Biomedical subjects

M Shiota

Publications and source records attributed to M Shiota.

At least 73 records · Page 4Linked to original sources

PubMed1997

Effects of vagal blockade on the counterregulatory response to insulin-induced hypoglycemia in the dog.

Our aim was to determine whether vagal transmission is required for the hormonal response to insulin-induced hypoglycemia in 18-h-fasted conscious dogs. Hollow coils were placed around the vagus nerves, with animals under general anesthesia, 2 wk before an experiment. On the day of the study they were perfused with -15 degrees C ethanol for the purpose of blocking vagal transmission, either coincident with the onset of insulin-induced hypoglycemia or after 2 h of established hypoglycemia. In a separate study the coils were perfused with 37 degrees C ethanol in a sham cooling experiment. The following parameters were measured: heart rate, arterial plasma glucose, insulin, pancreatic polypeptide, glucagon, cortisol, epinephrine, norepinephrine, glycerol, free fatty acids, and endogenous glucose production. In response to insulin-induced hypoglycemia (42 mg/dl), plasma glucagon peaked at a level that was double the basal level, and plasma cortisol levels quadrupled. Plasma epinephrine and norepinephrine levels both rose considerably to 2,135 +/- 314 and 537 +/- 122 pg/ml, respectively, as did plasma glycerol (330 +/- 60%) and endogenous glucose production (150 +/- 20%). Plasma free fatty acids peaked at 150 +/- 20% and then returned to basal levels by the end of the study. The hypoglycemia-induced changes were not different when vagal cooling was initiated after the prior establishment of hypoglycemia. Similarly, when vagal cooling occurred concurrently with the initiation of insulin-induced hypoglycemia (46 mg/dl), there were no significant differences in any of the parameters measured compared with the control. Thus vagal blockade did not prevent the effect on either the hormonal or metabolic responses to low blood sugar. Functioning vagal afferent nerves are not required for a normal response to insulin-induced hypoglycemia.

Animals↗

PubMed1997

Caries-inducing activity of the hydrogenated derivative of an isomaltooligosaccharide mixture in rats.

The caries-inducing activity of the hydrogenated derivative of an isomaltooligosaccharide mixture (IMO-H) was evaluated in vitro for its acidogenicity and in vivo an experimental caries system with specific-pathogen-free (SPF) rats. Streptococcus sobrinus 6715 (serotype g) did not produce a significant amount of acid from IMO-H, whereas Streptococcus mutans MT8148 (serotype c) gradually produced a small amount of acid, although the degree was less than that of sucrose. In vivo experiments were conducted on rats which were provided with the test sugars at two different times: at the time of organism inoculation, and after the organisms had become completely established. IMO-H did not induce significant dental caries in rats infected with the S. sobrinus 6715 or S. mutans MT8148R strain.

Acids↗

PubMed1997

Effects of a hydrogenated isomaltooligosaccharide mixture on glucan synthesis and on caries development in rats.

The caries inhibitory effect of the hydrogenated derivative of an isomaltooligosaccharides mixture (IMO-H) was examined in vitro and in vivo experiments. IMO-H could not be used as a substrate for the crude glucosyltransferases (GTases) of Streptococcus sobrinus 6715 to synthesize water-insoluble glucan. Moreover, it not only significantly inhibited the synthesis of water-insoluble glucan from sucrose, but also the sucrose-dependent adherence of these growing cells the glass surfaces. In the in vivo experiment, the addition of IMO-H to a sucrose-containing diet resulted in significant reduction of caries development in specific-pathogen-free (SPF) rats infected with S. sobrinus 6715.

Animals↗

PubMed1997

[Clinical study of occlusal forces on dental implants].

The object of this investigation was to analyze occlusal force in patients applied an implant-supported prosthesis. The occlusal force was measured on four free end saddle patients applied 10 dental implants (F. E.) and two bounded saddle patients 4 dental implants. The pressure sensitive sheet and the image scanner (Dental Prescale 50H type R and Occluzer FPD 703, Fuji Photo Film Co.) were used. The occlusal force (O. F.) occurred in implanted portion was almost the same as that on a natural tooth. O. F. and O. F. bearing rate (B. R.) on the posterior dentitions applied implants tended to increase toward the distal side. The total O. F. had a tendency to increase after applying implant-supported prosthesis, and comparing implanted side with non-implanted (natural teeth) side, B. R. was equilibrium. On the other hand, occlusal contact areas, O. F. and B. R. were decreased at the most distal tooth of residual dentition on the implant side of F. E.

Aged↗

PubMed1997

[Clinical studies of learning disability. Part III: Prevalence of children with suspected learning disabilities].

The prevalence of children with suspected learning disabilities (LD) was investigated. One thousand and eight-hundred-eighty-nine pupils at ordinary elementary classes were evaluated by class teachers. We defined suspected LD as a condition with normal IQ (not less than 70) and low PRS score (not more than 65). Eighteen children (12 boys, 5 girls, and 1 with sex unknown) were considered as suspected LD with this criterion. The prevalence of suspected LD at elementary schools was 0.95%, the lowest figure as compared to those in previous reports. The suspected LD children were studied for the LD type and school grade. Verbal LD was not found, non-verbal LD was found in 6 children, and mixed type in 11. In the study of their school grades, the third grade suspected LD children were the largest. There was a significant decrease in number at higher school grades.

Age Factors↗

PubMed1997

[Clinical studies of learning disability. Part IV : A prospective study of children with risk factors for learning disability at three year-old screening--clinical examinations in 1995].

We are following children with risk factors for learning disability (LD) at three year-old screening prospectively. In 1995, one child reportedly as normal in 1994 was considered to have a possibility of LD. The complaints of their parents had shifted to underachievement. In several children, their poor social skill in school and family was considered to be more serious in 1995 than in 1994. All children who were clumsy in early childhood showed non-optimal motor co-ordination on minor neurological examinations by Touwen. This suggested that non-temporary neurological impairments led them to LD.

Child↗

PubMed1997

CD30-positive anaplastic large cell lymphoma in childhood: expression of p80npm/alk and absence of Epstein-Barr virus.

CD30(+)-anaplastic large cell lymphoma (ALCL) is a distinct clinicopathologic entity of non-Hodgkin's lymphoma that is immunologically heterogeneous. Bimodal age distribution, a nonrandom chromosome abnormality [t(2;5)(p23;q35)] that produces a chimeric protein p80npm/alk, and a variable (5-47%) association with Epstein-Barr virus (EBV) have been reported. We reviewed 36 cases of ALCL (19 were children < 20 yr and 17 were adults) by focusing on the presence or absence of p80npm/alk protein and EBV. Immunophenotyping studies were performed on frozen and/or paraffin sections before initiation of chemotherapy. The p80 protein was immunohistochemically examined, and EBV-encoded RNA transcripts were detected by in situ hybridization. Among 19 cases in children, 13 cases had a T-cell and 6 cases had a null-cell phenotype. p80 Was detected in 16 (84.2%) of 19 cases in children and 3 (17.6%) of 17 cases in adults. All of the 19 cases of p80-positive ALCL were positive for epithelial membrane antigen, regardless of age. EBV genome was not detected in any of 19 cases in children and in only 2 of 15 cases in adults. ALCL in childhood seems to constitute a homogeneous entity characterized by expression of p80 and absence of EBV. The association of EBV is also infrequent in adult ALCL among Japanese patients.

Adolescent↗

PubMed1997

Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity.

Some anaplastic large cell lymphomas (ALCLs) carry a specific chromosomal translocation, t(2;5)(p23;q35). Recently, we found a novel hyperphosphorylated 80-kDa protein tyrosine kinase, p80, in ALCLs with t(2;5). Subsequent cDNA cloning revealed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene (Morris et al.). Meanwhile, the clinicopathologic features of p80-carrying ALCLs have remained unclear. Paraffin sections of 105 cases of ALCL were immunostained using anti-p80 antibody, and 30 of them were shown to express p80. Clinicopathological comparison between p80-positive and -negative ALCLs revealed that p80-positive cases occurred in a far younger patient age group and the patients showed a far better 5-year survival rate. These data showed that p80-positive ALCL is a distinct entity both clinically and pathogenetically, and should be differentiated from p80-negative ALCL.

Adolescent↗

PubMed1997

[Smoking behavior, knowledge and attitudes of freshmen students].

A questionnaire on smoking behavior, knowledge of smoking-related diseases and attitudes toward the passive exposure to smoking was administered and results analyzed for differences in (1) region, (2) major area of study in the university, (3) grade and (4) date of survey on smoking behavior, knowledge and attitude of the freshmen students. (1) 294 urban and 217 provincial university students, (2) 138 freshmen at the Department of Pharmacology and 156 freshmen at the Department of Technology, (3) 136 freshmen of Y. University and 158 freshmen in senior high school of Yamaguchi prefecture, and (4) 217 freshmen surveyed in 1990 and 136 freshmen surveyed in 1995 were the subjects. The results were as follows; 1) The percentage who had smoked once ranged from 0 to 3% among the senior high school girls and female students at minor universities. However, the percentage for male students ranged from 26% to 44% in each survey. There were clear gender differences in smoking behavior. 2) The proportion of students who admitted that they had smoked cigarettes was 30.9% for urban students and 38.6% for provincial university students, but was not a significant difference. There were no significant differences between urban and provincial students regarding knowledge of smoking-related diseases or attitudes toward passive smoke. 3) The proportion of students who admitted that they had smoked cigarettes was 44.0% for the Department of Pharmacology and 26.2% for the Department of Technology, a significant difference. There were no significant differences between pharmaceutical and engineering students in knowledge of smoking-related diseases or attitudes toward passive smoke. 4) The proportion of students who admitted that they had smoked cigarettes was 27.4% for university freshmen and 1.6% for senior high school freshmen. There was a significant difference between the two. The percentage who replied that the smoker must be considerate to non-smokers tended to be higher in the senior high school students than the university students. However, there was no significant differences between the two groups of students in knowledge of smoking-related diseases or attitudes toward passive smoke. 5) Although the proportion of students who admitted that they had smoked cigarettes was 38.6% in the 1990 survey and 27.4% in the 1995 survey, this was not a significant difference. The percentage of students in the 1990 survey who indicated an awareness of the relationship between smoking and coronary heart diseases was significantly greater than the percentage of students who indicated a similar awareness in the 1995 survey. These results suggest that the differences in the grade and the department of the university (or the nature of school) must be considered when surveying smoking behavior. It does not appear to be necessary, however, to consider regional differences or the date of survey, if students were surveyed relatively recently, concerning smoking behavior, knowledge of smoking-related diseases and attitudes toward the effect of passive exposure to smoking.

Adolescent↗

PubMed1996

Characterization of the transforming activity of p80, a hyperphosphorylated protein in a Ki-1 lymphoma cell line with chromosomal translocation t(2;5).

We have molecularly cloned a cDNA encoding a protein uniquely expressed and hyperphosphorylated at tyrosine residues in a Ki-1 lymphoma cell that contained chromosomal translocation t(2;5). The encoded protein p80 was shown to be generated by fusion of a protein-tyrosine kinase and a nucleolar protein B23/nucleophosmin (NPM). The coding sequence of this cDNA turned out to be virtually identical to that of the fusion cDNA for NPM-anaplastic lymphoma kinase (ALK) previously cloned from the transcript of the gene at the breakpoint of the same translocation. Overexpression of p80 in NIH 3T3 cells induced neoplastic transformation, suggesting that the p80 kinase is aberrantly activated. The normal form of p80 was predicted to be a receptor-type tyrosine kinase on the basis of its sequence similarity to the insulin receptor family of kinases. However, an immunofluorescence study using COS cells revealed that p80 was localized to the cytoplasm. Thus, subcellular translocation and activation of the tyrosine kinase presumably by its structural alteration would cause the malignant transformation. We also showed that a mutant p80 lacking the NPM portion was unable to transform NIH 3T3 cells. Thus, the NPM sequence is essential for the transforming activity, suggesting that the chromosomal translocation is responsible for the oncogenesis. Finally, Shc and insulin receptor substrate 1 (IRS-1) were tyrosine-phosphorylated and bound to p80 in p80-transformed cells. However, mutants of p80 that were defective for binding to and phosphorylation of Shc and insulin receptor substrate 1 could transform NIH 3T3 cells. Association of these mutants with GRB2 was still observed, suggesting that interaction of p80 with GRB2 but not with Shc or IRS-1 was relevant for cell transformation.

3T3 Cells↗

PubMed1996

Molecular characterization of the t(2;5) (p23; q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease.

The precise cellular origin and the pathogenetic mechanism(s) leading to the neoplastic transformation of anaplastic large cell lymphoma (ALCL) and the Reed-Sternberg cell of Hodgkin's disease (HD) remains largely uncertain. Classical cytogenetic analysis has shown a unique translocation involving bands 2p23 and 5q35 bands in a variable number of ALCLs. It has been recently shown that the nucleophosmin/B23 (NPM) gene (5q35) and a novel anaplastic lymphoma kinase (ALK; 2p23) are the fused genes of t(2;5). To investigate the presence and the precise frequency of NPM-ALK gene products among ALCL and HD cases, a large and well-characterized panel of ALCL (n = 49) and HD (n = 72) cases was studied using multiple strategies including reverse transcriptase-polymerase chain reaction (RT-PCR), Southern blot analysis, and immunohistochemistry. Overall, 6 (3 T and 3 null) of 49 ALCL and 3 (2 nodular sclerosis and 1 mixed cellularity) of 72 HD showed the presence of NPM-ALK transcripts by RT-PCR. NPM-ALK gene rearrangements were detected in all RT-PCR, NPM-ALK-positive ALCL by Southern blot analysis. Furthermore, in all the available cases we were able to show the presence of ALK-related protein using a specific polyclonal antiserum recognizing the cytoplasmic domain of ALK by immunohistochemistry. Our data show that NPM-ALK gene transcripts are identified in a subpopulation of ALCL, almost exclusively in T or null cell in origin, and in rare cases of HD. These findings show that some HD may be closely related to ALCL, giving us new insights on the pathogenesis and possibly biologic evolution of HD.

Anaplastic Lymphoma Kinase↗

PubMed1996

Elevated serum level of soluble HLA class I antigens in patients with systemic lupus erythematosus.

OBJECTIVE: To examine the clinical significance of serum soluble HLA class I antigens (sHLA class I) in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: Serum levels of sHLA class I were measured by enzyme-linked immunosorbent assay, using a monoclonal antibody against monomorphic determinant of HLA class I (W6/32) and an enzyme-labeled polyclonal antibody to human beta 2-microglobulin. RESULTS: The serum sHLA class I concentration was 1.85 +/- 1.15 micrograms/ml (mean +/- SD) in 27 patients with SLE (P < 0.0001 versus normal controls, P = 0.0001 versus RA), 0.61 +/- 0.34 micrograms/ml in 16 patients with RA (P = 0.02 versus normal controls), and 0.41 +/= 0.20 micrograms/ml in normal controls. The HLA class I levels were significantly correlated with the SLE Disease Activity Index (r = 0.62, P = 0.0004) and with a reduction of CH50 levels (r = -0.60, P = 0.0007). A longitudinal analysis of patients with SLE indicated that serum sHLA class I levels fluctuated in conjunction with other disease activity markers. CONCLUSION: Serum sHLA class I may be useful as a disease activity marker of SLE. The mechanism of secretion and the physiologic role of sHLA class I require further study.

Adolescent↗

PubMed1996

Changes in renal blood flow measured by radionuclide angiography following exhausting exercise in humans.

We measured renal blood flow (RBF) repeatedly in six male volunteers following exhausting cycling exercise using radionuclide angiography (RA) with technetium 99 m phytate (99 mTc-phytate), which is a nondiffusible radio-active tracer for kidney imaging and which is taken up quickly by the liver after injection into the circulation. The relationships between changes in RBF and creatinine clearance (Ccr), urine volume (UV) and plasma hormone involved in the regulation of renal function were also investigated. A bolus of 99 mTc-phytate (92.5 MBq.ml-1) was injected into the brachial vein via a catheter, while each subject was maintained in a supine position with his back to a scinticamera, which was connected to a computer for data processing. The pool transit time (PTT) was calculated from the time-concentration flow curve in the left kidney following injection of the bolus. The PTT normalized by the PTT of the heart (PTTn: kidney PTT/heart PTT), and the change in the reciprocal of PTTn (1/PTTn) were used as indices of the change in RBF. The resting RBF was also measured simultaneously by both RA and the para-aminohippuric acid (PAH) clearance method (CPAH). Post-exercise RBF was measured only by RA within 60 s of exercise, then again within 30 and 60 min of exercise on different days, since RBF can be measured successively only three times even with the use of 99 mTc-phytate. The resting value of 1/PTTn was converted to the value of CPAH corrected for haematocrit, and post-exercise change of 1/PTTn (RBF) was represented as a change in the value of CPAH in order to express a definite numerical change, rather than a percentage change, from resting RBF. The RBF decreased by 53.4% immediately after exercise, and remained decreased by 17.5% 30 min after and by 21.1% 60 min after exercise in comparison with the resting value. The RBF was found to be correlated with changes in Ccr (r = 0.773, P < 0.001), UV (r = 0.598, P < 0.001), and the concentrations of plasma angiotensin II (r = -0.686, P < 0.001) and noradrenaline (r = 0.652, P < 0.001) after exercise. However, there were no significant correlations between the changes in plasma aldosterone ([Ald]) and plasma noradrenaline, or in [Ald]p1 and plasma angiotensin II concentrations. The change in [Ald]p1 did not coincide with the variation in reabsorption of Na+ in the renal tubules. Results of the present study showed that change in Ccr after exhausting exercise depended mainly on change in RBF and that changes in UV and osmolality after exhausting exercise were induced not only by change in RBF, but also by changes in reabsorption of water and solutes in the renal tubules. It is suggested that changes in reabsorption of water and solutes might be influenced by metabolites induced by exercise and an increased release of hormones, other than aldosterone, involved in the regulation of renal function.

Adult↗

PubMed1996

Inability of hyperglycemia to counter the ability of glucagon to increase net glucose output and activate glycogen phosphorylase in the perfused rat liver.

We examined the ability of hyperglycemia to alter the ability of glucagon to activate phosphorylase and stimulate glucose output in perfused rat livers. The livers were perfused with a Krebs-Henseleit buffer containing washed bovine erythrocytes and albumin at 37 degrees C for 90 or 120 minutes, In the first 60 minutes, the livers were perfused with insulin (10 microU/mL), glucagon (11 pg/mL), and glucose (105, 230, or 440 mg/dL). In the second 30 or 60 minutes, the glucagon concentration in the perfusate was elevated to 44, 88, 176 or 352 pg/mL or the infusion of glucagon was terminated. In the presence of glucose at 105 mg/dL, the termination of glucagon infusion decreased phosphorylase activity and glucose output. In contrast, the elevation of glucagon from 11 to 352 pg/mL activated phosphorylase and increased net glucose output in a dose-dependent manner. A linear correlation was observed between net glucose output and glycogen phosphorylase activity. An elevation of the glucose concentration from 105 to 230 or 440 mg/dL decreased net glucose output from 0.81 +/- 0.03 to 0.66 +/- 0.09 or -0.004 +/- 0.21 mg/min/100 g body weight, respectively, but did not cause significant change in phosphorylase-a activity (105 mg/dl, 50 +/- 11; 230 mg/dL, 40 +/- 2; 440 mg/dL, 69 +/ 3 mU/mg protein). The elevation of the glucagon concentration from 11 to 88 microU/mL in the presence of glucose at 105, 230, or 440 mg/dL increased net glucose output by 0.65 +/- 0.06, 0.61 +/- 0.08 or 0.64 +/- 0.26 mg/min 100 g body weight and raised phosphorylase-a activity by 65 +/- 5, 82 +/- 11, or 55 +/- 4 mU/mg protein, respectively. These results suggest that hyperglycemia decreases net hepatic glucose output without changing the activity of phosphory-lase-a. Further hyperglycemia does not alter the ability of glucagon to activate phosphorylase or to stimulate net hepatic glucose output.

Animals↗

PubMed1996

Decreased ureagenesis from alanine, but not from ammonia and glutamine, in the perfused rat liver after partial hepatectomy.

Ureagenesis from ammonia, alanine, and glutamine in the liver after partial hepatectomy (PH) was determined by using the liver-perfusion system. The maximum rate of ureagenesis from ammonium chloride (10 mmol/L) in hepatectomized (HX) rats at 24 hours after surgery was obtained in the presence of ornithine, lactate, and pyruvate, and it was almost identical to that in sham-operated (SO) rats. The rate of urea production from glutamine (1 mmol/L or 10 mmol/L) in HX rats was significantly lower than that of SO rats with a concomitant decrease in hepatic glutaminase activities. However, the rate of urea synthesis from glutamine (1 mmol/L) in the presence of added ammonia (0.5 mmol/L) was accelerated approximately 10-fold, and the significant difference in the rate of urea formation between HX and SO rats was abolished. This result indicates that there is enough glutaminase to generate ammonia from glutamine in the liver of HX rats. The rate of urea production from alanine (1 mmol/L or 10 mmol/L) in HX rats was significantly decreased at 24 hours following surgery, while that of SO rats was increased. The decreased formation of urea from alanine was not seen at 72 and 120 hours after the operation. These results suggest that during the proliferation phase of liver regeneration, a reduction of ureagenesis from alanine facilitates the remnant liver to make nonessential amino acids such as aspartate. This metabolic alteration might be related to the proliferation of liver cells.

Alanine↗

PubMed1996

Phorbol ester, but not endotoxin, desensitizes mannan-induced glycogenolysis in the perfused rat liver.

Mannan, a ligand for the mannose/N-acetylglucosamine (GlcNAc) receptor, induces suppression of oxygen consumption and increases glucose production in the perfused rat liver, and repeated infusion of mannan causes desensitization of the responses. In this study, we examined whether activation of Kupffer cells by endotoxin and phorbol ester alters the glycogenolytic responses to mannan. Infusion of lipopolysaccharide (LPS, 10 micrograms/ ml) in the perfusate failed to inhibit the responses to mannan. Intravenous administration of LPS (1 mg/kg) 6 and 24 h before perfusion did not desensitize the responses to mannan, suggesting that the responses through mannose/GlcNAc receptors in the liver are retained even after activation of Kupffer cells by LPS. In contrast, prior infusion of phorbol 12-myristate 13-acetate (PMA, 100 nM) in vitro abolished the glycogenolytic responses to subsequently infused mannan, but not that to norepinephrine (100 nM), while prior infusions of 4-alpha-phorbol 12,13-didecanoate (100 nM), A23187 (50 nM), or forskolin (1 microM) had no effect on the mannan-induced responses. H-7, an inhibitor of protein kinase C, reduced the glycogenolytic responses to mannan, while it failed to restore the desensitization. These results suggest that protein kinase C may be involved in the process of glycogenolysis by mannan, but is unlikely to be involved in the homologous desensitization of the responses.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1996

The clinicopathological features of anaplastic large cell lymphomas expressing p80NPM/ALK.

The classification of malignant lymphoma has been based on morphological and immunophenotypical findings for a long time. Recently, as chromosomal and genomic abnormalities which closely relate to the specific subtypes of lymphoma are revealed, these factors becoming much more important in the evaluation of differences in clinicopathological features of the various lymphoma subtypes. Anaplastic large cell lymphoma (ALCL) is a subtype of non-Hodgkin's lymphoma (NHL) involving large CD30+ neoplastic cells, which occasionally carries the chromosomal translocation t(2;5)(p23;q35). We have recently found a novel hyperphosphorylated 80-kDa protein tyrosine kinase, p80 which is expressed specifically in human ALCLs with this translocation. Subsequent cDNA cloning showed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene. In order to clarify the clinicopathologic features of p80-carrying ALCLs, we developed an anti-p80 polyclonal antibody, which immunoprecipitated, immunoblotted and immunostained p80 specifically. When paraffin sections of 105 cases of ALCL were stained using the anti-p80 antibody, 30 were shown to be p80 positive Clinicopathological comparison between p80-positive and p80-negative ALCLs revealed that the p80-positive cases occurred in a much younger patient age group and that the patients showed a far better 5-year survival rate. These data suggest that p80-positive ALCL is a distinct entity and should be differentiated from p80-negative ALCL.

Age of Onset↗

PubMed1996

The (2;5)(p23;q35) translocation in cell lines derived from malignant lymphomas: absence of t(2;5) in Hodgkin-analogous cell lines.

The CD30+ anaplastic large cell lymphoma (ALCL) represents a new lymphoma entity thought to be related to Hodgkin'S disease (HD), but displaying also its own unique features. Cytogenetic studies of ALCL have demonstrated the presence of a (2;5)(p23;q35) translocation in a substantial number of these cases. Recently, the t(2;5) has been cloned and described to represent fusion of the NPM gene with the ALK gene on chromosome 5. To better define the spectrum of lymphomas containing this abnormality we have analyzed 50 continuous human cell lines established from various types of non-Hodgkin's lymphoma, ALCL and HD. In a first step, the expression of the NPM-ALK fusion gene was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). In a second step, the t(2;5)-carrying cells were tested for the translation of functional chimeric mRNA into a fusion protein by immuno-staining of single cells with a polyclonal antibody. The NPM-ALK fusion transcript and the p80 protein were detected in eight of nine ALCL cell lines. We were unable to find PCR evidence for the t(2;5) in any of the non-ALCL cell lines including other CD30+ cell lines. As all seven bona fide HD cell lines were NPM-ALK-negative, these results do not support the notion that the t(2;5) represents a chromosomal aberration common to both ALCL and HD.

Anaplastic Lymphoma Kinase↗