Biomedical subjects

Y Kishimoto

Publications and source records attributed to Y Kishimoto.

At least 127 records · Page 7Linked to original sources

PubMed1995

Allele-specific mutations involved in the pathogenesis of endemic gallbladder carcinoma in Chile.

Although gallbladder carcinoma is one of the most frequent neoplasms in Chile, there is limited information about the molecular changes involved in its pathogenesis. We investigated the incidence of ras gene mutations and loss of heterozygosity (LOH) at the following genes/loci: p53, DCC, rb, 5q 3p, 8p, and 9p. We precisely microdissected 194 relevant areas from paraffin-embedded microslides from 25 gallbladder carcinomas and their accompanying nonneoplastic lesions (which were present in 15 cases) from patients in Chile. The specimens were analyzed by PCR-based assays for LOH, and we designed a RFLP method for ras mutations and immunohistochemistry for p53 protein overexpression. We determined that LOH at p53 (91%), 9p (50%), 8p (44%) and DCC (31%) are frequent events and that LOH at p53, 9p, and DCC are early events, while ras mutations and LOH at 3p, rb, and 5q occurred occasionally. LOH at p53 occurred more frequently and earlier than protein overexpression. The mean number of mutations present in invasive carcinomas was 2.1, and in six cases, LOH at the p53 gene was the sole mutation detected. The same allele was lost in 61 (93%) of 71 nonneoplastic foci as in the corresponding invasive carcinomas for all four mutations studied. The odds of this occurring by chance are approximately 4 x 10(-15). Although clonality cannot be excluded, allelic loss appears to be highly directed, but the mechanism for allele-specific mutations remains to be determined.

Adenocarcinoma↗

PubMed1995

Molecular cloning, sequencing, and expression of the genes encoding adenosylcobalamin-dependent diol dehydrase of Klebsiella oxytoca.

The pdd genes encoding adenosylcobalamin-dependent diol dehydrase of Klebsiella oxytoca were cloned by using a synthetic oligodeoxyribonucleotide as a hybridization probe followed by measuring the enzyme activity of each clone. Five clones of Escherichia coli exhibited diol dehydrase activity. At least one of them was shown to express diol dehydrase genes under control of their own promoter. Sequence analysis of the DNA fragments found in common in the inserts of these five clones and the flanking regions revealed four open reading frames separated by 10-18 base pairs. The sequential three open reading frames from the second to the fourth (pddA, pddB, and pddC genes) encoded polypeptides of 554, 224, and 173 amino acid residues with predicted molecular weights of 60,348 (alpha), 24,113 (beta), and 19,173 (gamma), respectively. Overexpression of these three genes in E. coli produced more than 50-fold higher level of functional apodiol dehydrase than that in K. oxytoca. The recombinant enzyme was indistinguishable from the wild-type one of K. oxytoca by the criteria of polyacrylamide gel electrophoretic and immunochemical properties. It was thus concluded that these three gene products are the subunits of functional diol dehydrase. Comparisons of the deduced amino acid sequences of the three subunits with other proteins failed to reveal any apparent homology.

Amino Acid Sequence↗

PubMed1995

Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma.

BACKGROUND: Deletions in the short arm of chromosome 3 (3p) are present in most lung carcinomas. OBJECTIVE: To investigate the role of these chromosome 3p deletions in the pathogenesis of non-small cell lung carcinomas. DESIGN: Seven archival, paraffin-embedded, surgically resected lung cancer specimens were studied. Fifty precisely identified malignant and preneoplastic lesions present in bronchi, bronchioles, and alveoli were microdissected from stained slides and analyzed for allele loss using polymerase chain reaction-based assays for dinucleotide repeat polymorphisms at three chromosome 3p loci (3p14, 3p21.3, and 3p25). SETTING: University-based medical center and affiliated hospitals. SUBJECTS: Samples were analyzed from seven patients who underwent surgical resection with curative intent for non-small cell lung cancer and whose specimens included extensive multifocal areas of preneoplastic lesions (hyperplasia, metaplasia, dysplasia, or noninvasive cancer). RESULTS: Lymphocytes from all seven cases were heterozygous (ie, informative) for all three microsatellites analyzed. Six (86%) of seven invasive cancers had loss of heterozygosity at one or more chromosome 3p sites. In the accompanying preneoplastic lesions, loss of heterozygosity was detected in none of two normal bronchioles, 13 (76%) of 17 hyperplasias, six (86%) of seven dysplasias, and four (100%) of four noninvasive cancers. Loss of heterozygosity was detected throughout the respiratory tract, in bronchi, bronchioles, and alveoli. In 18 (78%) of 23 preneoplastic lesions, the specific alleles lost were identical to those lost in the corresponding carcinomas. The probability of this happening by chance is 5.3 x 10(-3). CONCLUSIONS: Deletions in the short arm of chromosome 3 occur at the earliest stage (hyperplasia) in the pathogenesis of lung cancer and involve all regions of the respiratory tract. Allele loss is highly specific, but its mechanism remains unknown. Our findings may be of considerable biologic, prognostic, and clinical significance.

Aged↗

PubMed1995

Identification of the binding and activating sites of the sphingolipid activator protein, saposin C, with glucocerebrosidase.

Saposin C is a sphingolipid activator protein of 8.5 kDa that activates lysosomal glucocerebrosidase. Previously, we synthesized and characterized a synthetic full-length human saposin C protein that displays 85% of the activity of the native saposin C. In this study we use shorter synthetic peptides derived from the saposin C sequence to map binding and activation sites. By determining the activity and kinetic constant (Kact) values of these peptides, we have identified two functional domains, each comprising a binding site adjacent to or partially overlapping with an activation site. Domains 1 and 2 are located within amino acid positions 6-34 and 41-60, respectively. The activation sites span residues 27-34 and 41-49, whereas binding sites encompass residues 6-27 and 45-60. Peptides containing the sequences of either domain displayed 90% of the activity of the full-length synthetic saposin C. Domain 2, however, bound to glucocerebrosidase by at least an order of magnitude more strongly than domain 1. Binding sites within these domains contain sequences that are excellent candidates for forming amphipathic helical structures. Competition assays demonstrated that the binding of one domain to glucocerebrosidase prevents binding of the other domain, and that saposin A and saposin C bind to the same sites on glucocerebrosidase. A model predicting a saposin C:glucocerebrosidase complex with a stoichiometry of 4:2, respectively, is presented.

Amino Acid Sequence↗

PubMed1995

Frequent loss of the short arm of chromosome 9 in resected non-small-cell lung cancers from Japanese patients and its association with squamous cell carcinoma.

We analyzed 87 Japanese non-small-cell lung carcinomas (NSCLC) including 30 squamous cell, 51 adenocarcinomas and 6 large-cell carcinomas for loss of heterozygosity (LOH) on the short arm of chromosome 9, and we correlated our findings with clinicopathological features. We used four polymorphic microsatellite markers on 9p (interferon A gene, D9S171, D9S126, and D9S169), which flank the critical region (9p21-22) involved in lung cancer. We observed alterations of DNA sequences at 9p in NSCLC (27 of 82 informative cases or 33%). Concordance among the four markers was high (87%), indicating that the deletions often were relatively large. The 27 genetic alterations observed on 9p include 26 examples of LOH, 1 homozygous deletion, and 1 case with LOH and evidence of microsatellite alteration characterized by shift in band mobility. We noted a high frequency of LOH at 9p especially in squamous cell carcinoma (17 of 29 informative cases or 59%), and in poorly differentiated NSCLC (12 of 23 informative cases or 52%). There was no correlation between LOH at 9p and the other clinical parameters, including survival, gender, tumor size and the presence of regional or distant metastases. In contrast to other reports, we found only rare instances of homozygous deletions (1%) and microsatellite alteration showed as a mobility shift (1%). Our findings demonstrate that LOH at the short arm of chromosome 9 is correlated with squamous cell and poorly differentiated carcinomas in Japanese patients with NSCLC.

Base Sequence↗

PubMed1995

Identification of the neurotrophic factor sequence of prosaposin.

Prosaposin, recently identified as a neurotrophic factor (1), is the precursor of saposins A, B, C, and D. The neurotrophic activity of prosaposin resides in the saposin C domain. We have pinpointed the active sequence to a linear 12-mer located in the NH2-terminal sequence of saposin C (LIDNNKTEKEIL). Nanomolar concentrations of a 22-mer peptide encompassing this region stimulated neurite outgrowth and choline acetyltransferase activity, and prevented cell death in neuroblastoma cells. In primary cerebellar granule cells, the 22-mer also stimulated neurite outgroth. Studies of the neuroblastoma line NS20Y using a radiolabeled 18-mer from the neurotrophic region identified a high-affinity (Kd = 70 pM) binding site indicative of receptor-ligand interaction. The 22-mer stimulated protein phosphorylation of several proteins, some of which were tyrosine-phosphorylated after brief exposure similar to saposin C. Circular dichroism studies demonstrated that the 22-mer was converted from a random to a helical structure by addition of ganglioside GM1. The results are consistent with receptor-ligand binding by the peptide initiating a signal transduction cascade and resulting in neuronal differentiation.

Amino Acid Sequence↗

PubMed1995

Interactions of a very long chain fatty acid with model membranes and serum albumin. Implications for the pathogenesis of adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an inherited disorder of fatty acid metabolism marked by accumulation of very long chain saturated fatty acids (VLCFA), especially the 26-carbon acid, hexacosanoic acid (HA), in membranes and tissues. We have studied interactions of 13C-enriched HA with model membranes (phospholipid bilayer vesicles) and bovine serum albumin (BSA) by 13C NMR spectroscopy to compare properties of HA with those of typical dietary fatty acids. In phospholipid bilayers the carboxyl group of HA is localized in the aqueous interface, with an apparent pKa (7.4) similar to other fatty acids; the acyl chain must then penetrate very deeply into the membrane. Desorption of HA from vesicles (t1+2 = 3 h) is orders of magnitude slower than shorter chain fatty acids. In mixtures of vesicles and BSA, HA partitions much more favorably to phospholipid bilayers than typical fatty acids. BSA binds a maximum of only 1 mole of HA at one binding site. Calorimetric experiments show strong perturbations of acyl chains of phospholipids by HA. We predict that disruptive effects of VLCFA on cell membrane structure and function may explain the neurological manifestations of ALD patients. These effects will be further amplified by slow desorption of VLCFA from membranes and by the ineffective binding to serum albumin.

Adrenoleukodystrophy↗

PubMed1995

Effects of indigestible dextrin on glucose tolerance in rats.

A recently developed indigestible dextrin (IDex) was studied for its effects on glucose tolerance in male Sprague-Dawley rats. IDex is a low viscosity, water-soluble dietary fibre obtained by heating and enzyme treatment of potato starch. It has an average molecular weight of 1600. An oral glucose tolerance test was conducted with 8-week-old rats to evaluate the effects of IDex on the increase in plasma glucose and insulin levels after a single administration of various sugars (1.5 g/kg body weight). The increase in both plasma glucose and insulin levels following sucrose, maltose and maltodextrin loading was significantly reduced by IDex (0.15 g/kg body weight). This effect was not noted following glucose, high fructose syrup and lactose loading. To evaluate the effects of continual IDex ingestion on glucose tolerance, 5-week-old rats were kept for 8 weeks on a stock diet, a high sucrose diet or an IDex-supplemented high sucrose diet. An oral glucose (1.5 g/kg body weight) tolerance test was conducted in week 8. Increases in both plasma glucose and insulin levels following glucose loading were higher in the rats given a high sucrose diet than in the rats fed a stock diet. However, when IDex was included in the high sucrose diet, the impairment of glucose tolerance was alleviated. Moreover, IDex feeding also significantly reduced accumulation of body fat, regardless of changes in body weight. These findings suggest that IDex not only improves glucose tolerance following sucrose, maltose and maltodextrin loading but also stops progressive decrease in glucose tolerance by preventing a high sucrose diet from causing obesity.

Animals↗

PubMed1995

Hypocholesterolemic effect of dietary fiber: relation to intestinal fermentation and bile acid excretion.

Rat cecal contents were static-cultured with three kinds of dietary fibers and examined for the production of short-chain fatty acids after 24h of cultivation. The total amount and molar ratio of acetate, propionate and butyrate (n = 8) were 7.20 +/- 0.62 mM and 38:19:43 with indigestible dextrin (ID), a low-viscosity, water-soluble dietary fiber, 10.88 +/- 0.46 mM and 49:5:46 with pectin (PE), a high-viscosity, water-soluble dietary fiber, and 1.83 +/- 0.19 mM and 64:11:25 with corn fiber (CF), a water-insoluble dietary fiber, respectively (the corresponding values obtained with glucose were 10.59 +/- 0.37 mM and 15:27:58). Next, rats were kept on a cholesterol- and bile acid-free high-sucrose diet. At the completion of the 8-week feeding period, the serum total-cholesterol levels were significantly lower, at 57.6 +/- 3.8 (n = 8), 63.2 +/- 4.67 (n = 7), and 77.8 +/- 3.7 mg/dl (n = 9), in the ID-, PE-, and CF-supplemented diet groups, respectively, than in the control group given no dietary fiber (92.7 +/- 3.8 mg/dl, n = 7). The cecal propionate production was significantly increased in both the ID and PE groups, while the fecal excretion of bile acids was increased in all three fiber groups compared to the control group. In addition, there was a significantly negative correlation between the serum total-cholesterol level and cecal propionate production in the ID group, between the serum cholesterol level and bile acid excretion in the CF group, and between the serum cholesterol level and cecal propionate production or bile acid excretion in the PE group. These results suggest that the degree of intestinal fermentation and bile acid excretion, which are considered to be associated with the hypocholesterolemic action of dietary fiber, varies with each kind of dietary fiber.

Acetates↗

PubMed1995

Effects of intravenous injection and intraperitoneal continual administration of sodium propionate on serum cholesterol levels in rats.

To examine the effects of sodium propionate on serum cholesterol levels, rats were given sodium propionate intravenously and intraperitonealy. Six-week-old male Sprague-Dawley rats were kept on a cholesterol-free semisynthetic diet for 2 weeks, fasted, and given 400 microliters of saline solution intravenously supplemented with 0.01-10 mg sodium propionate. Three hours after injection of 1 mg of sodium propionate, the serum total-cholesterol level was significantly reduced (85.4 +/- 4.0 mg/dl) compared with its starting level (102 +/- 3.4 mg/dl), with the reducing effect lasting for 24 h. The intensity of the reduction increased proportionately with increased sodium propionate concentrations from 0.01 to 1 mg. Next, to evaluate the influence of continual sodium propionate administration on serum cholesterol levels, 6-week-old male rats were implanted with an osmotic pump intraperitonealy (ALZET Model 2ML2, pumping rate: 5.0 microliter/h; duration: 14 days; reservoir volume: 2,000 microliters). At day 14, serum total-cholesterol levels were reduced by continual sodium propionate administration at both 0.12 and 1.2 mg/day. The maximum percentage change in the serum total-cholesterol level was 78.5 +/- 6.7% of its starting level (111 +/- 7.1 mg/dl), observed at 1.2 mg/day at day 7. These results indicate that sodium propionate can reduce serum total-cholesterol levels in vivo.

Animals↗

PubMed1995

Long-term decrease in serum N-terminal propeptide of type III procollagen in patients with chronic hepatitis C treated with interferon alfa.

To evaluate the effect of interferon alfa (IFN-alpha) on the hepatic extracellular matrix, we investigated the changes in serum N-terminal propeptide of type III procollagen during and after 4 months of INF-alpha treatment in 178 treated and 45 nontreated patients with chronic hepatitis C. Serum pretreatment levels in nonresponders were significantly higher than those in long-term and short-term responders, but those levels were not different in the latter two groups. Serum propeptide levels decreased significantly during and after IFN-alpha therapy in the treated patients, although those levels were unchanged in the nontreated patients. This decrease was sustained for 12 months after IFN-alpha was completed not only in long-but also in short-term responders and nonresponders. Serum propeptide levels decreased in those with elevated pretreatment levels, but not in those with normal initial levels, whereas serum transaminase levels decreased similarly in both groups. The changes in serum propeptide levels during and after treatment were more closely correlated with the initial levels compared with those in serum transaminase levels. These results suggested that IFN-alpha treatment induces the long-term suppression of active fibrogenesis in chronic hepatitis C independent of antiviral and anti-necroinflammatory effects, thus preventing progression to cirrhosis.

Alanine Transaminase↗

PubMed1994

Musculotopic organization in the motor trigeminal nucleus of the reeler mutant mouse.

We examined the musculotopic organization in the motor trigeminal nucleus and the somatotopical arrangement in the trigeminal ganglion of the normal and reeler mice. To determine whether or not masticatory motoneurons are malpositioned in the reeler mouse, we injected horseradish peroxidase (HRP) into the masticatory muscles of normal and reeler mice. Injections of HRP into the jaw-closing muscles, i.e., the masseter and temporalis muscles, labeled large multipolar neurons in the dorsolateral division of the motor trigeminal nucleus of both normal and reeler mice. Similar injections into the jaw-opening muscles, i.e., the anterior belly of the digastric muscle and mylohyoid muscle, labeled large multipolar neurons in the ventromedial division of the motor trigeminal nucleus of both mouse strains. Thus, the normal myotopical arrangement of the masticatory muscles on the motor trigeminal nucleus is preserved in the reeler mouse. However, detailed analysis revealed that jaw-opening motoneurons were more widely scattered in the reeler mouse than in the normal control. To examine the somatotopical arrangement of the first-order sensory neurons in the trigeminal ganglion of the normal and reeler mice, we subcutaneously injected Fast blue (FB) into the mental region and Diamidino yellow (DY) into the vibrissal region of the same animals. No differences in distribution patterns of FB-labeled and DY-labeled neurons in the whole-mounted trigeminal ganglion could been seen between these two strains, suggesting that migration of trigeminal ganglion cells, which are derived from the neural crest and placode, is not deranged by the reeler genetic locus.

Animals↗

PubMed1994

K-ras mutations are a relatively late event in the pathogenesis of lung carcinomas.

We investigated preneoplastic lesions associated with lung cancer to determine at what stage in lung carcinogenesis K-ras mutations appear. We selected six archival lung cancer resection cases that had ras mutations. We precisely microdissected 74 relevant areas from paraffin-embedded sections. K-ras mutations at codons 12, 13, and 61 were determined by the designed restriction fragment length polymorphism method using mismatched nested primers and confirmed by direct sequencing. All samples of invasive and metastatic cancers had K-ras mutations, as did four of five lesions of noninvasive cancer. Mutations were detected in only 1 of 12 dysplastic lesions and were absent from hyperplastic and normal-appearing cells. In all cases, the specific point mutations and the mutational pattern in the tumors, metastases, and the corresponding noninvasive lesions were identical. These results indicate that K-ras mutations arise relatively late in the pathogenesis of lung cancer and may be associated with the appearance of the malignant phenotype.

Carcinoma, Non-Small-Cell Lung↗

PubMed1994

Identification of prosaposin as a neurotrophic factor.

Prosaposin was identified as a neurotrophic factor stimulating neurite outgrowth in murine neuroblastoma (NS20Y) cells and choline acetyltransferase (ChAT) activity in human neuroblastoma (SK-N-MC) cells. The four naturally occurring saposins, which are derived by proteolytic processing of prosaposin, were tested for activity. Saposin C was found to be active, whereas saposins A, B, and D were inactive as neurotrophic factors. Dose-response curves demonstrated that nanomolar concentrations of prosaposin and saposin C stimulated neurite outgrowth and increased ChAT activity. Prosaposin and saposin C exerted activity by a mechanism independent of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3. Binding assays utilizing saposin C as a ligand gave two saturable binding constants, a high-affinity (Kd = 19 pM) and a low-affinity (Kd = 1 nM) constant, with 2000 and 15,000 sites per NS20Y cell, respectively. Phosphorylation stimulation experiments demonstrated that brief treatment with prosaposin or saposin C enhanced phosphorylation of a variety of proteins, some of which contained phosphorylated tyrosine(s). Since both cell lines were also stimulated by ciliary neurotrophic factor (CNTF) as well as prosaposin, inhibition was tested by utilizing an anti-gp130 monoclonal antibody, which specifically inhibited CNTF stimulation; this antibody did not inhibit prosaposin or saposin C stimulation. These results indicate that prosaposin and saposin C are neurotrophic factors which initiate signal transduction by binding to a high-affinity receptor that induces protein phosphorylation.

Animals↗

PubMed1994

Lineage determination of CD7+ CD5- CD2- and CD7+ CD5+ CD2- lymphoblasts: studies on phenotype, genotype, and gene expression of myeloperoxidase, CD3 epsilon, and CD3 delta.

The gene expression of myeloperoxidase (MPO), CD3 epsilon, and CD3 delta molecules, the gene rearrangement of T-cell receptor (TCR) delta, gamma, and beta and immunoglobulin heavy (IgH) chain, and the expression of cell-surface antigens were investigated in seven cases of CD7+ CD5- CD2- and four cases of CD7+ CD5+ CD2- acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LBL) blasts, which were negative for cytochemical myeloperoxidase (cyMPO). More mature T-lineage blasts were also investigated in a comparative manner. In conclusion, the CD7+ CD5- CD2- blasts included four categories: undifferentiated blasts without lineage commitment, T-lineage blasts, T-/myeloid lineage blasts, and cyMPO-negative myeloblasts. The CD7+ CD5+ CD2- blasts included two categories; T-lineage and T-/myeloid lineage blasts. The 11 cases were of the germ-line gene (G) for TCR beta and IgH. Four cases were G for TCR delta and TCR gamma. The others were of the monoclonally rearranged gene (R) for TCR delta and G for TCR gamma or R for both TCR delta and TCR gamma. The expression or in vitro induction of CD13 and/or CD33 antigens correlated with the immaturity of these neoplastic T cells, since it was observed in all 11 CD7+ CD5- CD2- and CD7+ CD5+ CD2-, and some CD7+ CD5+ CD2+ (CD3- CD4- CD8-) cases, but not in CD3 +/- CD4+ CD8+ or CD3+ CD4+ CD8- cases. CD3 epsilon mRNA, but not CD3 delta mRNA, was detected in two CD7+ CD5- CD2- cases, while mRNA of neither of the two CD3 molecules was detected in the other tested CD7+ CD5- CD2- cases. In contrast, mRNA of both CD3 epsilon and CD3 delta were detected in all CD7+ CD5+ CD2- cases, indicating that CD7+ CD5- CD2- blasts at least belong to T-lineage. The blasts of two CD7+ CD5- CD2- cases with entire germ-line genes and without mRNA of the three molecules (MPO, CD3 epsilon, and CD3 delta) were regarded as being at an undifferentiated stage prior to their commitment to either T- or myeloid-lineage. The co-expression of the genes of MPO and CD3 epsilon in a CD7+ CD5- CD2- case MPO, CD3 epsilon, and CD3 delta in a CD7+ CD5+ CD2- case suggested the presence of some overlapping phase for T- and myeloid-lineage commitment during immature stages of differentiation. This helps understand the conversion of some T-ALL/LBL cases to acute myeloblastic leukemia (AML).(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

PubMed1994

Stimulation of acid ceramidase activity by saposin D.

Ceramide is ubiquitously present in plasma membranes and plays a pivotal role in metabolism of sphingolipids. In addition, ceramide and its hydrolytic product, sphingosine, may have important roles as second messengers for cell function and survival. Ceramide is hydrolyzed by both acid and alkaline ceramidase. In this investigation, saposin D was found to stimulate the acid, but not the alkaline, ceramidase. With a crude membrane enzyme preparation, the stimulation was about fourfold. Saposin D is one of four saposins (sphingolipid activator proteins) that are derived from a single precursor protein, prosaposin. Saposins, A, B, and C had no significant effect on ceramidase activity. A kinetic study showed that the stimulation by saposin D was caused by decreasing its Km value for ceramide without a significant change in its Vmax value. A binding study demonstrated that saposin D, as well as saposins A, B, and C, binds to ceramide at neutral pH but not at acidic pH. Preliminary evidence suggests that partially purified acid ceramidase contains bound saposin D. These findings suggest that saposin D facilitates acid ceramidase activity primarily by interaction with the enzyme. The function of saposin D as a modulator of ceramide concentration in vivo has been suggested by the accumulation of ceramide in tissues of patients with total saposin deficiency.

Acid Ceramidase↗

PubMed1994

Occurrence of prosaposin as a neuronal surface membrane component.

Prosaposin is a precursor of four saposins that are required for the lysosomal hydrolysis of sphingolipids by specific hydrolases. Besides its precursor role, prosaposin also exists as a secreted protein. The present investigation reveals that prosaposin also exists as an integral component of the surface membranes of neuronal cells. Subcellular fractionation studies demonstrate that the membrane-bound prosaposin occurs specifically in plasma membranes of NS20Y rat neuroblastoma cells. An immunohistochemical study of the neuroblastoma cells using rat prosaposin-specific antibodies also showed that a portion of prosaposin is located on the surface of neurites as well as on cell bodies. Similar histochemical studies with antibodies that specifically recognized human prosaposin revealed the presence of prosaposin in dendrites, axons, and cell bodies of subcortical and spinal cord neurons in both human adult brain and in fetal brain (24-wk gestation). These findings suggest an important role of prosaposin in neuronal development.

Amino Acid Sequence↗

PubMed1994

Unbalanced 1;7 translocation in myelodysplastic syndrome following treatment of acute myeloblastic leukemia with an 8;21 translocation.

The chromosome der(1;7)(q10;p10) consists of the short arm of chromosome 7 and the long arm of chromosome 1, and is a common abnormality in treatment-related leukemia and myelodysplastic syndrome. Here we describe a 39-year-old Japanese man with acute myeloblastic leukemia (FAB-M2) exhibiting t(8;21)(q22;q22). He entered complete remission after induction therapy, and intensification therapy including alkylating agents was subsequently continued for 3 years. The patient then developed pancytopenia; bone marrow aspiration revealed myelodysplastic syndrome exhibiting the der (1;7) chromosome. To our knowledge, this is the first reported case of such an abnormality in myelodysplastic syndrome secondary to acute myeloblastic leukemia with the 8;21 translocation.

Adult↗