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Biomedical subjects

S Gibson

Publications and source records attributed to S Gibson.

At least 73 records · Page 4Linked to original sources

Synthesis and muscarinic activities of 3-(pyrazolyl)-1,2,5,6-tetrahydropyridine derivatives.

A series of 3-(pyrazolyl)-1,2,5,6-tetrahydropyridine derivatives (B) was synthesized and tested for muscarinic activity in receptor binding assays using [3H]-oxotremorine-M (3H-OXO-M) and [3H]-pirenzepine (3H-PZ) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined using binding studies measuring their potencies to inhibit the binding of 3H-OXO-M and 3H-PZ. Preferential inhibition of 3H-OXO-M binding was used as an indicator for potential muscarinic agonistic properties; this potential was confirmed in functional studies on isolated organs. All compounds with agonistic properties showed 3H-PZ/3H-OXO-M potency ratios in excess of 20. In contrast, for antagonists this ratio was found to be close to unity. Mono-halogenation resulted in compounds (4b and 4d) with M3 agonistic properties as shown by their atropine sensitive stimulant properties in the guinea pig ileum, but with very little or no M1 activity. Some minor in vivo effects were observed for both these compounds, with the iodinated compound 4d inducing salivation. Compound 4d also showed some positive mnemonic properties in rats where spatial short-term memory had been compromised by temporary cholinergic depletion. These data indicate that some M3 agonism may be desired in therapeutic agents aimed at the treatment of the cognitive deficits of Alzheimer's disease patients.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Impaired processing of proopiomelanocortin in corticotroph macroadenomas.

The regulation and secretion of the ACTH precursors POMC and pro-ACTH were assessed directly using a 2-site immunoradiometric assay in six patients with pituitary macroadenomas (> or = 1.2 cm in diameter) and 27 patients with Cushing's disease due to a microadenoma. ACTH precursor levels were elevated in patients with macroadenomas (150-3690 pmol/L; normal range, < 5-40 pmol/L) and significantly higher than those in microadenoma patients (median, 29 pmol/L; range, 9-104 pmol/L; P < 0.001). Patients with macroadenomas also had increased ACTH precursor/ACTH ratios (15-181:1) compared with microadenoma patients (median, 5:1, range, 0.7-18.5:1; P < 0.001). ACTH precursors were unresponsive to high dose dexamethasone in patients with macroadenomas, whereas ACTH and cortisol responses varied. After CRH administration, ACTH precursors were unchanged, whereas cortisol increased significantly, suggesting the release of biologically active ACTH. This study clearly demonstrates reduced processing of POMC to ACTH in large pituitary tumors, a characteristic usually associated with tumors causing the ectopic ACTH syndrome, and provides evidence for differential regulation of ACTH precursors and ACTH by glucocorticoid and CRH. Variation in the clinical symptoms of patients with corticotroph macroadenomas may be attributable to differences in biological potency between the ACTH precursors and ACTH.

Adenoma↗

CD28 delivers costimulatory signals independently of its association with phosphatidylinositol 3-kinase.

CD28, a cell-surface molecule expressed by T cells, delivers costimulatory signals during the activation of T cells by Ag. Stimulation of CD28 induces its association with phosphatidylinositol 3'-kinase (PI3-K), raising the possibility that PI3-K plays a critical role in CD28 signaling. We find, however, that wortmannin, a potent inhibitor of PI3-K, does not block CD28-mediated costimulation of Jurkat (a human T cell line) or of murine CD4+ T cells. To address further the role of PI3-K in CD28-mediated signaling, we expressed mutant murine CD28 molecules in Jurkat cells. Mutation of Tyr 170 of murine CD28 to Phe abrogates the association of murine CD28 with PI3-K but does not affect the ability of murine CD28 to augment IL-2 production by Jurkat cells in response to the combination of ionomycin and PMA. Conversely, a mutant of murine CD28 that has a Tyr at position 170 but has Phe substitutions at the remaining three cytoplasmic tyrosines retains the ability to associate with PI3-K and has an impaired ability to deliver a costimulus that augments IL-2 production. CD28, therefore, can deliver costimulatory signals independently of its interaction with PI3-K, and association with PI3-K is insufficient to mediate the full effector function of CD28. Optimal signaling by CD28 requires the integrity of one or more of the carboxyl-terminal three Tyr residues.

Androstadienes↗

Activation and interaction with protein kinase C of a cytoplasmic tyrosine kinase, Itk/Tsk/Emt, on Fc epsilon RI cross-linking on mast cells.

Cross-linking of the high-affinity IgE receptor (Fc epsilon RI) on mast cells induces rapid phosphorylation on serine, threonine, and tyrosine residues and increases the enzymatic activity, of a Tec subfamily tyrosine kinase, Itk/Tsk/Emt (Emt). The pleckstrin homology domain of Emt at its amino-terminal interacts directly with multiple isoforms of protein kinase C (PKC) in vitro. In addition, a portion of Emt is physically associated with multiple isoforms of PKC in intact mast cells. PKC phosphorylates a bacterial fusion protein containing the pleckstrin homology domain of Emt in vitro. Coexpression of Emt in COS-7 cells with Ca(2+)-dependent PKC isoforms (alpha, beta I, or beta II) induces an enhancement in tyrosine phosphorylation of Emt. In vivo inhibition of PKC expression or activity attenuates tyrosine phosphorylation and enzymatic activity of Emt induced upon Fc epsilon RI cross-linking. These data collectively suggest that PKC phosphorylates Emt and activates its autophosphorylating activity. Alternatively, PKC could activate another tyrosine kinase that phosphorylates Emt, or PKC-mediated phosphorylation of Emt may render it a target for another tyrosine kinase. In any case, PKC appears to play a major role in the activation of Emt induced upon Fc epsilon RI cross-linking.

Animals↗

The squirrel monkey as an animal model of pelvic relaxation: an evaluation of a large breeding colony.

OBJECTIVE: Findings of pelvic relaxation have been reported in up to 50% of older adult female squirrel monkeys. To evaluate further the potential use of the squirrel monkey as an animal model of pelvic relaxation, we objectively observed and described the perineal findings of 160 adult females. The aim of this study was to examine the relationship of perineal findings to age and parity, factors thought to predispose women to pelvic relaxation. STUDY DESIGN: The urethra, cervix, and anterior and posterior segments of the vagina were evaluated. The degree of support loss at each site was documented. Genital measurements were obtained by previously reported methods. The findings were tested for association with elements of obstetric history, age, and subspecies. RESULTS: The females represented three subspecies and ranged from 3 to 17 years old with parities of 0 to 10. The proportion of females with normal support was inversely related to increasing parity and age. Although birth weights, frequency of dystocia at term, and requirement for cesarean section did not differ significantly between females with and without evidence of prolapse, animals with multiple sites of prolapse tended to have infants with higher birth weights. Animals without prolapse were significantly younger and less likely to have been delivered of a term infant (p < 0.001). Subspecies differences unrelated to age or parity were found for each of the genital measurements. Differences were also found between animals with normal perineal findings and those with findings of prolapse. Animals with prolapse had shorter perineal bodies (p < 0.001), greater genital hiatal ratios (p < 0.001), and wider genital hiatal measurements (p < 0.001). Females with abnormal pelvic findings were of increased parity (4.0 vs 1.6, p < 0.001) and age (9.4 vs 6.3 years, p < 0.001) compared with those normal pelvic findings. CONCLUSION: Analysis of genital prolapse in a large population of breeding squirrel monkeys demonstrated an association of loss of pelvic support with age and parity. A tendency for loss of support at multiple sites was associated with obstetric complications. These observations support continuing investigation into the nature and cause of spontaneous pelvic relaxation in this species and support the potential use of this nonhuman primate as an animal model.

Age Factors↗

Elevated levels of adrenocorticotropin (ACTH) precursors in post-adrenalectomy Cushing's disease and their regulation by glucocorticoids.

The ACTH precursor pro-opiomelanocortin (POMC) undergoes specific endoproteolytic cleavages in the anterior pituitary gland to give ACTH-(1-39). ACTH precursors circulate in normal subjects and are high both in the ectopic ACTH syndrome and in patients with aggressive pituitary adenomas. This study examines plasma levels of ACTH precursors and ACTH in 24 patients with post-adrenalectomy Cushing's disease, in 10 of whom computed tomography showed evidence of tumor progression. ACTH precursors were higher in post-adrenalectomy Cushing's disease (median 97.5 pmol/L, range 26-647 pmol/L) than in untreated Cushing's disease (median 29 pmol/L, range 9-104 pmol/L) and normal controls (5-40 pmol/L) (P < 0.001) and were significantly higher in patients with larger tumors (median 175 pmol/L, range 52-647 pmol/L) than in the remainder (median 41 pmol/L, range 26-510 pmol/L) (P = 0.02). Surprisingly, pro-opiomelanocortin (POMC) processing to ACTH was enhanced in post-adrenalectomy patients (ratio 1 +/- 0.5) compared with Cushing's disease (5.6 +/- 0.8) and normal subjects (5.3 +/- 0.9). After hydrocortisone ACTH precursors rose in 36% of post-adrenalectomy patients (increase 15-78%) and remained within 10% of basal levels in 46%. Six patients had a rise in precursors and a fall in ACTH suggesting differential regulation of these peptides. In conclusion, whereas ACTH precursors are high in post-adrenalectomy Cushing's disease and higher levels correlate with tumor progression, processing of precursors to ACTH is enhanced.

Adolescent↗

Multiparameter flow cytometric DNA analysis of effusions: a prospective study of 36 cases compared with routine cytology and immunohistochemistry.

Single-parameter flow cytometry (SFCM) is limited in its ability to detect aneuploid and diploid malignant cells or accurately estimate S-phase fractions (SPF) in effusions because of the high degree of contamination by benign mesothelial cells and inflammatory cells. We examined 36 pleural and peritoneal fluids by conventional cytology and multiparameter FCM (MFCM) to analyze the DNA content of cells expressing epithelial markers cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, BRST-1, or BRST-3 (B72.3) and compared the results to those found with SCFM. The cases were also studied by immunohistochemistry using the same antibody panel. By routine cytology, 14 of the 36 cases were classified as carcinomas, 11 as reactive, 1 as mesothelioma, and 10 as suspicious. MFCM allowed reclassification of 5 of the 10 suspicious cases as carcinomas and the remaining 5 as reactive cases based on ploidy and marker expression. Whereas SFCM detected only 13 nondiploid carcinomas, MFCM detected 4 diploid and 15 nondiploid carcinomas. All reactive cases were diploid by SFCM or MFCM. The mesothelioma case showed were distinct peaks by MFCM, a diploid peak with SPF of 13.4% and a tetraploid peak with SPF of 36.1%. The SPF of the nondiploid carcinomas ranged from 5.9 to 50.4% and diploid carcinomas, from 3.5 to 14.5% when gated on epithelial cells. The reactive cases had SPF ranging from 0.4 to 4.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

CD28 is associated with and induces the immediate tyrosine phosphorylation and activation of the Tec family kinase ITK/EMT in the human Jurkat leukemic T-cell line.

T lymphocytes require two signals to be activated. The antigen-specific T-cell receptor can deliver the first signal, while ligation of the T-cell surface molecule CD28 by antibodies or its cognate ligands B7-1 (CD80) or B7-2 has been demonstrated to be sufficient for the delivery of the second signal. Signaling via CD28 and the T-cell receptor results (i) in their costimulation of T cells to produce numerous lymphokines including interleukin 2 and (ii) in the prevention of anergy induction. Little is known about the pathway by which CD28 mediates its signals except that protein-tyrosine phosphorylation is involved. We show here in human Jurkat cells that the Tec-family protein-tyrosine kinase ITK/EMT (p72ITK/EMT) is associated with CD28 and becomes tyrosine-phosphorylated and activated within seconds of CD28 ligation. This tyrosine phosphorylation of p72ITK/EMT is rapid (within 30 sec), occurs in the absence of LCK activation, and precedes tyrosine phosphorylation of the guanine nucleotide exchange factor VAV. Secondary crosslinking of CD28 is unnecessary for the induced tyrosine phosphorylation of p72ITK/EMT. Thus, tyrosine phosphorylation of p72ITK/EMT may represent one of the earliest events in CD28 signaling. This demonstrates that a member of the Tec family of protein tyrosine kinases, similar to members of the Src and Syk families, plays a role in the activation of T cells. Furthermore, the data demonstrate that p72ITK/EMT, and by analogy other members of the Tec family, responds to extracellularly generated signals.

CD28 Antigens↗

Urea kinetic modeling at high urea clearances: implications for clinical practice.

The original description of urea kinetic modeling in hemodialysis was based on a single pool of fluid equal to total body water. This assumption is valid only if the rate of transport between compartments is sufficiently rapid compared with the rate of urea removed by hemodialysis. We have reexamined the issue of urea compartmentation using 10 patients with initial BUN values ranging from 28 to 101 mg/dL who were studied while on high flux hemodiafiltration. Sampling was carried out at times as short as 1 minute after the beginning of the treatment. In 4 patients, samples were also drawn after the dialysis ended. The measured BUN values were used to fit a two-compartment, variable-volume kinetic model. The mean urea diffusive clearance of the dialyzer during the treatment was 503 mL/minute, and the bidirectional urea clearance between compartments was 1,282 mL/minute. The percentage of total body water in the rapidly exchangeable compartment was 35.4%. Comparison with a one-compartment, variable-volume model showed a statistically better fit for all patients with the more complex model. In the 4 patients studied in the postdialysis period, the rebound in BUN ranged from 22% to 24%. These studies show that, at high urea clearances, the urea distribution space and, therefore, dialysis modeling requires two compartments. These results explain the majority of the rebound in urea concentration observed 30 to 60 minutes following the discontinuation of the dialysis treatment and point out an improved strategy for monitoring the efficiency of the treatment delivered to the patient.

Blood Urea Nitrogen↗

Identification of a gene that complements an Arabidopsis mutant deficient in chloroplast omega 6 desaturase activity.

Membrane lipids of the fad6 (formerly fadC) mutant of Arabidopsis, which is deficient in chloroplast omega 6 desaturase activity, have increased levels of monounsaturated fatty acids and are deficient in trienoic fatty acids. A putative fad6 cDNA clone was isolated by probing a cDNA library with a degenerate oligonucleotide based on a conserved region within known omega 3 desaturase genes. Expression of the cDNA in transgenic plants of a fad6 mutant restored normal levels of all fatty acids. When used as a hybridization probe, the cDNA identified a restriction fragment-length polymorphism that co-segregated with the fad6 mutation. Thus, on the basis of a genetic complementation test and genetic map position, the fad6 gene is encoded by the cDNA. The cDNA encoded a 418-amino acid polypeptide of 47,727 D that displayed a high degree of sequence similarity to a delta 12 desaturase from the cyanobacterium Synechocystis. The fad6 gene exhibited less sequence homology to any known higher plant desaturase, including an endoplasmic reticulum-localized omega 6 desaturase corresponding to the Arabidopsis fad2 gene.

Amino Acid Sequence↗

Cloning of a temperature-regulated gene encoding a chloroplast omega-3 desaturase from Arabidopsis thaliana.

Previous genetic evidence suggested that the fad8 and fad7 genes of Arabidopsis thaliana encode chloroplast membrane-associated omega-3 desaturases. A putative fad8 cDNA was isolated by heterologous hybridization using a gene encoding an endoplasmic reticulum-localized omega-3 desaturase (fad3) as a probe. The cDNA encodes a protein of 435 amino acid residues with a molecular mass of 50,134 D. Constitutive expression of the cDNA in transgenic plants of a fad7 mutant resulted in genetic complementation of the mutation, indicating that the fad7 and fad8 gene products are functionally equivalent. Expression of the fad8 cDNA in transgenic plants often resulted in the co-suppression of both the endogenous fad7 and fad8 genes in spite of the fact that these two genes share only about 75% nucleotide identity. In contrast to all other known plant desaturases, including fad7, the steady-state level of fad8 mRNA is strongly increased in plants grown at low temperature. This suggests that the role of fad8 is to provide increased omega-3 desaturase activity in plants that are exposed to low growth temperature. The fad8-1 mutation created a premature stop codon 149 amino acids from the amino-terminal end of the fad8 open reading frame, suggesting that this mutation results in a complete loss of fad8 activity.

Amino Acid Sequence↗

ACTH precursors characterize the ectopic ACTH syndrome.

OBJECTIVE: ACTH is secreted by the pituitary following processing of larger molecular weight precursors, proopiomelanocortin and pro-ACTH. Ectopic ACTH syndrome refers to the secretion of ACTH by non-pituitary tumours, but the predominant circulating form of proopiomelanocortin-related peptides remains unclear. PATIENTS: Fifteen patients with ectopic ACTH syndrome were compared to 20 patients with pituitary-dependent Cushing's syndrome, 22 patients with small cell lung carcinoma but no evidence of Cushing's syndrome, and 25 controls. DESIGN AND MEASUREMENTS: Measurement of plasma ACTH and ACTH precursors using specific monoclonal-based immunoradiometric assays at 0900 h and, in five patients with ectopic ACTH syndrome, at 15-minute intervals for 6-24 hours. RESULTS: ACTH precursors were grossly elevated in patients with ectopic ACTH syndrome (median 2194, range 139-18000 pmol/l) compared to patients with Cushing's disease (median 33, 8-73 pmol/l, P < 0.001), patients with small cell lung carcinomas (38, 8-117 pmol/l, P < 0.001) and controls (26, 10-39 pmol/l, P < 0.001). ACTH levels were also elevated in ectopic ACTH syndrome (0900 h median 34, 11-152 pmol/l) compared to patients with Cushing's disease (0900 h median 8, 3-19 pmol/l), but not to the same degree as ACTH precursors. In contrast with Cushing's disease, ACTH was secreted in a non-pulsatile fashion. ACTH precursors but not ACTH itself correlated with plasma cortisol in patients with ectopic ACTH syndrome (r = 0.65, P < 0.05). Chromatographic analysis of plasma from a patient with ectopic ACTH syndrome confirmed ACTH precursors and not ACTH to be the predominant circulating form. With the cross-reactivity of proopiomelanocortin and pro-ACTH in the ACTH IRMA of < 1 and < 10% respectively, ACTH precursors could represent all the ACTH immunoreactivity in patients with ectopic ACTH syndrome. CONCLUSIONS: Ectopic 'ACTH' is characterized by aberrant processing of proopiomelanocortin and should be more accurately referred to as 'ectopic ACTH precursor syndrome'.

ACTH Syndrome, Ectopic↗

Differential release of proopiomelanocortin-derived peptides from the human pituitary: evidence from a panel of two-site immunoradiometric assays.

In humans, proopiomelanocortin (POMC) and the peptides derived from it have been individually identified in plasma under differing conditions. However, direct quantitative comparison has proved difficult because of the limitations of RIAs. Using a panel of monoclonal antibodies recognizing different regions of POMC, we have developed specific two-site immunoradiometric assays (IRMAs) for the ACTH precursors (POMC and pro-ACTH), ACTH, beta-lipotropin (beta LPH), beta-endorphin (beta EP), and the N-terminal POMC fragment (N-POC). We have quantified these peptides directly in plasma from normal subjects under basal conditions and in response to different regulatory factors. Basal levels of ACTH precursors, 5-40 pmol/L, were greater than or equal to ACTH, less than 0.9-11.3 pmol/L; N-POC, 5.6-16.8 pmol/L; beta LPH, 2.5-6.7 pmol/L; and beta EP less than or equal to 1.7 pmol/L. ACTH, N-POC, beta LPH, and beta EP levels increased in parallel in response to metyrapone (n = 8) and decreased in response to dexamethasone (n = 8), whereas ACTH precursor concentrations did not respond. After human CRH administration, peripheral concentrations of ACTH, N-POC, and beta LPH showed similar increments (median increment, 163%, 145%, and 172%, respectively; n = 6). POMC peptide responses to human CRH were also assessed in inferior petrosal sinuses draining the pituitary in 20 patients with pituitary-dependent Cushing's disease. In these patients, the increment in ACTH after CRH exceeded that in ACTH precursors by 4-fold (median, 459% and 96%). An increase in the ratios of ACTH/N-POC and ACTH/beta LPH was also apparent after CRH stimulation. The increment in beta EP after CRH always exceeded the increments in POMC and beta LPH. In summary, these data suggest that significant concentrations of ACTH precursors are present in the circulation of normal subjects, that ACTH precursors are not regulated in the same way as the processed POMC peptides, and that ACTH and beta EP are preferentially released from the pituitary in response to CRH.

Adrenocorticotropic Hormone↗

A gene encoding a chloroplast omega-3 fatty acid desaturase complements alterations in fatty acid desaturation and chloroplast copy number of the fad7 mutant of Arabidopsis thaliana.

Mutations at the fad7 locus of Arabidopsis thaliana (previously called fadD) cause decreased desaturation of dienoic fatty acids in chloroplast lipids in plants grown at elevated temperatures. This suggested that the fad7 locus encodes a chloroplast omega-3 desaturase that catalyzes the desaturation of lipid-linked 18:2 and 16:2 fatty acids. In order to clone the fad7 gene, it was first genetically mapped relative to the flanking restriction fragment length polymorphism markers 4547 and 2488A on chromosome 3, and yeast artificial chromosomes covering the locus were identified. A putative desaturase cDNA clone that was isolated by low stringency heterologous probing with a cDNA for an endoplasmic reticulum-localized omega-3 desaturase (fad3) hybridized to the yeast artificial chromosomes and could not be resolved from the locus by restriction fragment length polymorphism mapping. Expression of the cDNA in transgenic fad7 mutant plants resulted in restoration of wild type fatty acid composition and suppression of a previously observed effect of the fad7 mutation on chloroplast number, indicating genetic complementation. The structural gene contained seven introns within a coding sequence of 1338 base pairs, which encodes a 446-amino acid polypeptide of 51,172 daltons. The amino-terminal region of the fad7 gene product contained a consensus chloroplast transit peptide. Except for the amino-terminal domain, the deduced amino acid sequence of the fad7 gene product had high homology to the fad3 gene product, indicating that fad7 encodes an omega-3 desaturase and that the two genes arose from a common ancestral gene. There was no apparent effect of growth temperature on the steady-state levels of fad7 mRNA in wild type plants.

Amino Acid Sequence↗

Identification, cloning, and characterization of a novel human T-cell-specific tyrosine kinase located at the hematopoietin complex on chromosome 5q.

Signal transduction through the T-cell receptor and cytokine receptors on the surface of T lymphocytes occurs largely via tyrosine phosphorylation of intracellular substrates. Because neither the T-cell receptor nor cytokine receptors contain intrinsic kinase domains, signal transduction is thought to occur via association of these receptors with intracellular protein tyrosine kinases. Although several members of the SRC and SYK families of tyrosine kinases have been implicated in signal transduction in lymphocytes, it seems likely that additional tyrosine kinases involved in signal transduction remain to be identified. To identify unique T-cell tyrosine kinases, we used polymerase chain reaction-based cloning with degenerate oligonucleotides directed at highly conserved motifs of tyrosine kinase domains. We have cloned the complete cDNA for a unique human tyrosine kinase that is expressed mainly in T lymphocytes (EMT) and natural killer (NK) cells. The cDNA of EMT predicts an open reading frame of 1866 bp encoding a protein with a predicted size of 72 Kd, which is in keeping with its size on Western blotting. A single 6.2-kb EMT mRNA and 72-Kd protein were detected in T lymphocytes and NK-like cell lines, but were not detected in other cell lineages. EMT contains both SH2 and SH3 domains, as do many other intracellular kinases. EMT does not contain the N-terminal myristylation site or the negative regulatory tyrosine phosphorylation site in its carboxyterminus that are found in the SRC family of tyrosine kinases. EMT is related to the B-cell progenitor kinase (BPK), which has recently been implicated in X-linked hypogammaglobulinemia, to the TECI mammalian kinase, which has been implicated in liver neoplasia, to the more widely expressed TECII mammalian kinase, and to the Drosophila melanogaster Dsrc28 kinase. Sequence comparison suggests that EMT is likely the human homologue of a recently identified murine interleukin-2 (IL-2)-inducible T cell kinase (ITK). However, unlike ITK, EMT message and protein levels do not vary markedly on stimulation of human IL-2-responsive T cells with IL-2. Taken together, it seems that EMT is a member of a new family of intracellular kinases that includes BPK, TECI, and TECII. EMT was localized to chromosome 5q31-32, a region that contains the genes for several growth factors and receptors as well as early activation genes, particularly those involved in the hematopoietic system. Furthermore, the 5q31-32 region is implicated in the genesis of the 5q- syndrome associated with myelodysplasia and development of leukemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗