Biomedical subjects

A Nagasaki

Publications and source records attributed to A Nagasaki.

At least 19 recordsLinked to original sources

PubMed2001

Activated protein C prevents endotoxin-induced hypotension in rats by inhibiting excessive production of nitric oxide.

BACKGROUND: Excessive production of nitric oxide (NO) by the inducible isoform of NO synthase (iNOS) is critically involved in endotoxin (ET)-induced hypotension. Tumor necrosis factor-alpha (TNF-alpha) plays an important role in induction of iNOS. Because activated protein C (APC), a physiological anticoagulant, inhibits TNF-alpha production, it might prevent hypotension by inhibiting excessive production of NO. In this study, we examined this possibility using a rat model of septic shock. METHODS AND RESULTS: Intravenous administration of APC prevented both ET-induced hypotension and the increases in plasma levels of NO(2)(-)/NO(3)(-). The hypotension was also inhibited when APC was administered 30 minutes after ET administration. APC inhibited the increases in lung levels of iNOS activity by inhibiting expression of iNOS mRNA in animals given ET. APC significantly inhibited the increases in lung tissue levels of TNF-alpha and expression of TNF-alpha mRNA in animals given ET. Neither DEGR-F.Xa, a selective inhibitor of thrombin generation, nor DIP-APC, an active site-blocked APC, showed any effect on these ET-induced changes. Both inhibition of TNF-alpha production by leukocytopenia and treatment with anti-rat TNF-alpha antibody produced effects similar to those induced by APC. Aminoguanidine, a selective inhibitor of iNOS, inhibited both the hypotension and the increases in plasma levels of NO(2)(-)/NO(3)(-) in this animal model. CONCLUSIONS: These observations strongly suggest that APC inhibits iNOS induction by decreasing TNF-alpha production, leading to the prevention of ET-induced hypotension. Furthermore, such effects of APC were not dependent on its anticoagulant effects but rather on its serine protease activity.

Amino Acid Chloromethyl Ketones↗

PubMed2001

Clinical and biologic characteristics for recurring neuroblastoma at mass screening cases in Japan.

BACKGROUND: It is said that most cases detected by neuroblastoma mass screening at 6 months of age tend to have a favorable clinical course after a surgical resection either with or without mild chemotherapy. However, a few cases have an unfavorable outcome. In the current study, the authors analyzed the clinical and biologic characteristics for recurring neuroblastoma in mass screening cases. METHODS: In 245 cases detected through mass screening in the Kyushu area in Japan, the clinical data and biologic features (N-myc status, DNA ploidy, Shimada histology, neuron-specific enolase (NSE), ferritin) were investigated, whereas, in particular, the data for recurring cases also were analyzed. RESULTS: Of 245 cases, 28 tumors had one or more biologically unfavorable prognostic factors, and 6 patients experienced recurrence. Three of the six patients with recurring disease underwent a complete resection of the primary tumor, whereas three cases had undergone an incomplete resection of the tumor. Regarding the initial chemotherapy, three cases received mild chemotherapy, two cases received no chemotherapy, and one case had high-dose multidrug chemotherapy. Regarding biologic prognostic factors, four of six cases with recurring disease had one or more unfavorable factors, whereas two cases had no unfavorable factors. Regarding the outcome after recurrence, four cases are CR, one case has a stable residual tumor, and one case died of disease with N-myc amplification. CONCLUSIONS: Most neuroblastomas detected by mass screening at 6 months of age have biologically favorable factors. However, approximately 10% of the cases had one or more unfavorable factors and thus might have a higher risk of recurrence than the patients with no unfavorable factors. Conversely, some cases with recurring disease had no unfavorable factors; however, the reason for this is still unclear. A long-term follow-up for mass screening cases is important, and it also might be necessary to research the established biologic factors and identify other new prognostic factors.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Genetic approaches to dissect the mechanisms of two distinct pathways of cell cycle-coupled cytokinesis in Dictyostelium.

Dictyostelium discoideum is a unique experimental organism which allows genetic analysis of the mechanism of cytokinesis of the animal type, and a number of mutations which affect cytokinesis in one way or other have been identified. Myosin II filaments accumulate in the equatorial region, and myosin II-null cells cannot divide in suspension, indicating that active, myosin II-dependent constriction of the cleavage furrow contributes to bisection of the cell. We refer to this method of cytokinesis as cytokinesis A. On substrates, however, myosin II-null cells divide efficiently in a cell cycle-coupled manner. This adhesion-dependent but myosin II-independent division method, which we termed cytokinesis B, is carried out by a pathway that is genetically distinct from that of cytokinesis A. Morphological analyses suggested that cytokinesis B is driven by radial traction forces generated along polar peripheries, which indirectly cause furrow ingression. Identification of two redundant pathways have allowed us to search genes involved in either pathway by mutagenizing cells which are already defective in one of the pathways. This approach enabled us to identify a number of novel cytokinesis-related genes, as well as to reclassify known genes as cytokinesis-related.

Animals↗

PubMed2000

Induction of endothelial nitric-oxide synthase in rat brain astrocytes by systemic lipopolysaccharide treatment.

In the brain, three isoforms of nitric oxide (NO) synthase (NOS), namely neuronal NOS (nNOS, NOS1), inducible NOS (iNOS, NOS2), and endothelial NOS (eNOS, NOS3), have been implicated in biological roles such as neurotransmission, neurotoxicity, immune function, and blood vessel regulation, each isoform exhibiting in part overlapping roles. Previous studies showed that iNOS is induced in the brain by systemic treatment with lipopolysaccharide (LPS), a Gram-negative bacteria-derived stimulant of the innate immune system. Here we found that eNOS mRNA is induced in the rat brain by intraperitoneal injection of LPS of a smaller amount than that required for induction of iNOS mRNA. The induction of eNOS mRNA was followed by an increase in eNOS protein. Immunohistochemical analysis revealed that eNOS is located in astrocytes of both gray and white matters as well as in blood vessels. Induction of eNOS in response to a low dose of LPS, together with its localization in major components of the blood-brain barrier, suggests that brain eNOS is involved in early pathophysiologic response against systemic infection before iNOS is induced with progression of the infection.

Animals↗

PubMed2000

Improved survival for patients with advanced neuroblastoma after high-dose combined chemotherapy based in part on N-myc amplification.

BACKGROUND/PURPOSE: In spite of many different kinds of chemotherapy for neuroblastoma, the prognosis for advanced neuroblastoma remains unsatisfactory. In particular, the outcome of advanced neuroblastoma with high copies of the N-myc gene tend to be poor. Therefore, the new high-dosage combined chemotherapy regimens for advanced neuroblastoma based in part on the N-myc amplification status has been utilized in the Kyushu area of Japan since 1991. This study aims to investigate whether these new regimens based in part on N-myc amplification have improved the survival rate of stage III and stage IV patients in comparison with the old regimens. METHODS: Between 1983 and 1995, 77 patients over 1 year of age and with stage III or IV neuroblastoma were registered in the Kyushu Area. Between 1983 and 1990, 49 patients received 1 of 2 combined chemotherapy regimens consisting of cyclophosphamide, cisplatin plus VM-26, and Adriamycin plus DTIC. Since 1991, two new regimens (New A1 and A3) have been administered based on the N-myc amplification status in a total of 28 patients. The New A1 regimen, which consists of cyclophosphamide, cisplatin, Adriamycin, and VP-16 has been administered in cases of less than 10 copies of N-myc, whereas the A3 regimen, consisting of a higher dose of cyclophosphamide, cisplatin, Adriamycin, and VP-16, has been administered in cases of more than 10 copies of N-myc. The survival rate was then compared between the old regimens and the new regimens. RESULTS: The 3-year survival rate (61.5%) for patients treated by the new regimens was significantly higher than that (32.7%) for patients treated by the old regimens (P <.01). Regarding the 24 cases of more than 10 copies of N-myc, the 3-year survival rate (35.9%) of the 13 patients treated by the A3 regimen was higher than that (0%) of the 11 patients treated by the old regimens (P <.05). However, in the 19 stage IV patients treated by the new regimens, the 3-year survival rate (11.1%) of the 9 cases of more than 10 copies was significantly lower than that (77.8%) of the 10 cases of less than 10 copies of N-myc (P <.01). CONCLUSIONS: These results suggest that high-dose combined chemotherapy based in part on the N-myc amplification status significantly improved the prognosis of patients with advanced neuroblastoma. However, stage IV patients with N-myc amplification still require a more effective treatment modality.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Down-regulation of CD98 in melphalan-resistant myeloma cells with reduced drug uptake.

Although melphalan has been used as a therapeutic reagent for multiple myeloma, many patients become refractory. To elucidate the mechanism of resistance to melphalan, we generated a melphalan-resistant myeloma cell line, KHM-11(EMS), by treating a parental line, KHM-11, with a mutagen, ethylmethanesulfonate. KHM-11(EMS) is 55 times more resistant to melphalan. gamma-Glutamylcysteine synthetase, P-glycoprotein, multidrug-resistance-associated protein, lung-resistance-related protein and the Bcl-2 family of proteins were not responsible for the drug resistance in KHM-11(EMS). Intracellular incorporation of melphalan to myeloma cells was determined by using [(14)C]-labeled melphalan. Accumulation of melphalan in KHM-11(EMS) was 43% of KHM-11, while the efflux rates were comparable in both cell lines. The uptake of melphalan was inhibited by the addition of L-phenylalanine, indicating that melphalan is incorporated through the L-phenylalanine transporter as reported previously. Expression of CD98, which was recently cloned as an L-phenylalanine transporter, was 6-fold decreased in KHM-11(EMS), suggesting that CD98 may be correlated with the incorporation of melphalan. CD98 expression and incorporation of melphalan were analyzed in fresh purified myeloma cells from 5 patients. All myeloma cells from 4 cases expressed CD98 at a high level and incorporated melphalan. However, tumor cells from 1 case expressed CD98 at low levels and did not incorporate melphalan. Taken together, reduced melphalan uptake could be responsible for the drug resistance in KHM-11(EMS), and down-regulation of CD98 may be related to this phenomenon. Further investigation of the correlation between impaired drug uptake and down-regulation of CD98 in myeloma cells should be important to understand the mechanism of resistance to melphalan.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Expression of citrulline-nitric oxide cycle in lipopolysaccharide and cytokine-stimulated rat astroglioma C6 cells.

Nitric oxide (NO) is involved in many physiological and pathological processes in the brain. NO is synthesized from arginine by nitric oxide synthase (NOS), with citrulline generated as a by-product of the reaction. Thus, citrulline can by recycled to arginine by argininosuccinate synthetase (AS) and argininosuccinate lyase (AL) via the citrulline-NO cycle. Rat astroglioma C6 cells were treated with bacterial lipopolysaccharide (LPS), interferon-gamma (IFNgamma) and tumor necrosis factor-alpha, and the expression of the enzymes of the citrulline-NO cycle was investigated by RNA blot and immunoblot analyses. NO production from arginine and citrulline was also assessed. iNOS mRNA and protein were induced 6-12 h after stimulation with LPS and cytokines and decreased at 24 h. AS mRNA increased up to 12 h and decreased at 24 h. AS protein increased gradually up to 48 h. On the other hand, AL mRNA remained unchanged by stimulation. NO production from arginine was enhanced by the treatment with LPS and cytokines. NO production was also observed when arginine was replaced by citrulline. These results indicate that NO production is enhanced in LPS- and cytokine-stimulated C6 cells due to induction of iNOS and that the citrulline-arginine recycling is important for NO production.

Animals↗

PubMed1999

Expression of inducible nitric oxide synthase and enzymes of arginine metabolism in Fusarium kyushuense-exposed mouse lung.

Expression of inducible nitric oxide (NO) synthase (iNOS) and related enzymes of arginine metabolism in the mouse lung exposed to filamentous fungus Fusarium kyushuense was studied by RNA blot, immunoblot, and histological analyses. When mice were exposed intranasally to the fungi only once, no induction of iNOS mRNA was observed. However, when the animals were infected again 6 days after the first exposure, iNOS mRNA was induced, reached a maximum 12-24 h after the exposure, and decreased to an undetectable level at 48 h. mRNAs for cationic amino acid transporter-2 (CAT2) and argininosuccinate synthetase were induced gradually, reached a maximum at 24 h, and decreased at 48 h. Arginase II mRNA increased at 24 h and decreased markedly at 48 h. On the other hand, arginase I mRNA started to increase at 24 h and reached to a much higher level at 48 h. Ornithine decarboxylase and ornithine aminotransferase mRNAs were also induced. Immunoblot analysis showed that iNOS, argininosuccinate synthetase, and arginase I and II proteins were induced with similar kinetics as those of their respective mRNAs. In histological examination, fungal elements were observed in the bronchoalveolar lumen at 3-6 h, decreased at 12 h, and almost disappeared at 48 h. Small granuloma appeared 3 h after the infection and their size increased with time. These results suggest that NO is produced in the mouse lung in response to F. kyushuense exposure and that the NO production is regulated by CAT2, the citrulline-NO cycle, and arginase isoforms. Enhanced synthesis of polyamines and proline (and thus collagen) is also suggested.

Amino Acid Transport Systems, Basic↗

PubMed1999

Analysis of 1,992 patients with anorectal malformations over the past two decades in Japan. Steering Committee of Japanese Study Group of Anorectal Anomalies.

BACKGROUND/PURPOSE: This report describes the results of a group study of the Japanese Study Group of Anorectal Anomolies (JSGA) to determine the relative incidence of specific types of anorectal anomaly in Japan, and includes discussion of rectourethral fistula regarding the relationship between the levels of the fistula and blind end of the rectum, low type deformity, rare types, and associated anomalies. METHODS: A total of 1,992 patients (1,183 boys and 809 girls) registered from 1976 to 1995 were analyzed. RESULTS: High-type deformities accounted for 26.0% of cases, intermediate 10.7%, low 57.2%, miscellaneous 4.5% and unclassified 1.8%. The most frequent deformity was male anocutaneous fistula (n = 364), followed by male rectourethral fistula (n = 333), and female anovestibular fistula (n = 241). There were 42 rectovesical fistulas in boys and 93 rectocloacal fistulas in girls. Covered anus complete occurred at the same frequency (10.1% of low deformities) as covered anal stenosis. In rectourethral fistula, the blind end of the rectum lay at or above the level of the P-C line in 40.3% of cases, at or above the M line in 39.6% and at the vicinity of the I line in 20.2%, respectively. There was no parallel relationship between the site of the fistula opening and the level of the rectal pouch. The overall incidence of patients having one or more associated anomalies was 45.2%: 70.6% in high deformity, 60.7% in intermediate, and 31.3% in low. The rate of association of Down's syndrome with deformities without fistula (40.3%) was significantly higher than with deformities with fistula (0.3%). CONCLUSIONS: Rectovesical fistula and covered anus complete were not infrequent deformities in this series. We consider that at least 20% of rectourethral fistula should be categorized as intermediate or low deformity from the viewpoint of the position of the rectal pouch. A significant preponderance of Down's syndrome in the deformities without fistula suggests that further investigation of associated anomalies in comparision with other congenital diseases may provide insights into the pathogenesis of anorectal malformation in the field of molecular genetics.

Anal Canal↗

PubMed1999

Detection of inducible nitric oxide synthase (iNOS) mRNA by RT-PCR in ATL patients and HTLV-I infected cell lines: clinical features and apoptosis by NOS inhibitor.

Various tumors have been reported to express an inducible form of nitric oxide synthase (iNOS), and nitric oxide (NO) may affect the clinicopathological features of these tumors. Previously, Burkitt's lymphoma and Epstein-Barr virus (EBV)-infected cells were shown to express iNOS constitutively at a low level. We analyzed iNOS expression by the reverse transcriptase-polymerase reaction method (RT-PCR) in eight HTLV-I-infected cell lines (five were ATL-derived lines and there were in vitro transformed lines), nine ATL patients (three were chronic, two were acute, and four were lymphoma type), and an HTLV-I-negative T cell line (CEM). In four ATL derived and in all three in vitro transformed cell lines, iNOS was expressed constitutively, but it was not expressed in CEM cells. Four out of nine ATL patients also showed iNOS expression. The expression of iNOS was found in all subtypes of ATL. Three of four iNOS-positive patients had infiltration of ATL cells to organs such as skin, lung, or liver. In NOS inhibitor (NG-monomethyl-L-arginine: L-NMMA)-containing medium, an iNOS-positive ATL cell line (K3T) showed growth inhibition and DNA ladder. Although only a limited number of patients was analyzed, our results suggest that NO may be involved in the invasive character of ATL cells. The NOS inhibitor can induce apoptosis in an ATL cell line, as it does in EBV-infected cell lines.

Apoptosis↗

PubMed1999

Expression of PRAD1/cyclin D1 in plasma cell malignancy: incidence and prognostic aspects.

We analysed PRAD1/cyclin D1 expression in 20 patients with plasma cell malignancy by Northern analysis. 6/17 multiple myeloma patients and 3/3 plasma cell leukaemia patients showed PRAD1/cyclin D1 expression. This incidence appeared to be higher than the expected incidence based on previous studies. Southern analysis did not show rearrangement of the bcl-1 region. Although there was no statistical difference, the PRAD1/cyclin D1 negative group showed a 1-year survival of 81.8%, 3-year survival of 45.5% and 5-year survival of 22.7%, and those for the PRAD1/cyclin D1 positive group were 63.5%, 16.9% and 16.9%, respectively. Further study is required to determine whether PRAD1/cyclin D1 expression is a prognostic factor.

Aged↗

PubMed1999

Expression of arginase II and related enzymes in the rat small intestine and kidney.

Arginase, which catalyzes the conversion of arginine to urea and ornithine, and consists of a liver-type (arginase I) and a non-hepatic type (arginase II). Arginine is also used for the synthesis of nitric oxide and creatine phosphate, while ornithine is used for the synthesis of polyamines and proline, and thus collagen. Arginase II mRNA and protein are abundant in the intestine (most abundant in the jejunum and less abundant in the ileum, duodenum, and colon) and kidney of the rat. In the kidney, the levels of arginase II mRNA do not change appreciably from 0 to 8 weeks of age. In contrast, arginase II mRNA and protein in the small intestine are not detectable at birth, appear at 3 weeks of age, the weaning period, and their levels increase up to 8 weeks. On the other hand, mRNAs for ornithine aminotransferase (OAT), ornithine decarboxylase, and ornithine carbamoyltransferase (OCT) are present at birth and their levels do not change much during development. Arginase II is elevated in response to a combination of bacterial lipopolysaccharide, dibutyryl cAMP, and dexamethasone in the kidney, but is not affected by these treatments in the small intestine. Immunohistochemical analysis of arginase II, OAT, and OCT in the jejunum revealed their co-localization in absorptive epithelial cells. These results show that the arginase II gene is regulated differentially in the small intestine and kidney, and suggest different roles of the enzyme in these two tissues. The co-localization of arginase II and the three ornithine-utilizing enzymes in the small intestine suggests that the enzyme is involved in the synthesis of proline, polyamines, and/or citrulline in this tissue.

Animals↗

PubMed1999

Regulation of the genes for arginase isoforms and related enzymes in mouse macrophages by lipopolysaccharide.

Arginase exists in two isoforms, the hepatic (arginase I) and extrahepatic types (arginase II). Arginase I is markedly induced in rat peritoneal macrophages and rat tissues in vivo by bacterial lipopolysaccharide (LPS). In contrast, both arginase I and arginase II are induced in LPS-activated mouse peritoneal macrophages. In the present study, expression of arginase isoforms and related enzymes was studied in mouse tissues in vivo and in peritoneal macrophages with RNA blot and immunoblot analyses and enzyme assay. When mice were injected intraperitoneally with LPS, inducible nitric oxide synthase (iNOS) and arginase II were induced early in the lung and spleen. mRNAs for argininosuccinate synthase (AS) and ornithine decarboxylase (ODC) were also induced early. In comparison, arginase I was induced later in the lung. Early induction of iNOS, arginase II, AS, ODC, and cationic amino acid transporter 2 and late induction of arginase I were observed in LPS-activated peritoneal macrophages. These results indicate that the genes for the two arginase isoforms are regulated differentially. Possible roles of the arginase isoforms in the regulation of nitric oxide production and in polyamine synthesis are discussed.

Animals↗

PubMed1999

Establishment and characterization of a CD95 (Fas/Apo-1)-negative myeloma cell line.

Although expression of CD95 (Fas/Apo-1) on myeloma cells has been reported, its significance is not clearly understood. We established a myeloma cell line, KHM-11ad (11ad), from a parental cell line, KHM-11, by collecting cells adhered to a plastic dish. KHM-11 cells have been reported to be positive for CD45 and CD95 (Fas/Apo1), and negative for a myelomonocytic antigen, CD13. Interestingly, CD95 was not detected in 11ad. Expression of CD45 was also significantly decreased in 11ad cells while expression of CD13 was detected in these cells. The growth rate of 11ad cells was 1.7 times lower than that of KHM-11 cells. Analysis of adhesion molecules showed that expression of VLA4 and CD44 was significantly suppressed in 11ad. The IC50 of melphalan (L-PAM) for 11ad cells was 50 times higher than that for KHM-11, indicating that 11ad is significantly refractory to L-PAM than KHM-11 cells. Induction of apoptosis by doxorubicin and cycloheximide was suppressed in 11ad cells compared with those in KHM-11 cells. Western blot analysis for Bcl-2 family of proteins showed that Bax was expressed at a 2.2 times lower level in 11ad cells than in KHM-11 cells while there was no difference in expression of Bcl-2, Bcl-Xs nor Bcl-XL. These results suggest that CD95-negative myeloma cells may have characteristics as follows: (1) slow proliferation; (2) low sensitivity to apoptosis; (3) low expression of VLA4, CD44 and Bax. Although these intraclonal variations were based on the findings of cell lines, these may reflect similar variations in vivo. The 11ad line may be a suitable model for analyzing intraclonal variation of myeloma cells.

Antigens, Surface↗

PubMed1998

Dictyostelium TRFA homologous to yeast Ssn6 is required for normal growth and early development.

The TPR (tetratricopeptide repeat) family became widespread during evolution, having been found from bacteria to mammals. By means of restriction enzyme-mediated integration, we have identified a Dictyostelium gene (trfA) highly homologous to a Saccharomyces cerevisiae gene encoding a TPR protein, Ssn6 (Cyc8), which functions as a global transcriptional repressor for diverse genes. The deduced amino acid sequence of the Dictyostelium gene product, TRFA, contains 10 consecutive TPR units as well as Gln repeats, Asn repeats, and a region rich in Glu, Lys, Ser, and Thr. The sequences of some of the 10 TPR units in TRFA are more than 70% identical to the corresponding units in Ssn6. The trfA- cells produced smooth plaques on a bacterial lawn and failed to aggregate normally when starved on a plain agar plate. Individual trfA- cells also failed to correctly respond to cAMP, although the adenylyl cyclase of trfA- cells was expressed upon starvation and activated by stimulation with cAMP as in the wild-type cells. When cultured in a rich medium in suspension, they grew more slowly and stopped growing at a lower density than the wild-type cells. Furthermore, they divided into cells of various sizes and tended to be much smaller than the wild-type cells. These pleiotropic defects of the trfA- cells suggest the possibility that Dictyostelium TRFA may regulate the transcription of diverse genes required for normal growth and early development.

Amino Acid Sequence↗

PubMed1998

A novel Dictyostelium discoideum gene required for cAMP-dependent cell aggregation.

Using a method of random insertional mutagenesis called REMI (restriction enzyme-mediated integration), we isolated two mutant strains of Dictyostelium discoideum with a defect in cAMP-dependent cell aggregation. On bacterial lawns, both of the cells formed large and smooth plaques. When starved in a non-nutrient medium, they became elongated and extended pseudopods very frequently like starved wild type cells. However, they never formed streams toward an aggregation center. Genomic DNA fragments flanking the sites of insertion of the REMI tag were rescued from the mutant cells. The fragments contained one common open reading frame encoding a protein of 1148 amino acid residues. The protein's sequence is homologous to those of two hypothetical proteins of S. cerevisiae and S. pombe.

Amino Acid Sequence↗

PubMed1998

Multiple myeloma associated with serum amino acid disturbance and high output cardiac failure.

We experienced a plasma cell leukemia (PCL) patient complicated with high output cardiac failure (HOCF), proved as his elevated cardiac index and pulmonary artery wedge pressure and decreased systemic vascular resistance index in a hemodynamic study. We found no possible causes of HOCF. Interestingly, HOCF was improved as PCL responded to intensive chemotherapy. On the other hand, he showed consciousness disturbance, and had frequent attacks of generalized seizure. His electroencephalogram showed slow waves, and a spike and wave complex. Hyperammonemia and abnormal amino acid distribution were also found. This abnormal serum amino acid distribution, especially elevated glycine level, was different from that seen in chronic liver failure, and he had no hepatic disease. After intensive chemotherapy, the serum ammonia level and glycine level decreased. In this patient, PCL seemed to be responsible for HOCF, hyperammonemia, and abnormal amino acid distribution. We experienced two more cases of multiple myeloma (MM) with HOCF, hyperammonemia, abnormal serum amino acid distribution, and consciousness disturbance of unknown origin. Those two cases showed slow waves in the electroencephalogram. Improvement was seen in their HOCF, hyperammonemia, and abnormal amino acid levels after chemotherapy. The possibility of MM as a cause of HOCF is discussed.

Adult↗

PubMed1998

Establishment of a monoclonal antibody to human myeloma cell: relation to chemotherapy and extramedullar infiltration.

Resistance of myeloma cells to melphalan (L-PAM) is a serious problem. To investigate mechanisms of drug resistance, we generated a monoclonal antibody, clone O3, to melphalan-resistant myeloma cells, KHM-11R. Western blot analysis showed that molecular weight of O3 antigen was approximately 90 kDa. Expression of O3 antigen was approximately two times higher in KHM-11R than in parental melphalan sensitive cell line, KHM-11. O3 was preferentially expressed in plasma cell, B-cell, and monocytic cell lines, but not in T-cell lines. Analysis of bone marrow samples from myeloma patients revealed that 13 of 23 samples expressed O3 antigen at various levels, and that O3 antigen expression in patients correlate with preceding chemotherapy, advanced clinical stage and extramedullar invasion of myeloma cells. Furthermore, patients expressing O3 antigen at the time of diagnosis tended to have poor prognosis. The investigation of O3 antigen in myeloma cells will be useful to reveal the pathophysiology of extramedullar invasion and the mechanism of cell killing by melphalan.

Adult↗