Polynucleotide-protein interactions in the translation system. Identification of proteins interacting with tRNA in the A- and P-sites of E. coli ribosomes.

Ultraviolet irradiation (lambda = 254 nm) of ternary complexes of E. coli 70 S ribosomes with poly(U) and either Phe-tRNAPhe (in the A-site) or NAcPhe-tRNAPhe (in the P-site) effectively induces covalent linking of tRNA with a limited number of ribosomal proteins. The data obtained indicate that in both sites tRNA is in contact with proteins of both 30 S and 50 S subunits (S5, S7, S9, S10, L2, L6 and L16 proteins in the A-site and S7, S9, S11, L2, L4, L7/L12 and L27 proteins in the P-site). Similar sets of proteins are in contact with total aminoacyl-tRNA and N-acetylaminoacyl-tRNA. However, here no contacts of tRNA in the P-site with the S7 and L25/S17 proteins were revealed, whereas in the A-site total aminoacyl-tRNA contacts L7/L12. Proteins S9, L2 and, probably, S7 and L7/L12 are common to both sites.


Site specific enzymatic cleavage of RNA.

The hybridization of a DNA oligonucleotide a specific tetramer or longer) will direct a cleavage by RNase H (EC 3.1.4.34) to a specific site in RNA. The resulting fragments can then be labeled at their 5' or 3' ends, purified, and sequenced directly. This procedure is demonstrated with two RNA molecules of known sequence: 5.8S rRNA from yeast (158 nucleotides) and satellite tobacco necrosis virus (STNV) RNA (1240 nucleotides).


Specific fluorescent labeling of 7-(aminomethyl)-7-deazaguanosine located in the anticodon of tRNATyr isolated from E. coli mutant.

Under-modified E. coli tRNATyr that contains 7-(aminomethyl)-7-deazaguanosine in place of Q nucleoside can be chemically modified by dansyl chloride under neutral conditions. Fluorescent labelling specifically occurred only in the 7-(aminomethyl)-7-deazaguanine moiety. The modified tRNATyr was found to be active both in aminoacylation and in binding to ribosomes.


Molecular cloning and nucleotide sequence of the human growth hormone structural gene.

An almost complete cDNA copy of human growth hormone has been cloned and sequenced. The nucleotide sequence confirms the known protein sequence and predicts the sequence of a precursor region of 26 amino acids. We have compared the nucleotide sequence to that for the homolgous proteins, rat growth hormone and human chorionic somatomammotropin (Seeburg et al. and Shine et al., Nature 270, 486 (1977)). There appears to be evolutionary conservation of mRNA sequence features not related to protein structure.


Sequence of 1019 nucleotides encompassing one of the inverted repeats from the yeast 2 micrometer plasmid.

A sequence of 1019 nucleotides encompassing one of the 600 base inverted repeats and non-repeated flanking regions has been determined in the type A yeast 2 micrometers plasmid cloned in pMB9. Methods are described for applying the Maxam-Gilbert sequencing procedure to DNA fragments labelled at the 3'-end using a T4-polymerase exchange/repair reaction and for sequencing 5'-end labelled fragments using dideoxy-nucleotides as chain terminators in the presence of E. coli DNA polymerase (nach Klenow). A notable feature of the sequence is its unusual content of symmetry elements. In one region of 140 nucleotides, 137 are involved in a complex arrangement of direct and inverted repeats linked by palindromic sequences.


Studies on gene control regions XII. The functional significance of a lac operator constitutive mutation.

The functional significance of a lac operator constitutive mutation has been determined. The transition adenine-thymine to guanine-cytosine was shown to be a constitutive mutation simply because thymine contains the functionally important 5-methyl group whereas cytosine does not. The remainder of the base pair is of no consequence. The experimental approach was to synthesize various modified operators containing cytosine, 5-methyl-cytosine, and 5-bromocytosine. The synthetic operator containing a guanine-cytosine base pair displays an eightfold reduction in stability with lac repressor whereas the operator containing 5-methylcytosine binds repressor at least as tightly as does the wild type sequence. Results published previously have shown that a similar decrease in stability of the repressor-operator complex can be obtained simply by substituting uracil for thymine or by inverting the base pair to thymine-adenine. All these results taken together implicate the thymine 5-methyl as the only important functional group recognized by the lac repressor at this base pair. Further confirmation of this conclusion was obtained by substitution of 5-bromocytosine and 5-bromouracil at this base pair. Both altered the stability of the repressor-operator complex by about the same percent suggesting that the bromine atom was the important determinant of complex stability for 5-bromopyrimidine analogs.


The synthesis of oligodeoxyribonucleotides using RNA ligase.

T4 RNA ligase catalyzes the addition of a single deoxyribonucleoside 3',5'-bisphosphate to the 3'-hydroxyl of oligodeoxyribonucleotides (Hinton et al. (1978) Biochemistry 17, 5091). We have determined improved conditions for this reaction which give yields equal to or greater than 85% when any of five common deoxyribonucleoside bisphosphate (pdAp, pdCp, pdGp, pdTp, or pdUp) are added to dA(PDA)4. A low ATP concentration, which is constantly maintained by a regeneration system composed of phosphocreatine, creatine kinase, and myokinase, contributes to the attainment of high yields. The addition of RNase A and spermine also enhances the rates and yields of the reactions. These conditions facilitate the use of RNA ligase as a reagent for the stepwise synthesis of DNA of defined sequence.


Binding of magnesium ions and ethidium bromide: comparison of ribosomes and free ribosomal RNA.

Comparative studies of free ribosomal RNA and ribosomes were made with two probes, Mg++ ions and ethidium bromide, which interact with RNA in different ways. Mg++. E. coli 16 S rRNA and 30 S ribosomes were equilibrated with four different buffers. Equilibration required several days at 4 degrees and several hours at 37 degrees. In all buffers ribosomes bound more Mg than free rRNA, the difference sometimes reaching 20--30%. Ribosomes were more resistant than free rRNA to heat denaturation and their denaturation was more highly cooperative. Ribosomes that bound more Mg++ had higher denaturation temperatures. Ethidium bromide. Fluorescence enhancement studies of ethidium intercalation showed the free 16 S rRNA to have 50--80 binding sites per molecule. A large fraction of these sites were present and accessible in the ribosome, but their ethidium-binding constants were reduced by an order of magnitude. In addition, free rRNA contained a small number of very strong binding sites that were virtually absent in the ribosomes.


The glutamyl-tRNA synthetase of Escherichia coli: substrate-induced protection against its thermal inactivation.

The substrates-induced protection against the heat-inactivation of the glutamyl-tRNA synthetase has been investigated. tRNAGlu and ATP protect efficiently the enzyme, whereas glutamate does not. In the presence of tRNAGlu, glutamate induces an additional protection to that given by the tRNAGlu alone. A weak synergism was observed between ATP and tRNAGlu, whereas no synergism was detected between ATP and glutamate. These results suggest that tRNAGlu and ATP, but not glutamate are able to bind to the free enzyme form; glutamate binds only to the Enzyme.tRNAGlu and to the Enzyme.tRNAGlu.ATP complexes. The presence of the three substrates induces a higher stabilization of the enzyme than that expected from the protection observed for the various other substrates combinations, suggesting the existence of a marked synergism between the three substrates against the heat-inactivation of the enzyme. The protection constants determined from this study are similar to the dissociation constants determined by direct binding experiments and to the Km values determined kinetically.


Determination of the recognition sites of cytosine DNA-methylases from Escherichia coli SK.

Two different cytosine DNA-methylases, NI and GII, are present in Escherichia coli SK. The GII methylase recognizes the five-member symmetric sequence: 5'...NpCpCpApGpGpN...3'. This sequence is identical with the recognition site of the hsp II type determined by RII plasmid but, in contrast to RII methylase, the GII enzyme methylates cytosine located on the 5' side of the site. By analogy with the isoshizomery of the restricting endonucleases, RII and GII DNA methylaeses may be called isomethymers which recognize the same site but methylate different bases. Since the phage of the SK and hsp II phenotypes is effectively restricted in respective cells it may be assumed that the isomethymeric modification does not provide any protection against the corresponding restrictases. NI methylase recognizes the five-member symmetric site which represents an inverted sequence of the GII site: 5'...NpGpGpApCpCpN...3'. In this case cytosine at the 3'-end of the recognition site is methylated.


Introductory address: lessons to be learned from high altitude.

A historical account of the important landmarks in man's experience with the high altitude environment is followed by comments on the important stages in the understanding of its physiological effects. The work of The Mount Logan High Altitude Physiology Study on acute mountain sickness is reviewed from its inception in 1967 until the present.


[Partial anomalous pulmonary venous drainage of the left lung into the innominate vein (author's transl)].

From 5 cases of partial anomalous pulmonary venous drainage of the left lung into the innominate vein, it has been thought of interest to situate this type of venous anomaly among the partial anomalous pulmonary venous drainage classification. It is revealed in 2 different ways. In adults, this malformation sets the problem of the diagnosis of an abnormal chest Xray, without symptom. In children, this vascular abnormality is discovered during the exploration of a congenital cardiopathy which causes the main symptoms. Embryological data are reviewed and statistics of frequency which lead to show that this type of partial anomalous venous drainage is often misunderstood, particularly with regard to anomalous venous drainage of the right lung.


[Comparative study of the titre of circulating antibodies and the results of the iodine radioisotope indication test of the thyroid gland in chronic autoimmune thyroiditis].

A total of 293 patients with chronic autoimmune thyroiditis were observed. The circulating antibody titre to thyroglobulin was determined and 131I-radioindication of the thyroid gland was made in 65 patients. The mentioned studies were diagnostically informative in the complex examination of patients with chronic autoimmune thyroiditis.


[Glomerular filtration and vascular permeability in diabetes mellitus].

Renal function (glomerular filtration) and vascular permeability were studied in 89 patients with diabetes mellitus by means of labeled renotropic compounds. There was a direct relationship between the reduced glomerular filtration, severity and duration of the disease, condition of compensation, age and body weight of diabetic patients, and the presence of diabetic vascular lesions. Vascular permeability proved to be increased in the form of diabetes mellitus and in patients with marked renal pathology.


Association of central nervous system sarcoma with familial polyposis coli.

Familial polyposis of the colon is associated with an increased incidence in other parts of the body of benign and malignant, soft and hard connective tissue tumours. Clinical details and autopsy findings are reported in a 35-year-old man with familial polyposis who died from reticulum cell sarcoma (microglioma) involving his brain stem and upper spinal cord. While other central nervous system malignancy has been reported in association with familial polyposis, a sarcomatous tumour has not been previously described. In the clinical assessment of patients with familial polyposis the possibility should be considered of associated tumours in extracolonic sites, including the central nervous system.


Sodium valproate: dose-plasma level relationships and interdose fluctuations.

Individual dose-plasma level relationships were studied in 14 chronically treated epileptics, 10 of whom were concomitantly receiving other anticonvulsants besides valproate. Linear regression analysis showed each individual relationship to be linear with correlation co-efficients ranging from 0.9137 to 0.9997. A considerable inter-individual variation was found to exist in the slopes of the regression lines (range: 0.86 to 5.72). This may be the consequence of differences in absorption characteristics and metabolic handling of the drug. The results indicate that a proportional rise in plasma sodium valproate levels can be expected following dosage increments in an individual patient. Hourly plasma sodium valproate measurements for 6 hours between 2 successive doses, in the same group of patients, showed that the mean percentage change in post-dose peak plasma levels was 44.5%, and range from 20.7 to 153.5%. Plasma levels returned to values close to pre-dose starting levels 6 hours after the administration of a dose. The large degree of inter-dose fluctuation between doses indicates that it is preferable to use pre-dose plasma sodium valproate levels to guide the clinical management of epileptic patients.


An evaluation of bromocriptine in the treatment of Parkinson's disease.

22 patients entered a double-blind trial to test the efficacy of bromocriptine therapy in patients with Parkinson's disease already established on conventional levodopa therapy. 3 patients on placebo withdrew when no improvement occurred and control became complicated. 4 patients on active drug withdrew because of various symptoms, but in only 1 case were these (nausea and vomiting) thought to be a real drug effect. Of the 15 patients who completed the trial, 9 were on active drug and 6 were on placebo. Although more than half the patients in each group were subjectively improved, measurement scales of functional disability and physical examination revealed no significant change in either group. Side effects encountered included nausea, dyskinesiae and hallucinations. It is concluded that bromocriptine does not offer any additional benefit in most patients with Parkinson's disease who are well stabilised on levodopa therapy, but may have a place in those patients who encounter side effects due to fluctuations in serum and tissue levels of levodopa.


A review of some aspects of the pharmacology of levodopa.

Levodopa has become established as the treatment of choice in Parkinson's disease. It is adsorbed by an active mechanism from the small bowel. Its pharmacological activity depends upon the formation of dopamine and possibly other metabolites. Its beneficial effect in Parkinson's disease probably depends upon temporarily restoring the ability of degenerating nigro-striatal cells to release dopamine. Its main side effect, that of dyskinesia, may reflect a direct action of dopamine on striatal receptors. Peripheral decarboxylase inhibitors reduce the incidence of levodopa-induced nausea, probably by lowering the concentration of dopamine in the area postrema. The introduction of levodopa in the treatment of Parkinson's disease is generally regarded as one of the uncommon examples in medicine where effective therapy has resulted from systematic research rather than seredipity. As our knowledge of the pharmacology of levodopa grows, we may be forced to admit that perhaps the right drug was chosen for the wrong reasons.


Major factors affecting cadaver renal transplant outcome in a single center.

In this center, 3 major factors have favorably improved cadaver renal allograft survival rates. The good risk recipient has been associated with a better graft survival and lower mortality. This factor cannot easily be controlled because of an increasing percentage of poor risk recipients awaiting transplantation in most major centers. Recipient blood transfusions administered both before transplantation and at the operating table have led to a better allograft survival in our center. Cadaver donor genotyping with haplotype matching of donor-recipient pairs has resulted in an improved graft survival. As sharing of kidneys between centers becomes more common, it is encouraging to note that one method of preservation is not superior to the other.


Epidemic renal transplant rejection associated with influenza A victoria.

1) IAV infection seems to trigger acute renal allograft rejection frequently, especially in the first few months post-transplant, and these rejections are severe with a high rate of ultimate graft loss; 2) seroconversion occurred in most cases despite high dose steroids; 3) the course of IAV was prolonged and associated with a high incidence of complications in patients on high dose steroids.


Detection of antidonor antibody: advantages of fibroblast target cells.

Donor specific alloantibody was monitored in 40 kidney transplants for 3 most post-transplant. Two 51Cr release assays were used: complement-dependent lysis and antibody-dependent cell-mediated cytotoxicity. Fibroblast, lymphocyte, and lymphoblast target cells were all tested whenever possible. Antibody was detected in only 6 of 22 patients who achieved satisfactory function (creatinine less than 3 at 3 mos), but in 15 of 18 patients who had an unfavorable outcome (return to dialysis or creatinine greater than 3 at 3 mos). The association of antifibroblast antibody with poor function was particularly striking: in the 33 patients in whom donor fibroblasts were tested, none of 20 with good function had detectable antibody, whereas 10 of 16 with graft loss or poor function had detectable antibody. Studies with mouse fibroblasts indicated that the association of antifibroblast antibody with graft destruction may be explainable in terms of selective expression of various alloantigens on fibroblasts.


The correlation of kidney transplant survival with lymphocyte mediated cytotoxicity on B cell targets.

A LMC micromethod using specific B lymphocyte target cells labeled with a fluorescent dye has been developed to select matched donors and recipients for kidney allotransplantation. The fluorescence of the B lymphocyte target cells was 85% or less of control levels in 9 of 28 patients. In 8 of these 9 hosts graft loss occurred. Nineteen sets of target cells showed 90-95% of control fluorescence. Only 5 of these recipients lost their transplants (p less than 0.01). The fluorescent LMC test correlates with successful renal transplant outcome when the target cells are purified B cells.


Retransplantation in children.

Evaluation of 75 cadaver donor retransplants revealed that the primary factor influencing allograft survival is patient responsiveness as reflected by sensitization with preformed cytotoxic antibodies. Actuarial allograft survival rates for nonpresensitized (less than 5%) and moderately presensitized (5-50%) recipients were significantly (p less than 0.001) better than those of highly presensitized (greater than 50%) recipients. Although HLA antigen histocompatibility did not have a statistically significant effect on retransplant outcome, it appeared to influence allograft survival in the highly presensitized recipient. An approach to the management of children who lose an initial or subsequent allograft is indicated by these data.


Isolation and mapping of plasmids containing the Salmonella typhimurium origin of DNA replication.

A purified EcoRI restriction endonuclease fragment that determines resistance to kanamycin and is incapable of self-replication was used to select autonomously replicating fragments from an EcoRI digest of a Salmonella typhimurium F' plasmid containing the chromosomal region believed to include the S. typhimurium origin of DNA replication. Both the F factor and S. typhimurium chromosome replication origins were cloned by this procedure. The EcoRI fragmentment containing the S. typhimurium origin of replication is 19.4 kilobase pairs long and includes functional asp+ and uncB+ genes. Restriction endonuclease analysis of deletions obtained from the S. typhimurium origin plasmid indicated that the replication origin (ori region) is contained within a 3.3-kilobase pair region. Comparison with Escherichia coli origin plasmids shows colinearity of gene arrangement on the chromosomes in this region and suggests that some, but not all, regions of the nucleotide sequence in the origin region may be conserved (identical) in these two bacterial species.


Real-time solvent exchange studies of the imino and amino protons of yeast phenylalanine transfer RNA by Fourier transform NMR.

Real-time solvent exchange measurements using Fourier transform NMR at 270 MHz are presented. By means of the fast gel filtration column techniques originally developed for tritium exchange experiments, we were able to replace the solvent of a tRNA sample from an 1H2O to an 2H2O buffer and obtain a useful spectrum in 2-5 min. At 15 degrees C, there are 5 +/- 1 lowfield (-11 to -15 ppm relative to 2,2-dimethyl-2-silapentane-5-sulfonate) imino protons with exchange half times of minutes to hours. In addition, the m7G-46 C(8) proton and several amino protons are observed to exchange with similar rates. Analogous studies on unfractionated yeast tRNA suggest that such a class of slowly exchanging imino protons is present in several tRNAs, and that the activation energy for exchange is small [[approximatley 5 kcal/mol (21 kJ/mol)]. We speculate that these imino resonances arise from D-stem protons and that their slow exchange reflects stabilization by the numerous tertiary interactions involving this stem and the Mg2+ bound at the P-10 bend.


Steroid treatment for routine immunosuppression in cadaver renal transplantation. A survey of hospitals.

A review of data from 22 hospitals in the U.S. and Canada, comprised of information on 1700 kidney transplant patients, shows a consistent pattern with respect to usage of steroids both as routine treatment and for rejection episodes. High doses are associated with greater patient mortality. Graft survival is also adversely affected by very high doses, but only in the immediate post-transplant period. Our data suggest that for optimal graft and patient survival the dosage of steroids should be less than 150 mg/day of methylprednisolone on days 1-3, less than 50 mg/day of prednisone on days 4-21, less than 30 mg/day on days 22-30, and less than 20 mg/day between one mo and one yr.


Physical map of the recA gene.

We have cloned the recA gene of Echerichia coli K12 and some of its restriction fragments on the plasmid cloning vehicle pBR322. The recA gene was mapped with regard to the restriction sites of EcoRI, BamHI, Pst I, Hha I, Hae III, HinfI, and Taq I restriction endonucleases. The recA promoter was localized by the binding of RNA polymerase to restriction fragments. The initiation point of transcription of recA mRNA and the direction of transcription were determined from in vitro transcription of recA gene fragments and from analysis of the polypeptides made in maxicells that contain plasmids carrying only part of the recA gene.


Contacts between Escherichia coli RNA polymerase and thymines in the lac UV5 promoter.

I have identified those 5 positions of thymines in the lac UV5 promoter that lie close to bound Escherichia coli RNA polymerase (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6). Although ultraviolet irradiation of DNA with 5-bromouracil substituted in place of thymine normally cleaves the DNA at the bromouracils, a protein bound to the DNA can perturb these cleavages at those locations at which the protein lies close to the bromine. In the lac promoter most of these contacts lie in three regions. Four contacts lie in the region where transcription initiates; four lie in the "Pribnow box," which is located about 10 base pairs upstream from the initiation site; and three more lie in the "-35 region," located about 35 base pairs upstream from the initiation site. The "Pribnow box" and the "-35 region" are regions whose sequences are partially conserved between promoters and in which most promoter mutations are located; thus, contacts in these two regions probably represent sites of sequence-specific recognition by RNA polymerase.


Evidence from ultraviolet absorbance measurements for a codon-induced conformational change in lysine tRNA from  Escherichia coli.

From experiments with equilibrium dialysis it was concluded earlier that formation of the codon-anticodon complex triggers a conformational change in the tertiary structure of tRNAPhe from Escherichia coli. A similar conformational transition is demonstrated here in the poly(A)/tRNALys system. C-G-A or C-G-A-A was used as a probe for the conformational transition in tRNA. These probes bound to tRNAPhe and tRNALys more strongly in the presence of the corresponding codons than in the absence. In order to verify these data by an independent method, the decrease in absorbance at 300 nm that occurs on formation of the codon-anticodon complex in tRNALys (which contains 2-thio-5-methylaminomethyluridine, s2mam5U) was used. The binding constants for formation of A3 . tRNALys (Ka = 2.4 . 10(4) M-1) and A4 . tRNALys (Ka = 2.5 . 10(5) M-1) are very close to those obtained by equilibrium dialysis. In the presence of C-G-A the apparent binding constant of A3 to tRNA was raised 10-fold to 2.5 . 10(-5) M-1. It was calculated that the constant for the binding of C-G-A to the binary complex A3 . tRNALys is approximately 2 . 10(4) M-1, whereas binding to the free tRNA is lower than 10(3) M-1. Under appropriate conditions binding of A3 to tRNALys can be induced directly by the addition of C-G-A. These data demonstrate that codon-anticodon complex formation induces a conformational change in the tRNA that as a consequence allows the binding of a trinucleoside diphosphate, presumably to the T-psi-G region.


Subunit stoichiometry and molecular weight of the pyruvate dehydrogenase multienzyme complex from Escherichia coli.

The molar ratio of the component enzymes of the pyruvate dehydrogenase multienzyme complex from Escherichia coli was found to be 1.8:1.7:1[pyruvate decarboxylase (E1):dihydrolipoyl transacetylase (E2):dihydrolipoyl dehydrogenase (E3)]. This ratio was determined by measuring the Coomassie blue staining of the constituent enzymes after sodium dodecyl sulfate/polyacrylamide slab gel electrophoresis. The above ratio is the average of four separate experiments with two different enzyme preparations. The average molecular weights of the individual enzymes were found to be 96,000, 76,000, and 55,000 for E1, E2, and E3, respectively, by sodium dodecyl sulfate and sodium dodecyl sulfate/8 M urea polyacrylamide gel electrophoresis and by column chromatography in 6 M guanidine . HCl. The molecular weight of E2 was reduced to 33,000-36,000 after extensive reduction and alkylation with iodoacetamide. The molecular weights of the complex, E1, and E3 were found to be 4,800,000, 182,000, and 104,000, respectively, with low-angle laser light scattering. Both E1 and E3 are dimeric under the conditions employed. If octahedral symmetry is assumed for the E2 core, a polypeptide chain ratio of 24:24:12 (E1:E2:E3) is in good agreement with the measured molar ratio of component enzymes and the molecular weight of the pyruvate dehydrogenase complex.


Initiator tRNAs have a unique anticodon loop conformation.

Transfer RNA (tRNA) molecules have been labeled with 32P at the 5' end and subjected to S1 nuclease digestion. The products were analyzed by high-resolution gel electrophoresis. Three initiator tRNAs and six chain-elongating tRNAs were examined. S1 nuclease cleaved Escherichia coli tRNAfMet, yeast tRNAfMet, and mammalian tRNAfMet at the same two positions in the anticodon loop. In contrast, S1 nuclease cleaved the anticodon loop of E. coli tRNAmMet, yeast tRNAmMet, yeast tRNAPhe, Schizosaccharomyces pombe tRNAPhe, E. coli tRNA2Glu, and E. coli tRNATrp (su+) at four positions generally, except where a modified nucleotide in the wobble position inhibited the enzyme. The marked contrast between these cleavage patterns suggests a different conformation for the anticodon loops of these two classes of tRNA molecules. It is suggested that the specialized conformation in the anticodon loop of initiator tRNAs may be due to a special sequence of GC base pairs in the adjoining anticodon stem.


Molecular cloning and partial characterization of delta-crystallin cDNA sequences in a bacterial plasmid.

Double-stranded cDNA synthesized from delta-crystallin mRNA isolated from lens fiber cells of 15-day-old embryonic chicken was cloned in Escherichia coli chi 1776 in the Pst I site of the plasmid pBR322 by using the oligo(dC) . oligo(dG) joining procedure. Twelve Amps Tetr transformants contained sequences complementary to purified delta-crystallin [32P]cDNA. One of the recombinant clones (p delta Cr-2) had an insert of 1241 +/- 240 base pairs, as judged by R-looping analysis with purified delta-crystallin mRNA. The inserted cDNA represents at least 69% of the delta-crystallin coding sequences. p delta Cr-2 was further characterized by restriction analysis, protection of delta-crystallin [3H]cDNA from digestion by S1 nuclease, and hybrid-mediated arrest of delta-crystallin mRNA translation in vitro. p delta Cr-2 provides an invaluable probe for additional analysis of the primary structure, gene organization, and regulated synthesis of delta-crystallin, the principal protein synthesized during lens differentiation in the chicken embryo.


Entrapment of a bacterial plasmid in phospholipid vesicles: potential for gene transfer.

Entrapment of pBR322 DNA within liposomes was demonstrated by (i) its comigration with liposomes on Sepharose 4B columns, (ii) resistance of its biological activity to DNase digestion, and (iii) identification of plasmid DNA on agarose gels after lipid extraction. The biological activity of the liposome-entrapped plasmid was determined by transformation assays. The incubation of intact liposomes, containing entrapped pBR322, with competent Escherichia coli cells in the standard transformation mixture resulted in the appearance of tetracycline-resistant colonies at a frequency of 1% of the control frequency. Importantly, this frequency was unaffected by the addition of DNase to the incubation mixture, whereas transformation by free pBR322 DNA was totally eliminated after treatment with DNase.


Ten-nanometer filaments and mitosis: maintenance of structural continuity in dividing endothelial cells.

By indirect immunofluorescence the behavior of the 10-nm filaments was studied at various stages of mitosis in guinea pig vascular endothelial cells. Interphase cells contain a ring of 10-nm filaments that encircles the nucleus and is maintained in a plane parallel to the substrate. During prophase and metaphase the cells round up and the 10-nm filament ring becomes wavy though still a closed structure. As anaphase progresses the ring then elongates into a rectangle that contains the spindle apparatus and chromosomes. In late telophase, cytokinesis cleaves the 10-nm filaments into crescents at the site of the contractile ring. These crescents then close into rings in the daughter cells. If cytokinesis is inhibited with 5 microgram of cytochalasin B per ml, then cleavage of the 10-nm filaments is blocked and the daughter nuclei remain surrounded by the parent ring. At no point during mitosis does the array of 10-nm filaments undergo major disassembly. These results indicate that, in contrast to the other major cytoplasmic structures, ventral microfilament bundles and cytoplasmic microtubules, which disassemble and reassemble during mitosis, 10-nm filaments remain intact throughout this process. The possibility is discussed that these filaments may function in transport of organelles and structural proteins, and provide the daughter cells with topological information about placement and assembly of these elements within the microtrabecular lattice.


Occurrence of crossed strand-exchange forms in yeast DNA during meiosis.

The crossed strand-exchange form (Holliday structure, half chiasma) has been predicted as an intermediate in the genetic recombination of eukaryotes. We report here the detection of this form in the yeast plasmid, 2-micron DNA, isolated during meiosis. Physical mapping has previously suggested that two forms of 2-micron DNA arise because of recombination between inverted repeat regions. After appropriate digestion with restriction endonuclease, a crossed strand-exchange form intermediate in this recombination would yield an X-shaped form resistant to loss by branch migration because of nonhomology in sequences flanking the region of homology. We first generated this X-shaped form artificially by reannealing melted restriction fragments of 2-micron DNA. This enabled us to develop a procedure for the physical separation of the X-shaped form by agarose gel electrophoresis. We then used this electrophoretic procedure to isolate a naturally occurring form of identical structure from the 2-micron DNA of meiotic cells. Electron microscopy demonstrated that the exchange junction had the expected configuration of strands and indicated that the junction occurred within the region of homology.


Detection of substance P in the central nervous system by a monoclonal antibody.

Peptides with transmitter-like characteristics are being found in many brain areas. The application of immunocytochemical and radioimmunoassay methods has contributed much to the clarification of these neuronal systems. Here we report the development of a rat monoclonal antibody produced by a hybrid myeloma and its application to the study of one of these peptides, substance P. The hybrid clone, isolated after fusion of mouse myeloma cells with hyperimmune rat spleen cells, allowed us to obtain a standardized and permanent source of monoclonal substance P antibodies in a culture cell system. This antibody recognizes the COOH-terminal part of substance P in radioimmunoassay down to 10-20 fmol. It does not crossreact with other known mammalian brain peptides tested. By immunofluorescence the antibody was shown to bind specifically and with a remarkably low background to nerve terminals and cell bodies located in clearly defined nuclear organizations of the central nervous system.


Sequential cleavage of proinsulin by human pancreatic kallikrein and a human pancreatic kininase.

A pancreatic endopeptidase localized to the beta-cells of the pancreas by immunohistochemical techniques has been purified to homogeneity by following its functional and antigenic characteristics as a glandular kallikrein (EC 3.4.21.8). The enzyme gave a single stained band on alkaline disc gel electrophoresis which corresponded in location with the kinin-generating activity eluted from a replicate gel, was of 54,000 molecular weight by gel filtration, was devoid of caseinolytic activity, elicited a monospecific antiserum in a rabbit, and gave a line of complete identity with a single constituent in pancreatic extract, crude urine, and purified urokallikrein when analyzed with monospecific antibody to urokallikrein. The pancreatic glandular kallikrein generated three cleavage products of increasing anodal mobility from bovine and porcine proinsulin, and the presence of pancreatic kininase or bovine carboxypeptidase B increased the quantity of these products. Although the conversion products did not correspond to diarginyl- and monoarginylinsulin, the product of intermediate mobility was also obtained when proinsulin was treated with a low concentration of trypsin in the presence of kininase. The most rapidly migrating product did correspond to desalanylinsulin in the reference standard. Kininase alone had no action on proinsulin, and aprotinin prevented cleavage by kallikrein alone or in combination with kininase. Although the chemical structure of the proinsulin cleavage products has not been established, human pancreatic kallikrein is considered a putative activator of proinsulin because of its location in the beta-cell, its preferential action on proinsulin and kininogen as compared to azocasein, and its capacity to generate insulin intermediate products that are further modified by human pancreatic kininase or bovine carboxypeptidase B.


A DNA primase specified by I-like plasmids.

An enzyme has been isolated from Escherichia coli strains harboring the I-like plasmid R64drd11, which is capable of initiating DNA synthesis on the circular, single-stranded DNA of phages phi X174, fd, and G4. In the conversion of these templates to duplex forms in vitro, the enzyme can substitute for the functions of E. coli dna B-dnaB-dnaC-dnaG proteins, E. coli RNA polymerase, and E. coli dnaG protein, respectively. The enzyme requires all four ribonucleoside triphosphates for optimal activity, although a combination of ATP, CTP, and GTP can almost completely satisfy the rNTP requirement. The enzyme appears to cooperate specifically with DNA polymerases III because single-stranded DNA-dependent synthesis takes place in extracts deficient in DNA polymerases I and II but not in extracts from a dnaZ mutant. Highly purified enzyme preparations consist mostly of two major polypeptides, Mr 140,000 and 180,000, when analyzed by sodium dodecyl sulfate gel electrophoresis. These polypeptides cosediment with the enzyme activity through a glycerol gradient with a sedimentation coefficient of 3.6 S. DNA priming activity in extracts of E. coli strains harboring the mutant plasmids R64drd11 or ColIdrd1, which are derepressed in functions of conjugational DNA transfer, severalfold higher than the activity from strains carrying the corresponding wild-type plasmid. This correlation suggests that the enzyme may play a role in conjugational DNA synthesis.


Permeabilization of cells for studies on the biochemistry of bacterial chemotaxis.

The cell membranes of Salmonella typhimurium and Escherichia coli have been made permeable in order to introduce S-adenosylmethionine into the cell for study of the course of methylation. A series of protein bands in the Mr 60,000 region were methylated, the specific bands and the extent of methylation depending on the attractant used. The change in levels of methylation was essentially the same as the in vivo responses, indicating that the permeabilization procedure maintains the relative relationships of the cellular proteins. A shift in intensity of the methylated bands occurred over time, indicating that a sequential process is involved in the methylation of these proteins. The permeabilization technique appears to offer major advantages in tracing the biochemical processes of the behavioral system.


Isolation of a condensed, intracellular form of the 2-micrometer DNA plasmid of Saccharomyces cerevisiae.

We have initiated an investigation of the proteins bound in vivo to the 2-micrometer DNA plasmid found in the yeast Saccharomyces cerevisiae by examining its intracellular form. To isolate 2-micrometer DNA without disturbing proteins bound to the plasmid, an extract was prepared from a strain lacking mitochondrial DNA and the nuclear chromatin was removed from the extract by centrifugation. When the DNA in this extract was sedimented through a sucrose gradient containing 0.15 M NaCl, plasmid DNA had a sedimentation coefficient of approximately 70. This S value is greater than the S value of 25 for naked, superhelical 2-micrometer DNA. Cosedimenting with the DNA were proteins of the same size as the histone proteins associated with yeast nuclear chromatin. Digestion of the plasmid DNA with micrococcal nuclease and electrophoresis of the resulting DNA fragments revealed that segments of discrete sizes are protected from degradation. Examination of the plasmid DNA protein complex by electron microscopy showed nucleosome structures. We conclude that 2-micron DNA exists as a condensed chromosome body within the cell.


Communication between dissimilar subunits in aspartate transcarbamoylase: effect of inhibitor and activator on the conformation of the catalytic polypeptide chains.

Although local, direct effects of ligand binding to proteins are readily differentiated conceptually from gross, indirect conformational changes in regions of the protein remote from the site of binding, it has been difficult experimentally to distinguish between them. In oligomeric proteins, for example, the binding of ligands to one chain may cause a conformational change in the unliganded chains, but many physical chemical probes are not sufficiently discriminating to demonstrate where the change occurred. Evidence has been lacking as to whether the inhibitor, CTP, or the activator, ATP, in binding to the regulatory chains of the allosteric enzyme aspartate transcarbamoylase (aspartate carbamoyltransferase; carbamoylphosphate:L-aspartate carbamoyltransferase, EC 2.1.3.2) causes a conformational change that is propagated throughout the enzyme to the catalytic chains. To demonstrate this "communication" of effects of binding at one site on the conformation of other polypeptide chains, we constructed molecules containing native regulatory subunits and enzymically active nitrated catalytic subunits having one sensitive nitrotyrosyl chromophore per polypeptide chain. These hybrid molecules exhibited the characteristic regulatory properties of the native enzyme. Upon the addition of CTP the population of molecules was shifted toward the constrained or T state, as shown by the change in the sedimentation coefficient and the altered enzyme kinetics. Moreover, there was a decrease in absorbance at 430 nm due to the altered environment of the nitrated catalytic polypeptide chains. In contrast, ATP caused a shift toward the relaxed or R conformation, and the absorbance due to the nitrotyrosyl residues was increased. Different types of experiments indicated that the modified enzyme molecules are in a preexisting equilibrium that is perturbed by CTP or ATP; the resulting conformational changes in the nitrated catalytic subunits are detected by opposite alterations in their absorbance spectrum.


Amino acid sequence and physicochemical similarities between streptococcal M protein and mammalian tropomyosin.

The amino-terminal sequences of two peptides of type 24 streptococcal M protein show similarities with that of rabbit skeletal muscle tropomyosin, having up to 40% identical residues and probabilities of occurring by chance as low as P less than 10(-5). In addition, a hexapeptide (Glu-Ala-Glu-Lys-Ala-Ala) that is found five times in the M24 protein was shown to be identical to a sequence in tropomyosin. Similarities are also seen in the amino acid compositions and physicochemical properties of the two proteins. The amino-terminal sequences of peptides from another bacterial surface protein, staphylococcal protein A, are highly correlated with segments of two other myofibrillar proteins, rabbit actin (P less than 10(-7)) and rabbit myosin A1 light chain (P less than 10(-6)). The data presented suggest that a close structural relationship exists between mammalian muscle proteins and the biologically active surface proteins of staphylococci and streptococci. In addition, the correlation between sequences in M protein and tropomyosin represents direct evidence of a structural similarity at a molecular level between a streptococcal protein and a mammalian muscle component and may therefore prove relevant to the pathogenicity of the streptococcus.


Reconstitution of RNase P activity from inactive RNA and protein.

RNase P preparations from Escherichia coli can be separated into RNA and protein by chromatography, in buffers containing 7 M urea, on Sephadex G-200, DEAE-Sephadex, or CM-Sephadex columns. Neither RNA nor protein components alone exhibits any RNase activity. RNase P activity can be reconstituted by mixing separated RNA and protein components in buffer containing 7M urea followed by dialysis of this mixture to remove the urea. Of several purified RNAs tried, only M2 RNA, the RNA species found in purified RNase P, is active in the reconstitution experiments.


Ribosome structure: localization of 3' end of RNA in small subunit by immunoelectronmicroscopy.

The 3' end of the RNA in the 30S ribosomal subunit of Escherichia coli has been modified by oxidation with sodium periodate and conjugation with the (mono) dinitrophenyl derivative of ethylenediamine. Antibodies, induced with dinitrophenyl-bovine serum albumin, interact with the modified ribosomal subunits. Electron micrographs of negatively stained antibody-subunit complexes show individual ribosomal subunits to which a single antibody molecule is bound and subunit dimers cross-linked by an IgG molecule. The modified 3' terminus has been localized to a single site on the upper portion of the platform region of the 30S subunit. This location is consistent with earlier placements of proteins that react with the 3' end of the RNA.


Insertion and turnover of macrophage plasma membrane proteins.

The composition, insertion, and turnover of externally disposed proteins on the macrophage plasma membrane were analyzed. Cells labeled with [35S]methionine were incubated with the nonpermeant reagent trinitrobenzene sulfonic acid to introduce the trinitrophenyl moiety on free amino groups of externally oriented membrane proteins. The cells were then incubated with rabbit anti-dinitrophenyl IgG and the immune complexes formed with the trinitrophenyl-proteins were isolated from detergent lysates of the cells by using fixed Staphylococcus aureus as the immunoadsorbent. Proteins isolated by this method were analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The interval between the release of newly synthesized proteins from ribosomes and their appearance at the cell surface, where they became accessible to trinitrobenzene sulfonic acid, was studied in pulse-chase experiments. The "transit" time of four major membrane glycoproteins (48,000--310,000 Mr) ranged from 36 to 55 min and their appearance on the cell surface occurred in a relatively synchronous fashion. The turnover of most proteins of molecular weight above 50,000 was very slow (t1/2 greater than 80 hr) and was rather synchronous. Two exceptions were the 310,000 Mr protein, which was lost with a t1/2 = 21 hr, and a major glycoprotein (Mr 48,000), which exhibited more complex kinetics. Although the overall turnover of surface proteins was biphasic in nature, the rapid phase of protein loss was largely due to low molecular weight species.


High-frequency transformation of yeast by plasmids containing the cloned yeast ARG4 gene.

Hybrid ColE1 plasmids, containing cloned DNA from the yeast ARG4 region [e.g., pYe(arg4)1], transform yeast arg4 mutants to ARG4(+) with a frequency of 10(-4) (about 10(3) transformants per mug of plasmid DNA) and can replicate autonomously without integrating into the yeast genome. The yeast transformants are genetically unstable when grown on nonselective medium, but can be readily grown and maintained on minimal medium lacking arginine. The existence of unintegrated replicating plasmid DNA in the yeast transformants was demonstrated by Southern gel hybridization and by transformation of Escherichia coli argH mutants with DNA preparations from yeast transformants and subsequent recovery of intact plasmid DNA from the bacterial transformants. Plasmid DNAs recovered from the E. coli-yeast-E. coli "shuttle" remain essentially unchanged, as judged by DNA restriction fragment patterns. Some plasmid mutations leading to increased efficiency of expression of the ARG4 gene in E. coli do not appear to affect expression of the cloned ARG4 gene in yeast. Appropriate derivatives of these ARG4 plasmids are of potential usefulness as vectors for cloning genes in yeast and for studying the mechanism of yeast DNA replication.


Immunotitration of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in various physiological states.

The immunotitration of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase [mevalonate:NADP+ oxidoreductase [CoA-acylating), EC 1.1.1.34], the major regulatory enzyme in cholesterol biosynthesis, by HMG-CoA reductase antiserum is described. This technique provides the advantage that one can rapidly measure relative changes in both enzyme concentration and enzyme activity in different physiological states by using enzyme samples all the way from crude liver microsomes to purified enzyme. Regarding the diurnal rhythm of HMG-CoA reductase, the major difference noted between animals killed near the middle of the dark period (D 4.5) compared to animals killed near the middle of the light period (L 4.5) was in the concentrations of HMG-CoA reductase present, rather than in the activity of the enzyme, with substantially more enzyme found near mid-dark. Cholestyramine treatment resulted in both an increased concentration of HMG-CoA reductase and a catalytically more active enzyme. On the other hand, cholesterol feeding resulted in both a decreased concentration of HMG-CoA reductase and a catalytically less active enzyme.


Unstable transpositions of his4 in yeast.

Unstable transpositions in yeast have been selected in which the his4C gene from chromosome III is inserted into chromosome XII. This event is associated with the generation of a recessive lethal mutation, resulting from the integration of his4C into an essential gene. Strains with these transpositions are viable as diploids or aneuploids for chromosome XII. The event that generates the transpositions does not lead reciprocally to a deletion on chromosome III, implying that synthesis of a new copy of his4C and subsequent transposition may have occurred. The his4C transpositions are unstable and give rise to C- segregants at a high frequency, as a result of either precise excision of the his4C gene (restoring function of the gene into which insertion had occurred) or chromosome loss.


Identification and characterization of a self-regulated repressor of translocation of the Tn3 element.

Gene fusions that bring expression of the lacZ gene under control of transcriptional and trnaslational signals within the transposable element Tn3 have been used to study regulation of Tn3-specified proteins. A gene encoding a 21,355-Mr peptide that represses translocation of Tn3 and acts at the level oquenced; amber, missense, and cis-dominant (operator-constitutive) point mutations in this gene have been isolated and characterized.


Enkephalin- and somatostatin-like immunoreactivities in human adrenal medulla and pheochromocytoma.

By using the Coons indirect immunofluorescence technique, enkephalin-like immunoreactivity with a granular localization was observed in human adrenal medullary gland cells and pheochromocytomas. In two of the tumors and in a few adrenal gland cells, a somatostatin-like peptide could also be identified. Catecholamine cell types were visualized on adjacent sections with antisera to the synthesizing enzymes dopamine-beta-hydroxylase [DBH; dopamine beta-monooxygenase; 3,4-dihydroxyphenylethylamine, ascorbate: oxygen oxidoreductase (beta-hydroxylating), EC 1.14.17.1] and phenylethanolamine-N-methyltransferase (PNMT; noradrenalin N-methyltransferase; S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.28). In the normal adrenal medulla more DBH- than PNMT-immunoreactive gland cells were observed. In the adrenal pheochromocytoma both DBH- and PNMT-positive cells were seen, whereas the two extra-adrenal tumors contained only DBH. These findings correlated well with plasma catecholamine measurements. Finally, enkephalin immunoreactive fibers and somatostatin immunoreactive cells were observed in a sympathetic ganglion extirpated together with one of the tumors.


Formation and involution of Mallory bodies ("alcoholic hyalin") in murine and human liver revealed by immunofluorescence microscopy with antibodies to prekeratin.

Antibodies raised against prekeratin intensely and specifically stain, in immunofluorescence microscopy, Mallory bodies ("alcoholic hyalin") present in livers of human alcoholics and griseofulyin-treated mice. The high sensitivity of this method allows the identification of small distinct cytoplasmic structures that are observed during early stages of Mallory body formation, especially frequent in the perinuclear cytoplasm, as well as during stages of Mallory body disintegration and disappearance, such as after withdrawal of the drug. In the latter situation, the prekeratin-containing small particles exhibit a characteristic pattern of arrangement in the hepatocyte periphery. Electron microscopy illustrates that such small bodies are heap-like aggregates of typical Mallory body filaments. Immunofluorescence studies with antibodies to isolated prekeratin polypeptides from bovine hoof or muzzle epidermis show that Mallory body filaments, in particular those in human liver, are immunologically more closely related to prekeratin of tonofilaments from living epidermal cells (stratum spinosum). The data indicate that Mallory bodies contain a pathologic form of prekeratin-like material. They also suggest that disorders of cytoskeletal structures of the intermediate-sized filament class are associated with specific diseases and can be visualized and characterized by immunofluorescence microscopy by using antibodies to constitutive proteins of such filaments.


Simple cannula for repeated intracerebral drug administration in rats.

A simply constructed cannulation system for chronic implantation in rats is described. The guide cannula, stylet and injection cannula are all made from stainless steel tubing, require litte time to construct, and are designed for minimum brain damage and atraumatic infusion into unanesthetized rats.


Action of propranolol in mania: comparison of effects of the d- and the l-stereoisomer.

The antimanic action of high doses of the beta-receptor blocking agent propranolol was investigated by the use of a double-blind placebo controlled ABA design. For comparison, the d-stereoisomer (which is practically devoid of beta-blocking activity) was used. 6 trials were performed with d-propranolol, 6 trials with the racemic mixture. From dose-effect relations one can conclude that the d-stereoisomer is about half as effective against manic syndromes as the racemic mixture. From this finding it can be concluded that the antimanic action of propranolol is at least partially due to a mechanism independent of its beta-blocking action.


Clinical profile and serum concentration of viloxazine as compared to amitriptyline.

The antidepressive effect of viloxazine (300 mg/d) was investigated during three weeks in 41 patients with depressive syndromes requiring drug-treatment against amitriptyline (150 mg/d), using a controlled double-blind design. Viloxazine differs from amitriptyline by selective inhibition of norepinephrine re-uptake, whereas amitriptyline acts also on serotonin re-uptake. Psychopathological changes were documented by means of the Hamilton Depression Rating Scale, the Bf-S (v. Zerssen), the AMDP-System, and videotaped recordings. Besides routine clinical-chemical tests, the serum concentrations of viloxazine and partly of amitriptyline were determined. Repeated EEG-recordings were evaluated by spectral analysis. The number of global responders and non-responders -- defined according to the final HDRS-scores -- was equally distributed between the two drug-groups. The AMDP-evaluation suggests that viloxazin has a somewhat more marked and more rapid effect on symptoms of retardation, whereas amitriptyline acts predominantly on depressive mood, disturbances of sleep and vital feelings. The EEG-profile of both drugs was similar to the spectral changes seen under tricyclic antidepressants, through only the viloxazine-induced changes reached statistical significance on the 10th and 20th day, the variability of the EEG-recordings being greater in the amitriptyline group. The viloxazine blood levels showed a remarkably low inter- and intraindividual variance. Steady state was reached at day 5 at the latest. Amitriptyline serum concentrations still increased between the 10th and the 21st day. The average blood concentration of viloxazine was higher in the responder- than in the non-responder-group.


Prediction of lofepramine-response in depression based on response to partial sleep deprivation.

The improvement of depression after partial sleep deprivation in the second half of the night (sd) is tested for its predictory power for the therapeutical efficacy of pharmacotherapy with lofepramine. In a group of 15 patients with depression, we found that in contradiction to the findings of Wirz-Justice and collaborators (1976), the velocity of the antidepressive effect of sd has no predictive value. On the other hand, the amount of depression improvement after sd is of predictive value. This is independent of the time of occurrence of the improvement peak after sd. An improvement of more than 35% measured in the Bf-S or in the H.DRS on the first or the second day after sd is highly predictive for a good response to three weeks of 210 mg lofepramine per day (p = .05).


[Differential indication of trimipramine - results of a controlled multiclinical study].

The antidepressants trimipramine and imipramine were compared within the framework of a multiclinical study performed under the conditions of a controlled clinical experiment. There has been found a time-different remission of affective und psychomotoric symptoms. The panthymoleptic action of trimipramine and other antidepressants is discussed with reference to these results. Trimipramine influences psychotic states, especially if in depression anxiety is combined with agitation, also in hypochondriac forms of depression.


[Dr. John Rittmeister - neurologist and resistance fighter].

He was born in Hamburg on 21st August 1898 and beheaded in the Plötzensee penitentiary on 13th May 1943. Our colleague was a personality combining professional striving and political commitment into a dialectic unity. The more important biographic data are given, the co-operation in the Schulze-Boysen-Harnack organisation is described as far as it has become known, and Rittmeister's scientific works are mentioned.


[In memory of C.L. Kahlbaum].

The author wants to refer to C.-L. Kahlbaum, to one of the important German neurologists and psychiatrists. The life of Kahlbaum and his scientific results have been described in brief. Of especial value with regard to the treatise of the author is, that he knows both parts of the interior and exterior of the hospital of Kahlbaum of that time existing till now and the documents of the archives of the town of Görlitz. The importance and necessity of knowledge and investigation of psychiatrical tradition have been shown in this treatise.


Induction of mutations by photodynamic action of thiopyronine in Saccharomyces cerevisiae.

The induction of cytoplasmic and nuclear mutations by the photodynamic action of thiopyronine is demonstrated in a haploid strain of Saccharomyces cerevisiae that has been isolated as a photodynamic sensitive mutant. No significant increase in corresponding mutation frequencies could be observed in a strain resistant to photodynamic inactivation by thiopyronine.


[Critical evaluation of penitentiary treatment in a comparison of normal and mentally ill prisoners].

The literature on the treatment in regard of criminals, normal or mentally unbalanced, has been particularly abundant in recent years. The present work reviews some of it, with a view to establishing some evaluation criteria in respect of treatment, in its practical implementation and at the level of scientific research in the sector. In the first part of this work, starting from recent and drastic criticisms on treatment, that point out the inefficacy of it in respect of a decrease in the relapsation rate, an analysis is carried out, on the basis of the latest research work, of the methods of execution and of the results obtained by the various treatment methodologies applied; also highlighted are the weak spots that still exist, at the level of methodological approach, in the scientific research sector, as well as the poor integration existing between the latter and administrative structures of the criminal execution setup. The second part of the work chiefly deals with of the psychiatric features of the treatment vis-à-vis normal or mentally unbalanced convicts; as it is pointed out, psychiatric treatment is confronted with special difficulties in its intramural application, owing to the ever existing conflicting views between the experts and the administrative setup; the efficacy and the possibility of implementation are pinpointed, of some therapeutic treatment methodologies (individual psychotherapy--group psychotherapy--group counseling). A picture emerges therefrom that is by far less alarming than the initial assumption: the practical application of the treatment may be improved and made more effective, whilst the rôle psychiatry must acquire in the work towards the rehabilitation of the criminal, must be necessarily defined.


The hemodynamic significance of massive pneumopericardium in preterm infants with respiratory distress syndrome. Clinical and experimental observations.

Radiographic and clinical data were evaluated in 12 preterm infants with pneumopericardium complicating ventilator therapy of respiratory distress syndrome. Eight infants had massive or tension pneumopericardium, reflected by bradycardia, hypotension, and cyanosis of abrupt onset; cardiac size decreased dramatically but returned to approximately the former size after aspiration of the pneumopericardium. In puppies, pneumopericardium large enought to reduce heart size by 32 +/- 3% caused decreased mean arterial pressure (-22 +/- 7%) and right ventricular peak systolic pressure (-11 +/- 2%) and increased right ventricular diastolic and intrapericardial pressures. These findings suggest that pneumopericardium per se causes severe hemodynamic compromise. When it is large enought to reduce heart size, drastic circulatory impairment is produced and pericardiocentesis should be performed immediately.


Evaluation of acute post-transplant renal failure by ultrasound.

Autotransplantation of the kidney was performed in seven adult mongrel dogs. A model of acute tubular necrosis (ATN) was developed by subjecting the kidney to warm ischemia (37 degrees C) for 40 to 60 minutes. Serial ultrasound examinations were performed every 12 hours until the animal died or was killed. Sonographic findings were correlated with laboratory and histological data. Throughout the course of ATN, the characteristic normal echo pattern of the kidney remained unchanged in six of seven dogs. In one animal there were changes in the renal cortex, while the medullary pyramids showed no alteration from the base-line study. This contrasts with extensive abnormalities found during rejection.


Hook and snare technique for intravascular retrieval.

A combination of the hook catheter and snare techniques for retrieval of intravascular foreign bodies is described. Using this method, removal time was shortened and the procedure simplified.


Dual actions of prostacyclin (PGI2) on the rat pregnant uterus.

Using strips of rat pregnant uterus, treated with indomethacin to suppress spontaneous contractility, the oxytocic activity of prostacyclin was compared with other prostaglandins. A prostacyclin concentration of 32 ng/ml elicited uterine contractions in all experiments. In this respect prostacyclin was 80 times more active than 6-oxo-PGF1 alpha but less active than PGE2 or PGF2 alpha. Apart from a direct stimulant effect, prostacyclin also exhibited an indirect potentiating action. In threshold concentrations prostacyclin caused a 3-fold potentiation of threshold doses of oxytocin. A lesser 1.5-fold potentiation of PGE2 alpha was also observed. The implications of these findings in relation to prostacyclin playing a role in parturition are discussed.


The major product of PGG2 metabolism by aortic microsomes is 6, 15-dioxo-PGF1 alpha.

Incubations of PGG2 with aortic microsomes yielded two products which were not formed in boiled enzyme control, one of which was 6-oxo-PGF1 alpha. The major metabolite was identified by gas-liquid chromatography-mass spectrometry as 6,15-dioxo-PGF1 alpha. Thus, unlike PGH2, PGG2 is probably converted to 15-hydroperoxy PGI2 which subsequently decomposes to 6, 15-dioxo-PGF1 alpha.


Metabolism of prostacyclin. III. Urinary metabolite profile of 6-keto PGF1 alpha in rat.

The in vivo metabolism of 6-keto PGF1 alpha was investigated in rats. Following continuous intravenous infusion for 14 days the urinary metabolites were isolated and identified. A substantial amount of unchanged 6-keto PGF1 alpha was recovered in the urine. The metabolic pattern very closely resembles that of PGI2 in rats. Metabolites were found which represented 15-dehydrogenation, beta-oxidation, omega and omega-1-hydroxylation and oxidation. Previous work showed that 6-keto PGF1 alpha is very poorly oxidized by 15-PGDH. We administered 15-[H3]-PGI2 and 15-[H3]-6-keto PGF1 alpha to rats and measured urinary tritiated water as an index for in vivo 15-PGDH activity. The results showed that PGI2 and 6-keto PGF1 alpha were both oxidized to the 15-keto product, although the rate of oxidation of PGI2 was greater than that of 6-keto PGF1 alpha. We concluded that the administered PGI2 was oxidized by 15-PGDH before hydrolysis to 6-keto PGF1 alpha. A portion of the dose is probably hydrolzyed before 15-dehydrogenation.


Beneficial actions of prostacyclin in traumatic shock.

Prostacyclin (PGI2) infused at a rate of 350 ng/kg/min significantly increased survival time in rats subjected to Noble-Collip drug trauma from 2.7 +/- 0.3 to 4.6 +/- 0.2 h (p less than 0.01) compared with traumatized rats given only the vehicle (Tris buffer). Moreover, PGI2 treated rats exhibited significantly lower circulating cathepsin D and myocardial depressant factor (MDF) activities, indicative of lower lysosomal disruption and lower toxic factor formation. PGI2 induced vasodilation in rats as well as these other protective effects.


Effects of intracerebroventricular administration of prostaglandins I2, E2, F2 alpha and indomethacin on blood pressure in the rat.

The effects of intraventricularly administered prostaglandins I2 (PGI2), E2 (PGE2), F2alpha (PGF2 alpha) and indomethacin on systemic blood pressure were investigated in conscious rats. PGI2 (1.25--10 micrograms/kg) decreased blood pressure in a dose-related manner, whereas PGE2 (100--1000 mg/kg) dose-dependently increased blood pressure. Both PGF2 alpha (0.31--20 micrograms/kg) and indomethacin (0.625--40 micrograms/kg) had no effects on blood pressure. These results indicate that intraventricular injection of PGI2 or PGE2 can induce significant changes in blood pressure, while endogenous prostaglandins synthesized in the brain seem to play a minor role in direct regulation of systemic blood pressure in the rat.


Arachidonic acid causes lysis of human platelets in an artificial medium: protection by plasma.

Addition of 1 or 2 mM of arachidonic acid (AA) to a washed platelet suspension (WPS) resulted in an instantaneous rise of light transmission (LT) in the platelet aggreagameter. The LT curves showed no evidence ofshape change patterns and the recording pen showed no fluctuations. This rise of LT was not affected by the absence of CaCl2, or the presence of PGI2 or ASA. However, LT curves, showing shape change patterns and with pen fluctuations, were obtained when plasma, serum or albumin was included in the test system. These latter form of LT curves were also obtained in WPS samples exposed to lower concentrations of AA. Electron microscopic examination of these samples revealed varying degrees of lysis of every platelet in WPS exposed to 1 mM of AA. Numerous lyzed platelets were also found in samples either exposed to 0.5 mM of AA in the absence of added plasma, serum or albumin, or exposed to 1 mM of AA in the presence of 5% of added plasma or 2.5 mg/ml albumin. The LT curves of these samples showed shape change patterns and pen fluctuations. These results indicate a pitfall of relying on platelet aggregometry alone in the study of certain AA-induced responses of washed platelets.


[Localization of a gene responsible for ozone sensitivity in Escherichia coli].

A gene, ozrC, responsible for sensitivity to ozone in Escherichia coli, was localized on the E. coli chromosome between argEH and metA by means of analysis of cotransduction frequencies of the gene ozrC with certain gene markers in the malB region of the chromosome.


[An extensive bleeding burn followed by recovery in a hemophiliac].

In a patient with Haemophillia A, of the medium type, suffering from a third degree infected burn of the right lower limb grafting with free sliced skin created a bleeding surface of approximately 1 500 sq. sm. size. Detected, investigated, prepared, followed up and corrected in an efficient manner the patient recovered fully at 9 days after surgery without any complications.


Prostaglandin F2 alpha and cardiovascular system: review of studies conducted in dogs.

The study was designed to investigate the effect of PGF2 alpha on the arterial, cardiac and venous system and the respiration of dogs. PGF2 alpha was administered in single, graded doses as well as by i.v. perfusion. In addition, PGF2 alpha was given intra-arterially into the common carotid artery, by inhalation and by infiltration into the barosensitive zone of the carotid sinus. The interaction by drugs acting on ganglia, the catecholamine stores and the muscarinic, histaminergic, serotonergic, adrenergic and purinergic junctions, and by drugs with depressive effects at the prostaglandin receptors, also were studied. We have shown that PGF2 alpha exhibits direct, reflexes and modulator effects.


Studies on the mode of action of partially thiolated polycytidylic acid (MPC), a novel type of antineoplastic agent.

Partially thiolated polycytidylic acid (MPC), a representative member of the "antitemplate" class of novel chemotherapeutic agents, is a potent inhibitor of the E. coli DNA-dependent RNA polymerase. It inhibited 50% of the enzymic reaction at a concentration of 6 micrometers. Kinetic studies indicated that MPC had no effect on the chain elongation of the transcription process, but it appeared to inhibit the initiation of RNA synthtesis presumably by competing with the DNA template for binding to the RNA polymerase. Binding studies, using a gel filtration method, showed that MPC and the RNA polymerase formed a stable complex which was not dissociated by 0.3 M NaCl. It is inferred that mixed disulfide linkage(s) might have been formed between the enzyme and MPC. The implications of these findings are discussed.


Donor- and organ-specific evaluation of antibodies eluted from canine lung allografts rejected by immunosuppressively treated and untreated recipients.

Using elution techniques, the humoral lung allograft rejection in immunosuppressively treated versus untreated recipients is analyzed at the donor organ specific level. The antibodies were evaluated quantitatively and qualitatively by elution of lung graft bound immunoglobulins and by testing the eluates against donor lung antigen using passive hemagglutination and indirect immunofluorescence. By correlating the results in those assays, a considerable amount of humoral anti-donor lung antibodies could be proved only in dogs not treated immunosuppressively, and there was no accordance with the results of direct immunofluorescence by quantification. The difference in the organ-bound antibodies between immunosuppressively treated and untreated lung grafts seems to be remarkable because of a similar mononuclear infiltration. Thus, enabling a specific improvement of some previous speculations about the lung-specific humoral alloimmune reaction, this type of rejection seems to be similar to rather stereotypical allograft rejection, but may be modified by a standard immunosuppression with methylprednisolone and azathioprine.


[Effects of different levels of PEEP on PaO2, PaCO2, shunt and static compliance in A.R.D.S. (author's transl)].

This study points out that in acute respiratory distress syndrome, the positive end-expiratory pressure (PEEP) had in every case the same action on functional residual capacity and static lung compliance. However its results on PaO2, PaCO2 and circulation are often different from patient to patient according also to the different levels of PEEP. The level of optimal PEEP is that which opens the largest number of alveoli; it is better defined by the value of PaO2 on 100% oxygen than by static compliance.


Intensive therapy of acute hepatic insufficiency in dogs by heterotopic liver allotransplant.

The efficacy of heterotopic liver transplantation to support life and to correct metabolic disturbances in the presence of acute hepatic failure was tested in 70 dogs. Acute hepatic failure was induced by two-stage ischaemic damage to the animals' livers and by biliary obstruction. The donor liver was stored for 3 h by the method of intermittent perfusion. The graft was placed in the right paravertebral gutter. The inflow was arterial only. No immunosuppressive agents were administered. During the postoperative period the main biochemical indices decreased and returned to almost normal values by the fourth day. The auxiliary liver was able to correct the clotting of blood. There was significant regression of encephalopathy, which was confirmed by encephalographic monitoring. Special attention was paid to the adaptation of the stored graft after revascularization. Resuscitation from hepatic failure and subsequent survival of transplanted animals confirmed the significant therapeutic effect of heterotopic allotransplant.


[Optimal positive and expiratory pressure in adult respiratory distress syndrome (author's transl)].

We defined a new optimal positive end expiratory pressure (PEEP) in the adult respiratory distress syndrome (ARDS). The optimal PEEP is the one which allows to obtain a PaO2 greater than or equal to 400 mmHg and/or an intrapulmonary shunt less than or equal to 15 p. cent, the cardiac output being held constant. 14 cases of ARDS have been treated by this method with encouraging results. The earlier optimal PEEP was applied, the more effective it was.


[Functional approach to asthma (author's transl)].

The different pulmonary function tests which enable the diagnosis of asthma and its functional criterium, reversible bronchial obstruction, are reviewed. It is our opinion that in epidemiology where the diagnosis should be made "on the spot" in a simple, rapid and non-aggressive manner, the most appropriate tests are the following: the FEV1 or other forced expiration parameters, to which could be added the measurements of closing volume, the slope of phase III, and/or flow-volume curves using two gas mixtures. The modifiers of bronchomotricity could confirm the reversible nature of the bronchial obstruction.


[The metastatic potential of primary central nervous tumours (author's transl)].

Anatomical and clinical findings in 9 cases of primary brain tumors with metastases within (7 cases) or outside of (2 cases) the nervous system are reported. A review of the published literature revealed 248 cases of histologically-confirmed central nervous system tumors with metastases outside of the nervous system. These secondary sites are seen more frequently in adult males. Their frequency, in descending order, was gliomas (39,5 p. 100), meningeal tumors and sarcomas (28,2 p. 100), neuronal tumors (14,1 p. 100), lymphoma-microgliomas (12,5 p. 100), pineal body tumors (4 p. 100), and melanomas (1,6 p. 100). Ten cases out of 248 developed through a shunt. Nineteen cases were discovered without any surgical operation. There are still many unknown factors concerning their pathogenesis. It appears, however, than in some series of patients the prolongation of the survival-rate and the late effects of surgical operation are positive factors for metastatic dissemination.


Advances in plasmatic fractions used in blood transfusion.

I tried to give a bird's eye view of some of the intriguing recent advances in the production and clinical use of albumin, immunoglobulins, coagulation factors, protease inhibitors and plasma enzyme preparations. I aimed to put into the limelight of my lecture the basic differences between the reaction of plasma proteins in solutions in the test tube or on model surfaces in vitro as opposed to the well-balanced intricate protein-protein and cell membrane-plasma protein interactions in vivo. In the light of these recent advances we have to reassess the biological properties, structural and functional integrity of our plasma protein preparations. In spite of technical and regulatory difficulties new fractionation techniques have to break through. Especially gentle techniques which do not denature proteins are badly needed. Purified albumin with an adequate fatty acid content seems to be the safest and therapeutically most useful preparation among the albumin containing fractions. PPF and even albumin are, however, not so safe as we have thought. There is an urgent need to fight more intensively against their unjustified use. There is a growing need for specific immunoglobulins, coagulation factors, protease inhibitors and therapeutically useful enzyme preparations.


[Arteriographic findings in a Schipper's fracture at the shaft of the femur (author's transl)].

This report on a Schipper's fracture at the shaft of the femur in a twelve-year old boy is preceded by a systematic tabulation of the various non-traumatic types of fracture and a general synopsis of stress fractures. At the time of a first exacerbation of pain which had been persisting for several weeks, the x-ray film showed periostal callus formation and a discrete, transverse zone of increased density. Four weeks later, this zone had widened, the central region showing a fine, tape-like translucence. The arteriogram showed a local increase in the number of vessels in the vicinity of the stress fracture.


[Value of immunofluorescent methods for the diagnosis of inflammatory disorders of the buccal mucosa (author's transl)].

Following their use of immunofluorescent methods for establishing a diagnosis in about fifteen cases of mainly inflammatory disorders of the buccal mucosa, the authors discuss the procedures used and their value in buccal bullous diseases, and also in lupus erythematosus, lichen, and aphthosis.


[Craniofacial trauma. Value and methods of early treatment. 70 cases (author's transl)].

The two essential problems posed by craniofacial trauma are assessed in the light of 70 collected cases. Firstly, the "time" of treatment. Immediate surgery by two teams, neurosurgical and maxillofacial, may be justified in the presence of craniocerebral lesions. This occurs rarely. The cranial problem is often explored during the first 3 or 4 days and with the exception of certain cases of immediate or delayed coma, maxillofacial treatment may be undertaken early. The treatment of cerebrospinal fluid fistulae remains controversial. Secondly, the surgical technique. Accent is placed upon two points which are still discussed : cutaneous phase and bone phase in open trauma ; reconstruction of the cranial level and the facial mass by fixation using plates or steel wire, bone grafts or inert materials, with in particular surgery for fractures of the floor of the orbit in all cases. A number of clinical cases suggest that suitability of eclectism in this surgical approach to craniofacial trauma.


Dissociation of the intrinsic factor--vitamin B12 complex by bile: contributing factor to B12 malabsorption in pancreatic insufficiency.

Human bile incubated with vitamin B12 bound to intrinsic factor in human gastric juice will effectively dissociate this complex, and the vitamin will transfer to non-intrinsic factor unsaturated binding protein(s) contained in bile. Preincubation of the bile with pancreatic enzymes, particularly trypsin, and pepsin, decreases this effect of bile on the intrinsic factor--vitamin B12 complex by digesting the unsaturated binder(s) in the bile. These studies help explain why there is malabsorption of tracer amounts of vitamin B12 in some patients with pancreatic insufficiency, and why this abnormality is correctable by the administration of pancreatic extract.


Carcinoembryonic antigen (CEA) in the gastric mucosa after partial gastrectomy.

Carcinoembryonic antigen (CEA) was studied by the three-layer bridge immunoperoxidase technique in gastric biopsy specimens taken from 49 patients, 13--20 years after partial gastrectomy. Routine histological examination revealed various degrees of chronic atrophic gastritis in all patients. A positive CEA reaction was found in 6 out of 9 with malignant or premalignant mucosal changes and in 4 out of 40 without these changes. In two cases of carcinoma the biopsies revealed a positive CEA reaction. In 4 patients with carcinoma diagnosed 1--2 years after the first examination the initial nonmalignant biopsies were CEA-positive in one case. All biopsies from mucosa with severe dysplasia and adenomatous polyps were CEA-positive. Four patients without malignant or premalignant changes in the gastric mucosa had CEA-positive biopsies. No carcinoma has been found in these patients at re-examinations after 1 year. The results indicate that the occurrence of immunohistochemically detectable CEA may be associated with malignant transformation of the gastric mucosa. The value of this method in screening patients at increased risk of gastric carcinoma will be further explored.


Effect of IgM fractions with or without rheumatoid factor activity on antigen-antibody reactions.

The effect of isolated IgM fractions, with or without rheumatoid factor (RF) activity, on reactions between human albumin and rabbit anti-human albumin, human IgG and rabbit anti-human IgG, and tetanus toxoid and human anti-tetanus toxoid was assessed in the antigen excess zone. RF-active fractions increased and RF-negative IgM fractions decreased the amount of free antigen. The immune complexes that were affected by RF IgM fractions differed in composition from those affected by normal IgM fractions.


The effects of pharmacologic agents on immune-complex-induced redistribution of B-lymphocyte Fc receptors.

The effects of pharmacologic agents on the immune-complex-induced redistribution of B-lymphocyte Fc receptors (and, as a control, the anti-Ig induced redistribution of surface Ig) were examined. Immune-complex-induced capping of B-cell Fc receptors was moderately to markedly inhibited by the combination of colchicine and cytochalasin B, the Ca++ ionophore A23187, and the local anaesthetic lidocaine but was only slightly inhibited by cytochalasin B alone and was not inhibited by colchicine alone. Inhibition of capping was not due to the inhibition of binding of immune complexes to the B-lymphocytes or to decreased cell viability since these effects were absent. Preformed immune complex-Fc receptor caps were disrupted by A23187, lidocaine, and the combination of colchicine and cytochalasin B, but not by either colchicine or cytochalasin B alone. The effects of the pharmacologic agents were similar for Fc receptors and surface Ig in all cases. These results suggest that ligand bound Fc receptors are affected by cytoskeletal structures and that the ligand-induced redistribution of two distinct B lymphocyte surface receptors (fc receptors and surface Ig) occurs by similar or identical mechanisms.


Mouse erythrocyte rosette formation by human lymphoid cell lines.

Lymphoid cell lines have been studied with respect to mouse erythrocyte rosette formation, a marker for B cells. Cells from six B-cell lines out of fifteen tested were able to form mouse erythrocyte rosettes. When this capacity was studied after neuraminidase pretreatment of the cells, it defined three groups of B lymphoid cell lines according to their reactivity. However, these groups could not be correlated to any of the other B-cell markers, and especially mouse erythrocyte rosette formation appeared unrelated to the class of the immunoglobulin present on the cell surface. Non B-cell lines were never found to form such rosettes. The capacity of B-cell lines to form mouse erythrocyte rosette was further demonstrated to be relatively insensitive to trypsin treatment, and results are presented suggesting some degree of cell cycle dependency of the expression of this marker.


In situ effector mechanisms in rat kidney allograft rejection. III. Kinetics of the inflammatory response and generation of donor-directed killer cells.

We have isolated and identified the infiltrating inflammatory cells from rejecting rat kidney allografts. The first host cells to appear in the graft, already a few hours after the transplantation, are monocytes and lymphocytes. Both T and B lymphocytes contribute to the infiltrate: at early stages of rejection most of the infiltrating lymphocytes have the high electrophoretic mobility of (resting) T cells, whereas later during the rejection most of the infiltrating lymphocytes display the slow mobility of (resting) B cells. The blast response follows 2 days after the influx of lymphocytes. The (B) plasmablast response takes place somewhat earlier and is higher in magnitude than the (T) lymphoblast response. Macrophages appear 1.5 days after the influx of monocytes. The inflammatory cells proliferate rapidly: after 1 h of pulse-labelling with 3H-TdR in vivo up to 24% of the infiltrating leucocytes are labelled. Most labelled cells are blast cells or lymphocytes, although a small but distinct population of labelled monocytes is also detected in situ. The in situ blast and proliferative responses precede the corresponding responses in the host central lymphatic system, i.e. spleen, blood and lymph nodes. The inflammatory leucocytes are isolated from the allograft parenchymal cells via 1 g velocity sedimentation. They are strongly and specifically cytotoxic in the 6 h 51Cr release assay to donor-derived lymphoid target cells in vitro. The peak in situ cytotoxic activity in the graft takes place already on day 5 after the transplantation, whereas in the central lymphatic system the cytotoxic cells are detected later and peak values are obtained only after the activity in situ has declined. The findings emphasize the role of the graft as the site of sensitization of kidney transplantation (peripheral sensitization) and the complex nature of the inflammatory response responsible for allograft rejection.


[Specific position of physical therapy in psychiatry].

It is pointed out that in modern psychiatry physical therapy has to be integrated as therapeutic tool beside psychopharmacology, verbal psychotherapy and occupational therapy. The expression physical therapy is used here in a large sense. As an example endogenous depression is chosen to show which conditions are necessary when using physical therapy in a rational way. Concerning the other groups of psychiatric disorders it was referred in the book "Physikalische Therapie in der Psychiatrie" ("physical therapy in psychiatry").


[Music therapy, its indications, goals and possibilities].

After a short historical introduction the author presents an overview on the various methods used in music therapy with respect to their goals and their limits. There are quite different forms of receptive and active music therapy in individual and group therapy. Finally, the author describes the evolution of two cases of individual music therapy.


[Senile plaques, neuro-fibrillar degeneration and other associated cerebral lesions (morphology and pathogenetic theory].

A brief review about present knowledge on morphology of brain degenerative alterations in the elderly, their topography, their correlations and the various pathogenic theories. The particular pathoclisis of some areas is reported, i.e. the pathoclisis of some hippocampal areas for neurofibrillary tangles and senile plaques, the pathoclisis of the IVth layer of calcarinian cortex for dyshoric angiopathia. These morphological pecularities must be correlated to more recent data concerning alterations of neurotransmitters and their enzymes.


[History of the Psychiatric Outpatient Clinic of Basel].

On the fourth of June 1923 the Psychiatric out-patient clinic was opened in the city of Basle as an administratively affiliated, but locally separated department of the Psychiatric University Hospital. The first head of the Psychiatric out-patient clinic was Jakob Klaesi, who was a head-physician in the Friedmatt at the same time. The life and work of the various directors of the out-patient clinic are mentioned. Developmental tendencies in the Psychiatric out-patient clinic--which moved 1977 into the general Hospital (Kantonsspital)--and the various diagnoses with the course of time are discussed.


Prolapsed lumbar disc treated with intramuscularly administered dexamethasonephosphate. A prospectively planned, double-blind, controlled clinical trial in 52 patients.

Prompted by previously results of systemic steroid treatment of symptoms of prolapsed lumbar disc, which appeared to be promising, dexamethasone phosphate was tested in a controlled, double-blind clinical study. 52 patients were included in the study: 25 received dexamethasone phosphate, 24 received placebo and 3 patients dropped out. Upon termination of the study the two groups were found to be comparable as to age, sex, duration of symptoms and degree of heavy work. We were not able to demonstrate any effect of dexamethasone phosphate on the following parameters pain, paraesthesia, paresismuscular weakness, disturbances of reflexes, and Laseque. Nor was there any difference in the length of hospitalization.


Bronchial carcinoma. III. Quantitative measurements of the quality of survival. A prospective randomized study of the result of therapy in inoperable patients with localized disease.

Fifty-four bronchial carcinoma patients in clinico-anatomical stages 1-3 of the disease (localized disease) were randomly assigned to groups for radiotherapy, cyclophosphamide and placebo treatment, respectively. The results were assessed by the survival time and the quality of survival. The median survival time was 6.7 months for radiotherapy, 12.4 months for cyclophosphamide and 11.3 months for placebo. The median total sum of vitagram points was 44.5 for radiotherapy, 90.2 for cyclophosphamide and 81.8 for placebo. When calculated per month, the median sum of vitagram points was 6.2 for radiotherapy, 6.6 for cyclophosphamide and 7.0 for placebo. No significant differences were found between the treatment groups with respect to average survival time and and average vitagram point sums.


[Systemic lupus erythematosus--clinical aspects and laboratory findings].

In a retrospective multicenter study 106 patients with systemic lupus erythematosis were analyzed who had had the disease for an average of 8.6 years, and from whom an average of 8 sera were tested within 3 years for current immunologic parameters. Cumulative clinical data showed arthropathies in 86% of the patients, exanthema (67%), cytopenia (58%), and involvement of the kidney (45%), lung (43%) and heart (24%). In at least 1 serum per patient the following immune abnormalities were found: antinuclear antibodies (98%), anti-native DNA (92%), low C3 (71%), low C4 (82%), circulated immunocomplexes (70%) and cold lymphocytotoxins (46%). A clinical score and an immunological score was introduced and the two items were compared: the immune data from a single serum do not provide long-range prognostic information. The present disease state is best reflected by the total immune score, C3 and C4 with, however, many exceptions. Within the disease course of some SLE patients, periods were observed during which no pathological immune serologic data are measureable. This phenomenon may pose diagnostic problems.


Cold lymphocytotoxins in connective tissue disorders.

Sixty-eight patients with various connective tissue disorders, 5 relatives of patients and 26 members of staff from the Centre for Rheumatic Diseases were studied for the presence in their sera of cold lymphocytotoxic antibodies. Antibodies were found in 71 percent of patients with systemic lupus erythematosus, 27 per cent of patients with rheumatoid arthritis, 0 per cent of the small group of relatives and 3.8 per cent of the controls. Absorption studies did not show T or B specificity of the antibodies. The control group, working in close proximity to the patients or their sera did not show any increased incidence of antibodies as compared to control groups of other studies. Red blood cell anti I or HI was found in the sera of 28 per cent of those with cold lymphocytotoxic antibodies. No correlation was found between the presence of the antibodies and number of blood transfusions or pregnancies, increasing age, R3 titre or antinuclear factor.


Antibacterial prophylaxis--a clinician's view.

The principles of antibacterial prophylaxis and its advantages and disadvantages are reviewed. Controlled trials have shown chemoprophylaxis to be beneficial notably in preventing recurrences of rheumatic carditis and urinary infections and in controlling sepsis after cardiac and hip joint surgery and mid thigh amputations. The recently introduced metronidazole prophylaxis for gastrointestinal and gynaecological operations appears highly effective. The use of prophylaxis is briefly discussed in other situations where its value is less certain or where, in the author's opinion, it is contraindicated.


Overview of some aspects of occurrence, formation and analysis of nitrosamines.

This review principally addresses a number of aspects of the occurrence and formation of the nitrosamines, highlighting principal areas of potential concern ranging from the spectrum of nitrosatable moieties found in the environment (e.g., secondary and tertiary amines, quaternary ammonium compounds, ureas, carbamates and guanidines), specific examples of nitrosamines found in food, alcoholic beverages, feed (and their significance for carcinogenesis bioassays), air and water. The factors influencing in vitro and in vivo nitrosation and the evidence for the latter in man are also discussed. Additionally, germane areas of the analysis of nitrosamines are reviewed with a focus on the major areas of concern and requirements of extreme sensitivity and selectivity in addition to the problems of artifacts in the analytical procedures.


Heparin: an old drug with a new paradigm.

Recent studies have shown that heparin is a biochemical representative of a distinct class of compounds known as linear anionic polyelectrolytes. Members of this class are mixtures of individual highly negatively charged chains that show a wide spectrum of specific reactions with biologically active proteins. Upon administration, heparin chains enter a cellular pool and effectively prevent thrombosis by increasing the electronegative potential of the vessel wall. Anticoagulant activity is an unusual feature of a few heparin chains and appears to play a minor role in many clinical uses and in physiological and pathological responses.


Antibodies to sporozoites: their frequent occurrence in individuals living in an area of hyperendemic malaria.

Serum samples from 158 West Africans were tested for antibodies against sporozoites, the vector stage of the malaria parasite. Antibodies specific for Plasmodium falciparum sporozoites were detected by means of the circumsporozoite precipitation assay and indirect immunofluorescence. More than 90 percent of the serum samples from adults gave positive immunofluorescent reactions against falciparum sporozoites, whereas most of the samples from children gave low or negative reactions.


Calcium dependence of toxic cell death: a final common pathway.

Primary cultures of adult rat hepatocytes were treated in the presence or absence of extracellular calcium with ten different membrane-active toxins. In all cases more than half the cells were killed in 1 to 6 hours in the presence but not in the absence of extracellular calcium. An effect of calcium on the primary mechanism of membrane injury by any of the agents cannot be implicated. Viability, as determined by trypan blue exclusion correlated well with other indices of viability such as plating efficiency and the hydrolysis of fluorescein diacetate. It is concluded that the cells are killed by processes that involve at least two steps. In each type of injury, disruption of the integrity of the plasma membrane by widely differing mechanisms is followed by a common functional consequence involving extracellular calcium, and most likely representing an influx of calcium across the damaged plasma membrane and down a steep concentration gradient. This later step represents, or at least initiates, a final common pathway for the toxic death of these cells.


Rapid killing of single neurons by irradiation of intracellularly injected dye.

A simple technique for rapidly killing all or part of single neurons consists of filling the cell with Lucifer Yellow CH and irradiating all or part of it with intense blue light. Such treatment kills the irradiated part of the cell within a few minutes. Adjacent cells are not affected.


Rheumatic syndromes in endocrine disease.

It is not widely appreciated that endocrine disease may present primarily as rheumatic syndromes, sometimes spectacular in onset, more commonly insidious and subtle, making their true recognition difficult. The underlying hormonal, biochemical, and metabolic events have understandable reflection in the structure and function of bone, joint, and muscle.


Pharmacology of the neonate.

Drugs need not necessarily be administered directly to the neonate, but may reach the newborn infant as a result of drug administration to the mother during gestation, at parturition, or during the course of lactation. The processes of absorption, distribution, metabolism and excretion of drugs in the neonate are discussed. Differences between the neonate and the adult in this regard are outlined. The pharmacology and pharmacokinetics of specific drugs to which the neonate may be exposed are discussed.


Rudolf Virchow and Heinrich Schliemann. An essay on the friendship of two great men.

This essay briefly relates the great friendship between two great men whose origins and curricula vitae differed exceedingly, but whose common scientific interest in archaeology was to unite them closely. Virchow, a medical doctor, and Schliemann, a doctor of science, were able eventually to secure safekeeping for the Trojan treasure discovered by Schliemann, whose contributions to the culture of our Western civilization have not been surpassed. What has happened to the Trojan treasure since the occupation of Berlin is a question still unanswered.