Stomach motility and lyspafen

The effects of spermidine and spermine at varying concentrations upon the replicative ability of human fibroblasts in cell culture have been studied. The average concentrations of spermidine causing a 50% inhibition of prolifertion (ID50) after 3 days of growth for three normal cell strains and three strains derived from patients with cystic fibrosis (CF) were 4.4 X 10(-6) +/- 1.2 M and 6.2 X 10(-6) +/- 2.1 M, respectively. The values for spermine were 2.0 X 10(-6) +/- 0.5 M for normal and 2.2 X 10(-6) +/- 0.1 M for fibroblasts from cystic fibrosis patients. No significant difference between the replicative ability of normal and CF cell strains was seen over a wide range of polyamine concentrations employed for a period of up to 3 days.     

Effect of polyamines and cystic fibrosis serum on glucose transport

The effect of plasma or serum from homozygotes and heterozygotes for the cystic fibrosis (CF) gene on the active uptake of 3-0-14C-methyl-D-glucose (3-0-14C-MDG) by rat jejunal epithelium was studied. Furthermore, the role of the polyamine, spermidine, and its products of metabolic degradation on glucose transport were investigated, and a relationship to the pathogenesis of membrane dysfunction in cystic fibrosis was postulated. Glucose transport in everted rat jejunal rings was used in the study. Results were expressed as 3-0-14C-MDG concentration ratio between the intracellular (ICF) and the extracellular fluid spaces (ECF) of the jejunal rings at the end of a 60 min incubation period. The mean ratio obtained from incubations of the rat jejunal rings in medium consisting of Krebs-Ringer-bicarbonate buffer and the labeled sugar was considered as 100% uptake. When plasma or serum, with or without spermidine, was mixed with the medium in a volume ratio of 1:3, a decrease in the active uptake of 3-0-14C-MDG was observed, expressed as percent inhibition. Percent inhibition of 3-0-14C-MDG uptake obtained when the rat jejunal rings were incubated in normal plasma was compared to that obtained with plasma from cystic fibrosis genotypes. It was found that: 1) plasma from 25 homozygous children had greater inhibitory effect on glucose uptake than plasma from 26 normal children; 2) plasma from 9 heterozygous women had greater inhibitory effect than that from 6 normal women; 3) the inhibitory effect of plasma from 3 homozygous children was not influenced by dialysis; 4) the inhibitory effects of paired plasma and serum samples from 9 homozygotes were comparable; 5) spermidine added to the incubating electrolyte solution did not affect glucose transport; 6) the addition of spermidine to reaction mixtures containing normal plasma potentiated the inhibitory effect; and 7) mixing and incubation of fresh bovine serum with reaction mixtures containing plasma from homozygotes decreased the inhibitory effect. The predominant inhibitory effect of plasma or serum from homozygotes and heterozygotes for the CF gene appears to be related to a nondialyzeable molecule(s). It does not seem to reflect the presence of high plasma glucose levels in cystic fibrosis nor to be the result of competitive inhibition between sugars. It does not seem to be the result of sodium or other electrolyte differences. A similar inhibitory effect is acquired by normal plasma after the addition of spermidine. On the other hand, plasma from CF homozygotes loses its inhibitory effect after incubation with fresh bovine serum. These findings may indicate that products of metabolic degradation of spermidine are responsible for the inhibitory effect of glucose transport and suggest the possibility of a role in abnormal polyamine metabolism in the pathogenesis of cystic fibrosis.     

Infectious complications of lung transplantation. Impact of cystic fibrosis

It has been suggested that the presence of airway pathogens prior to lung transplantation (LT) in patients with cystic fibrosis (CF) may place these patients at a higher risk for infectious complications after LT. There is particular concern regarding patients colonized with multiresistant Pseudomonas, including P. cepacia, and fungi, including Aspergillus. We report our experience with LT for patients with CF and compare the results with those of patients with LT for other indications. Between January 1990 and March 1993, we performed LT for 27 patients with CF and 32 without CF. Nearly all (89%) of the patients with CF were colonized with P. aeruginosa; many were cultured with P. cepacia (19%) and Aspergillus (63%). The non-CF group rarely had organisms identified pre-LT. No patients with CF underwent pre-LT sinus drainage or received pre-LT treatment for Aspergillus. All of the patients received perioperative antibiotics and a standard regimen of immunosuppression and prophylactic antibiotics. The incidence of infectious complications was the same in the two groups; however, there was an association between obliterative bronchiolitis and pulmonary infections. One of the patients with CF with P. cepacia died as a result of this organism. None of the patients with CF required treatment for Aspergillus post-transplant. We conclude that patients with CF, despite the presence of airway pathogens, are at no greater risk of infectious complications after LT than are other patients.     

Polyamines as markers of response and disease activity in cancer chemotherapy

One hundred twenty-four patients with hematological and solid neoplasms had pretreatment urinary polyamine determinations. Putrescine, spermidine, and spermine were all significantly increased as compared to normals (p less than 0.001). Polyamine levels were directly related to disease activity and tumor burden. In patients with multiple myeloma, putrescine levels were significantly correlated with clinical disease activity as well as the in vitro labeling index of marrow plasma cells. Spermidine values reflected tumor cell burden. Serial studies in 56 patients indicated that greater than twofold rise in urinary spermidine during treatment was highly correlated with cell kill and subsequent clinical response (p less than 0.001). Serum polyamine levels in 17 patients were found to be comparable to urinary values. Our data indicate that polyamine determinations can potentially be clinically useful, i.e., baseline values as indicators of tumor cell mass and growth fraction, and increases in spermidine during treatment as an excellent marker of tumor cell kill.     

Role of the liver in interorgan homeostasis of glutathione and cyst(e)ine

There are many pathological changes in patients with cystic fibrosis (CF) which can lead to alterations in drug disposition. Although, in patients with CF, the extent of drug absorption varies widely and the rate of absorption is slower, bioavailability is not altered. Plasma protein binding for the majority of drugs studied did not differ in patients with CF compared with control groups. The difference in volume of distribution of most drugs between patients with CF and healthy individuals vanished when corrected for lean body mass. Despite hepatic dysfunction, patients with CF have enhanced clearance of many, but not all, drugs. Phase I mixed-function oxidases are selectively affected: cytochrome P450 (CYP) 1A2 and CYP2C8 have enhanced activity, while other CYP isoforms such as CYP2C9 and CYP3A4 are unaffected. Increased phase II activities are also demonstrated: glucuronyl transferase, acetyl transferase (NAT1) and sulfotransferase. The increased hepatic clearance of drugs in the presence of CF may be the consequence of disease-specific changes in both enzyme activity and/or drug transport within the liver. The renal clearance (CLR) of many drugs in patients with CF is enhanced although there has been no pathological abnormality identified which could explain this finding: glomerular filtration rate and tubular secretion appear normal in patients with CF. The precise mechanisms for enhanced drug clearance in patients with CF remain to be elucidated. The optimisation of antibiotic therapy in patients with CF includes increasing the dose of beta-lactams by 20 to 30% and monitoring plasma concentrations of aminoglycosides. The appropriate dosage of quinolones has not been definitively established.     

Mapping of a Coccidioides immitis-specific epitope that reacts with complement-fixing antibody

We have previously cloned the cDNA fragment that encodes the complement fixation antigen of Coccidioides immitis. The recombinant protein was highly sensitive in detecting CF antibody in sera from patients with coccidioidomycosis but was not specific to C. immitis, as evidenced by its reactivity with sera from patients with histoplasmosis and, to lesser extent, blastomycosis. We undertook this study to determine if the epitope(s) that reacts with CF antibody is the same or differs from the epitopes that are shared with Histoplasma capsulatum and Blastomyces dermatitidis. PCR-generated CF/chitinase cDNA fragments were cloned and examined for their reactivity in enzyme-linked immunosorbent assays using sera from patients with coccidioidomycosis, histoplasmosis, or blastomycosis. A peptide domain comprised of amino acid residues 20 through 310 was shown to express an epitope(s) that is specific to anti-Coccidioides CF antibody. The peptide detected serum antibody in 21 (95%) of 22 patients with active coccidioidomycosis and was without reactivity with sera from 20 patients with histoplasmosis, 15 patients with blastomycosis, and 14 healthy subjects. Antibody titers to the recombinant peptide directly correlated with CF antibody titers (P < 0.01), and preadsorption of reference CF antiserum with the peptide ablated the reactivity of the antiserum in the immunodiffusion assay for CF antibody. The delineation of a recombinant peptide that has both sensitivity and specificity will provide a valuable tool for detecting CF antibody and for evaluating the role of CF antibody in the host response to C. immitis.     

Blood pressure changes during short-term fluoxetine treatment

PURPOSE: To evaluate the potential diagnostic role of mediastinal sonography in patients with cystic fibrosis (CF), we screened the mediastinum of adult CF patients with and without signs of infection and healthy controls. METHODS: Fifty-four consecutive adult patients with CF and 53 healthy volunteers underwent high-resolution mediastinal sonography. The paratracheal region and aorticopulmonary window of each subject were examined for lymph nodes. Each patient was screened for clinical signs of infection. RESULTS: Lymph nodes were detectable in the mediastinum of 39 of 50 CF patients (78%); the mean total lymph node volume was 1.5 +/- 1.7 cm3. Lymph nodes were detectable in the mediastinum of 31 of 50 controls (62%); the mean total lymph node volume in this group was 0.3 +/- 0.3 cm3 (p < 0.001). In the 30 CF patients with signs of infection, the mean total lymph node volume was larger (2.0 +/- 1.8 cm3) than in the 20 CF patients without signs of infection (0.7 +/- 0.9 cm3; p = 0.002). CONCLUSIONS: These results indicate that lymph node volume determination by high-resolution mediastinal sonography may help assess inflammatory activity in patients with CF.     

Absence of Oxalobacter formigenes in cystic fibrosis patients: a risk factor for hyperoxaluria

BACKGROUND: Patients with cystic fibrosis have an increased risk of hyperoxaluria, and of subsequent nephrocalcinosis and calcium-oxalate urolithiasis. Oxalate homoeostasis is controlled, in part, by the intestinal bacterium, Oxalobacter formigenes. The loss of this bacterium from the gut flora is associated with an increased risk of hyperoxaluria and calcium-oxalate urolithiasis. We investigated whether the absence of O. formigenes and the presence of hyperoxaluria are correlated in cystic fibrosis (CF) patients. METHODS: Stool specimens from 43 patients with CF aged 3-9 years and from 21 similarly aged healthy volunteers were examined for O. formigenes by culture and DNA analysis. At the same time, 24 h urine samples were collected and analysed for oxalate and other factors that promote or inhibit stone formation. FINDINGS: 15 (71%) of 21 healthy volunteers but only seven (16%) of 43 CF patients were colonised with O. formigenes. Detection of O. formigenes in six of these seven patients required DNA-based identification, suggesting low numbers of colony-forming units, and the CF patient with normal numbers of O. formigenes was the only one of the 43 patients who had not been treated with antibiotics. All seven CF patients colonised with O. formigenes had normal urinary oxalate levels, but 19 (53%) of 36 patients not colonised with O. formigenes were hyperoxaluric, with the most severe hyperoxaluria occurring in young patients. INTERPRETATION: Absence of O. formigenes from the intestinal tract of CF patients appears to lead to increased absorption of oxalate, thereby increasing the risk of hyperoxaluria and its complications (eg, nephrocalcinosis, urolithiasis). Prolonged widespread use of antibiotics, and alterations of the gastrointestinal tract that occur in CF, may induce a permanent decolonisation in CF patients.     

Gastric emptying and lingual lipase activity in cystic fibrosis

To identify gastric factors likely to contribute to fat maldigestion and malabsorption in cystic fibrosis (CF), gastric emptying time, secretion rate, and preduodenal lipolytic activity were studied. Gastric emptying of a liquid test meal and gastric acid secretion were determined in five CF teenagers with pancreatic insufficiency and in five healthy controls. During the first hr, the rate of gastric emptying exhibited a linear pattern in both CF patients and controls. Neither the emptying time nor the gastric secretion rate was different. Lingual lipase activity was measured in eight other CF patients with pancreatic insufficiency and in eight controls. Lipase activity was higher (P less than 0.05) in CF patients than in controls with values (mean +/- S.E.) of 34.48 +/- 11.59 and 12.65 +/- 5.60 mumole butyric acid min-1 ml-1, respectively. No correlation with age or body surface was observed. Intragastric lipolysis of a butterfat triglyceride test meal was fast in both groups, but more extensive (P less than 0.05) in CF patients than in controls. The data show that in CF with pancreatic insufficiency, gastric factors contributing to the first step of fat digestion are preserved. In fact, lingual lipase activity was found to be increased, and a more complete intragastric lipolysis was documented.     

Linkage analysis of geographic and clinical clusters in Pseudomonas cepacia infections by multilocus enzyme electrophoresis and ribotyping

Multilocus enzyme electrophoresis and ribotyping were used to characterize 83 strains of Pseudomonas cepacia, mostly isolated from cystic fibrosis (CF) patients, although a number of isolates from non-CF nosocomial infections and reference environmental strains were represented. Twenty enzyme electrophoretic types (ETs) were determined; of these, one clone (ET12) was associated with six of nine ribotypes (RTs) said to be geographically representative of the United Kingdom and all of the Ontario (Canada) isolates from CF patients. This clone was not associated with nosocomial infections or environmental strains and was never found in CF isolates from British Columbia or Nova Scotia, Canada, or a center in the eastern United States. Individual isolate EcoRI RT signatures did not cluster geographically as did the ET signatures by clonal analysis. Frequently RTs occurred in more than a single ET. Known point source focal nosocomial outbreaks were typified by single ETs and stable RTs. Dendrographic analysis of the strains grouped those strains from CF patients, nosocomial outbreaks, and environmental sources into separate ET families, and diversity analysis indicated that, with the exception of ET17, CF isolates clustered in unique and closely related ETs different from those from nosocomial and environmental sources. This study has also shown the potential of multilocus enzyme electrophoresis to monitor the intercontinental spread of P. cepacia strains in CF patients, and this may have a significant impact on plans for CF patient summer camps and design of infection control practices. Whether the intercontinental ET12 clone, which predominates in the United Kingdom and the province of Ontario, linked by summer camp acquisition, has increased virulence for CF patients remains to be established.     

The chronocorrection of disorders in the blood coagulation rhythm with kurantil in patients with decompensated rheumatic heart defects

The circadian pattern of hemocoagulation was studied in patients with decompensated rheumatic heart disease (DRHD) concurrent with stages I-II circulatory failure (CF) during complex treatment or medical treatment with disaggregants. Biorhythmological studies demonstrated that in patients with DRHD and CF chronotherapy with curantyl had some advantages over the traditional therapy during complex drug therapy. In these patients, the chronopatterns of circadian rhythms of hemocoagulative parameters tended to normalize under the influence of curantyl chronotherapy, by diminishing the signs of external desynchronization. Advantages of chronotherapy over the traditional treatment found in patients with DRHD and stages I-II CF, as manifested by its clinical effect in shorter periods (on days 4-5) when small daily and course doses of the drug were used. Based on the biorhythmological studies of hemostatic parameters, a method of curantyl chronotherapy was developed for patients with DRHD and stages I-II CF, which may optimize the therapeutical process in patients with this abnormality.     

The efficacy of pneumocalorimetry for the quantitative evaluation of treatment results in patients with pneumoconiosis and rheumocarditis

The respiratory system conditioning function (CFRS) was evaluated with the aid of pneumocalorimetry by taking account of respiratory thermic losses spent to warm breathing air in the volume of vital capacity. There were 100 patients with pneumoconiosis and 49 ones with rheumatic carditis. In the course of treatment of patients with pneumoconiosis, both occurrence and degree of insufficiency of the conditioning function (CF) got decreased, with reduction in CF insufficiency degree being 60% in those patients faring well owing to the treatments administered, and 40% in those not having benefited much from the treatment. 73% of patients with rheumatic carditis experienced, under the influence of the treatment received, decline in the degree of CF insufficiency. Thus, pneumocalorimetric criterion described above will, we believe, help in quantitating the efficiency of treatment of CF insufficiency.     

Identification of common cystic fibrosis mutations in African-Americans with cystic fibrosis increases the detection rate to 75%

Cystic fibrosis (CF)--an autosomal recessive disorder caused by mutations in CF transmembrane conductance regulator (CFTR) and characterized by abnormal chloride conduction across epithelial membranes, leading to chronic lung and exocrine pancreatic disease--is less common in African-Americans than in Caucasians. No large-scale studies of mutation identification and screening in African-American CF patients have been reported, to date. In this study, the entire coding and flanking intronic sequence of the CFTR gene was analyzed by denaturing gradient-gel electrophoresis and sequencing in an index group of 82 African-American CF chromosomes to identify mutations. One novel mutation, 3120+1G-->A, occurred with a frequency of 12.3% and was also detected in a native African patient. To establish frequencies, an additional group of 66 African-American CF chromosomes were screened for mutations identified in two or more African-American patients. Screening for 16 "common Caucasian" mutations identified 52% of CF alleles in African-Americans, while screening for 8 "common African" mutations accounted for an additional 23%. The combined detection rate of 75% was comparable to the sensitivity of mutation analysis in Caucasian CF patients. These results indicate that African-Americans have their own set of "common" CF mutations that originate from the native African population. Inclusion of these "common" mutations substantially improves CF mutation detection rates in African-Americans.     

Increased iron and ferritin content of sputum from patients with cystic fibrosis or chronic bronchitis

PURPOSE: Extracellular free iron, or iron bound to ferritin, may promote oxidative injury and bacterial growth in airways of patients with chronic airway inflammation due to cystic fibrosis (CF) or chronic bronchitis (CB). In this study, we assessed sputum content of total iron, ferritin, and transferrin in patients with CF or CB as well as sputum from normal subjects with acute airway inflammation caused by viral upper respiratory tract infections (URTIs). METHODS: Spontaneously produced sputum was obtained from 33 subjects, including 10 subjects with CF, 18 subjects with CB (10 acute exacerbations, 8 with stable CB), and 5 subjects with URTIs (control subjects). After lysing and dilution, total iron concentrations were determined by controlled coulometry, ferritin was measured by radioimmunoassay, and transferrin was measured by enzyme-linked immunosorbent assay. RESULTS: Iron was not present in detectable amounts in control sputums, but ferritin was present (6+/-2 ng/mg protein, mean+/-SE), as was transferrin (2.37+/-0.44 microg/mg). Compared with control subjects, concentrations of iron in sputum were increased in patient groups with higher amounts in CF patients (242+/-47 ng/mg, p<0.01) than CB patients with acute exacerbations or patients with stable CB (98+/-50 and 42+/-12 ng/mg, p<0.05 for both). Ferritin content of sputum was also increased in each group, with CF patients (113+/-22 ng/mg, p<0.001) higher than CB patients (acute, 45+/-10 ng/mg; stable, 87+/-24 ng/mg; p<0.01 for both). Compared with control subjects, sputum transferrin was decreased in CF patients (1.09+/-0.40 microg/mg, p<0.05), but not CB patients. CONCLUSIONS: These findings indicate there are increased airway concentrations of total iron and ferritin-bound iron in patients with CB and, to a greater extent, in patients with CF. Particularly in CF patients who also demonstrated decreased airway concentrations of transferrin, ferritin-bound iron in airways may promote oxidative injury and enhance bacterial growth.     

Health and education: alternative courses for the development of nursing personnel

The disposition behavior of trientine, a selective copper-chelating drug for Wilson's disease, and its metabolites in normal patients with Wilson's disease and rats were studied. A high concentration of metabolites appeared in blood samples of patients and rats in the early stage after administration of trientine. Furthermore, large amount of trientine metabolites were excreted into the urine of patients. These results suggest that trientine is remarkably subjected to a first-pass effect. The drug concentration area under the curve (AUC) of the unchanged form and the metabolites of trientine in patients was not dependent on the administered dosage. It seems that the absorption process is an important factor for the disposition behavior of trientine, we have also investigated the uptake characteristics of trientine by rat intestinal brush-border membrane vesicles. The uptake characteristics of trientine were similar to the physiological polyamines, spermine and spermidine. The uptake rate of trientine was dose-dependently inhibited by spermine and spermidine. Moreover, spermine competitively inhibited the uptake of trientine with a Ki value of 18.6 muM. This value is very close to the Km value for spermine (30.4 muM). These data suggested that the uptake mechanism of trientine in rat small intestinal brush-border membrane vesicles was almost identical to that of spermine and spermidine, and that the physiological polyamines seem to have the ability to inhibit the absorption of trientine from the gastrointestinal tract.     

The analysis of methamphetamine hydrochloride by thermal desorption ion mobility spectrometry and SIMPLISMA

The treatment of malaria tropica is becoming difficult because of the increasing drug resistance rates of Plasmodium falciparum against several of the currently available antimalarias. A fixed combination of rifampicin, co-trimoxazole and isoniazid (CotrifazidTM, CF) was found to be highly effective for the treatment of malaria tropica. The aim of the present study in Kenya was to scrutinize this finding in a 14-day trial. Patients with malaria tropica were given in an open, double-arm randomized study CF for 5 days, or chloroquine or pyrimethamine/sulphadoxine as the control. Because of an apparently better activity and tolerance of CF, the randomization had to be stopped after the enrollment of 50 patients. A total of 61 patients in both groups (35 of them between 2 months and 6 years of age) were available for final analysis. All 41 patients treated with CF, originally positive in their blood smears, turned negative; in 2 cases blood smear positivity reappeared on day 14. There were 7 failures in the control group, 4 of them a primary one. Four of those failures were turned negative with CF, 2 failed with CF also, and 1 disappeared. The tolerance of CF was excellent even in infants. In our experience, CF is very well suited for the treatment of malaria tropica, also in cases of apparent drug resistance of P. falciparum against other antimalarials, and even in severe cases of the disease.     

Pregnancy in patients with cystic fibrosis

With increasing life span of patients with CF, more women with CF are becoming pregnant and others are seeking information about the risks involved during pregnancy and delivery. A striking limitation of the available information is the lack of large prospective studies of pregnant patients with CF matched for age and disease severity compared with their non-pregnant cohorts. A study investigating the effect of pregnancy on morbidity and mortality is being completed by the Cystic Fibrosis Foundation. We recommend that all women with CF be offered contraceptive measures and counseling on the maternal and fetal risks of pregnancy, including the genetic risks for the child. The issue of who will raise the child in the event of subsequent morbidity or maternal mortality should ideally be prospectively discussed.     

Effects of gravity on tracheal mucus transport rates in normal subjects and in patients with cystic fibrosis

A noninvasive, radionuclide imaging technique for measuring the rate of mucus clearance in the trachea (RT), was used to study gravitational effects on mucus clearance in 13 patients with cystic fibrosis (CF), average age 17 years; 7 normal, nonsmoking adults, average age 26 years; and a normal subject who was recovering from an acute upper respiratory tract infection (URTI). In the upright position, nine of the CF patients and the subject with URTI demonstrated abnormal tracheal mucus clearance which approached normal when they were placed in 25 degrees headdown position. The normal subjects and two of the CF patients showed no significant difference in the RT measured in the two positions. The results of the study indicate that the force of gravity can be a major influence on tracheal mucus clearance in CF and URTI subjects. This conclusion supports the use of postural drainage as an effective form of therapy in patients with cystic fibrosis.     

The spermidine transport system is regulated by ligand inactivation, endocytosis, and by the Npr1p Ser/Thr protein kinase in Saccharomyces cerevisiae

We have characterized the regulation of spermidine transport in yeast and identified some of the genes involved in its control. Disruption of the SPE2 gene encoding S-adenosylmethionine decarboxylase, which catalyzes an essential step in polyamine biosynthesis, upregulated the initial velocity of spermidine uptake in wild-type cells as well as in the polyamine transport-deficient pcp1 mutants. Exogenous spermidine rapidly inactivated spermidine transport with a half-life of approximately 10-15 min via a process that did not require de novo protein synthesis but was accelerated by cycloheximide addition. Conversely, reactivation of spermidine influx upon polyamine deprivation required active protein synthesis. The stability of polyamine carrier activity was increased 2-fold in polyamine-depleted spe2 deletion mutants, indicating that endogenous polyamines also contribute to the down-regulation of spermidine transport. Ligand-mediated repression of spermidine transport was delayed in end3 and end4 mutants that are deficient in the initial steps of the endocytic pathway, and spermidine uptake activity was increased 4- to 5-fold in end3 mutants relative to parental cells, although the stability of the transport system was similar in both strains. Disruption of the NPR1 gene, which encodes a putative Ser/Thr protein kinase essential for the reactivation of several nitrogen permeases, resulted in a 3-fold decrease in spermidine transport in NH4(+)-rich media but did not prevent its down-regulation by spermidine. The defect in spermidine transport was more pronounced in NH4(+)- than proline-grown npr1 cells, suggesting that NPR1 protects against nitrogen catabolite repression of polyamine uptake activity. These results suggest that (a) the polyamine carrier is an unstable protein subject to down-regulation by spermidine via a process involving ligand inactivation followed by endocytosis and that (b) NPR1 expression fully prevents nitrogen catabolite repression of polyamine transport, unlike the role predicted for that gene by the inactivation/reactivation model proposed for other nitrogen permeases.     

Transcription of ppk from Acinetobacter sp. strain ADP1, encoding a putative polyphosphate kinase, is induced by phosphate starvation

Congenital bilateral absence of the vas deferens (CBAVD) is supposed to be due to defective activity of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) in the genital tract. With the aim of studying CFTR activity in vivo we measured nasal potential difference (NPD) in a group of CBAVD subjects, who were then compared with normal control subjects and CF patients. Sodium transport, measured under basal conditions and after amiloride superinfusion, was normal in almost all CBAVD patients, who had NPD values similar to those of normal control subjects. Chloride transport was studied by measuring NPD during perfusion with a chloride-free solution and isoproterenol. Under these circumstances CBAVD patients as a whole showed normal chloride secretion. However, three subjects with CBAVD had abnormal NPD values. They had either elevated sweat chloride concentrations together with symptoms of mild CF, or compound heterozygosity (DeltaF508/R117H). In conclusion the group of CBAVD patients as a whole presented normal bioelectric properties of nasal epithelium, suggesting normal CFTR activity. In a small subgroup NPD was abnormal, suggesting a diagnosis of CF, later confirmed by elevated sweat chloride concentrations or positive DNA testing. We suggest that CBAVD patients with altered NPD should undergo further clinical follow-up in order to detect possible late complications of CF.