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In eubacteria, the tRNA transglycosylase (Tgt) in specific tRNAs exchanges a guanine in the anticodon for 7-aminomethyl-7-deazaguanine, which is finally converted to queuosine. The tgt gene of Escherichia coli has been mapped at 9 min on the genome, and mutant pairs containing an intact or mutated tgt allele were obtained after transduction of the tgt locus by P1 bacteriophages into a genetically defined E. coli strain (S. Noguchi, Y. Nishimura, Y. Hirota, and S. Nishimura, J. Biol. Chem. 257:6544-6550, 1982). These tgt mutants grew anerobically with fumarate as an electron acceptor, while nitrate or trimethylamine N-oxide could not be reduced. Furthermore, molybdate reductase activity was almost lacking and the characteristic absorption maxima, corresponding to cytochrome a1 and the cytochrome d complex, were not detectable in low-temperature reduced-minus-oxidized difference spectra in anaerobically grown cells. Transduction of the mutated tgt locus into another E. coli recipient resulted in tgt mutants without anaerobic defects. Transformation of the original tgt mutants with an fnr gene-containing plasmid reversed the anaerobic defects. Clearly, the original tgt mutants harbor a second mutation, affecting the anaerobic regulator protein Fnr. The results suggest that fnr is involved in anaerobic control of components of the cytochrome d complex and of the redox system that transfers electrons to molybdate. F' plasmids containing a fused lacI-lacZ gene with the nonsense codon UAG at different positions in the lacI part were transferred to E. coli strains with a mutated or nonmutated tgt locus but intact in fnr. A twofold increase in the frequency of incorrect readthrough of the UAG codon, dependent on the codon context, was observed in the tgt mutant and is suggested to be caused by a tRNA(Tyr) with G in place of queuosine.

By using a [(signal) + (noise)] − (noise) digital averaging technique in order to reduce the offset drift, an improvement of about a factor 100 has been obtained in the sensitivity of a pyroelectric detector array (PDA). Different applications of the apparatus for measurement of infrared and far‐infrared beam characteristics are also presented.

The effect of immunosuppressive agents in different glomerulopathies is reviewed and some guidelines for their use in clinical practice are proposed. The immunological aspects of pyelonephritis and interstitial nephritis are studied to evaluate future possibilities of either therapeutic immunosuppression or immunization in these diseases.

Native glutathione S-transferases are composed of subunits with apparent molecular weights of 25,000, 23,500, or 22,000 which form either homo- or heterodimers. Glutathione S-transferases A, C, and X which contain two subunits with molecular weights of 23,500 yielded similar but nonidentical proteolytic fragmentation patterns. Fragments unique to the subunits of the homodimers A and X were present in decreased intensities in the patterns of form C. Two-dimensional electrophoresis under denaturing conditions showed single nonoverlapping spots for transferases A and X, while form C yielded two spots corresponding in position to those obtained from forms A and X. Renaturation of dissociated glutathione S-transferase C yielded enzymatically active transferases A, C, and X. These results indicate that form C is a heterodimer composed of one subunit from the homodimeric transferases A and X. This was substantiated by NH2-terminal sequence analysis showing extensive NH2-terminal homology amongst all three forms. However, in the positions where forms A and X yielded different residues, both amino acids were detected in the sequence of form C, indicating that the two subunits of Mr = 23,500 are the products of two different genes. NH2-terminal sequence analysis of the heterodimeric glutathione S-transferase B which is composed of subunits with molecular weights of 22,000 and 25,000 revealed a single unique sequence which bore no resemblance to the sequences of either forms A or X. Despite the identical NH2-terminal sequences, proteolytic fragmentation of the separated subunits showed markedly different fragmentation patterns. This indicates that two different mRNAs code for these two subunits.

Das Auftreten von Komplikationen wahrend und nach operativen Eingriffen last sich trotz Verbesserung der Anaesthesiemethoden nicht sicher ausschliesen. Die Auswertung von rund 30 000 Narkoseprotokollen des eigenen Institutes erbrachte, das Herzrhythmusstorungen im intra- und postoperativen Verlauf als Komplikation in ihrer Haufigkeit hinter den Hypotensionen an zweiter Stelle liegen. Im wesentlichen sind Tachyarrhythmien, Extrasystolien und Uberleitungsstorungen zu nennen.

HELP code is employed to study the impact to a projectile on heavily confined, inert, solid explosive Comp B3. Temperature rise due to shock compression and plastic deformation, in both the explosive and the metal confinement, is estimated. In addition, the effect of variation of the imapct parameters, such as projectile diameter, projectile velocity and confinement thickness on the rise in temperature is studied. It is concluded that usually shock is a dominant mechanism responsible for significant heating of the explosive. However, in certain situations, plastic deformations may lead to violent reaction in confined explosives.

The complement system may be activated by two pathways, the classical and the alternate. To evaluate their respective participation in different forms of glomerulonephritis, the plasma values of C3, C4, C3PA, C1q and properdin were determined in 70 patients. In systemic lupus erythematosus (LED), acute poststreptococcal glomerulonephritis (AGN) and septicemia the classical pathway appears to be mainly involved, whereas the amplification loop and the alternate pathway seem to be of secondary importance. By contrast, in membranoproliferative glomerulonephritis (MPGN) the alternate pathway plays a major role. However, the present data suggest that activation of the classical pathway may often be involved as well. In minimal change glomerulonephritis no signs indicating involvement of the complement system were apparent. Follow-up observation demonstrated a correlation between decreases in plasma complement concentrations and the clinical severity of the primary disease in LED, AGN and septicemia, but not in MPGN.

In a retrospective study of 34 patients with hairy cell leukemia treated with recombinant interferon-alpha 2, we have observed a hematological remission rate of 97%. The true complete remission rate based on bone marrow findings was 17%. Although complete remissions can be obtained only in a few cases, treatment with interferon is justified in cytopenic patients since long-standing clinically meaningful improvement of the peripheral blood values can be attained. If interferon is stopped in the remission phase, the blood values deteriorate in 40% of the patients within 5 months. In contrast, it appears that the remission can be maintained with intermittent administration of interferon weekly or even every other week. As compared to splenectomized patients, granulocyte recovery is delayed in nonsplenectomized patients. However, after several months of treatment there is no difference in peripheral blood values between splenectomized and non-splenectomized patients. In the light of the present results, primary splenectomy remains justified in a selected group of patients for whom the risk of surgery (due to low granulocytes and/or platelets) is low and for whom careful evaluation predicts a high potential for long-standing remission after splenectomy. In the other cases, initial interferon therapy seems justified.

A rabbit antiserum was prepared against the C-terminal peptide of 21 amino acids from the human heat shock protein hsp70. These antibodies were shown to be specific for this highly inducible heat shock protein (72 kilodaltons [kDa] in rat cells), and for a moderately inducible, constitutively expressed heat shock protein, hsc70 (74 kDa). In six independently derived rat cell lines transformed by a murine cDNA-genomic hybrid clone of p53 plus an activated Ha-ras gene, elevated levels of p53 were detected by immunoprecipitation by using murine-specific anti-p53 monoclonal antibodies. In all cases, the hsc70, but not the hsp70, protein was coimmunoprecipitated with the murine p53 protein. Similarly, antiserum to heat shock protein coimmunoprecipitated p53. Western blot (immunoblot) analysis demonstrated that the hsc70 and p53 proteins did not share detectable antigenic epitopes. The results provide clear immunological evidence for the specific association of a single heat shock protein, hsc70, with p53 in p53-plus-ras-transformed cell lines. A p53 cDNA clone, p11-4, failed to produce clonable cell lines from foci of primary rat cells transfected with p11-4 plus Ha-ras. A mutant p53 cDNA clone derived from p11-4, SVKH215, yielded a 2- to 35-fold increase in the number of foci produced after transfection of rat cells with SVKH215 plus Ha-ras. When cloned, 87.5% of these foci produced transformed cell lines. SVKH215 encodes a mutant p53 protein that binds preferentially to the heat shock proteins of 70 kDa compared with binding by the parental p11-4 p53 gene product. These data suggest that the p53-hsc70 protein complex could have functional significance in these transformed cells.

The effect of a minimal intervention strategy on maintenance of weight lost through either energy restriction alone or exercise alone during the previous year was studied in a sample of middle-aged men. At the end of the initial year of weight loss, dieters (n = 44) and exercisers (n = 46) were randomly assigned to either an intervention condition, comprising monthly mailed informational packets and monthly to quarterly telephone contacts, or an assessment-only condition. The intervention had a significantly greater impact on weight maintenance in exercisers than it did in dieters. In addition, dieters showed a more variable pattern of weight gain and weight loss during the maintenance year than did exercisers. Based on 7-day food records and a 7-day physical activity recall questionnaire, exercisers reported a greater energy intake and a greater amount of time spent in vigorous activity relative to dieters at both the beginning and the end of the maintenance year. We conclude that exercise is easier to maintain in men using minimal contact strategies than dietary approaches to weight control focusing on modification of energy intake, with subsequent benefits in terms of both overall maintenance and stability of weight.

Kaum ein anderes Narkosemittel hat so viele Diskussionen entfacht wie Ketamine. Die Ursache liegt in den besonderen pharmakologischen Eigenschaften, die die Substanz von allen bisher bekannten Anaesthetika unterscheidet. Die kreislaufstimulierende Wirkung, die sich in einem Anstieg von Blutdruck und Pulsfrequenz ausert, konnte in ihrer klinischen Bedeutung eher kritisch beurteilt werden, da sie mit einer Erhohung des Sauerstoffverbrauchs sowie einer Herabsetzung der Ischamietoleranz des Herzens gekoppelt ist.

Rifampicin (RMP) induziert nach mehrtagiger Gabe die mischfunktionellen Oxygenasen in der Leber, so das auch sein eigener Metabolismus beschleunigt wird (Eigeninduktion, Acocella 1978a). Wie wir beobachteten, nahmen die RMP-Plasmaspiegel unter oraler Dauertherapie starker ab als bei intravenoser Applikation (Musch et al. 1982; Loos et al. 1983). Klinisch zeigten 30 initial mit RMP intravenos behandelte Patienten mit offener Lungentuberkulose eine schnellere Sputumnegativierung und Rontgenbefundbesserung im Vergleich zu 48 oral therapierten Patienten (Kombinationstherapie: RMP-Isoniazid-Ethambutol). So war z. B. die Sputumkulturkonversion nach dem 1. Behandlungsmonat bei intravenoser RMP-Gabe doppelt so hoch (63%) wie bei oral behandelten Patienten (27%). Der Azetyliererstatus wie auch die tagliche Gabe von 5 oder 10 mg Isoniazid/kg Korpergewicht oder die Verabreichung von Streptomycin anstatt von Ethambutol hat dagegen keinen wesentlichen Einflus auf den Behandlungserfolg im 1. Monat. Entscheidend war vielmehr, das unter intravenoser RMP-Gabe hoher Plasmaspiegel, auch Spitzenkonzentrationen, uber die ersten Behandlungswochen erreicht wurden als bei oraler RMP-Applikation. Als Erklarung fur diesen unterschiedlichen Therapieerfolg und Plasmaspiegel-verlauf erscheint eine Induktion des RMP-Metabolismus in der Darmschleimhaut moglich (Musch et al. 1982).

We have investigated the responsiveness of established rat hepatocyte cell cultures to inducers of cytochrome P-450. One Reuber hepatoma-derived line (Fu5-C8), which under normal culture conditions produces no detectable cytochrome P-450(MC) or cytochrome P-450(PB)--the major cytochrome P-450 isozymes induced by 3-methylcholanthrene and phenobarbital, respectively--was tested for the ability to accumulate either cytochrome P-450 isozyme in response to treatment with various xenobiotics. By immune-precipitation from [35S]-methionine-labeled cell extracts, using monospecific anticytochrome P-450(MC) antibody or monoclonal anticytochrome P-450(PB) antibody, it was demonstrated that these cells possess the capability to synthesize cytochrome P-450(MC) in response to 3-methylcholanthrene treatment, while none of the drug treatments caused the synthesis of detectable quantities of cytochrome P-450(PB). RNA extracted from Fu5-C8 cells directed the in vitro synthesis of immune-precipitable cytochrome P-450(MC) only after treatment of the cells with 3-methylcholanthrene. Kinetic analysis of the response of these cells to 3-methylcholanthrene induction revealed detectable levels of immune-precipitable cytochrome P-450(MC) 2 h after drug treatment with maximal induction occurring between 12 and 16 h of exposure. Another cell line (HF 1.5), obtained originally by hybridization of Fao X H5 variants of a Reuber H35 hepatoma, produces cytochrome P-450(MC) and also cytochrome P-450(PB) constitutively, as determined by specific immune-precipitation from labeled cell extracts. Exposure of confluent monolayers to either phenobarbital or 3-methylcholanthrene resulted in an induction of cytochrome P-450(PB) or cytochrome P-450(MC), respectively. Double-labeling immunofluorescence studies indicate that all cells in the culture produce albumin and most of the cells produce cytochrome P-450(MC), but only a subset of cells synthesize cytochrome P-450(PB). Our results demonstrate that some continuously dividing hepatocyte cell cultures retain the capacity to respond to xenobiotics, including phenobarbital, a response which is typically exhibited by fully differentiated liver cells. Such established hepatocyte cell cultures should prove useful for investigating the mechanism of induction of cytochrome P-450(PB).

ROENTGENOGRAMS of the wrists of children taken casually during the past few years, in private practice, have revealed such a large number of unsuspected conditions that the procedure has now been established as routine. There are a number of pathologic entities in children the existence of which can frequently be readily detected or suggested by roentgenograms of the wrists. Of these, some may be discovered at their incipience, while in others, which are in advanced or clinically obscure stages, focus may be brought for the first time on the underlying cause by the use of this procedure. The distal ends of the ulna and radius are the optimal sites for the demonstration of the earliest rachitic lesions by roentgenogram. All of the metaphysial changes of scurvy appear earliest and are most marked at the sites of most rapid growth and most active endochondral bone formation, among which are the distal

It is well known that tumor necrosis factor (TNF) can have both contrary and pleiotropic effects in anti-tumor immune response. In the present study, we prepared two different tumor cell-based immunotherapy models: MCA38 adenocarcinoma and GL261 glioma intracranial interleukin-2 (IL-2)-based. Each tumor was transfected to express IL-2 with or without expression of the soluble form of tumor necrosis factor receptor type II (sTNFRII). Although mice in which TNF is blocked survive longer than IL-2 alone (35.2 versus 26 days), the reverse was observed for GL261 glioma. The differential effect on tumor growth implies enhanced TNF sensitivity of GL261 compared to MCA38. This notion is supported by the observation that TNF induces apoptosis in GL261 but not MCA38 tumors. We further examined tumor infiltrating CD11b+F4/80+ macrophages (or tumor-associated macrophages: TAM) for TNF production in vivo and found that TAM express cell surface TNF implying a role in eliminating glioma cells mediated by the cell surface form of TNF.

Commentary on Robinson, W. T. 1988. Marketing mix reactions to entry. Marketing Sci. 7 368–385.

Commentary about the article Dolan, R. J. 1987. Quantity discounts: Managerial issues and research opportunities. Marketing Sci. 6 1–22.

• The effect of a minimal intervention strategy on maintenance of weight lost through either energy restriction alone or exercise alone during the previous year was studied in a sample of middle-aged men. At the end of the initial year of weight loss, dieters (n = 44) and exercisers (n = 46) were randomly assigned to either an intervention condition, comprising monthly mailed informational packets and monthly to quarterly telephone contacts, or an assessment-only condition. The intervention had a significantly greater impact on weight maintenance in exercisers than it did in dieters. In addition, dieters showed a more variable pattern of weight gain and weight loss during the maintenance year than did exercisers. Based on 7-day food records and a 7-day physical activity recall questionnaire, exercisers reported a greater energy intake and a greater amount of time spent in vigorous activity relative to dieters at both the beginning and the end of the maintenance year. We conclude that exercise is easier to maintain in men using minimal contact strategies than dietary approaches to weight control focusing on modification of energy intake, with subsequent benefits in terms of both overall maintenance and stability of weight. (Arch Intern Med.1989;149:2741-2746)

Forty-seven patients with jejunal diverticulosis were identified at the University California, Davis Medical Center, Sacramento, by a review of patient medical records from 1980 to 1986. Fourteen patients had complications that could be directly attributed to the presence of diverticula. Six patients had evidence of a malabsorption syndrome and responded to administration of broad-spectrum oral antibiotics. One patient had recurrent bouts of an asymptomatic pneumoperitoneum. A total of seven patients required operative intervention for the following conditions: massive gastrointestinal tract bleeding, two patients; mechanical small-bowel obstruction, two patients; and diverticulitis with perforation, three patients. One patient died. Nineteen patients had symptoms of epigastric pain, early satiety, and bloating for which no cause other than the presence of jejunal diverticulosis was found. Jejunal diverticulosis was an incidental finding in 14 patients treated for other gastrointestinal tract problems.

Meeting abstracts T cells play a critical role in host defense against viruses, intra- and extracellular microbes, and tumors. Because foreign antigen is presented amongst a vast majority of self-antigens, T cells have evolved the unique ability to discriminate "self" from "non-self" with high