High incidence of nitrosamine-induced tumorigenesis in mice lacking DNA repair methyltransferase

The enzyme O6-methylguanine-DNA methyltransferase repairs alkylation- induced DNA damage, O6-methylguanine and O4-methylthymine, the former being formed more frequently. Previously, by means of gene targeting, we generated mice in which alleles for methyltransferase were disrupted. We now use these mouse lines, which are totally deficient in methyltransferase activity, to examine protective effects of the enzyme against tumor formation. In gene-targeted female mice given an i.p. injection of 5 mg/kg of dimethylnitrosamine, a larger number of liver and lung tumors occurred, as compared with normal female mice treated in the same manner. In male mice given a lower dose of carcinogen, the difference between normal and gene-targeted mice was statistically insignificant although more tumors did form in the gene-targeted mice. Methyltransferase apparently afforded protection from nitrosamine- induced tumorigenesis.      

Experience of expandable metallic stents for central airway obstruction

The aim of this study was to investigate retrospectively the efficacy of expandable metallic stents (EMSs) for severe respiratory distress in patients with central airway obstruction. Twenty patients with central airway obstructions were treated with an EMS. An intraluminal stricture was present in 15 and an extraluminal stricture in 5 patients. Of the 15 patients with intraluminal stenosis, 11 exhibited symptomatic improvement. All 11 patients had tumor infiltration occupying less than 50% of the endoluminal diameter. The other four patients with intraluminal stenosis had tumor infiltration occupying > 50% of the endoluminal diameter and demonstrated no improvement. All five patients with extraluminal stenosis were improved. EMS is useful for an extraluminal stricture in the central airway and the effect of EMS for intraluminal stenosis is related to the degree of infiltration and of tumor progression itself.      

Laser-induced fluorescence studies of the biodistribution of carotenoporphyrins in mice.

The biodistribution of two recently developed tumour markers, trimethylated (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour-bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after administration, the carotenoporphyrin fluorescence was measured in tumoral and peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities. The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the first one is close to the peak of the tissue autofluorescence. The tumour and the liver were the two tissue types showing the strongest carotenoporphyrin-related fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak substance-related fluorescence. In most tissue types, the fluorescence intensities decreased over time. A few exceptions were observed, notably the liver, in which the intensity remained remarkably constant over the time period investigated.     

Herzoperationen wegen Herztumoren in Deutschland – Ergebnisse eienr Umfrage für das Jahr 1996

Zusammenfassung Zahlen zur H?ufigkeit von Herztumoren im operativen Krankengut liegen bisher für die Bundesrepublik Deutschland nicht vor. Um einen entsprechenden überblick für das Jahr 1996 zu erhalten, wurde allen 77 herzchirurgischen Zentren der Bundesrepublik Deutschland ein standardisierter Fragebogen zugesandt. Daten von 65 der 77 Herzzentren (=84%) waren schlie?lich verfügbar: 187 Patienten waren wegen Myxomen, lediglich 44 wegen nichtmyxomat?sen Tumoren, davon 28 wegen malignen prim?ren oder sekund?ren Herztumoren, operiert worden. Im Jahr 1996 waren somit 0,32% (231/72 763) der Eingriffe mit Herz-Lungen-Maschine (erfa?t 72 763 von insgesamt 87 372) wegen eines Herztumors vorgenommen worden. Ausgehend von diesen operativen Daten liegt die Inzidenz ausschlie?lich der prim?ren Tumoren des Herzens zumindest bei 3 Tumoren pro 1 Million Einwohner pro Jahr (253 Tumoren/81,814 Millionen Einwohner). Wenn auch kleine Tumoren asymptomatisch und unentdeckt bleiben k?nnen, wird heute doch die Mehrzahl prim?rer kardialer Tumoren durch Echokardiographie, Computer- und Kernspintomographie bereits zu Lebzeiten des Patienten diagnostiziert, und diese Patienten werden in aller Regel einer Operation zugeführt. Somit werden gut 0,3% aller Eingriffe mit Herz-Lungen-Maschine in Deutschland wegen Herztumoren durchgeführt, wobei es sich weit überwiegend um Myxome handelt. Eingegangen: 23. September 1997, Akzeptiert: 11. Februar 1998     

Value of contrast-enhanced MRI of breast after silicone implant

Summary Early recognition of recurrence and work-up of clinically indeterminate lesions may be impaired after reconstruction with silicone implants due to superimposition of the implant or to scarring. This study was undertaken to evaluate the use of contrast-enhanced MRI in patients with silicone implant after breast cancer. Contrast-enhanded MRI was offered to 169 patients. Comparative two- to three-view mammography was also performed in 169 patients, as well as comparative sonography in 144 patients. Conventional imaging and clinical examination detected only 8/13 recurrences, whereas 12/13 were detected by MRI. One recurrence had been visible as a strongly enhancing 2-mm dot in a previous examination (2 years before), but was not called. It was therefore counted as false negative. In addition, multicentricity was detected by MRI alone in two of three cases. MRI correctly diagnosed scar tissue in all cases with indeterminate findings. However, due to false-positive calls caused by enhancing granulomas specificity could not be improved. Contrast-enhanded MRI allowed decisive additional information in our study group and improved the sensitivity significantly (concerning all diagnoses). Contrast-enhanded MRI is recommended in patients with diagnostic problems or high risk of recurrence after silicone implants.      

Is colonic electrical activity a similar phenomena to small-bowel electrical activity?

PURPOSE: This study was designed to investigate colonic spike bursts regarding 1) their migration behavior, 2) their pressure correlates, and 3) comparing colonic short spike bursts with spike bursts from migrating myoelectric complex from the small bowel. METHODS: Rectosigmoid electromyography and manometry were recorded simultaneously in seven normal volunteers and electromyography alone in five others during two hours of fasting and for two hours after one 2,100-kJ meal. One patient with an ileostomy was also studied by the same method to record the migrating myoelectric complex from the terminal ileum during fasting. RESULTS: Three kinds of spike bursts were observed in the pelvic colon: rhythmic short spike bursts, migrating long spike bursts, and nonmigrating long spike bursts. The meal significantly increased the number of migrating and nonmigrating long spike bursts (from 25 to 38.7 percent of the recording time; P <0.01). These bursts of potentials showed a peak 15 minutes after the meal, which may be caused by the gastrocolic reflex. Migrating long spike bursts started anywhere along the rectosigmoid and migrated from there aborad 82 percent of the time and orad or in both directions in 10 or 7 percent of the time, respectively. They originated pressure waves 99 percent of the time. Short spike bursts were more frequent before the meal (15.1 percent before and 9.6 percent after the meal), but the difference was not significant; they neither propagated nor initiated pressure waves detected by the miniballoon. CONCLUSIONS: Migrating long spike bursts were the only potentials that migrated, sometimes for short distances. Short spike bursts are a different phenomenon from the small-bowel migrating myoelectric complex because they do not migrate; they can occur during the postprandial period and never originated intraluminal pressure waves.Supported by a grant from the Instituto Nacional de Investigação Científica, Proc. DBI-22086.Presented at the meeting of the Portuguese Congress of Gastrenterology, Vila Moura, Portugal, June 2 to 5, 1993.     

Conditionally replicating luciferase reporter phages: improved sensitivity for rapid detection and assessment of drug susceptibility of Mycobacterium tuberculosis.

TM4 is a lytic mycobacteriophage which infects mycobacteria of clinical importance. A luciferase reporter phage, phAE40, has been constructed from TM4 and was previously shown to be useful for the rapid detection and drug susceptibility testing of Mycobacterium tuberculosis. However, the lytic nature of the phage results in a loss of detectable light output and limits the sensitivity of detection. We describe several strategies aimed at improving the luciferase activity generated by TM4 luciferase phages, including (i) varying the position of the luciferase gene in the phage genome, (ii) isolating host-range mutants of the phage, and (iii) introducing temperature-sensitive mutations in the phage such that it will not replicate at the infecting temperature. Several new phages generated by these methods show increased intensity of luciferase production compared to the first-generation reporter phage phAE40, and one phage, phAE88, also demonstrates an enhanced duration of luciferase activity. This has allowed the detection of as few as 120 BCG cells and the determination of drug susceptibilities of M. tuberculosis in as little as 1 day.     

Oligoclonal populations of T and B cells in a case of angioimmunoblastic T-cell lymphoma predominantly infiltrated by T cells of the VB5.1 family.

AIMS: Immunohistological and molecular characterisation of a case of peripheral T-cell lymphoma (PTCL) of angioimmunoblastic T-cell lymphoma (AILD) type. METHODS: Frozen and paraffin wax sections of the diagnostic lymph node were stained with a panel of T- and B-cell lineage monoclonal antibodies. DNA was isolated from the paraffin wax embedded biopsy material for T-cell receptor (TCR) and immunoglobulin (Ig) PCR amplification, and resultant PCR products were cloned and sequenced. RESULTS: Immunohistological analysis of the presenting lymph node was consistent with an extensive infiltrate of pleomorphic CD3+CD8+ lymphocytes. Most (>80%) of these infiltrating CD3+ cells were also positive for the TCR VB5.1 gene family product, and were shown to be oligoclonal by TCRB PCR amplification and sequencing. Three oligoclones of B cells were also demonstrable by PCR amplification with Ig heavy chain primers and sequencing, a finding at variance with the diagnosis of AILD. CONCLUSIONS: These data demonstrate the complexity and heterogeneity of PTCL which require extensive histological examination and molecular characterisation.     

Antigenicity of a synthetic peptide from glucosyltransferases of Streptococcus mutans in humans.

Human salivary immunoglobulin A (IgA) and serum IgG antibodies to the Streptococcus mutans glucosyltransferases (Gtfs) and to a synthetic peptide of 19 amino acids from a conserved region in the Gtfs (residues 435 to 453) were determined in young adults by enzyme-linked immunosorbent assay. Varying levels of antibody to Gtfs were detected in saliva or serum, with significantly higher levels of antibody to GtfD than to GtfB/C or GtfC. Anti-Gtf IgA levels in saliva did not correlate with those of IgG in serum. Caries-free (CF) volunteers exhibited significantly higher salivary IgA antibody levels to the peptide and to GtfB/C or GtfC than did the caries-active (CA) subjects. Preincubation of CF saliva and serum with the peptide inhibited the antibodies to the Gtfs in a dose-dependent manner, whereas preincubation of the samples from the CA group resulted in only partial inhibition. Our results indicated that this 19-amino-acid peptide includes one of the major B-cell epitopes of Gtfs and that CF individuals have higher titers of antibodies than CA subjects.