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Biomedical subjects

K Matsui

Publications and source records attributed to K Matsui.

At least 199 records · Page 11Linked to original sources
PubMed1998

[Cyclin D1 overexpression in laryngeal carcinomas].

Overexpression of cyclin D1 has been found in a variety of malignancies and is suggested to be related to tumor progression. We immunohistochemically investigated the overexpression of cyclin D1 protein in 92 laryngeal carcinomas. Twenty-eight (30.4%) of the carcinoma specimens showed overexpression of cyclin D1. This overexpression was not related to the tumor stage, lymph node metastasis, or clinical outcome. However, the overexpression of cyclin D1 in patients with local recurrence was significantly higher than in patients with no recurrence. Cyclin D1 immunohistochemical staining is considered to be a useful marker for predicting tumor recurrence.

Biomarkers, Tumor↗
PubMed1998

Clinicopathologic features of neuroendocrine carcinomas of the stomach: appraisal of small cell and large cell variants.

OBJECTIVE: To clarify the clinicopathologic features of neuroendocrine carcinomas (NECs) of the stomach, we reviewed 56 cases of surgically treated gastric carcinomas with a solid growth or with areas containing patterns characteristic for neuroendocrine (NE) tumors. METHODS: Of the 56 cases reviewed, we selected 33 cases of NEC based both on histologic patterns common to NE tumors and on histochemical/immunohistochemical results. RESULTS: The average age of patients with NEC was 69.8 years (range, 44-92 years). The majority of patients were men (male-female ratio, 23:10). The most frequently affected site was the upper third (46%) of the stomach. Grossly, 9 cases of NEC were fungating and 24 were ulcerated. As compared with 23 patients with non-NEC tumors, the patients with NECs had a worse prognosis. Histologically, NECs had a variety of histologic patterns, including solid, organoid, trabecular, pseudoglandular, spindle cell, and rosettelike. Based on both cell size and morphologic features, we subdivided NECs into 2 variants, namely, small cell NEC and large cell NEC. Our series included 12 cases of small cell NEC and 21 cases of large cell NEC. CONCLUSIONS: Compared with small cell NECs, large cell NECs had a higher mitotic count, larger polygonal cells, a lower nuclear-cytoplasmic ratio, coarser nuclear chromatin, and more frequent conspicuous nucleoli. Large cell NEC was an aggressive tumor with a very poor prognosis (median survival time, 15.2 months; 1-year survival rate, 58%), which approached that for small cell NEC.

Adult↗
PubMed1997

Multiple pathways for SOS-induced mutagenesis in Escherichia coli: an overexpression of dinB/dinP results in strongly enhancing mutagenesis in the absence of any exogenous treatment to damage DNA.

dinP is an Escherichia coli gene recently identified at 5.5 min of the genetic map, whose product shows a similarity in amino acid sequence to the E. coli UmuC protein involved in DNA damage-induced mutagenesis. In this paper we show that the gene is identical to dinB, an SOS gene previously localized near the lac locus at 8 min, the function of which was shown to be required for mutagenesis of nonirradiated lambda phage infecting UV-preirradiated bacterial cells (termed lambdaUTM for lambda untargeted mutagenesis). A newly constructed dinP null mutant exhibited the same defect for lambdaUTM as observed previously with a dinB::Mu mutant, and the defect was complemented by plasmids carrying dinP as the only intact bacterial gene. Furthermore, merely increasing the dinP gene expression, without UV irradiation or any other DNA-damaging treatment, resulted in a strong enhancement of mutagenesis in F'lac plasmids; at most, 800-fold increase in the G6-to-G5 change. The enhanced mutagenesis did not depend on recA, uvrA, or umuDC. Thus, our results establish that E. coli has at least two distinct pathways for SOS-induced mutagenesis: one dependent on umuDC and the other on dinB/P.

Bacterial Proteins↗
PubMed1997

New tester strains of Salmonella typhimurium lacking O6-methylguanine DNA methyltransferases and highly sensitive to mutagenic alkylating agents.

Salmonella typhimurium YG7104 and YG7108 are derivatives of the Ames tester strain TA1535, and have chromosomal deletions of the ogtST gene or both the ogtST and adaST genes, respectively. The ogtST and adaST genes encode O6-methylguanine DNA methyltransferases that are involved in the repair of DNA damage caused by alkylating agents. The sensitivities of these strains to 15 mutagens with different structures were tested and compared with those of the parent strain TA1535. Deletion of ogtST or ogtST plus adaST substantially increased the sensitivity of strain TA1535 to the mutagenicity of alkylating agents, such as N-ethyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate or dimethylnitrosamine (DMN). Preincubation of the chemical with S9 mix and bacteria for 20 min at 37 degrees C before pouring them together on agar plates was not necessary to detect the mutagenicity of DMN when strain YG7104 or YG7108 was used as a tester strain. Introduction of plasmid pKM101 did not enhance but rather decreased the sensitivity of YG7104 and YG7108 to alkylating agents. Since the new strains are highly sensitive only to alkylating agents, they will be useful to detect the mutagenicity with high efficiency and to study the mechanism of mutagenesis induced by environmental alkylating agents.

Alkylating Agents↗
PubMed1997

Enzymatic synthesis of the glycosides of calystegines B1 and B2 and their glycosidase inhibitory activities.

Several glycosides of calystegines B1 and B2 were synthesized by use of rice alpha-glucosidase and the whole cells of Rhodotorula lactosa, and their glycosidase inhibitory activities were investigated. Incubation of mixture of calystegine B1 and maltose with rice alpha-glucosidase gave 3-O-alpha-D-glucopyranosylcalystegine B1 (2, 11.3%). An enzymatic beta-transglucosylation reaction of calystegines B1 or B2 with cellobiose using the whole cells of R. lactosa gave 3-O-beta-D-glucopyranosylcalystegine B1 (1) (0.9%) or 4-O-beta-D-glucopyranosylcalystegine B2 (3, 11.2%), respectively, while similar beta-transgalactosylation of calystegine B2 from lactose gave 4-O-beta-D-galactopyranosylcalystegine B2 (4, 10.1%). The glycosylation of calystegines B1 and B2 markedly decreased or abolished their inhibition against beta-glucosidase, alpha- or beta-galactosidase. Compound 4 however retained more or less the potency of calystegine B2 against trehalase. Interestingly, compound 1 was a noncompetitive inhibitor of rice alpha-glucosidase, with a Ki value of 0.9 +/- 0.1 microM.

Animals↗
PubMed1997

Construction of mutants of Salmonella typhimurium deficient in 8-hydroxyguanine DNA glycosylase and their sensitivities to oxidative mutagens and nitro compounds.

8-Hydroxyguanine (8-OH-G) DNA glycosylase is an enzyme involved in repair of oxidative DNA damage, e.g., 8-OH-G in DNA. In order to assess the roles of 8-OH-G in spontaneous and chemically-induced mutagenesis, the mutMST gene encoding 8-OH-G DNA glycosylase of Salmonella typhimurium was disrupted in several Ames tester strains, i.e., S. typhimurium TA1535 (hisG46, uvrB-, rfa), TA1975 (hisG46, uvr+, rfa) and TA102 (hisG428, uvr+, rfa). The spontaneous mutation frequencies were increased 2.4 and 1.6 times, respectively, by the mutMST deletions in strains TA1535 and TA1975, which are spontaneously reverted to His+ by mutations mainly at G:C base pairs. The resulting strains YG3001 (TA1535 delta mutMST) and YG3002 (TA1975 delta mutMST) were 2 to 8 times more sensitive to the mutagenicities of methylene blue plus visible light, neutral red plus visible light and 2-nitrofluorene than the parent strains. The strain YG3002 but not YG3001 was about 30 times more sensitive to the mutagenicity of 4-nitroquinoline N-oxide than the parent strain TA1975. Neither hydrogen peroxide nor phenazine methosulfate was mutagenic in the mutMST-deletion strains as well as in the parent strains. In contrast, the mutMST deletion did not affect the spontaneous mutation frequency of strain TA102, which has an A:T base pair at the critical site for reversion. The sensitivities of strain TA102 to the chemicals were not enhanced by the mutMST deletion except for hydrogen peroxide. These results suggest that 8-OH-G in DNA plays important roles in spontaneous mutagenesis occurring at G:C base pairs in S. typhimurium, and some nitro aromatics such as 4-nitroquinoline N-oxide or 2-nitrofluorene as well as the photosensitizers plus visible light can produce 8-OH-G in DNA, thereby inducing mutations. In the case of 4-nitroquinoline N-oxide, 8-OH-G rather than DNA adducts seems to play major roles in mutagenesis in uvr+ background. The new strains could be useful for the evaluation of the roles of 8-OH-G in mutagenesis in S. typhimurium and permit the efficient detection of some oxidative mutagens in the environment.

4-Nitroquinoline-1-oxide↗
PubMed1997

IL-18 accounts for both TNF-alpha- and Fas ligand-mediated hepatotoxic pathways in endotoxin-induced liver injury in mice.

When LPS is administered to heat-killed Propionibacterium acnes-primed BALB/c nude mice, they develop endotoxin-induced liver injury. As previously reported, this liver injury can be prevented by treatment with an Ab against IL-18, a novel cytokine with the ability to induce IFN-gamma production and up-regulate functional Fas ligand (FasL) expression. To identify the pathologic role of IL-18 in this liver injury, we investigated the hepatic cytokine network and FasL induction after LPS challenge. After LPS challenge to BALB/c nude mice, their livers expressed IL-12 mRNA, followed by the induction of IFN-gamma and FasL mRNA and then by the late elevation of TNF-alpha mRNA, but stably expressed IL-18 mRNA. The TNF-alpha induction curve had two peaks. The first peak was the result of the direct reaction to LPS, and the late peak might have been induced, since P. acnes-elicited Kupffer cells showed one-peak TNF-alpha kinetics in response to LPS stimulation in vitro. LPS-activated P. acnes-elicited Kupffer cells secreted both IL-12 and IL-18, as determined by ELISA and bioassay, respectively. The in vivo administration of anti-IL-18 just before an LPS challenge suppressed not only the induction of IFN-gamma and the late TNF-alpha elevation, but also the FasL induction, resulting in the total prevention of liver injury, whereas such an anti-IL-12 treatment did not. Anti-IFN-gamma treatment reduced the late increase in TNF-alpha, but not FasL, resulting in a partial prevention of the liver injury. The administration of anti-TNF-alpha just before elevation of the late TNF-alpha peak also markedly, but incompletely, suppressed the LPS-induced liver injury. These data suggested that IL-18 activates both TNF-alpha- and FasL-mediated hepatocytotoxic pathways in endotoxin-induced liver injury.

Animals↗
PubMed1997

Specific alpha-galactosidase inhibitors, N-methylcalystegines--structure/activity relationships of calystegines from Lycium chinense.

An examination of the roots of Lycium chinense (Solanaceae) has resulted in the discovery of 14 calystegines, a cycloheptane bearing an amino group and three hydroxyl groups, and two polyhydroxylated piperidine alkaloids. Calystegines A7 and B5, in addition to the previously known calystegines A3, A5, A6, B1, B2, B3, B4, C1, C2 and N1, were isolated and determined as 1alpha,2beta,4alpha-trihydroxy-nortropane and 1alpha,2alpha,4alpha,7alpha-tetrahydroxy-nort ropane, respectively. L. chinense also had two polyhydroxytropanes bearing a methyl group on the nitrogen atom, unlike the previously reported nortropane alkaloids. They were established as N-methylcalystegines B2 and C1, and their N-methyl groups were found to be axially oriented from NOE experiments. 1Beta-amino-3beta,4beta,5alpha-trihydroxycyclohepta ne was also present in L. chinense and may be a biosynthetic precursor of the calystegines that occur in this plant. Two polyhydroxypiperidine alkaloids, fagomine and 6-deoxyfagomine, were isolated. Calystegine B2 is a potent competitive inhibitor of almond beta-glucosidase (Ki = 1.9 microM) and coffee bean alpha-galactosidase (Ki = 0.86 microM), while N-methylcalystegine B2 was a more potent competitive inhibitor of the latter enzyme (Ki = 0.47 microM) than the parent compound but showed a marked lack of inhibitory activities towards most other glycosidases. Since this compound is a very specific inhibitor of alpha-galactosidase and inhibits rat liver lysosomal alpha-galactosidase with a Ki of 1.8 microM, it may provide a useful experimental model for the lysosomal storage disorder, Fabry's disease. The addition of a hydroxyl group at C6exo, as in calystegines B1 and C1, enhances the inhibitory potential towards beta-glucosidase and beta-galactosidase but markedly lowers or abolishes inhibition towards alpha-galactosidase. Hence, the N-methylation of calystegine C1 did not enhance its inhibition of alpha-galactosidase. The chemical N-methylation of calystegines A3 and B4 markedly enhanced inhibition of coffee bean alpha-galactosidase, with Ki values of 5.2 microM and 36 microM, respectively, but almost eliminated their inhibitory potential towards beta-glucosidase and trehalase, respectively. Thus, methylation of the nitrogen atom significantly altered the specificity of the inhibitors.

Animals↗
PubMed1997

Cloning and expression of the neuromedin B receptor and the third subtype of bombesin receptor genes in the mouse.

We cloned the genes for the mouse homologue of the neuromedin B receptor (NMB-R) and the bombesin receptor subtype 3 (BRS-3). Both receptor genes consist of three exons with well-conserved intron-exon borders. Although the NMB-R gene spans more than 10 kb, the BRS-3 gene spans only about 4 kb. Comparison of the mouse and human receptor sequences indicates 90% (NMB-R) and 85% (BRS-3) sequence homology at the amino-acid level. In the adult mouse, the NMB-R mRNA is expressed in the brain, testis, esophagus, intestine and uterus, whereas the BRS-3 mRNA is expressed predominantly in the brain. In the brain, the NMB-R gene expression is prominent in the thalamic and olfactory regions, and the BRS-3 gene is expressed particularly in the hypothalamic region. In mouse testis, the NMB-R gene expression is prominent, and the expression of BRS-3 mRNA is barely detected. In contrast, BRS-3 has been shown to be expressed in rat testis and guinea-pig uterus, therefore it is possible that a different subtype of the bombesin receptor mediates the same response in different species. Together with the mouse GRP-R gene cloned previously, cloning of the mouse NMB-R and BRS-3 genes permits comparison of function and structure of the three bombesin receptor subtypes in the mouse.

Animals↗
PubMed1997

Proteasome regulation of activation-induced T cell death.

Lactacystin, a microbial metabolite that inhibits protease activity only in the proteasome, was used to study the role of the proteasome in the activation-induced cell death (AICD) of T cells. Lactacystin induces DNA fragmentation and apoptosis in a T cell hybridoma (DO.11. 10) in a dose-dependent manner. Between 1 and 10 microM, the mildly cytotoxic lactacystin inhibited the AICD of DO.11.10 cells cultured in anti-CD3-coated wells. Degradation of IkappaBbeta and the translocation of the NF-kappaB (p50/RelA) into the nucleus, which occurred at 1.5 hr after anti-CD3 activation, were inhibited by lactacystin. Lactacystin did not inhibit the expression of nuclear transcription factor Oct-1. The activation-induced expression of the immediate-early gene, Nur77, and the T cell death genes, CD95 (Fas) and CD95 ligand (FasL), were inhibited. Functional expression of FasL cytotoxicity and the increase of cell surface Fas were also inhibited. Lactacystin must be added within 2 hr of activation to efficiently block AICD. In addition, lactacystin failed to inhibit the killing of DO.11.10 by FasL-expressing allo-specific cytotoxic effector cells. These observations strongly suggest a direct link between the proteasome-dependent degradation of IkappaBbeta and the AICD that occurs through activation of the FasL gene and up-regulation of the Fas gene.

Acetylcysteine↗
PubMed1997

Propionibacterium acnes treatment diminishes CD4+ NK1.1+ T cells but induces type I T cells in the liver by induction of IL-12 and IL-18 production from Kupffer cells.

LPS injection into normal mice does not induce liver injury, while the same treatment of Propionibacterium acnes-primed mice induces severe liver injury, indicating that P. acnes treatment renders the mice susceptible to LPS. Since IFN-gamma sensitizes macrophages to LPS, we investigated the mechanism of induction and activation of IFN-gamma-producing (type 1) T cells by P. acnes. Twenty percent of liver lymphocytes of C57BL/6 mice are CD4+ NK1.1+ T cells that promptly produce IL-4 in response to anti-CD3 in vitro. However, P. acnes treatment diminished these lymphocytes. Therefore, liver lymphocytes from P. acnes-primed mice showed reduced IL-4 production. Furthermore, P. acnes treatment induced CD4- type 1 T cells in the liver. Isolated P. acnes-elicited Kupffer cells produced IL-12 and to a lesser degree IL-18 in vitro. Injection of anti-IL-12 Ab totally abrogated these actions of P. acnes, while injection of anti-IL-18 Ab caused only partial abrogation. Thus, administration of P. acnes diminished CD4+ NK1.1+ T cells, but induced type 1 T cells in the liver by induction of IL-12 and IL-18 production. Injection of IL-12 (approximately 1,000 ng) dose dependently diminished CD4+ NK1.1+ T cells, but induced type 1 T cells. In contrast, injection of IL-18 (approximately 1,000 ng) failed, although injection of a much larger dose of IL-18 (10,000 ng) or IL-18 (approximately 1,000 ng) with suboptimal doses of IL-12 (1-100 ng) diminished CD4+ NK1.1+ T cells in a dose-dependent manner. Thus, P. acnes treatment renders the mice highly susceptible to LPS by induction and activation of type 1 T cells.

Animals↗
PubMed1997

Preparation and biological activity of manno- and galacto-validamines, new 5a-carba-glycosylamines as alpha-glycosidase inhibitors.

Manno- and galacto-validamines, which are epimers of validamine, were semi-synthesized by the configurational inversion of validamine, a pseudo-sugar analogue of alpha-D-gluco-pyranose that has inhibitory activity for alpha-glucosidases. The inhibitory activities of these analogues were determined against several mannosidases and galactosidase. Manno-validamine shows potent inhibition for the alpha-mannosidases (competitive. K(i) = 4.6 x 10(-5) M for jack beans, and competitive, Ki = 2.8 x 10(-5) M for almonds), and galacto-validamine shows weak inhibition for the alpha-galactosidases (coffee bean and E. coli). The inhibitory effect of the epimers on the N-linked oligosaccharide-processing mannosidases involved in glycoprotein biosynthesis and lysosomal mannosidase from rat liver were also examined. Mannovalidamine shows potent inhibition on the endoplasmic reticulumal alpha-mannosidase (competitive, K(i) = 1.2 x 10(-6) M), Golgi mannosidases IA, II (competitive, K(i) = 2.8 x 10(-5) M), and lysosomal alpha-mannosidase (competitive, Ki = 1.7 x 10(-5) M).

Animals↗
PubMed1997

Targeted disruption of the gene encoding the classical nitroreductase enzyme in Salmonella typhimurium Ames test strains TA1535 and TA1538.

The gene encoding the 'classical nitroreductase' (CNR) of Salmonella typhimurium was disrupted. In this manner, cnr null mutant derivatives of strains TA1535 and TA1538 were constructed, and named YG7131 and YG7127, respectively. In both strain backgrounds, cnr gene disruption reduced nitrofurazone-reductase activity. This reduction almost completely eliminated the nitroreductase activity of strain TA1538. In contrast, the nitroreductase activity of strain TA1535 was much higher than that in TA1538. In this background, cnr gene disruption resulted in a reduction in nitroreductase activity by a similar absolute amount as in TA1538, but representing only about one-quarter of the original activity of TA1535. The results suggest that S. typhimurium has originally at least two distinct nitroreductases, one of which is already deficient in strain TA1538; the CNR is present in both TA1535 and TA1538. Also, these two strains (including their derivatives, TA98 and TA100) are not isogenic with regard to nitroreductase activity. After the introduction of plasmid pKM101, the sensitivities of the strains YG7132 and YG7128, the cnr-null mutants of TA98 and TA100, respectively, against several nitro compounds were compared with those of the conventional cnr-deficient strains TA98NR and TA100NR and the wild-type strains TA98 and TA100. The mutagenicities of 2-nitrofluorene and 1-nitropyrene in YG7132 or TA98NR were ten-fold lower than those of the compounds in TA98. Similarly, the mutagenicity of 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide in strain YG7128 or TA100NR was substantially lower than that of the compound in TA100. However, the mutagenicity of 2-nitronaphthalene in YG7128 was between those observed with TA100 and TA100NR, suggesting that a nitroreductase in S. typhimurium other than CNR is involved in the metabolic activation of this compound. The cnr gene of S. typhimurium positively hybridized with DNA at 13 min on the E. coli chromosome where the nfsB and nfnB genes of E. coli are mapped. These results suggest that the cnr gene of S. typhimurium is a counterpart of the nfsB and nfnB genes of E. coli, and that the newly constructed cnr-deletion strains are useful to assess the role of nitroreductases in the metabolic activation of mutagenic nitro compounds.

Blotting, Southern↗
PubMed1997

Proteasome regulation of Fas ligand cytotoxicity.

The role of NF-kappa B in regulating FasL-mediated cytotoxicity was investigated by using lactacystin. Lactacystin is a microbial metabolite known to inhibit only the protease activity of the proteasome, which is required for NF-kappa B translocation. When activated by immobilized anti-CD3 monoclonal antibody, hybridoma T cells (5D5) degraded I kappa B beta, translocated NF-kappa B into the nucleus, transcribed immediate-early genes and the Fas ligand (FasL) gene, and expressed FasL-mediated cytotoxicity. Lactacystin strongly blocked I kappa B beta degradation and the translocation of NF-kappa B (p50/RelA heterodimer), but had little effect on the expression of the transcription factors, Oct-1 and AP-1. Moreover, lactacystin did not inhibit the nuclear translocation of NF-ATp whereas cyclosporin A inhibited the translocation of both NF-kappa B and NF-ATp. The expression of c-myc and nur77, two immediate-early genes implicated in FasL gene activation, was blocked by lactacystin. Subsequently, the expression of FasL gene and FasL-mediated cytotoxicity was inhibited. LLnL, a well-known peptide aldehyde which inhibits the protease activities of the proteasome and cysteine proteases, also inhibited NF-kappa B translocation and FasL-mediated cytotoxicity. However, these events were not inhibited by the highly specific cysteine protease inhibitor E64. These observations provide further evidence that FasL cytotoxicity is regulated by the proteasome. Furthermore, lactacystin must be added early in order to efficiently inhibit the induction of FasL cytotoxicity, indicating that the early events are critical for FasL gene activation. Our study integrates the proteasome-dependent I kappa B degradation and NF-kappa B translocation into a T cell activation cascade which results in FasL gene activation and the expression of FasL-mediated cytotoxicity.

Acetylcysteine↗
PubMed1997

Cronkhite-Canada syndrome associated with carcinoma of the sigmoid colon: report of a case.

Cronkhite-Canada syndrome is generally accepted as being a benign disorder. We herein present a 66-year-old-male patient with Cronkhite-Canada syndrome who had a carcinoma of the sigmoid colon along with multiple colonic polyps, which included juvenile-type polyps, adenomas, and hyperplastic polyps. In the world literature, there have been 34 cases of Cronkhite-Canada syndrome associated with colorectal carcinoma among the 280 reported cases of this syndrome. This report thus adds to the growing evidence that Cronkhite-Canada syndrome may be a premalignant condition for colorectal carcinoma. A periodic examination of the colon is therefore advised in order to detect any development of colorectal carcinoma at an early stage.

Adenocarcinoma↗
PubMed1997

Cisplatin-based combination chemotherapy for elderly patients with non-small-cell lung cancer.

PURPOSE: To compare the response rates, toxicities and survival durations of elderly patients (70 years of age or more) with those of younger patients (less than 70 years of age) with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. PATIENTS AND METHODS: We analyzed retrospectively the data of 203 assessable patients entered on a prospective randomized trial of cisplatin-based combination chemotherapy. Chemotherapy consisted of three dosage regimens: (1) vindesine and cisplatin (VP); (2) mitomycin, vindesine and cisplatin (MVP); or (3) etoposide and cisplatin alternating with vindesine and mitomycin (EP/VM). RESULTS: A greater proportion of elderly patients had localized disease and more squamous cell carcinoma than non-elderly patients. The overall response rates were 44% in the elderly group and 28% in the non-elderly group. In the EP/VM arm, the response rate was significantly better in the elderly group than in the non-elderly group. The frequency of grade 4 leukocytopenia in the MVP and EP/VM arms in the elderly group was significantly greater than in the non-elderly group (P < 0.05). No differences were found in nonhematological toxicities between the two groups. There was no difference in overall survival between the groups. CONCLUSION: Elderly patients treated with mitomycin-containing regimens have higher hematologic toxicities than younger patients. The results of this study are consistent with the previously reported pharmacologic data on mitomycin suggesting altered pharmacokinetics in elderly patients. The improved response rate in the elderly patients was probably because more elderly patients had earlier disease, squamous cell carcinoma and better performance status. Cisplatin-based chemotherapy was tolerable for most elderly NSCLC patients with good performance status.

Age Factors↗
PubMed1997

A de novo recombination in the ABO blood group gene and evidence for the occurence of recombination products.

We have encountered a paternity case where exclusion of the putative father was only observed in the ABO blood group (mother, B; child, A1; putative father, O), among the many polymorphic markers tested, including DNA fingerprints and microsatellite markers. Cloning a part of the ABO gene, PCR-amplified from the trio's genomes, followed by sequencing the cloned fragments, showed that one allele of the child had a hybrid nature, comprising exon 6 of the B allele and exon 7 of the O1 allele. Based on the evidence that exon 7 is crucial for the sugar-nucleotide specificity of A1 and B transferases and that the O1 allele is only specified by the 261G deletion in exon 6 of the consensus sequence of the A1 allele, we concluded that the hybrid allele encodes a transferase with A1 specificity, resulting, presumably, from de novo recombination between the B and O1 alleles of the mother during meiosis. Screening of random populations demonstrated the occurrence of four other hybrid alleles. Sequencing of intron VI from the five hybrid alleles showed that the junctions of the hybrid alleles were located within intron VI, the intron VI-exon 7 boundaries, or exon 7. Recombinational events seem to be partly involved in the genesis of sequence diversities of the ABO gene.

ABO Blood-Group System↗