"Twin meiosis" and other ambivalences in the life cycle of Schizosaccharomyces pombe.

Diploid cells of the yeast Schizosaccharomyces pombe carrying the mating-type allele h(90) are capable of sporulation and copulation. After copulation karyogamy does not always occur. In this case both nuclei will undergo meioses separately (twin meiosis). Asci with eight haploid spores derive from this event. Diploid cells homozygous for the mating-type alleles h(+) or h(-) do not sporulate. However, their nuclei can perform meiosis when they are in a common cytoplasm with a diploid nucleus of compatible mating type.

Mating-Type Mutations in SCHIZOSACCHAROMYCES POMBE: Isolation of Mutants and Analysis of Strains with an h or h Phenotype.

Mutants defective in various steps of the sexual cycle have been isolated from homothallic strains of Schizosaccharomyces pombe by Bresch, Müller and Egel (1968). These mutants include heterothallic h(+) and h(-) strains. We have isolated additional h(+) and h(- ) mutants from homothallic strains. Those mutants which are due to mutations in the mating-type region were analyzed in detail. Our results show that the mating-type gene mat2 not only has a function in copulation and meiosis, but that it also regulates the formation of the map1 gene product (map1 is a mating-type auxiliary gene). Some of the h( -) mutants have lost only one of the three functions while others are defective in at least two, and perhaps all three, functions. Further, we show that the mat1(-) allele of h(90) strains can mutate to mat1(+) but that mutations in mat2 appear to affect the mutational behavior of mat1. Finally, we describe a new inactive mating-type allele, mat2*, which is different from mat2(0) in that it can mutate to mat2(+).

Influence of the mat1-M Allele on Meiotic Recombination in the Mating-Type Region of SCHIZOSACCHAROMYCES POMBE.

Angehrn and Gutz (1968) have shown that homozygosity for the mat1-M allele in diploid strains of Schizosaccharomyces pombe increases mitotic recombination between his7 and mat2. In this paper, we report that meiotic recombination frequencies can vary from 3.4 to 16.1 percent between his7 and his2 and that this variation is due to the combination of alleles at the mat1 and mat2 loci.

A new type of mutation in Schizosaccharomyces pombe: vegetative iodine reaction.

Colonies of Schizosaccharomyces pombe that contain ascospores (e.g., colonies of homothallic strains) turn black after treatment with iodine vapors. Heterothallic strains of S. pombe normally do not show this reaction. In experiments with the latter strains we found mutants which exhibit a positive iodine reaction though they do not contain ascospores. This phenotype is due to mutations in a new gene, vir1 (vegatative iodine reaction). The vir1 locus is not linked with the mating-type genes.--Strains of mating-type h-S are known not to give any spontaneous mating-type mutations. Mating-type mutations were also not found after treatment with nitrous acid.

Two Different h Mating Types in SCHIZOSACCHAROMYCES POMBE.

In the strains of Schizosaccharomyces pombe introduced by Leupold (1950, 1958) into genetic research, heterothallic and homothallic mating types are known. The mating types are determined by two closely linked genes. We show that two distinct heterothallic - mating types exist: a stable one (h(-S)) and an unstable one (h(-U)), which can mutate to heterothallism + and homothallism. A proposal for incorporation of the new mating type h(-U) into Leupold's two-gene scheme is discussed.

Gene conversion: a hitherto overlooked parameter in population genetics.

Gene conversion causes deviations from the 2:2 segregation of allele pairs in meiosis. Thus, gene conversion is a potential cause for changes of allele frequencies in populations. Equations are derived for the effects of conversion in a large random-mating population. The influence of gene conversion on allele frequencies is compared with that of spontaneous mutation and meiotic drive.

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.

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.

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.

[Drug therapy of peptic ulcer]. / Medikamentöse Therapie des Ulcus pepticum

Though the proper genesis of peptic ulcer is still unknown, one can proceed from the fact that the cause of the development of the defect is a disturbance of the equilibrium between aggressive and defensive factors on the surface of the stomach. It is taken the view that an uncomplicated ulcus duodeni and ulcus ventriculi should be treated in the outpatient department. Strong diet prescriptions are certainly not necessary, reduction of the consumption of nicotine and avoidance of nutrients increasing secretion and individually incompatible is, however, necessary. In duodenal ulcer anticholinergic remedies and antacids are the basis of the therapy as before; other principles of treatment are only of subordinated significance. In ulcus ventriculi a reduction of quality and quantity of the gastric mucus play, perhaps, an etiologic role. Since, apart from this, a reflux of bile takes place, the derivations of the Succus liquiritiae which further the formation of mucus and the Cerucal furthering the peristalsis are to be regarded as most essential therapeutic remedies. But principle of the therapy of ulcer must always be not only to treat the diseased organ, but to try to influence therapeutically on the whole man with his conflicts which are sometimes difficult to be solved and which manifest themselves only in the gastro-intestinal tract.

[The importance of endoscopy in oncology]. / Die Bedeutung der Endoskopie in der Onkologie

The importance of the praetherapeutic histological manifestation of tumours is emphasized. In many cases for this purpose an endoscopy with biopsy is necessary. A particular role plays the endoscopy in urology, bronchology and gastroenterology. The endoscopy significantly developed by the introduction of fully flexible glass fibre endoscopes. This particular considers the gastroenterology. Several regions, such as the duodenum, the small intestine and the colon, were thus first accessible to endoscopic biopsy. Indications and possibilities of the individual endoscopic methods are mentioned. As to the question, who individually should perform the endoscopy, the opinion is expressed that every specialist should perform the endoscopy in his field. The performance of all endoscopic methods by one specialist, independent on the speciality, actually gives some technical advantages, which, however, do not compensate the disadvantages concerning a qualified total diagnostics of the diseases. During the last years by the removal of the polyps the endoscopy in an increasing stage also becomes a therapeutic method. At present the technical possibilities of endoscopy came to a certain close. By all means necessary is, however, the further distribution of the endoscopic methods which depends on the availability of adequate endoscopes.

[The gastroscopic diagnosis of early stomach carcinoma]. / Die gastroskopische Erfassung des Magenfrühkarzinoms

A short report is given on the development of diagnostics of early gastric cancers, whereby it is especially referred to the importance of the Japanese investigations of this phenomenon. The notion of the early carcinoma for gastric carcinomata which have affected only the mucous membrane or only in a slight degree the submucosa is widespread. But it contains a notion of time which is falsely presumed. As we at present do not certainly know, whether the early gastric carcinomata, all over the world known as "early cancer", really could not fail in developing to advanced gastric carcinomata, the name "early" carcinoma is questionable. Concerning this question further investigations are necessary, which should be directed to the definition of a risk group of gastric cancer. Finally is reported on own results in the diagnosis of 12 early gastric cancers.

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⁺).

Gene activation by copy transposition in mating-type switching of a homothallic fission yeast.

Mating-type switching in homothallic clones of the fission yeast, Schizosaccharomyces pombe, appears to follow the same route as previously found for "mutations" from homothallism to heterothallic ⊕ strains. A copy of mat2-P is transposed to and inserted at mat1, where it functionally replaces the mat1-M allele, and only the mat1 segment is expressed (!) to determine the actual mating type: mat1-M(!) mat2-P = ⊖ ⇌ ⊕ = mat1-P(!) mat2-P. This phenomenon has hitherto been concealed by the high switch-back rate from ⊕ to ⊖ observed in homothallic wild-type strains. It only becomes apparent in the presence of mutant "switching genes", which retard the rates of mating-type interconversion and temporarily freeze one or the other state of gene activation at the mat1 segment. Mutations to lowered rates of switching are found to map both inside and outside the mating-type locus. While the internal mutations of this kind exert their effect autonomously in the cis-configuration, the unlinked mutations are recessive to their wild-type alleles.

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.