Localization of p27 beta4 binding protein gene (ITGB4BP) to human chromosome region 20q11.2
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
G Arrigo
Publications and source records attributed to G Arrigo.
The beta and gamma subunits of the human platelet-activating factor acetyl hydrolase isoform Ib (PAFAH1B2 and PAFAH1B3) map to chromosome 11q23 and 19q13.1, respectively.
Explore the source record for details and available documents.
1-Alkyl-2-acetylglycerophosphocholine Esterase↗
Human NRD convertase: a highly conserved metalloendopeptidase expressed at specific sites during development and in adult tissues.
We report the cloning of the human homologue of the rat metalloprotease N-arginine dibasic convertase (NRD convertase). This endopeptidase is responsible for the processing, at the Arg-Lys dibasic site on the N-terminal side of the arginine residue, of propeptides and proproteins. Comparisons of the human and rat full-length cDNAs show similarity and identity of 94 and 91%, respectively. In humans NRD convertase is predominantly expressed in heart, skeletal muscle, and testis. We have also studied the expression of this gene in mouse at various developmental stages and found that the neural tissue is the almost exclusive site of expression in early development (between E 10.5 and E 16.5). To gain information about the possibility that defects in this gene are linked to inherited neuromuscular disorders, we determined the chromosomal location of the human NRD convertase gene by FISH analysis, showing that the gene resides at 1p32.2.
Adult↗
A human homologue of the Drosophila melanogaster diaphanous gene is disrupted in a patient with premature ovarian failure: evidence for conserved function in oogenesis and implications for human sterility.
Premature ovarian failure (POF) is a defect of ovarian development and is characterized by primary or secondary amenorrhea, with elevated levels of serum gonadotropins, or by early menopause. The disorder has been attributed to various causes, including rearrangements of a large "critical region" in the long arm of the X chromosome. Here we report identification, in a family with POF, of a gene that is disrupted by a breakpoint. The gene is the human homologue of the Drosophila melanogaster diaphanous gene; mutated alleles of this gene affect spermatogenesis or oogenesis and lead to sterility. The protein (DIA) encoded by the human gene (DIA) is the first human member of the growing FH1/FH2 protein family. Members of this protein family affect cytokinesis and other actin-mediated morphogenetic processes that are required in early steps of development. We propose that the human DIA gene is one of the genes responsible for POF and that it affects the cell divisions that lead to ovarian follicle formation.
Amino Acid Sequence↗
The mouse Mid1 gene: implications for the pathogenesis of Opitz syndrome and the evolution of the mammalian pseudoautosomal region.
We have recently reported isolation of the gene responsible for X-linked Opitz G/BBB syndrome, a defect of midline development. MID1 is located on the distal short arm of the human X chromosome (Xp22. 3) and encodes a novel member of the B box family of zinc finger proteins. We have now cloned the murine homolog of MID1 and performed preliminary expression studies during development. Mid1 expression in undifferentiated cells in the central nervous, gastrointestinal and urogenital systems suggests that abnormal cell proliferation may underlie the defect in midline development characteristic of Opitz syndrome. We have also found that Mid1 is located within the mouse pseudoautosomal region (PAR) in Mus musculus , while it seems to be X-specific in Mus spretus. Therefore, Mid1 is likely to be a recent acquisition of the M. musculus PAR. Genetic and FISH analyses also demonstrated a high frequency of unequal crossovers in the murine PAR, creating spontaneous deletion/duplication events involving Mid1. These data provide evidence for the first time that genetic instability of the PAR may affect functionally important genes. In addition, we show that MID1 is the first example of a gene subject to X-inactivation in man while escaping it in mouse. These data contribute to a better understanding of the molecular content and evolution of the rodent PAR.
Abnormalities, Multiple↗
Optimization of haemodialysis frequency and duration. A computer simulation study.
Explore the source record for details and available documents.
Computer Simulation↗
Multiple congenital anomalies, brain hypomyelination, and ocular albinism in a female with dup(X) (pter-->q24::q21.32-->qter) and random X inactivation.
We report on an 18-month-old girl with multiple congenital anomalies (prominence of the metopic suture, fine hair, club foot, absence of the 12th rib, brachydactyly) and severe mental retardation. The funduscopic examination showed diffuse retinal hypopigmentation. Brain magnetic resonance image (MRI) showed signs of diffuse hypomyelination. On cytogenetic and molecular evidence, the karyotype was 46,X,dirdup(X) (pter-->q24::q21.32-->qter). The duplication of the PLP gene, involved in Pelizaeus-Merzbacher disease, was confirmed by fluorescent in situ hybridization (FISH). Both cytogenetic and molecular studies on the X chromosome inactivation status indicated a random pattern in lymphocytes and fibroblasts. This patient appears to be the first case of a female bearing a large duplication of Xq with a random X inactivation. The phenotype of this patient is compared to that of previously reported cases with Xq duplication.
Abnormalities, Multiple↗
Eleven X chromosome breakpoints associated with premature ovarian failure (POF) map to a 15-Mb YAC contig spanning Xq21.
Eleven balanced X-autosome translocations associated with premature ovarian failure (POF) were mapped to a YAC contig spanning most of Xq21 and constructed between the DXS223 and DXS1171 loci. The contig corresponds to a genomic region of about 15 Mb and contains the whole X-Y homologous region. The most proximal and most distal breakpoints associated with POF were mapped 15 Mb apart. The remaining breakpoints were localized along this large region, in the X-specific and in the X-Y homologous region. Four of the YACs contained two breakpoints in the same or in flanking STS intervals. Our results confirm the cytological findings and suggest that a minimum number of eight different genes in Xq21 may be involved with ovary development. Interruption of such loci could be the cause of POF.
Carrier Proteins↗
Characterization of proteinuria in primary glomerulonephritides. SDS-PAGE patterns: clinical significance and prognostic value of low molecular weight ("tubular") proteins.
In 145 patients with focal segmental glomerulosclerosis (43), membranous glomerulonephritis (72), and membranoproliferative glomerulonephritis (30), 71% with normal renal function (NRF) and 63% with nephrotic syndrome (NS), the proteinuria was evaluated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and classified into four main patterns: physiological (termed 70 kd), pure glomerular (150 kd), mixed with low molecular weight (LMW) proteins as low as 23 kd (23 kd), and mixed with very LMW proteins (20 to 10 kd; termed 10 kd). The relative frequencies were 70 kd, 0.7%; 150 kd, 1.4%; 23 kd, 61%; and 10 kd, 37%. Therefore, only the two patterns characterized by LMW ("tubular") proteins were compared to determine whether they have different clinical and prognostic significance. The serum creatinine (sCr) values (P < 0.0001), the degrees of proteinuria (P = 0.007), and the tubulointerstitial damage (P = 0.015) were significantly different in the two subgroups of patients with 23-kd and 10-kd LMW proteinuria; the difference for tubulointerstitial damage was at the limit of statistical significance after Bonferroni correction. In 82 patients with NRF at entry (sCr, 1.00 +/- 0.22 mg/dL; range, 0.6 to 1.4 mg/dL) and a follow-up of 46 +/- 22 months (range, 12 to 84 months), the predictive value of the 23-kd and 10-kd SDS-PAGE patterns on functional outcome (chronic renal failure [CRF] or clinical remission) was evaluated. A total of 12.5% of 64 patients with mixed 23-kd proteinuria and 50% of 18 patients with mixed 10-kd proteinuria developed CRF. At this time, the difference between the survival curves was highly significant (P = 0.0001), as it also was after correction for NS (P = 0.0002). When the statistical analysis was limited to 69 patients with sCr < or = 1.2 mg/dL, the difference was still highly significant (P = 0.0016), as after correction for NS (P = 0.0064). Clinical remission developed in 30% of 64 patients with 23-kd proteinuria and in 33% of 18 patients with 10-kd proteinuria; this difference was not significant. In a retrospective analysis of 20 patients (13 focal segmental glomerulosclerosis and seven membranous glomerulonephritis; 10 with the 23-kd pattern and 10 with the 10-kd pattern) treated with steroids alone or with steroids and cyclophosphamide, 80% of the patients with the 23-kd pattern and 30% of the patients with the 10-kd pattern were responsive to treatment (P = 0.025). The SDS-PAGE patterns of 54 patients with NRF at entry were again evaluated after 48 +/- 22 months: 11 patients who developed clinical remission had changed from a prevalent (91%) 23-kd pattern to a prevalent physiological (55%) or glomerular (36%) pattern; eight patients who had developed CRF showed an increase from 37% to 100% of the 10-kd pattern. In 35 patients with normal and stable renal function (sCr from 1.08 +/- 0.20 mg/dL to 1.06 +/- 0.19 mg/dL) who had persistent proteinuria (20 patients) or NS (15 patients), the rate of the 10-kd pattern increased from 6% to 46% (72% in persistent NS), suggesting an impairment of tubular protein reabsorptive function even without a concomitant impairment of glomerular filtration rate, a phenomenon that can be hypothetically attributed to tubular toxicity of persistent proteinuria. The characterization of proteinuria by SDS-PAGE in primary progressive glomerulonephritis is a useful clinical tool: it can be used to identify the main pathophysiologic determinants of excretion of LMW proteins and it has a predictive value on CRF outcome in patients with NRF, reducing the unpredictability of clinical evolution. In focal segmental glomerulosclerosis and membranous glomerulonephritis, it seems to be of predictive value on responsiveness to therapy; monitoring the SDS-PAGE patterns over time may give some insights into the relationship between the persistent protein loss and the progression of the disease.
Adolescent↗
Characterization of proteinuria in primary glomerulonephritides: urinary polymers of albumin.
In 142 patients with primary glomerulonephritis (GN), there were polymers of albumin (PAs) in the urine samples of 87% of 15 minimal-change disease (MCD) patients, 52% of 27 focal segmental glomerulosclerosis (FSGS) patients, 51% of 47 membranous glomerulonephritis (MGN) patients, 55% of 20 membranoproliferative glomerulonephritis (MPGN) patients, and 9% of 33 immunoglobulin A nephropathy (IgAN) patients (P = 0.000). In IgAN, only three patients with nephrotic syndrome were PA positive. The PAs were significantly correlated with nephrotic syndrome (NS) (P = 0.000) and with the degree of proteinuria, ranging from 8% in patients with proteinuria less than 0.5 g/d to 58% in patients with proteinuria > or = 15.0 g/d (P = 0.001), but 40% of the nephrotic syndrome patients were PA-negative despite values of proteinuria comparable to those of PA-positive patients, suggesting that the presence of PAs is not simply related to protein loss, but probably to some other unidentified factor or lesion. For 72 patients (43 with NS) (22 FSGS, 36 MGN, and 14 MPGN patients) with normal renal function at entry (serum creatinine, 1.02 +/- 0.23 mg/dL) and a mean follow-up duration of 52 +/- 27 months, for whom PAs were determined and urinary protein characterized by sodium-dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE) at the beginning of the follow-up period, the functional outcome was correlated with the patterns of proteinuria. Chronic renal failure (CRF) developed in 24% of all 72 patients, in 36% of the PA-positive patients, in 9% of the PA-negative patients (P = 0.007), in 44% of the SDS-PAGE 10-kd mixed glomerulotubular pattern patients, and in 17% of the SDS-PAGE 23-kd mixed-pattern patients (P = 0.001). The association of PAs with the 10-kd pattern enhanced the predictive value for CRF outcome: CRF developed in 62% of the PA-positive patients with the 10-kd pattern compared with 11% of the PA-negative patients with the 23-kd pattern (P = 0.0001). CRF developed in 32% of 43 patients with the nephrotic syndrome, in 48% of the PA-positive patients, and in 11% of the PA-negative patients (P = 0.037); in 50% of the 10-kd patients and in 24% of the 23-kd patients (P = 0.007); and in 70% of the PA-positive patients with the 10-kd pattern and 14% of the PA-negative patients with the 23-kd pattern (P = 0.001). In a retrospective study of 21 treated patients (11 FSGS, nine MGN, and one MPGN patient), a response to therapy with complete or partial remission was observed in 57% of all 21 patients; in 58% of patients with the nephrotic syndrome; in 88% of the PA-negative patients versus 38% of the PA-positive patients (P = 0.027); in 90% of the 23-kd patients versus 27% of the 10-kd patients (P = 0.004); and in 100% of the PA-negative patients with the 23-kd pattern versus 12% of the PA-positive patients with the 10-kd pattern (P = 0.001). In conclusion, urinary PAs are associated with GN characterized by lesions mainly localized in the glomerular capillary wall, with the presence of the nephrotic syndrome, and with the degree of proteinuria. In patients with FSGS, MGN, MPGN, and normal renal function at entry, the presence of polymers has a predictive value for CRF outcome; this value is enhanced by the contemporaneous presence of an SDS-PAGE proteinuric pattern with low molecular weight proteins up to 10-kd, which is known to be associated with diffuse tubulointerstitial lesions. Therefore, the best predictive value for either CRF outcome or for response to therapy was provided by a combination between a marker associated with the degree of proteinuria and the types of GN characterized by lesions mainly localized in the glomerular capillary wall and a marker associated with tubulointerstitial damage (SDS-PAGE mixed glomerulotubular pattern with low molecular weight proteins between 20 and 10 kd).
Adolescent↗
Assignment of the tenascin-R gene (Tnr) to mouse chromosome 4 band E2 by fluorescence in situ hybridization; refinement of the human TNR location to chromosome 1q24.
Explore the source record for details and available documents.
Animals↗
Molecular cloning, expression pattern, and chromosomal localization of the human Na-Cl thiazide-sensitive cotransporter (SLC12A3).
Electrolyte homeostasis is maintained by several ion transport systems. Na-(K)-Cl cotransporters promote the electrically silent movement of chloride across the membrane in absorptive and secretory epithelia. Two kidney-specific Na-(K)-Cl cotransporter isoforms are known, so far, according to their sensitivity to specific inhibitors. We have cloned the human cDNA coding for the renal Na-Cl cotransporter selectively inhibited by the thiazide class of diuretic agents. The predicted protein sequence of 1021 amino acids (112 kDa) shows a structure common to the other members of the Na-(K)-Cl cotransporter family: a central region harboring 12 transmembrane domains and the 2 intracellular hydrophilic amino and carboxyl termini. The expression pattern of the human Na-Cl thiazide-sensitive cotransporter (hTSC, HGMW-approved symbol SLC12A3) confirms the kidney specificity. hTSC has been mapped to human chromosome 16q13 by fluorescence in situ hybridization. The cloning and characterization of hTSC now render it possible to study the involvement of this cotransport system in the pathogenesis of tubulopathies such as Gitelman syndrome.
Adult↗
SDS-PAGE patterns and polymeric albumin in proteinuria of lupus glomerulonephritis.
Proteinuria was characterized by SDS-PAGE and by immunoblotting with anti-human albumin sera for the detection of urinary polymers of albumin (PA) in 40 patients with biopsy proven lupus glomerulonephritis (LN) (6 pts class III WHO, 24 pts class IV, 10 pts class V) with various clinical presentations (nephrotic syndrome with normal or impaired renal function, 14 pts; urinary abnormalities with normal or impaired renal function, 21 pts; clinical remission, 5 pts); in 25 pts, for whom the characterization of proteinuria and the renal biopsy were performed at the same time, the activity and chronicity index scores were calculated. The mixed SDS-PAGE patterns, characterized by the presence of low molecular weight proteins, were the more frequently found; the mixed patterns were significantly associated with interstitial leukocyte infiltration (p = 0.05) and glomerular sclerosis (p = 0.046) and nonsignificantly associated with higher values of serum creatinine; no SDS-PAGE pattern had predictive value on functional outcome at 36 months. Albumin polymers were present in 67% of pts; in active disease they were present in 33% of class III, in 100% of class IV and in 45% of class V WHO (p = 0.026); PA were not present in 5 pts with clinical remission (4 class IV and 1 class V WHO). The presence of PA was significantly associated with high values (> 10) of activity index (p = 0.009) and with extracapillary proliferation (p = 0.041). Serum creatinine was lower in patients without PA (Scr 1.0 +/- 0.4 mg/dl) than in those with PA (Scr 1.5 +/- 1.0 mg/dl), but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Clinical features of 24 patients on regular hemodialysis treatment (RDT) for 16-23 years in a single unit.
Careful investigation of the clinical conditions of patients on maintenance hemodialysis for about 20 years in a single dialysis unit was of great interest for evaluation of the pathological consequences in long-term survivors of insufficient correction of uremia and of the dialysis treatment "per se". We analyzed the outcomes for a cohort of 116 patients who started RDT before 1976 and the clinical conditions of the 24 patients still on RDT in our unit at the end of 1991 (average duration of treatment = 222 +/- 23 months). Actuarial survival was 72% at 10 years and 43% at 20 years. Rehabilitation of the 24 survivors was rather good: 13 were able to work, 8 were retired or unable to work, but able to care for most personal needs. Actual body weight, anthropometric parameters and biochemical parameters revealed a well-preserved nutritional status. Anemia improved from 23 +/- 7 at the start of RDT to 31 +/- 8 in the 21 patients never treated with erythropoietin. Blood pressure was normal without therapy in 18 patients and elevated in 6. Mild-to-moderate left ventricular hypertrophy was present in all the 6 patients with arterial hypertension and in only 6 of the 18 normotensive patients. The ratio of early diastolic filling to filling during atrial contraction (E/A ratio) was < 1 in 16 patients: it was 1.05 +/- 0.43 in 9 patients with stable intradialysis blood pressure and significantly lower (0.73 +/- 0.15) in 12 patients with recurrent intradialysis hypotension. Supraventricular arrhythmias were detected by Holter monitoring in 41% and ventricular arrhythmias in 35% of patients. Extensive vascular calcifications were present (in 100% of patients in the abdominal aorta), but only 4 patients showed clinical signs of peripheral vascular disease. Subperiosteal resorption was detected radiologically in the hands of 59% of patients. Bone histology, interpretable for only 20 patients, revealed no bone lesions in 1 case (5%), mild mixed osteodystrophy in 3 cases (15%), advanced mixed osteodystrophy in 5 cases (25%), osteodystrophy with predominant hyperparathyroidism in 2 cases (10%), osteodystrophy with predominant osteomalacia in 6 cases (30%), and aplastic bone disease in 3 cases (15%). Moderate aluminum staining was found in only 4 patients and was more marked in earlier biopsies taken before withdrawal of the aluminium-containing phosphate-binding drugs.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Hepatitis C virus genotype in patients with essential mixed cryoglobulinaemia.
We studied 54 patients with essential mixed cryoglobulinaemia (EMC), (23 males, 31 females) mean age 61 years (range 28-77). Forty-one (76%) had type II cryoglobulinaemia and 13 (24%) type III. Antibodies to HCV were detectable by second-generation ELISA in 49 patients (91%) with confirmed or indeterminate RIBA results. HCV RNA was detected by RT PCR using 5' UTR nested primers; HCV genotypes 1a, 1b, 2 and 3a were identified by genotype-specific core-region nested primers. All patients (49) with antibodies to HCV in their serum were HCV-RNA positive; 27 (55.1%) had HCV subtype 1b and 21 (42.8%) type 2. In one patient the HCV genotype could not be determined. The genotype distribution was not different from that found in patients with chronic hepatitis C without cryoglobulinaemia. However, the presence of HCV subtype 1b correlated significantly with signs of chronic hepatitis and presence of peripheral neuropathy. Severity of disease tended to be worse in patients infected with HCV subtype 1b, but this was mainly due to liver disease. HCV genotypes may influence the clinical expression and, in particular, the severity of liver involvement in patients with EMC. Extent and severity of EMC disease in general may also be affected by the different HCV genotypes. These findings may have therapeutical implications, since the different HCV genotypes respond differently to interferon treatment.
Adult↗
Blood volume modeling and refilling rate estimation in hemodialysis by continuous hemoglobin monitoring.
Eleven bicarbonate hemodialyses (HD) of 6 patients under constant ultrafiltration were continuously monitored with an optical Hb-meter, considered to be a marker of blood volume (BV) changes. A theoretical model was fed experimental data for prediction of blood volume and estimation of vascular parameters, and a time course of rate of refilling was extrapolated. The adequacy of the model was very good for the time course of BV prediction (r2 = 0.85-0.95, n = 11) and for plasma protein concentration (r2 = 0.83-0.86, n = 2). Parameters estimated included (mean-DS): filtration coefficient (Cf) = 0.22 (0.16) dl/min*mmHg, transcapillary hydrostatic pressure (DP) = 17.80 (3.44) mmHg and protein concentration of the refilling fluid (Cref) = 0.45 (0.30) g/dl. In conclusion our study has shown that the model chosen fits the observed BV profile well in all cases, thus the Hb data series can be used for BV dynamic modeling and for estimation of vascular parameters.
Adult↗
Biochemical aspects and clinical perspectives of continuous urea monitoring in plasma ultrafiltrate. Preliminary results of a multicenter study.
We tested a new biosensor for urea monitoring in the ultrafiltrate during PFD in a group of 5 hemodialyzed stable patients. The inspection of the UF-urea profile reflects the dynamical changes of the plasma urea concentration during diffusive dialysis and allows the fitting of the main mathematical models of urea kinetics. The biosensor efficiency was 98.4% on average (SD: 1.5%) at Uf fluxes varying from 45 to 55 ml/min (mean: 51 ml/min; SD: 3.2) and at Uf-urea concentrations varying from 23 to 165 mg/dl. The mean difference between Uf-urea determined by the laboratory method and Uf-urea assayed by the biosensor was -1.07 mg/dl and the 95% confidence interval ranged from -2.01 to 0.13 mg/dl. The mean difference between laboratory plasma urea and Uf-urea from the biosensor was on average -1.9 mg/dl and the estimated limits of agreement with a confidence of 95% were -3.16 and 0.64 mg/dl. Comparison between kinetic models and experimental profiles of plasma urea decrease, evaluations of recirculation and post-dialytic rebound, the role of Kt/V on-line during dialysis were the preliminary clinical applications of this biosensor.
Aged↗
Hearing loss in short- and long-term haemodialysed patients.
BACKGROUND: Hearing loss has been described in patients with chronic renal failure on regular dialysis treatment (RDT) with very different frequency, ranging from 20 to 75%; RDT does not seem to worsen hearing function for at least the first 5 years of treatment; no studies are available on patients on RDT for more than 10 years. METHODS: We performed an audiometric evaluation in 91 patients on RDT for various periods: group I (34 patients), < 5 years; group II (32 patients), 5-10 years; group III (25 patients), > 10 years; patients with histories of chronic otitis, ototoxic drug treatment, and chronic auditory trauma were excluded; the possible correlations with some biochemical parameters (urea, creatinine, PTH) were also looked for. RESULTS: Hearing loss was present in 77% of patients and 69.2% of ears; the percentage of patients with hypoacusia was higher in group III (84%) than in group I (76.3%) and II (71.7%), but the differences were not statistically significant. Hypoacusia was cochlear neurosensory in 61.5%, conductive in 6.5%, and mixed in 9.0% of patients; the percentage of patients with cochlear neurosensory hypoacousia was similar in the three groups (I, 61.7%; II, 59.3%; III, 64%). Hearing loss was of slight to moderate degree and not different in the three groups (I, 22.7 +/- 15 dB; II, 26.9 +/- 6.0 dB; III, 29.1 +/- 8.9 dB). There were no correlations between hearing loss and plasma creatinine and PTH values; patients with plasma urea > 200 mg/dl had higher percentage of hypoacousia (86%) than patients with plasma urea < 200 mg/dl (69%) (P = 0.06). CONCLUSIONS: Hearing loss, mainly cochlear neurosensory in type, is present in a high percentage of patients on RDT even at the beginning of treatment, but no negative effects on hearing can be correlated with the duration of dialysis.
Adult↗