thermosulfidooxidans gen. nov., sp. nov. The organism is presumed to play an active role in oxidation of sulphide ores and their warming in deposits.


[Physiological and biochemical characteristics of Bacillus subtilis variants that form amylase]. Physiologo-biochemical properties of four Bacillus subtilis variants R-623 (R, S, P  and M) were studied; the variants were isolated by inoculation of the cell population. All the four variants were shown to belong to the studied species and to possess common and specific properties. They differed in 11 characters: the size of cells and spores, the ability to hydrolyse starch, the mode of growth on specific media, the spectrum of antibiotic action, etc. Three variants (R, S and P) produced alpha-amylase, the M variant did not produce the enzyme.


[Characteristics of the cellular ultrastructural organization of the chemoheterotrophic blue-green alga, Chlorogloea fritschii]. Cellular ultrastructural organization was compared in photoautotrophic and chemoheterotrophic cultures of the blue-green alga Chlorogloea fritschii Mitra. Cells at the fourth stage of the life cycle of the culture in the phase of growth were studied in both cases. The structure of thylakoids was the main object of investigation. The cells of investigation. The cells of Chl. fritschii had a peculiar organization when they were cultivated in the dark on a medium containing glucose as a source of carbon and energy. These cells differed from photosynthetic cells by the structure of the cell wall, cytoplasm, and thylakoids. The cell wall can be entirely or partly absent. The cytoplasm has a lower electron density. The cell wall can be entirely or partly absent. The cytoplasm has a lower electron density. The thylakoids are arranged more random and less compact than in the cells grown in the light. Membranes which form these thylakoids, under identical conditions of fixation, contrasting and microscopy of preparations, look usually as one-layered rather than three-layered. Apparently, the ultrastructure of thylakoids on Chl. fritschii reflects the specificity of energy mechanisms that function in cells in the light and in the dark.


[Formation of the taxa of methane-oxidizing bacteria by numerical analysis methods]. Obligate methane oxidizing bacteria were classified within groups using numerical analysis and computer techniques. Employment of properties coinciding for all the species of the bacterial group under study was found to result in an insignificant (5--10%) change in the degree of similarity rather than in the redistribution of interrelationship; it had no effect on the formation of phenons. The Smirnov taxonomical analysis according to which the weight of a property is inversely proportional to its frequency has a number of advantages over other numerical methods where all the properties are assumed to be of equal value. Comparative evaluation of the data obtained by different methods which have been used by us to calculate the coefficients for coupled similarity of species (the coefficient of association, the coefficient of correlation, the index of distance, the coefficient of taxonomic ratio) shows that similar results are found in all the cases with respect to group division of the species belonging to the family Methylomonadaceae Leadbetter 1974. The species of methane oxidizing bacteria should be divided into the following genera: Methylosinus Whittenbury, Phillips a. Wilkinson 1970, Methylocystis Whittenbury, Phillips a. Wilkinson 1970, Methylococcus Foster a. Davis 1966, Methylomonas Leadbetter 1974.


[Effect of sulfur-containing nucleotide peptide on the morphology and nucleic acid content in Anabaena culindrica]. The exogenous action of a sulphur-containing nucleotidepeptide on Anabaena cylindrica caused an increase in the biomass of the alga by 76% as a result of acceleration of growth and larger dimensions of cells. The content of nucleic acids per cell also increased: that of DNA by 40%, that of RNA, by 11%.


Testing the TRH hypothesis of pineal function. In the Syrian hamster gonadal involution may be induced by exposure of the animal to darkness, short photoperiod, or blindness for several weeks. These conditions also influence body metabolism by inducing a substantial decrease in thyroxin concentrations. The role of the pineal gland in these phenomena has been demonstrated by experiments showing that if pinealectomized hamsters are subjected to darkness, short photoperiod, or blindness, their gonads do not involute and plasma thyroxin levels remain normal. Since thyrotrophin releasing hormone (TRH) causes the release of both prolactin and thyrotrophin from the pituitary we can predict on theoretical grounds that TRH mediates both pineal-gonad and pineal-thyroid phenomena. Melatonin may be the pineal hormone regulating hypothalamic TRH levels.


Design, devices, and discipline in operating room infection control. The prevention of surgical infection in the operating theatre is a complex pursuit. Every facet of activity, whether it is part of the surgical act itself or a remote activity with indirect effects on the surgical operation, constitutes part of the whole realm of infection control. These many facets may be divided into four main components, all interdependent: (a) the surgeon and his team (surgical technique; adherence to surgical anatomic, physiologic, and aseptic principles; discipline); (b) education and communiction--a functioning infections committee, repeated tutorials for all prefessional and technical operating room personnel, constant review of methods and systems, effective reporting of offenses, enforcement of discipline; (c) dependable support services--sterilizing techniques, barrier materials, apparel, laundry methods; materials handling and processing methods; efficiency and personal hygiene of all techincal and support personnel; discipline; and (d) environmental factors--architecture, engineering, and air handling; electrical and mechanical requirements; communication; discipline).


Utilization of the 16O(n,p) reaction for monitoring the output of 14 MeV neutron generators. A system based upon the 16O(n,p) 16N reaction has been developed for monitoring 14-MeV neutron production. The system has proven to be quite applicable for monitoring the output of a disk-shaped neutron source and computer analysis has shown it equally suitable for monitoring the output of cone-shaped neutron sources from gas targets presently being considered for cancer therapy.


Magnetic field modification of electron-beam dose distributions in inhomogeneous media. Modern curative radiotherapy requires higher doses to the tumor volume and, necessarily, minimal doses to the surrounding normal tissues. Attempts to use heavy charged particles to achieve such optimization are currently under investigation in many centers. Our data indicate that a static, superimposed magnetic field on a clinical electron-therapy beam also offers the capability of some "tailoring" of isodose distributions. Furthermore, a variable, superimposed magnetic field minimizes those tissue-generated dose heterogeneities which are inherent with all charged-particle beams. We suggest that magnetically modified, clinically available electron beams also offer a practical and less expensive means of achieving tailored, heterogeneity-corrected isodose distributions.


Magnetic modification of the electron-dose distribution in tissue and lung phantoms. Moderately strong transverse-magnetic fields were used to modify conventional electron-dose distribution in tissue- and lung-equivalent phantoms. Magnetically modified symmetrical-isodose contours and central-axis depth-dose curves were measured for central fields in the range of 9--18 kG, field gradients of approximately 5 kG/cm, and accelerator energies of 10--45 MeV. To the extent that our experimental field strengths and gradients can be reproduced clinically, the measurements showed that magnetic distributions can be generated (in tissue) which are superior to conventional distributions for the treatment of tumors lying at depths less than approximately 7 cm provided that the tumor cross-section dimensions are equal to or greater than tumor depth. The surface dose in tissue is typically reduced by approximately 40% compared to the conventional surface dose for treating the same tumor volume. For the lung phantom data, a significant reduction (less than approximately 50%) in the integrated central-axis dose to healthy tissue was achieved for tumor depths of 10--14 cm. The possibility of reproducing our experimental magnetic fields and gradients inside a patient under realistic clinical conditions is discussed.


Wedge-shaped dose distributions by computer-controlled collimator motion. We have recently installed a linear accelerator, modified to allow computer control of several machine parameters during irradiation of the patient. As an initial feasibility study of computer-controlled radiation therapy, its application to produce wedge-shaped dose distributions by moving the collimator jaws has been evaluated. The required collimator motions have been calculated with an iterative technique. When these routines were used during irradiations of phantoms containing radiographic film, a good correspondence between calculated and measured dose distributions was observed. It is concluded that computer-controlled motion of the collimator jaws to shape the dose distribution is technically feasible. Additionally, this technique has the advantage that the wedge angle can be continuously adjusted and the isodose curves optimized for a particular depth and field size.


Elongation effects on the Therac 6 linear accelerator. The effects of field elongation on the central-axis output at dmax and on the depth-dose curves for the 6-MV x rays from the Therac 6 linear accelerator are considered. These parameters are independent of the collimator angle for both square and elongated fields. The exchange of collimator pairs results in significant output differences but has a negligible effect on the depth-dose curves. Both the central-axis output at dmax and the depth-dose curves agree satisfactorily with the predictions of the equivalent-square technique. An alternative method of greater accuracy is also indicated for the prediction of central-axis outputs at dmax for elongated fields.


Evaluation of the Therac 6 linear accelerator for radiation therapy. The Therac 6 is new generation of low-energy linear accelerator. It incorporates a PDP-11/05 computer for beam control, treatment-factor input, and beam shutdown in the event of failure of the system. The performance of the unit has not been hindered by computer or software malfunction, and the computer has provided an excellent means for preventive maintenance and repair. Dosimetry parameters are similar to other 6 MV x-ray beams, and comparison to 60Co therapy beams shows that this unit may be more like 60Co units in penumbra and absence of off-axis peaking than other low-energy accelerators.


The localization of tRNAAsp2 genes from Drosophila melanogaster by "in situ" hybridization. Transfer RNAAsp2delta was isolated from Drosophila melanogaster by affinity chromatography on concanavalin A-Sepharose. The tRNA was iodinated "in vitro" with Na [125I] and hybridized "in situ" to salivary gland chromosomes from Drosophila. Subsequent autoradiography allowed the localization of the genes for tRNAAsp2 to the left arm of the second chromosome in the regions 29 D and E.


Bacillus subtilis dnaF: a mutation of the gene specifying the structure of DNA polymerase III. The characteristics of Bacillus subtilis dnaF, a mutation specifying a temperature sensitive phenotype, were examined to determine its relationship to polC, the gene specifying the structure of DNA polymerase III (pol III). Exposure of growing cells bearing dnaF to non-permissive temperature inhibited replicative DNA synthesis and specifically depressed the expression of pol III activity in crude extracts. Highly purified pol III derived from cells bearing dnaF was temperature.sensitive in its polymerase activity, indicating that dnaF is a specific, polC mutation which specifies a structurally altered enzyme.


[Determination of biological individuality by blood group studies]. Author deals with the possibility of determination of the biological individuality by serological methods. Determination of HL-A tissue-compatibility antigens and system of MN/Ss and Rh seen to be the most suitable tools. Alloantigens, serum proteins and group of enzymes characterize the biological individual i. e. serological methods can be used as a tool of the identification of a person. Author deals with the possiblity of determination of various razes. For this purpose investigation of the following systems are necessary: ABO-, Rh-, MN/Ss-, Kell-, Duffy-, Lutheran, Kidd, Lewis and Diego. Nevertheless, this problem is not yet solved.


[Autogenic training today (author's transl)]. Autogenic training (AT) creates an autonomic shift within the Hypnoid; in neurophysiological terms conceivable by a lower level of vigilance, synchronisation of EEG and modulation of afferent impulses. The said status differs clearly from wakefullness, drowsiness or sleep. AT however means more than just achievement of a hypnoidal state by ways of the classical six standard exercises, but to our opinion its use within a complex psychotherapy. We very much combine it with analytically orientated group therapy. Accordingly we oppose mass presciption of the standard exercises outside the medical sphere. Application of AT outside of psychotherapy within "psychohygienic indication" should carefully be considered only with strongly motivated persons, as otherwise the lack of motivation is likely to lead to failures.


[Bone sarcoma (author's transl)].

[Bone sarcoma (author's transl)]. Sarcogenesis essentially follows two laws: The frequency of sarcoma is distributed according to the mesenchymal cell content in the different sections of the body. The sites of predilection are found within the same tissue systems in zones of increased growth activity and cell division. Clinical oncogenic statistics show that other factors apart from quantity of sarcogenic noxae and latent period are important in producing the malignancy. The synopsis of histology, X-ray findings and clinical examination is significant for diagnosis and for prognosis the degree of spread (TNM classification), localization and therapy. Early operation is still the most successful and most decisive therapeutic measure. The necessity for a supervised cancer follow-up is also shown in these tumors.


[Results of operative treatment of acute perforating gastroduodenal ulcer (author's transl)]. In this report of 264 operatively treated gastroduodenal perforations, differentiated, and where possible definitive, therapy is attempted. By omitting simple oversewing in favor of primary resection, bionomic operation or the combined procedure, primary lethality is reduced to one third and the late results of the survivors significantly improved. Resections are indicated in benign pyloric stenosis and gastric ulcer. The bionomic operation is particularly to be preferred in young patients.


[The diagnostic value of ejaculate cultures in acute unspecific epidiymitis (author's transl)]. Bacteriological cultures of the ejaculates of 28 patients with acute unspecific epididymitis yielded in 6 cases growth of organisms which were considered to be the cause of the disease. Tests with conventional clinical antibiotics showed organism resistance in half of these cases. Because of possible contamination of the ejaculate with organisms in the urethra and in the preputial area, the results of bacteriological cultures of the ejaculate must be evaluated critically. But a bacteriological ejaculate culture should be carried out in all cases of acute epididymitis at the first consultation so that the antibiotic treatment can be begun immediately afterwards with a tetracycline preparation. If the cultures prove to be tetracycline resistant an appropriate antibiotic can then be substituted.


[Recent findings in dermatophytic skin diseases (author's transl)]. The most important current research centers on immunobiological questions. It is suggested that the delayed Trichophyton reaction is the immune mechanism which protects patients after a primary dermatophyte infection. Griseofulvin is the treatment of choice today. The questionnaire sent to all practising dermatologists in Germany investigated the frequency of certain possible serious side effects. The new once daily 500 mg griseofulvin tablet will have to be in clinical use for some time yet before its efficacy can be assessed.


[The uric acid-lowering action of benzbromarone effervescent granules and allopurinol. Comparative studies (author's transl)]. The daily administration of 25 mg effervescent granules is about equipotent with a daily dose of 200 mg allopurinol, giving due attention to the caution necessary for uricosuric therapy. The daily administration of 50 mg benzbromarone effervescent granules has a slight but significantly greater uric acid-lowering effect than treatment with 300 mg allopurinol per day. The tolerance of benzbromarone in the active form named was good in all cases. Side effects were not observed. Since benzbromarone as effervescent granules is taken with plenty of fluid this takes care of an increased fluid intake and introduces a motivation for doing so.


[Significance of clearance values in advanced renal insufficiency (author's transl)]. Under physiological conditions there is satisfactory agreement between the clearance values of endogenous creatinine and inulin in humans. In chronic renal insufficiency the endogenous creatinine clearance cannot be considered as an index for glomerular filtrate because of considerable individual variations. In spite of this limitation endogenous creatinine clearance proves to be a sensitive test for hospital and general practice to estimate the loss of renal function in chronic progressive renal diseases if the loss of function has not yet led to an increase of the serum creatinine concentration.


[Surgical and dietetic problems of subtotal resection of the small intestine in adults (author's transl)]. The human body badly tolerates the extensive loss of the small intestine by resection. Malabsorption of various substances is followed by severe deficiency symptoms. In recent years a longer survival with a satisfactory general condition was achieved by intensive postoperative care and adequate diet--in our own cases even in adults and in old age.


[Criminological aspects of the clarification of alkaloid intoxications (author's transl)]. At the turn of the century medical and suicidal alkaloid intoxications, especially with atropine, morphine and strychnine were relatively frequently observed. Apart from morphine, they have today largely disappeared from the view of the general practitioner so that the associations are difficult to interpret in spite of clinical observation. This is shown in 5 observations of which only three could be confirmed as atropine poisoning; one was fatal. The symptoms of intoxication by atropine (or scopolamine) may be misinterpreted as alcoholization, so that chemical analysis is not thought of soon enough. In the differential diagnosis more use should be made of the possibility of a blood alcohol determination in the hospital, but combined effects must, of course, be reckoned with.


[Defibrination with the snake venom enzyme arwin in peripheral arterial obstructive disease. Possibilities and limitations (author's transl)]. Defibrination with the snake venom enzyme Arwin is one of the numerous possibilities for the therapy of peripheral arterial obstructive disease. The number of complications is relatively small. In 58 patients with peripheral arterial occlusive disease stages III to IVa treated with Arwin the success rate was 50--60%. The ultrasonic Doppler pressures in the arteries of the ankle can be helpful for indicating Arwin therapy. Complications were not observed in combined treatment with hemodilution, intraarterial injection or simultaneous administration of heparin.


[The effect of bemetizide-triamterene on the serum and whole body potassium in hypertensive patients (author's transl)]. The hypotensive effect of Bemetizide (B)/Triamterene (T) and its action on the potassium balance was investigated in 10 patients with renovascular hypertension. Within 14 days treatment with 50 mg B and 100 mg T a significant fall in the mean blood pressure of 174/106 to 143/95 mm Hg occurred. Whereas the serum potassium concentration fell by an average of 4.2 +/- 0.5 to 3.9 +/- 0.6 mEq/1 the whole body potassium showed only a slight insignificant regression by 50 and 80 mEq after 2--4 weeks; however, the potassium content related to the body weight remained unchanged. In contrast to monotherapy with chlorthalidone or hydrochlorothiazide, treatment with a combination of B and T caused no significant alteration of the intracellular content of potassium.


Exogenous immunoglobulin and the macrophage origin of Reed-Sternberg cells in Hodgkin's disease. We studied Reed-Sternberg cells from 14 patients with Hodgkin's disease to learn whether they had monoclonal immunoglobulin synthesized by the cell or polyclonal immunoglobulin of external origin. Double-label immunofluorescence with F(ab')2 anti-serums to human light chains showed that cytoplasmic immunoglobulin of individual Reed-Sternberg cells is always polyclonal and usually associated with membrane-bound immunoglobulin of the same type. The predominant immunoglobulin was IgG; in one case IgM was also present. In vitro studies confirmed the internalization of exogenous IgG and phagocytosis of immune complexes by viable Reed-Sternberg cells. Their exclusion of trypan blue dye and lack of albumin and fibrinogen suggests relatively specific uptake of immunoglobulin, mediated by the Fc receptor or antigen (or antigens) associated with Hodgkin's disease at the cell membrane. Our studies support other recent evidence that the Reed-Sternberg cell is derived from a macrophage.


Advanced ovarian adenocarcinoma. A prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy. Eighty patients with advanced ovarian adenocarcinoma were treated in a prospective, randomized trial comparing a four-drug combination--hexamethylmelamine, cyclophosphamide, methotrexate and 5-fluorouracil--with the oral alkylating agent, melphalan. Treatment with the four-drug combination was associated with a significantly increased overall response rate (75 vs. 54 per cent) (P less than 0.05), more complete remissions (33 vs. 16 per cent) and longer median survival (29 vs. 17 months) (P less than 0.02) but more severe toxicity than occurred with melphalan. Patients with minimal residual disease had a significantly higher overall response rate than patients with extensive residual disease (84 vs. 53 per cent) (P less than 0.05). Patients with advanced disease who achieved a complete remission documented by peritoneoscopy or laparotomy (or both) have a median survival that will exceed three years. The four-drug regimen is more effective than melphalan in the management of advanced ovarian adenocarcinoma.


Factors contributing to the declining mortality rate in renal transplantation. Recent modifications and refinements in the management of patients with renal allografts have diminished the mortality rate at our hospital to 2 per cent and 5 per cent at one year for patients receiving kidneys from related and cadaveric sources, respectively. Of 186 receiving transplants since 1974, seven (4 per cent) have died within one year of operation. The incidence of wound infections has been reduced from approximately 25 per cent in 1972 to 2 per cent since 1976 by the use of a single high dose of broad-spectrum antibiotics administered at the time of induction of anesthesia for any surgical procedure. Risk and limitations of immunosuppression have been better appreciated, ultrasound is used more often in the diagnosis of partial obstruction or perinephric fluid collections, and needle biopsy of the transplanted kidney has reduced the morbidity inherent in open biopsy. The contribution of sepsis as a cause of death has declined. The diminishing hazard of renal transplantation has made it an increasingly attractive treatment for end-stage kidney disease.