Saccharomyces cerevisiae cells lacking the homologous pairing protein p175SEP1 arrest at pachytene during meiotic prophase.

Saccharomyces cerevisiae cells containing null mutations in the SEP1 gene, which encodes the homologous pairing and strand exchange protein p175SEP1, enter pachytene with a delay. They arrest uniformly at this stage of meiotic prophase, probably revealing a checkpoint in the transition from pachytene to meiosis I. At the arrest point, the cells remain largely viable and are cytologically characterized by the duplicated but unseparated spindle pole bodies of equal size and by the persistence of the synaptonemal complex, a cytological marker for pachytene. In addition, fluorescence in situ hybridization revealed that in arrested mutant cells maximal chromatin condensation and normal homolog pairing is achieved, typical for pachytene in wild type. A hallmark of meiosis is the high level of homologous recombination, which was analyzed both genetically and physically. Formation and processing of the double-strand break intermediate in meiotic recombination is achieved prior to arrest. Physical intragenic (conversion) and intergenic (crossover) products are formed just prior to, or directly at, the arrest point. Structural deficits in synaptonemal complex morphology, failure to separate spindle pole bodies, and/or defects in prophase DNA metabolism might be responsible for triggering the observed arrest. The pachytene arrest in sep1 cells is likely to be regulatory, but is clearly different from the RAD9 checkpoint in meiotic prophase, which occurs prior to the pachytene stage.

[Familial Mediterranean fever. Case of a 48-year-old patient with recurrent abdominal pain]. / Familiäres Mittelmeerfieber. Ein Fall eines 48 Jahre alten Patienten mit rezidivierenden Bauchschmerzen.

A 48 year-old male patient from Turkey underwent laparotomy 13 years before admission to one unit because of persistent pain in the upper abdomen and fever. Subsequently, he was repeatedly admitted to surgical departments with recurrent upper abdominal pain and fever. The patient was admitted for medical investigation to our department with fever and left pleuritic pain. During this observation period he repeatedly had attacks of fever lasting for one day with leucocytosis. The diagnosis of familial Mediterranean fever was made. Therapy with colchicine (1.5 mg/day) led to complete remission, maintained over the follow-up period of 2 years to date.

[Radionuclide imaging of parathyroid adenoma using the 201TI-99mTc substraction scintigraphy method]. / Mellékpajzsmirigy adenoma kimutatása 201TI-99mTc subtractiós szcintigráfiás eljárással.

Primary hyperparathyroidism is the most frequent parathyroid disease. Parathyroid adenomas account for the majority of primary hyperparathyroidism (81%) while carcinoma and diffuse hyperplasia occur less frequently (4% and 15%). Ten per cent of adenomas are located substernally. The difficulties of preoperative localization of parathyroid adenomas may lead to incomplete surgical removal. Therefore an accurate technique for preoperative localization of the parathyroid gland is of utmost importance. Various imaging methods are available (ultrasonography, computer tomography, angiography, etc.), each with their own limitations. Thus, a nuclear technique performed via 201Tl-99mTc dual isotope subtraction scintigraphy may well contribute to the safety of diagnostics. The authors present a case of parathyroid adenoma diagnosed by this method and confirmed histologically. The role of non-invasive techniques in preoperative localization of parathyroid adenomas protecting the patient from invasive procedures and repeated surgical explorations is highly emphasized.

Synthesis of potent heptapeptide analogues of cholecystokinin.

Nine new analogues of acetyl-CCK-heptapeptide (Ac-Tyr(SO3H)2-Met3-Gly4-Trp5-Met6-Asp7-Phe8-NH2 ) were synthesized by solid-phase methodology. In a first series, the Asp7 residue was replaced by hydroxy amino acid sulfate esters. In another series, Gly4 was substituted by D-Ala, while Trp5 and Met6 were replaced by their D enantiomer. The introduction of the sulfate ester was performed with a new, mild, crystalline, and stable reagent, pyridinium acetyl sulfate. Each analogue that contained Tyr(SO3H)2 and a hydroxy amino acid sulfate ester [Ser(SO3H), Thr(SO3H), or Hyp(SO3H)] in position 7 proved to be more potent (1.9, 1.7, and 3.0 times, respectively) than CCK-8 in vitro (isolated gallbladder strips). While devoid of gastrin-like activity in vivo, these analogues had potent anticonvulsive activity. The analogues containing a D-amino acid residue were less potent than the parent compound in vitro. The D-Ala4 replacement, however, yielded a compound that was 40% as potent as CCK-8 in the in vitro test but showed prolonged duration of action on sphincter Oddi. While the 7-substituted Ac-CCK heptapeptides are among the most potent CCK analogues reported so far, the D-Ala4 replacement resulted, for the first time, in prolonged activity in vivo.

Pentagastrin analogues containing alpha-aminooxy acids. VII. Catabolism in vivo and in vitro of a pentagastrin analogue containing N-terminal aminooxyacetyl residue.

In rat, BOC-NHO-1-14C-Ac-Trp-Met-Asp-Phe-NH2 (14C-I) is metabolised more slowly than BOC-1-14C-Gly-Trp-Met-Asp-Phe-NH2 (14C-II). Of the cytosol fractions of the rat organs the lung and pancreas exhibited a lower activity in the catabolism of BOC-NHOAc-Trp-Met-Asp-Phe-NH2 (I) than in that of BOC-Gly-Trp-Met-Asp-Phe-NH2 (II). In contrast, the cytosol fractions of the dog's lung, small intestine and pancreas hydrolysed I at a faster rate than they hydrolysed II.