Hyperspeckled mutants of Schizosaccharomyces pombe: frequent mating-type switching without detectable double-strand breaks.

Mating-type (MT) switching in homothallic (h90) strains of Schizosaccharomyces pombe is initiated by a DNA double-strand break (DSB) at the distal end of the expression cassette mat1. The cis-acting smt-s1 mutation C13-P11 reduces the frequency of MT switching. It is a small deletion mapping approximately 50 bp distal to the site of the DSB. From the h90 smt-s1 strain we isolated 13 mutants with a hyperspeckled iodine reaction. In these mutants the frequency of MT switching is increased. The mutations define nine different hsp genes, none of which maps in or close to the MT region. We tested one mutant of each gene for the presence of DSBs at mat1. Curiously, in none of the h90 smt-s1 hsp strains could DSBs be detected, although some sporulate nearly as efficiently as the h90 smt-n wild type. The hsp mutations show no effect in smt-0 strains; the smt-0 deletion abolishes MT switching completely. Furthermore, we tested the interaction of hsp1-1 with swi1, swi2 and swi7 mutations. hsp1-1 has no effect in swi2 strains, whereas it increases MT switching in swi7 and, to a lesser degree, in swi1 mutants.

Pantoprazole versus omeprazole in the treatment of acute gastric ulcers.

BACKGROUND: Pantoprazole is a new substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+,K(+)-ATPase. METHODS: The proton pump inhibitors pantoprazole and omeprazole were compared in a randomized, double-blind study in 219 patients with benign gastric ulcers. Patients received either pantoprazole 40 mg (n = 146) or omeprazole 20 mg (n = 73), once daily before breakfast for 4 weeks. Treatment was extended for a further 4 weeks if the ulcer had not healed. RESULTS: After 4 weeks, complete ulcer healing was seen in 88% of protocol-correct patients given pantoprazole and in 77% given omeprazole (between-group difference P < 0.05). At 8 weeks, the corresponding values were 97% and 96% (not significant). In the comparative intention-to-treat analysis there were no statistical differences between the treatment groups. Among the patients who had ulcer pain prior to treatment, 79% of the pantoprazole group and 68% of the omeprazole group were pain-free after 2 weeks, and after 4 weeks 88% and 81%, respectively (not significant). Pronounced improvement in the other gastrointestinal symptoms was seen in both groups. Only 10% of patients in each group reported adverse events. There were moderate increases in fasting serum gastrin levels with both treatments at 4 and 8 weeks. CONCLUSION: Pantoprazole, 40 mg once daily in the morning, is a highly effective, well tolerated treatment for acute, benign gastric ulcer. Pantoprazole and omeprazole were equally safe in the therapy of gastric ulcer.

The mating-type region of Schizosaccharomyces pombe contains an essential gene encoding a protein homologous to human modulators of HIV transactivation.

In Schizosaccharomyces pombe, an intrachromosomal crossover between the mating type (MT) expression locus and one of the silent donor cassettes is lethal due to the loss of the intervening L region. The region contains one essential gene, let1. This gene was cloned and sequenced. The deduced amino acid (aa) sequence of let1 shows extensive homologies with SUG1 from Saccharomyces cerevisiae. Significant homologies were also found with the human HIV transactivation modulators, MSS1 and TBP-1, as well as with subunit 4 of the mammalian 26 S protease. The data indicate that let1 is a member of a recently defined multigene family of ATPases.

Theoretical analysis of the effects of mitotic crossover in large yeast populations.

In a diploid yeast population which is heterozygous for a given marker, A1A2, mitotic crossover (mit. c.o.) between the centromere and the marker will give rise to homozygous daughter cells, A1A1 and A2A2. Since this causes a decrease in the frequency of A1A2 cells, mit. c.o. is an important population genetic process in vegetatively propagated yeast cultures. The effect of mit. c.o. is counteracted by mutations and, in the case of heterosis, by selection. We present a mathematical analysis of these interactions.

Analysis of DNA repair pathways of Schizosaccharomyces pombe by means of swi-rad double mutants.

In Schizosaccharomyces pombe 11 different switching genes (swi1 to swi10 and rad22) are known which are involved in mating-type (MT) switching. Mutations in swi5, swi9, swi10 and rad22 also cause an increased radiation sensitivity. We tested whether the survival of these mutants after UV irradiation is influenced by caffeine. We included rad1 and rad13 mutants in our experiments which do not affect MT switching. Several double and triple mutants were constructed. We were able to assign the switching genes to different repair pathways: swi9 and swi10 are involved in excision repair, rad22 has a function in recombination repair, while swi5 appears to be involved in a hitherto unknown pathway. This 'swi5 pathway' is stimulated (!) by caffeine. Previously it was found that the swi5 mutation also reduces meiotic recombination. As to rad genes, we found a few inconsistencies with previous reports in the literature.

Mating configurations in Schizosaccharomyces pombe strains of different geographical origins.

In genetic research with Schizosaccharomyces pombe the strains used are almost exclusively descendants of the clones originally isolated by Leupold. In the "standard" homothallic (h90) strain three closely linked mating-type (MT) genes are present in the MT region: the actual MT locus, mat1, and two silent cassettes, mat2 and mat3, respectively. Various rearrangements are known in the MT region, e.g., heterothallic h+ or h- strains arise by duplications or deletions. In the present paper we analysed the mating behavior and the configurations of the MT regions of 19 S. pombe isolates from different parts of the world. In comparison with the Leupold strains several new MT configurations were found.

A mutated swi4 gene causes duplications in the mating-type region of Schizosaccharomyces pombe.

Efficient mating-type (MT) switching in homothallic strains of Schizosaccharomyces pombe is significantly reduced if they have a mutation in any of the eleven known swi genes. The swi4 mutation causes heterothallic as well as homothallic segregants, both of which have duplications in the MT region. In contrast to homothallic strains, h+ swi4 strains yield only a few duplications. The duplications originate in the process of MT switching, presumably by mistakes in the resolution of DNA intermediates. They always consist of one cassette and one of the intervening sequences, L and K respectively. Strains with up to seven cassettes in the MT region were found. The possible modes of their origins are discussed.

Some of the swi genes of Schizosaccharomyces pombe also have a function in the repair of radiation damage.

In Schizosaccharomyces pombe the frequency of mating-type (MT) switching is reduced by mutations in the swi genes. The ten hitherto known swi genes can be subdivided into three classes: Ia, Ib and II. Strains having swi5 (class Ib), swi9 (class II) and swi10 (class II) mutations do not only show reduced MT switching, but also exhibit an increased sensitivity to UV- and gamma-rays. For that reason, 19 previously described rad genes were tested for their effect on MT switching. We found that swi9, "rad10", "rad16" and "rad20" are allelic with each other indicating that the former allocation of these rad mutations to three different genes must have been erroneous. Among the remaining 16 rad genes examined, rad22 seems to be a new class II swi gene. The double mutants swi5 swi9 and swi5 swi10, but not swi9 swi10, are much more sensitive to radiation than the respective single mutants. Thus a cumulative increase in sensitivity occurs only if the mutants belong to different classes; previously the same correlation was found with regard to cumulative effects in MT switching.

DNA distribution pattern in chronic gastritis. I. DNA ploidy and cell cycle distribution.

DNA distribution patterns were flow cytometrically recorded in gastric biopsy specimens from patients with chronic gastritis (CG) and chronic atrophic gastritis (CAG). DNA aneuploidy was found in 3 of 58 patients with CG and in 7 of 82 patients with CAG. Cell cycle analysis disclosed significantly higher percentages of cells in S-phase and G2M-phase, respectively, in CAG than in CG. With regard to the proliferative activity the total CAG group could be partially differentiated by the degree of severity. CAG with total atrophy showed significantly higher percentages of cells in S-phase than CAG with mild and moderate atrophy. CAG without dysplasia showed lower percentages of cells in S-phase and G2M-phase than CAG with severe dysplasia (p greater than 0.05). The occurrence of intestinal metaplasia was correlated to a significantly higher percentage of cells in G2M-phase.

[Atrophic corpus gastritis and autoimmune gastritis]. / Atrophische Korpusgastritis und Autoimmungastritis.

The authors tried to clarify relations between autoimmune gastritis and isolated atrophic corpus gastritis by bioptic corporal and antral examinations from 150 probands as well as examinations of gastrin in serum and parietal cell antibody tests. Only 30% of all patients examined with isolated atrophic gastritis of the corpus part revealed criteria of an autoimmune gastritis. Therefore investigations of antibodies against parietal cells are necessary to mark off both clinical pictures. This differentiation seems to be necessary regarding the high risk of gastric cancer following an autoimmune gastritis.

[Signet-ring-cell lymphoma. Light and electron microscopic study of gastric involvement]. / Das Siegelringzellymphom Eine licht- und elektronenmikroskopische Studie bei Befall des Magens.

The authors report on a malignant Non-Hodgkin lymphoma of the stomach of a 73-year-old male. Histologically, it was revealed to be a follicularly growing, obviously secondary centroblastic lymphoma. Crystalline cytoplasmic inclusions in numerous centrocytes have led to displacement of the nucleus to the cell margin and thus to the picture of a signet-ring-cell lymphoma. Electronmicroscopically, there were found big crystalline electron-dense deposits in the rough endoplasmic reticulum. The finding was compared with literature data, and the histological differential diagnosis is discussed.

Switching genes in Schizosaccharomyces pombe.

In homothallic (h 90) Schizosaccharomyces pombe strains mutants occur which exhibit reduced frequencies of mating-type switching. The colonies of such mutants show a mottled iodine reaction. The underlying mutations map either in a switching signal at matl or in switching (swi) genes which are not linked to the mating-type region. Forty-nine swi mutants were examined. They map in ten different swi genes, swil to swil 0. Seven swi genes were assigned to chromosomes I and II, respectively. - Two classes of swi genes can be distinguished: when plated, class I mutants yield only mottled colonies, whereas class II mutants yield mottled and iodine-negative colonies (most of the latter are h⁺).

A comparative study of early gastric cancer.

Authors provided a comparative study of early gastric cancers (EGC) which were found in the Cancer Research Centre of the Academy of Medical Sciences of USSR (Group A) and in the Central Institute of Cancer Research of the Academy of Sciences of GDR (Group B). The most frequent EGC-type in group B was type II, while types I and III were more frequent in group A. The rate of lymph node metastases in group A was 4,54% versus 16,2% in group B. Multicentric cancers were more often found in group A. These findings strengthen the opinion that early gastric cancer is not a uniform biological entity. Accuracy of x-ray and gastroscopic diagnoses was higher in group A. This fact surely contributes to the better prognosis of early gastric cancer in this group.

Difference in chromatin sensitivity to heparin of chronic atrophic gastritis, of carcinoma-free and carcinoma-bearing stomach in comparison with normal gastric mucosa and gastric carcinoma as revealed by flow cytometry.

DNA distribution patterns from gastric mucosal cells corresponding to four groups defined by histological examination were measured by flow cytometry before and after treatment with heparin, a polyanion. Group I comprised normal gastric mucosal cells; group II, chronic atrophic gastric mucosal cells originating from a carcinoma free stomach; group III, chronic atrophic gastric mucosal cells originating from a carcinoma bearing stomach; and group IV, malignant gastric mucosal cells. The heparin concentrations used were 1.25, 1.5, and 5 U/ml cell suspension. Heparin caused increases in fluorescence intensity and in coefficients of variation, which are interpreted as a reflection of alterations in chromatin structure. For the four groups investigated, the heparin-initiated changes were dependent, in varying degree, on concentration and time. Group I showed a much more extensive sensitivity to heparin than group IV. Group II and III reacted similarly to group I or group IV, depending on the source, i.e., either a carcinoma-free stomach or a carcinoma-bearing stomach. Further extension of this method might yield information concerning the real premalignant potential of a specific case of chronic atrophic gastritis.