Diagnosis of arterial atherosclerosis using laser-induced fluorescence

A study of the potential of laser-induced fluorescence for the characterization of human atherosclerotic plaque is reported. Pathologically-characterized specimens from autopsies were investigated using a pulsed nitrogen laser (λ=337 nm) as the excitation source and an optical multichannel analyser for the analysis of the fluorescence. Characteristic spectral features at 395, 420, 450 and 480 nm were utilized in forming different dimensionless contrast functions which were tested for discrimination properties. Plaque from aorta and coronary arteries was examined and could clearly be differentiated from the surrounding, histologically normal vessel wall. Imaging fluorescence measurements, processed for contrast enhancement, are also reported. Implications for spectroscopically guided laser angioplasty are discussed.     

Nucleic acid labeling with [3H]orotic acid and nucleotide profile in rats in protein deprivation, enteral and parenteral essential amino acid administration, and 5-fluorouracil treatment

Rats were fed a 0% casein diet for 1 week, with or without enteral or parenteral administration of essential amino acids, or a 25% casein diet, in one group supplemented with 5-fluorouracil treatment. Ninety minutes before sacrifice the rats were given a tracer of [3H]orotic acid. Incorporation into the acid soluble fraction, RNA, and DNA was determined in liver, small intestine, bone marrow, and kidney. Nucleotide profile was examined in liver and intestine. Protein deficiency caused inter alia a decrease in body weight; a decrease in RNA/DNA ratio and an increase in the specific RNA labeling in liver and kidney; an altered nucleotide profile in the liver; an increase in the nucleotide/DNA and RNA/DNA ratios and a decrease in the specific labeling of the acid soluble fraction, RNA, and DNA in the bone marrow. These changes were prevented to the same extent by giving essential amino acids, either orally or intravenously. The minor changes in intestinal nucleotide profile in protein deprivation were prevented to a slightly larger extent by amino acids orally than parenterally. 5-Fluorouracil treatment gave a decrease in the RNA/DNA ratio in the liver and kidney but an increase in the nucleotide/DNA and RNA/DNA ratios in the bone marrow. Nucleotide profiles were unaltered. The amount of DNA per gram of tissue decreased in bone marrow and increased in kidney. Parenteral administration per se resulted in almost no changes.     

Potentiation by dipyridamole of 5-fluorouridine antitumor activity against a rat adenocarcinoma in vivo

Rats were inoculated subcutaneously into both flanks with a transplantable adenocarcinoma of the colon. They were treated intravenously with either 5-FUrd (5-fluorouridine) or 5-FdUrd (5-fluoro-2'-deoxyuridine) with or without addition of dipyridamole 20 and 30 min later, respectively, for 3 consecutive days. Dipyridamole improved the antitumor activity of 5-FUrd but decreased that of 5-FdUrd.     

Effect of N-phosphonacetyl-L-aspartate and D-glucosamine on the incorporation of 5-fluorouridine into normal tissues and an adenocarcinoma in the rat

Cytostatic treatment of liver metastases from colorectal cancer has been of limited value. Higher drug levels in the target substances of the tumor may improve the results. It was the aim of this investigation to examine the effect of PALA (N-phosphonacetyl-L-aspartate) and D-glucosamine on the level of uracil nucleotides in the liver and in an N-methyl-N-nitrosoguanidine-induced adenocarcinoma of the colon transplanted to the liver of rats, and on the incorporation of 3H-FUrd into the acid-soluble fraction, the RNA and the DNA of the tumor and of several normal tissues. Combined treatment with PALA and D-glucosamine reduced the UTP pool in the liver and the tumor. D-glucosamine alone increased UDP-N-acetyl-hexosamine in liver tissue. Pretreatment with PALA and D-glucosamine increased incorporation of 3H-FUrd into RNA of the liver and kidney, and into the DNA fraction of the liver, but had no effect on 3H-FUrd incorporation in the tumor.     

The antitumor effect of a novel nitrosourea, tauromustine, at intravenous administration in rat. Cure of hepatomas.

The effect of intravenously injected tauromustine (TCNU) on tumor growth and body weight was studied in rats with subcutaneously implanted experimental carcinomas. With a colonic tumor, a single dose or that dose split on 4 consecutive days gave the same tumor growth delay but the body weight loss was less at the split dose. Injection of the single dose for 1 min, 30 min or 2 h each had the same effect. Rats of another strain were implanted with a hepatoma. 9 out of 10 rats were cured. A late effect was body weight loss due to disturbed growth of the teeth.     

High prevalence of Helicobacter Species detected in laboratory mouse strains by multiplex PCR-denaturing gradient gel electrophoresis and pyrosequencing

Rodent models have been developed to study the pathogenesis of diseases caused by Helicobacter pylori, as well as by other gastric and intestinal Helicobacter spp., but some murine enteric Helicobacter spp. cause hepatobiliary and intestinal tract diseases in specific inbred strains of laboratory mice. To identify these murine Helicobacter spp., we developed an assay based on PCR-denaturing gradient gel electrophoresis and pyrosequencing. Nine strains of mice, maintained in four conventional laboratory animal houses, were assessed for Helicobacter sp. carriage. Tissue samples from the liver, stomach, and small intestine, as well as feces and blood, were collected; and all specimens (n = 210) were screened by a Helicobacter genus-specific PCR. Positive samples were identified to the species level by multiplex denaturing gradient gel electrophoresis, pyrosequencing, and a H. ganmani-specific PCR assay. Histologic examination of 30 tissue samples from 18 animals was performed. All mice of eight of the nine strains tested were Helicobacter genus positive; H. bilis, H. hepaticus, H. typhlonius, H. ganmani, H. rodentium, and a Helicobacter sp. flexispira-like organism were identified. Helicobacter DNA was common in fecal (86%) and gastric tissue (55%) specimens, whereas samples of liver tissue (21%), small intestine tissue (17%), and blood (14%) were less commonly positive. Several mouse strains were colonized with more than one Helicobacter spp. Most tissue specimens analyzed showed no signs of inflammation; however, in one strain of mice, hepatitis was diagnosed in livers positive for H. hepaticus, and in another strain, gastric colonization by H. typhlonius was associated with gastritis. The diagnostic setup developed was efficient at identifying most murine Helicobacter spp.     

Focal nodular hyperplasia of the liver, benign hepatomas, oral contraceptives and other drugs affecting the liver.

Due to the claim of an association between focal nodular hyperplasia of the liver, benign hepatomas and oral contraceptives, the files in the departments of pathology at the university hospitals in Lund and Malm? were examined for these two diagnoses made since 1945 and 1957, respectively. 26 cases of focal nodular hyperplasia of the liver and 7 benign hepatomas were found, 18 and 2, respectively, in women. Since 1963, the year before oral contraceptives were introduced in Sweden, focal nodular hyperplasia has been diagnosed in 8 women in the reproductive period of life; 4 of these had taken oral contraceptives. The 4 diagnoses were established in 1972-1974. At most, 25 per cent of Swedish females between the ages of 15 and 44 years have been on oral contraceptives. The Swedish series of 28 patients with focal nodular hyperplasia comprised 3 epileptics and 3 diabetics. At least two of the epileptics had been treated with barbiturates and/or hydantoins. The prevalence of drug-treated epilepsy in Sweden is 0.4-0.5 per cent, and of diabetes about 2 per cent. The possible aetiological role of drugs provoking an increase of the smooth-surfaced endoplasmic reticulum of the liver and proliferation of vascular fibrous tissue in a part of the liver which preveiously may have been damaged by vascular disturbances or trauma, is considered. No relationship between benign hepatomas and drugs was found. The observations support the notion that oral contraceptives may be of aetiological importance in the development of focal nodular hyperplasia of the liver, although the material is too small for epidemiological and statistical analysis.     

Fatal varicella generalisata in a child with immunopathy and hereditary neurological syndrome

Summary A 4-year-old girl with immunopathy and a hereditary neurological syndrome [previously described in Acta Paediat. Scand. 55, 264 (1966)] succumbed with varicella generalisata. At autopsy hemorrhagic lesions were found in the skin, liver, lungs, pancreas and spleen. With the light microscope intranuclear inclusion bodies were seen in the liver, lungs and spleen. Under the electron microscope viral particles were found in these three organs and in the pancreas. Virus isolation in human embryonic cells with characteristics of varicella proved positive for heart-blood, skin and lungs. In the cerebrum there was a dysplasia of nerve cells in the cortex and basal ganglia and heterotopic nerve cells were found in the white matter. In the cerebellum there was a patchy loss of Purkinje cells, probably a dysplasia. Non-specific degeneration was seen in dorsal root ganglia and in the lateral corticospinal tracts. A younger brother of the patient shows a similar neurological syndrome. It seems reasonable to assume that the neurological syndrome is genetically determined. Whether an immunopathy is present in the brother is not known at present.

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Tödliche generalisierte Varicelleninfektion bei einem Kind mit Immundefekt und hereditärem neurologischem SyndromeFallbericht mit Autopsie, Elektronenmikroskopie und Virusisolierung

Zusammenfassung Ein 4 Jahre altes Mädchen mit Immundefekt und hereditärem neurologischem Syndrome [frühere Publikation in Acta Paediat. Scand. 55, 264 (1966)] verstarb an einer generalisierten Varicelleninfektion. Bei der Sektion fanden sich ausgedehnte hämorrhagische Nekrosen im Bereich der Haut, Leber, Lungen, Milz und des Pankreas. Lichtmikroskopisch konnten intranucleäre Einschlußkörper in der Leber, Milz und in den Lungen nachgewiesen werden. Außerdem wurden elektronenmikroskopisch Viruspartikeln in der Leber, Milz, den Lungen und im Pankreas beobachtet. Eine für Varicellen charakteristische Virusisolierung gelang durch Übertragung von Herzblut, Haut- und Lungengewebe auf menschliche embryonale Zellkulturen. Im Gehirn fanden sich die Zeichen einer Fehlbildung in Form von Nervenzelldysplasien in der Hirnrinde und den basalen Ganglien sowie einer Heterotopie von Nervenzellen in der weißen Substanz. Im Kleinhirn war ein unregelmäßiger Schwund von Purkinjezellen — wahrscheinlich ebenfalls als Ausdruck einer Dysplasie — nachweisbar. In den dorsalen Wurzelganglien und in den lateralen corticospinalen Bahnen bestand eine unspezifische Degeneration. Ein jüngerer Bruder zeigt ein sehr ähnliches neurologisches Syndrom wie die verstorbene Schwester. Es wird daher die Annahme vertreten, daß das neurologische Syndrome genetisch determiniert ist. Ob auch bei dem Bruder ein Immundefekt vorhanden ist, ist vorerst noch nicht bekannt.