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To evaluate splenic phenotype in autosomal dominant polycystic kidney disease (ADPKD) including presence of cysts and splenomegaly to determine if these are ADPKD related or represent unrelated incidental findings.The axial/coronal T2-weighted images of ADPKD patients (n=215) and age/gender-matched controls (n=215) were evaluated for the presence of T2-bright splenic lesions by three blinded observers. Spleen volume (SV) was evaluated in the context of clinical and imaging features as well as results of gene testing for PKD1 and PKD2 mutations.T2-bright splenic lesions were found in 16 of 215 (7%) ADPKD patients compared to 11 of 215 (5%) control patients (p=0.32) and their prevalence was similar in patients with either PKD1 or PKD2 mutations. Median SV was significantly higher in ADPKD patients than controls (236 [182; 313 ml] versus 176 [129; 264 ml], p0.0001). In multivariable analysis, height-adjusted SV (htSV) was not associated with the presence of liver cysts, haemorrhagic cysts, or infections; however, htSV was directly associated with height-adjusted total kidney volume (htTKV), a biomarker for ADPKD disease severity.The prevalence of T2-bright splenic lesions is similar in ADPKD patients and non-ADPKD controls, suggesting no relation to the diagnosis of ADPKD; however, splenic enlargement in ADPKD compared to controls could not be explained by liver cystic involvement, by infection/inflammatory conditions, or by haemorrhagic renal cysts. This combined with direct correlation of htSV with htTKV, a biomarker of ADPKD severity, suggests splenomegaly may be related to the pathogenesis of ADPKD.

1. Two-week old male chicks of a light-bodied strain were either fed ad libitum or given one (1M) or two (2M) 2-h meals per day. A fourth group was pair-fed (P1M) the amount of food which had been consumed by the 1M group on the preceding day. 2. Compared with ad libitum-fed counterparts, a marked increase in the relative weight of the storage organs (crop and gizzard) was observed in the meal-fed birds. The relative weight of the intestine was not affected by meal feeding but the ileal wall became thinner. 3. After food deprivation for 14 or 22 h, respectively, for the ad libitum and the meal-fed chicks, the weights of contents in the gastrointestinal tract (GIT) segments did not differ between treatments except for those of the gizzard and caecum. Food restoration resulted in an increase in the contents of the GIT of meal-fed chicks. The increments in the crop and gizzard contents were related to the severity of food restriction. The contents of the intestinal segments were quite similar in all treatments. 4. The activities of the digestive enzymes in the pancreas, expressed as units/g pancreas or units/kg body weight, were not significantly affected by feeding regime. In the small intestine of the meal-fed birds, marked increases in specific (units/g content) and relative (units/kg body weight) activities were observed of amylase and chymotrypsin when compared with their ad libitum-fed counterparts. The effect of meal feeding on trypsin activities was less pronounced.

1. Two-week-old male chicks of a light-bodied strain were fed one (1M) or two (2M) 2-h meals per day. An additional group was pair-fed (P1M) the amount consumed by the 1M group on the previous day. 2. After 21 days, final body weight of the 1M and 2M chicks attained 65% and 80%, respectively, of that of the control group fed ad libitum. The weight gain of the P1M chicks was equal to that of the 1M chicks. 3. Food consumption of chicks adapted to meals was not even throughout the feeding period. On day 16 of the experiment, the 1M birds consumed 65% of the meal during the first 30 min. P1M chicks behaved similarly to the 1M ones. The intake of the 2M chicks during each meal was exactly half of their daily consumption, despite the uneven time period between meals. 4. The time during which food remained in the gastrointestinal tract (GIT) was longer under the meal feeding regimes than in the ad libitum-fed groups. 5. Although neither body composition nor metabolisable energy was affected by meal regime, food utilisation was poorer in the 1M and P1M than in the ad libitum and 2M-fed chicks.

The effect of pulse low-frequency alternating electric field (HI-VAMAT-200 unit) on 24-h profile of arterial pressure was studied in 30 hypertensive patients. The evidence obtained at 24-h blood pressure monitoring showed that the above physiotherapy increased a nocturnal surge of arterial pressure and normalized its 24-h profile more effectively than conventional pharmacotherapy.

A beta-lactoglobulin (BLG)/luciferase gene vector (p907), composed of a luciferase intronless gene inserted between the second and sixth BLG exons was constructed. Stable transfections of CID-9 cells with this vector, as well as with a series of additional vectors, were performed to define regulatory regions within the BLG sequence, and the contribution of the SV40 polyadenylation (PA) site to luciferase expression. A relatively low level of luciferase activity was supported by vector p907. It was partially rescued by vector p906, in which the BLG 3' region, downstream of the luciferase cDNA, was replaced with the SV40 PA site. Flanking the SV40 region of vector p906, at its 3' end, with BLG sequences of exon 6/intron 6/exon 7 and the 3' region of the gene resulted in vector p904. This vector supported the highest luciferase activity, 10 times or 2.5 times higher than that measured in cells transfected with vectors p907 and p906, respectively. The induced activity supported by vector p904 is attributed to interaction between the SV40 PA site and elements of the distal part of the BLG 3' flanking sequences. The BLG 5' regulatory region of vector p904 encompasses a 3-kb promoter sequences. Deletion of 935 bp of its proximal end resulted in a 60% decrease in luciferase activity. Reduced activity was also seen with vector p915 lacking sequences of exon 1/intron 1/exon 2. This decrease could not be rescued with heterologous sequences of insulin intron 1, inserted upstream of the luciferase cDNA. Two sets of transgenic mice carrying vectors p907 and p904 were generated. Vector p907 supported only marginal luciferase activity in the mammary gland of all transgenic mice tested and luciferase RNA could not be detected by northern analysis. In contrast, 50% of the transgenic mice carrying vector p904 expressed luciferase RNA in the mammary gland and tissue-specific, hormonal-dependent activity was determined. However, the new p904 vector was not able to insulate the transgene from surrounding host DNA sequences, as reflected by its copy number-independent manner of expression. Nevertheless, vector p904 may represent a valuable tool for the expression of cDNAs in the mammary gland of transgenic animals.

The efficacy and safety of adding fluvoxamine to antipsychotic treatment in schizophrenic patients with mixed positive and negative symptoms was examined. Fifty-three patients selected for persistent negative and positive symptoms who were receiving antipsychotic treatment were randomly allocated to additional fluvoxamine (50-100 mg/day) or placebo in a double-blind manner. Fluvoxamine was associated with significant improvement in negative symptoms (Scale for the Assessment of Negative Symptoms) compared to placebo. The combination was well tolerated. Fluvoxamine augmentation of antipsychotics is safe in chronic schizophrenic patients with mixed positive and negative symptoms and may ameliorate negative symptoms in such patients.

The expression pattern of human serum albumin (HSA) in transgenic mice carrying various HSA genomic sequences driven either by the mouse whey acidic protein (WAP) or the sheep beta-lactoglobulin (BLG) promoters, was compared. The pattern of HSA expression in both WAP/HSA and BLG/HSA transgenic lines was copy number independent, and the major site of ectopic expression was the skeletal muscle. Although an equal proportion of expressors was determined in both sets of mice (approximately 25% secreting0.1 mg/ml), the highest level of HSA secreted into the milk in the WAP/HSA transgenic lines was one order of magnitude lower than in the BLG/HSA lines. Despite this difference, the HSA expression patterns in the mammary gland were similar and consisted of two levels of variegated expression. Studies using mammary explant cultures revealed a comparable responsiveness to the lactogenic hormones insulin, hydrocortisone, and prolactin, although the WAP/HSA gene constructs were more sensitive to the hydrocortisone effect than were the BLG/HSA vectors. When HSA vectors were stably transfected into the mouse mammary cell line CID-9, they displayed a hierarchy of expression, dependent upon the specific complement of HSA introns included. Nevertheless, the expression of HSA in four out of five WAP/HSA constructs was similar to their BLG/HSA counterparts. This construct-dependent, and promoter-independent, hierarchy was also found following transfection into the newly established Golda-1 ovine mammary epithelial cell line.

During a goat transgenic program that took place in Israel from July 1995 to February 1996, Saanen (n = 343) and Nubian x Damascus (n = 378) crossbred goats of mixed ages were used as donors (n = 433) and recipients (n = 288). The effects of season, age, number of surgical procedures, previous hormonal treatments and ovulation rate on the number of microinjectable embryos collected were studied. Likewise, the effects of these parameters on the pregnancy rate as well as the number of embryos transplanted, endogenous progesterone concentrations and exogenous progesterone supplementation were studied in recipient does. Following superovulation with ovine follicle stimulating hormone, 85% of the does responded with 13.6 ± 5.7 (mean ± S D) ovulations/doe. Age, month and number of previous hormonal treatments significantly affected the ovulation rate. The average recovery rate was 70%, and it was affected only by the ovulation rate. Pronuclei were visualized in about 30% of the flushed embryos (including unfertilized ova), and those were microinjected with human serum albumin gene construct. About 68% of the injected embryos underwent at least one division during an overnight incubation, and those embryos were transferred, giving about 2.0 transferred embryos per ovulated donor. Of the recipients, 86% responded following synchronization with 3.1 ± 1.6 (mean ± S D) ovulations per doe. Breed and month had a significant effect on the ovulation rate. Two or three microinjected embryos were transferred to each recipient, resulting in more than a 40% pregnancy rate during September to November. Lower pregnancy rates were obtained before and after that period. By monitoring plasma progesterone concentrations in the recipients it was found that progesterone concentration was correlated with the ovulation rate. However, the pregnancy rate was not affected by progesterone concentration. During January and February, 30 to 50% of the recipients failed to develop functional corpora lutea (CL) following embryo transfer, which explained the lower pregnancy rate in those months. Of the 86 kids born 4 were transgenic.

The pathogenicity-associated plasmid (pPATH) of Erwinia herbicola pv. gypsophilae was previously shown to be exclusively present in pathogenic strains and to contain a gene cluster encoding phytohormone biosynthesis. Sequence analysis of the DNA region located downstream from the cytokinin biosynthetic gene (etz) revealed homology to insertion sequences (IS) of the IS6 family. Southern blot analysis performed on plasmid DNA of E. herbicola pv. gypsophilae revealed the presence of six copies of this insertion-like element, which was designated as IS1327. Only pathogenic strains contained IS1327 and restriction fragment length polymorphism was observed among gypsophilae and beet pathovars of E. herbicola. Nonpathogenic deletion derivatives of pPATH contained fewer copies of IS1327, suggesting its presence in the deleted region. One copy of IS1327 (IS1327-R) was located 2.8 kb downstream from the IS element adjacent to the etz (IS1327-L) in a direct repeat.

Although an absolute difference of 10% (65,4 vs. 54,9%) in 5- and 9-year survival in breast cancer patients was recorded between the self-examination and control groups a large-scale randomized population-controlled study of 122,471 females has failed to provide significant differences (Log-rank - 0,774, p0.05). No significant decrease in mortality was observed in the self-examination group as compared with the untrained controls. As a result of providing more information to the population on risk factors. twice as many of the trained females consulted oncologists. Also, the number of early detection of breast tumor (T1-2NOMO) in both groups was 1,5-2,5 times that recorded elsewhere. Since 3,55 per 1,000 patients with breast tumors per year, aged 50-59, died of cardio-vascular disease, i.e. 3,1 times the expected 1,16 per 1,000, more attention should be focused on timely diagnosis and treatment of concomitant cardio-vascular pathology.

A third series of randomized evaluation of postoperative (adjuvant) hormone therapy (tamoxifen, sinestrol and orimeten) was carried out in breast cancer patients. The study group involved 1.332 reproductive and postmenopausal females with stage I-III tumors. The investigation established quite a range of 10-year survival evidence versus stage and reproductive status; however, no significant differences were recorded in either of the groups. Untoward side-effects were more frequent when treating with diethyl-stilbestrol (over 30%) than with tamoxifen (3.5%). No significant differences were registered in five-year total and recurrence-free survival in the treatment with orimeten or tamoxifen.

Conservative surgery (sectoral or segmental + axillary dissection) was performed in 278 patients with breast cancer (T1-2N0M0) at the Institute Clinic in 1990-1995. Following thorough morphological examination. 148 patients (53.2%) were selected to form a clinical study group for an investigation of the role of postoperative radiotherapy in the conservative treatment of breast cancer. Two groups-irradiation of the remaining breast tissue and controls-were formed on the basis of randomized data. Follow-up continued 3-60 months (average duration-37.7 months). Local recurrence was detected in 3 out of 73 (4.2%) patients of group I. A similar relapse was detected in 6 out of 75 (8.0%) patients of group II. No significant difference in total survival rates in the two groups was observed (97.3 and 96.0%; p0.05).

We studied the expression of human serum albumin (HSA) driven by the ovine beta-lactoglobulin promoter in the mammary glands of lactating mice from five independent transgenic strains, by employing combined in situ hybridization and immunostaining techniques. Four strains displayed a heterogeneous pattern of expression: mice of strains 91 and 92 expressed the transgene in only a fraction of the lobules, whereas in strains 69 and 83 all lobules contained cells expressing HSA. In all four strains the patterns of expression within expressing lobules corresponded to the morphology of alveolar cells and to the extent of local milk secretion, suggesting that filling of alveolus with secreted material was accompanied by asynchronous downregulation of transgene expression. In situ hybridization to the endogenous milk protein genes alpha-lactalbumin, beta-casein, and whey acidic protein revealed a uniform pattern of expression in lactating mammary glands of transgeneic and in four out of five non-transgeneic mice. In the fifth control mouse, we detected downregulation of gene expression in lobules containing alveoli distended by secreted milk. The pattern of expression of the three endogenous genes was greatly disturbed after a short (3-hr) unilateral closure of mammary glands, and very much resembled the pattern of expression of the HSA transgenes. These results demonstrate that transgeneic mice provide a useful model to study the factors that regulate the synthetic activity of mammary epithelial cells.

Recent advances in tests for the genotype for hemochromatosis and suggestions that the tests be used in mass screening programs for the disease raise the possibility of a large increase in the incidence of discrimination against people who are found to be homozygous for hemochromatosis. This paper presents cases of genetic discrimination drawn from a study of discrimination against people with a variety of genetic conditions. The cases discussed here involve employment and several types of insurance discrimination against people diagnosed with hemochromatosis who either are currently asymptomatic or whose condition is controlled by means of phlebotomies. There is no justification for these types of discrimination since people with controlled hemochromatosis suffer no excess mortality or morbidity. Our study suggests that genetic discrimination is already a serious problem and that any proposed screening program for hemochromatosis or other genetic condition must consider and attempt to mitigate its effects.

e15551 Background: Treatment-related CKD and hypertension (HTN) are emerging as problems in patients receiving multiple treatments for recurrent epithelial ovarian cancer (rEOC). Methods: 8 patient...

Infusion of 17-beta-estradiol for 3 h caused a more than 100% increase in the number of PRL receptors (PRL) in the microsomal liver fraction of male rats without affecting the hormone-receptor affinity. A small but significant increase in PRL receptors also was found in testes but not kidneys. Testosterone infusion to female virgin rats for a similar time period resulted in some nonsignificant decreases in PRL receptors in the liver but not the mammary gland or kidneys. Testosterone infusion to males or 17-beta-estradiol infusion to females did not change the number or affinity of PRL and growth hormone receptors. The level of serum PRL was not influenced during infusion with both hormones.

The contents of immunoglobulins, T-lymphocytes, immune rosette-forming cells and indirect hemagglutination test titer in serum and in synovial fluid before and after subcutaneous tuberculin were found in 44 patients with locomotor diseases of different etiology. A comparative assessment of immunologic indices in different groups of patients made in possible to substantiate diagnostic criteria surgical tuberculosis.

Mutants of Sporobolomyces roseus resistant to benzimidazole fungicides varied in their responses to 2-(thiazol-4-yl) benzimidazole (thiabendazole, TBZ), methyl 1-(butylcarbamoyl)-benzimidazol-2-yl carbamate (benomyl) and methyl benzimidazol-2-yl carbamate (carbendazim, MCB). Incorporation of [14C] MBC into trichloroacetic acid extracts of the sensitive strain S4 increased during a 2 h incubation period, whereas incorporation into the resistant mutant M55 was unchanged. [14C] MBC uptake by S4 cells was five times higher than that by M55. MBC was identified as the main radioactive compound inside the S4 cells and reached a level of 2.4 mug/100 mg dry wt. The compound MBC enters the cells of Sp. roseus by a temperature-, energy-, pH- and concentration-dependent transport system which may be specific for compounds containing a benzimidazole nucleus. It is suggested that tolerance of M55 to MBC is due to decreased permeability of the cell to this compound.

In peanuts cultivated in plots that were either artificially infested with Verticillium dahliae or non‐infested, soil application of FeEDDHA or foliar application of Ryplex (Fe, Zn, Cu and Mn) significantly increased yield only in plots where the fungus was present. Addition of FeEDDHA to eggplants infected with V. dahliae significantly reduced disease severity in calcareous soil. Coprogen B was the predominant siderophore produced by seven different strains of V. dahliae during a growth period of up to 18 days. Low amounts of dimerum acid and an additional unidentified siderophore were also detected. However, a decrease in coprogen B with a concomitant increase in dimerum acid and pH were measured in culture filtrates during a longer incubation period. A correlation was established between the pH value of the medium and the relative concentrations of the two siderophores. The magnitude of siderophore repression by iron varied among different isolates.

L-Asparagine uptake by Stemphylium botryosum is mediated by two distinct energy- and temperature-dependent transport systems. One permease is relatively specific for L-asparagine and L-glutamine and is present in nutrient-sufficient mycelium. The specific permease shows an optimum pH at 5.2, saturation kinetics (Km = 4.4 x 10(-4) M, Vmax = 1.1 mumol/g per min), competitive gradient of L-asparagine, and higher affinity towards the L-isomer of asparagine. Amide derivatives of L-asparagine (5-diazo-4-oxo-L-norvaline or L-aspartyl hydroxamate) are the most effective competitors, alpha-amino derivative (N-acetyl asparagine) is a moderate competitor, and alpha-carboxyl derivative (L-asparagine-t-butylester) shows only slight inhibition of the specific permease. Derivatives of L-glutamine are significantly less effective competitors than those of L-asparatine. The level of the specific permease is affected by nitrogen sources and increases approximately threefold upon starvation. The nonspecific permease possesses an optimum pH at 6.8, saturation kinetics (Km = 7 x 10(-5) M, Vmax = 5 mumol/g per min, Kt = 7.4 x 10(-5) M for L-leucine), and high affinity towards various types of amino acids.

SUMMARY: Urea and allantoin were accumulated by germinating spores of Geotrichum candidum in the presence of xanthine, uric acid or allantoin. The concentration of endogenous allantoin was 5 to 10 times higher than that of urea. The specific activities of uricase and allantoicase were increased about nine- and fivefold respectively by uric acid and allantoin. No induction of allantoinase and ureidoglycolase was detected. Results may suggest that the different levels of purine degradative enzyme during induction might favour allantoin accumulation and prevent urea from attaining a toxic concentration.

Either d - or l -leucine (10 −3 m ) and unsaturated long-chain fatty acids such as oleic, linoleic, and arachidonic (10 −4 m ) significantly stimulated macroconidia germination of Microsporum gypseum . Saturated long-chain fatty acids did not affect germination, whereas saturated short-chain fatty acids such as caprylic, hexanoic, and butyric were completely inhibitory. Germination was followed by an increase in endogenous respiration and a decrease in dry weight of approximately 5% at 4 hr. Endogenous fatty acids and soluble carbohydrates were utilized significantly during germination. Tritiated leucine, uridine, and thymidine were incorporated respectively into protein, ribonucleic acid (RNA), and deoxyribonucleic acid (DNA) fractions within the first 5 min of germination. Incorporation of oleic- 1-C 14 into RNA and protein was significantly increased after germ tube development. Net synthesis of RNA and protein started prior to germ tube protrusion. Increase in DNA could be detected only later. A significant increase in RNA and protein during the 4th hr of germination was correlated with vegetative development. Inhibition of respiration and incorporation of leucine- H 3 and uridine- H 3 into corresponding macromolecules by dl -fluorophenylalanine and phenethyl alcohol started before germ tube appearance. Griseofulvin significantly inhibited incorporation of uridine- H 3 and thymidine- H 3 , but not of leucine- H 3 . This inhibition occurred only after initial vegetative development. In contrast to the two other inhibitors, which substantially inhibited germination, griseofulvin only slightly retarded the period of germination and did not affect respiration.

THE reaction catalysed by glutamate dehydrogenase (GDH) is one of the principal routes by which ammonia is incorporated into organic nitrogen. Substrate-controlled changes in the rate of GDH synthesis were detected in microorganisms1,2, but have not been demonstrated in higher plants. A report on induction of GDH by ammonia in Lemma minor3 was later found by the same author to result from differential sensitivity of the enzyme to EDTA inhibition, rather than a true induction4. An approximately 3.5-fold increase in GDH concentration was observed in cucumber leaves during ammonium toxicity5; the nature of the activation process has not, however, been elucidated. The study described here is conclusive indication of an ammonium-dependent induction of GDH synthesis in plant tissue.

The results of an experimental study of polyamide fatigue strength are presented. Multiple flexing tests were performed on specimens rotating at 3000 cycles/min with a symmetrical load cycle in various media, including air (with and without blowing), volatile liquids (petroleum ether, ethanol, water), glycerin, and transformer oil. Fatigue strength is determined from (σN — log N) curves for 106 cycles. Dissipation of heat is found to be the main factor determining the effect of slightly aggressive media on fatigue strength. Values of the ratio fatigue strength/static strength (coefficient K) are presented.

Down regulation of prolactin (PRL) receptors resulting from i.v. infusion of oPRL or human growth hormone (hGH) into female virgin rats was demonstrated. A decrease of over 85% in the number of free receptors was achieved within 15 – 30 min using infusion of oPRL or hGH at 25 μg/h and remained at this level until the end of infusion. Ovine growth hormone or recombinant bovine growth hormone at ten-fold higher concentration had no effect at all. The decrease in the specific binding resulted from a lower number of binding sites and not from change in the dissociation constants. The decrease in the total receptors in the liver was more gradual and leveled off at 40 – 50% of the initial value. Our results suggest that a change in blood PRL or hGH level may lead to a new steady state in the number, occupancy and distribution of prolactin receptors.

Human skin fibroblasts synthesize and secrete complement Factor B, a component of the complement alternative pathway, when stimulated by mediators of inflammation such as lipopolysaccharide and various cytokines. Recombinant IL-6/IFN-beta 2 (E. coli) stimulates Factor B synthesis in fibroblasts but the effect is strongly potentiated by the addition of IFN-gamma. When both cytokines are added, the skin fibroblasts secrete significant amounts of biologically active Factor B detectable in a hemolysis test. This cooperative effect of IL-6, which is made by most tissue cells and monocytes and of IFN-gamma which is made by T-lymphocytes may play a role in local inflammatory processes. IL-6 and IFN-gamma also cooperate in the induction of (2'-5') A synthetase, a mediator of IFN action.

Short-term regulation of prolactin (PRL) receptors was studied in ketamine-anaesthetized 18-day pregnant or 7-day lactating female rats, by infusing them with various doses of oPRL or human growth hormone (hGH) for 0–3 h and measuring the binding of [ 125 I]oPRL of [ 125 I]hGH to the microsomal fractions prepared from the liver, mammary gland and kidneys of animals sacrificed at various states of infusion. Our main findings are: (a) In pregnant rats, only 30% of liver receptors are unoccupied and infusion with 25 μg/h for 3 h of either oPRL of hGH decreased both free and total receptors by 22–30% while infusion with 250 μg/ml caused an additional decrease only in the free receptors, (b) In the mammary gland and the kidney of pregnant rats, all receptors seem to be unoccupied; infusion with 25 μg/ml had none or a slight elevating effect on the number of both free and total receptors in the mammary gland but caused a significant 3-fold increase in the kidney; infusion with 250 μg/ml, however, resulted in a slight decrease in the mammary gland and a significant decrease in the kidney in both total and free receptors, (c) In the liver of the lactating rats, there was no significant difference between the number of free and total receptors, but in mammary gland, specific binding to the total receptor was higher than to the free ones indicating partial occupancy; infusion with 25 μg/ml caused a significant decrease in free and total liver receptors without a remarkable change in the mammary gland and some decrease (by infusion with hGH only) in the kidney, (d) In all cases, the changes in the specific binding resulted from the increase or decrease in receptor number and not from the change in receptor-hormone affinity, (e) In almost all cases, infusion with oPRL or hGH yielded similar results, (f) Infusion with both hormones did not affect the level of the endogenous rat prolactin. In conclusion, our results indicate the short-term regulation of PRL receptors by exogenous hormones is a complicated process which is affected by the level of the infused hormone, physiological state of the animal and may yield, simultaneously, different or even opposite changes in receptor number in various organs.