Biomedical subjects

M Fukumoto

Publications and source records attributed to M Fukumoto.

At least 163 records · Page 9Linked to original sources

PubMed1994

Immunohistochemical reactions for fibroblast growth factor receptor in arteries of patients with moyamoya disease.

The cause of moyamoya disease remains unknown, and pathophysiological mechanisms remain uncertain. Basic fibroblast growth factor (FGF) is a pluripotent polypeptide that has been shown to play roles in angiogenesis, tumorigenesis and many other processes. In a previous study, we demonstrated immunohistochemically that the amount of basic FGF was increased above normal in the superficial temporal artery (STA) of patients with moyamoya disease. To clarify the function of basic FGF in moyamoya disease, we have performed an immunohistochemical study of the STA using a polyclonal antihuman FGF receptor antibody and also have tested immunohistochemical reactions for basic FGF. Twelve surgical specimens of the STA from patients with moyamoya disease were studied. Twelve specimens of the STA from skin flaps of patients with other neurological diseases were also investigated for comparison. The sections of the STA from patients with moyamoya disease showed dense and strong FGF receptor and basic FGF immunoreactivity in endothelial cells, in cells scattered in the thickened intima, and in smooth muscle cells in the media. In contrast, the sections of the STA of control patients showed faint basic FGF immunoreactivity. The statistical analysis revealed a significant difference of basic FGF immunoreactivity between moyamoya disease and other neurological diseases (chi 2 = 23; P = 0.0001). Moderately intense FGF receptor immunoreactivity was observed in most control patients. However, the statistical analysis revealed a significant difference of FGF receptor immunoreactivity between moyamoya disease and other neurological diseases (chi 2 = 13.382; P = 0.0012).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

[Pregnancy and delivery in patients with lupus nephritis].

To investigate some of the problems associated with pregnancy and delivery in lupus nephritis, 13 pregnancies in 7 patients with inactive lupus nephritis and 5 pregnancies in one patient with primary antiphospholipid syndrome (PAPS) were compared with 36 pregnancies in 22 patients with primary nephrotic syndrome (NS). Furthermore, a follow-up survey during 0-8 years was made with 12 babies born to mothers with lupus nephritis. Some pregnancies during lupus nephritis were accompanied by disease exacerbation and worsening of renal function. There was a higher incidence of babies born with a low birth weight, and the incidences of fetal loss or premature birth and toxemia were higher in lupus nephritis than in NS. The number of babies with a low birth weight was significantly higher in patients with pregnancy-induced hypertension or skin lesion due to lupus erythematosus. The presence of antibodies against SSA/RO in the mother was associated with the occurrence of congenital heart block. Birth weight of babies born to mothers with lupus nephritis was low, but there were no statistical differences in the growth of babies after 6 months of age compared with babies born to normal women.

Adult↗

PubMed1994

Observations on handwashing and defecation practices in a shanty town of Lima, Peru.

Following a two-year cohort study of diarrhoeal diseases in children aged 0-35 months from a shanty town in Lima, 62 families were chosen for detailed observation of hygiene practices. All handwashing and defecation episodes which occurred during a 10-hour observation period (8am-6pm) were recorded. The youngest child in each family was selected as the index child for observation. Handwashing was seen on 483 occasions with 71% of the index children and 80% of mothers observed at least once. The use of clean water, soap and the thoroughness of the handwashing varied according to the purpose, with "better" behaviour observed more frequently when the person was preparing to go out. Forty-five index children (72%) were observed to defecate at least once. Infants defecated in their diapers or clothes; toddlers defecated more indiscriminately around the home area. Handwashing after defecation was rare (11% of occasions) and usually without soap. Faeces were often left accessible to children and animals (42% of occasions), especially when defecation occurred around the home/yard, and the data suggested this occurred more frequently in "higher" diarrhoea households. Stools deposited on the floor were usually just swept aside, covered with earth or eaten by dogs. Those deposited outside the home were frequently left untouched during the observation period or similarly cleared. Soiled clothes were usually left or washed separately, and stools in potties were thrown in latrines. These results suggest hygiene interventions might focus on clearance of stools from home surroundings, increased utilisation of potties and separate washing of soiled clothes.

Child, Preschool↗

PubMed1993

Loxiglumide (CR1505), a cholecystokinin antagonist, specifically inhibits the growth of human pancreatic cancer lines xenografted into nude mice.

BACKGROUND: Cholecystokinin is thought to be an important factor regulating the growth of human pancreatic cancers. The study was designed to evaluate the effects of the cholecystokinin antagonist loxiglumide (CR1505) on the growth of human pancreatic cancer. METHODS: Human gastrointestinal cancer xenografted tumors (one esophageal, one gastric, two colorectal, two biliary tract, and two pancreatic cancers) were transplanted into nude mice. The mice were given CR1505 at 250 mg/kg daily for 14 days, either subcutaneously or intragastrically, and the tumor volumes before and after treatment were compared. In vitro effects of CR1505 were assessed by measuring the DNA synthesis (3H-thymidine incorporation). RESULTS: CR1505 inhibited the growth of the two pancreatic cancer lines but did not inhibit the growth of the other lines. CR1505 also inhibited in vitro DNA synthesis in the two pancreatic cancer lines at lower concentrations than in the other lines. This pancreatic cancer-specific inhibitory effect of CR1505 was retarded by exogenously administered cholecystokinin in one pancreatic cancer line but was augmented in the other line. The effect of CR1505 was inhibited by oral administration of the trypsin-inhibitor camostate (FOY-305) in both pancreatic cancer lines. CONCLUSIONS: These results suggest that CR1505 may specifically inhibit the growth of human pancreatic cancers and may be suitable for clinical study. However, its antiproliferative effect may not necessarily be dependent on its cholecystokinin-antagonism but may be mediated through the proteolytic enzymes found in the lysosomes of the pancreatic cancer cells.

Animals↗

PubMed1993

Identification of protein tyrosine phosphatases expressed in murine male germ cells.

We cloned five cDNAs encoding putative protein tyrosine phosphatases (PTPs; protein-tyrosine-phosphatase phosphohydrolase, EC 3.1.3.48) from the murine testis by using degenerate primers and the polymerase chain reaction cloning technique. Two of them were identical to the mouse cytoplasmic PTP and PTP-1B. The remaining three were likely to represent the murine counterparts of human PTP delta, human PTP epsilon, and rat striatum-enriched PTP. The cells expressing these genes were determined either by in situ hybridization histochemistry or by Northern blot hybridization. Moreover, Northern blot hybridization revealed that the transcripts of PTP-1B, mouse cytoplasmic PTP and the murine homologue of human PTP delta were quantitatively and/or structurally regulated during germ cell development, suggesting their roles in spermatogenesis.

Amino Acid Sequence↗

PubMed1993

Expression of MDR1 gene in acute leukemia cells: association with CD7+ acute myeloblastic leukemia/acute lymphoblastic leukemia.

MDR1 gene expression was examined in acute leukemia cells from 75 Japanese patients at diagnosis (50 with acute myeloblastic leukemia [AML]: 10 M1, 18 M2, 5 M3, 8 M4, 9 M5; 25 with acute lymphoblastic leukemia [ALL]: 13 B-precursor, 12 T-lineage). The results of MDR1 mRNA expression by reverse transcriptase polymerase chain reaction were confirmed by immunostaining using the anti-P-glycoprotein monoclonal antibody UIC2 and by a functional study using the rhodamine efflux test. Morphologically, AML M1 cases had the highest incidence of MDR1 gene expression (6 of 10 patients). Phenotypically, CD7 and CD34 were the only surface markers that were significantly associated with MDR1 gene expression (P < .01). In CD7+CD4-CD8- ALL, which is thought to originate from the lymphohematopoietic stem cell, expressed the MDR1 gene with a high incidence (six of eight patients), whereas three surface CD3+ and one CD4+CD8+ T-cell ALL (T-ALL) did not have detectable MDR1 transcripts. Only two cases of 13 B-precursor ALL had MDR1 mRNA, one of which had the Philadelphia (Ph1) chromosome. No association was observed between MDR1 gene expression and CD34 positivity in ALL. Our results that MDR1 mRNA was frequently expressed in CD7+ AML and CD7+CD4-CD8- ALL, together with the previous reports indicating clinical similarities between these leukemias, provides a clue to clarify a relationship between CD7+ AML and CD7+CD4-CD8- ALL. In addition, MDR1 expression in CD7+ AML/ALL might be responsible for the poor response to conventional chemotherapies of these types of leukemia.

Adult↗

PubMed1993

Micronucleus test and erythropoiesis: effect of cobalt on the induction of micronuclei by mutagens.

The micronucleus test is used widely as an in vivo short-term assay for potential carcinogens. In the present study, results of the micronucleus test were affected by cobalt dichloride pretreatment. Cobalt dichloride was used to induce erythropoietin, a growth factor for erythropoiesis. The increase in mutagen-induced micronucleus response following cobalt pretreatment, therefore, may have been due to a change in the rate of erythropoiesis. The greatest interaction between cobalt pretreatment and mutagen treatment for the induction of micronucleated polychromatic erythrocytes (MPCE) occurred when mice were injected with 1,1-dimethylhydrazine (DMH) 12-24 hr after pretreatment with cobalt dichloride and killed 30 hr later. Increased sensitivity of the micronucleus test was attributable to the administration of mutagen during the differentiation and multiplication of erythroblast, which is presumed to have been accelerated by pretreatment with cobalt dichloride. An increased induction of MPCE in the bone marrow by two chemicals--benzo(a)pyrene, 2-naphthylamine--was also observed following pretreatment with cobalt dichloride.

2-Naphthylamine↗

PubMed1993

Chromosomal location and structure of amplicons in two human cell lines with coamplification of c-myc and Ki-ras oncogenes.

Gene amplification is a major mechanism through which oncogenes and genes responsible for drug resistance are overexpressed in neoplastic cells, and several models for structure of amplified units (amplicons) are postulated. In order to identify consistent changes associated with oncogene amplification, we analyzed chromosomal location and physical distance of amplicons of two independent human cell lines that have coamplified c-myc and Ki-ras oncogenes. In one cell line, KHC287, amplified c-myc genes were localized in two chromosomes and Ki-ras in three chromosomes. One marker chromosome was almost entirely encompassed by both amplified genes. In the other cell line, Lu-65, both of the amplified genes shared the same locus, on chromosome 12q+. The two genes, however, are more than 1500 kb apart in both cell lines. The above findings indicate that two different amplified genes became associated on one chromosome in two independent cell lines. This suggests that a common mechanism is associated with chromosomal rearrangements affecting different amplified genes.

Chromosome Mapping↗

PubMed1993

Liver damage in patients with colony-stimulating factor-producing tumors.

PURPOSE: We have demonstrated that colony-stimulating factor (CSF)-producing tumor cell lines produce not only CSF but also interleukin-1 (IL-1) and interleukin-6 (IL-6). Clinically, we have observed that patients bearing such tumors present with liver dysfunction and fever in addition to marked leukocytosis. The purpose of this study was to determine whether or not the liver damage was specifically related to CSF-producing tumors. PATIENTS AND METHODS: Clinicopathologic examinations were performed in six autopsied patients with CSF-producing tumors. We also transplanted two tumor cell lines (KHC287 and CHU-2), which produce granulocyte (G)-CSF, IL-1, and IL-6, to nude mice. RESULTS: Of the six patients, five had G-CSF- and one had granulocyte/macrophage (GM)-CSF-producing tumors. IL-1 and IL-6 concentrations in plasma or culture supernatant were elevated in these patients. Biochemical examinations revealed high serum enzyme levels of the biliary system in contrast to normal or slight increases in transaminase levels in all patients studied. Serum direct bilirubin was elevated in five of the six patients. Three common pathologic changes of the liver were found: (1) focal necrosis associated with neutrophil infiltration in the centrilobular zones, (2) fibrous change and enlargement of the portal area associated with neutrophil infiltration, and (3) intrahepatic cholestasis. The same pathologic changes, except for cholestasis, were reproduced in the liver of mice transplanted with KHC287 or CHU-2. CONCLUSION: These results indicate that patients with CSF-producing tumors have characteristic liver damage, and suggest a new paraneoplastic syndrome of leukocytosis and liver damage.

Aged↗

PubMed1993

SL/KH strain of mice: a model of spontaneous pre-B-lymphomas.

The SL/Kh strain of mice spontaneously develop two types of non-thymic lymphomas at a high incidence and very short latency. The major type of lymphomas induce systemic lymph node enlargement and hepatosplenomegaly, and the minor type, proliferation predominantly in bone marrow often associated with spinal paralysis. Phenotypes of both types of lymphomas are indistinguishable: they express B220, 6C3, c-kit but not Thy-1.1, Mac-1 and surface Ig. In both types of lymphomas, the immunoglobulin heavy chain gene is found clonally rearranged in the order of VH-D-JH, whereas the light chain gene remains in germ line configuration. About half of the primary lymphomas are dual or oligoclonal in origin. R-PCR also demonstrates expression of lambda 5, RAG-1 and RAG-2, which are specifically associated with pre-B stage lymphocytes. All these observations indicate that both types of the SL/Kh lymphomas are pre-B-lymphomas.

Animals↗

PubMed1993

A phase II study of 5-fluorouracil, cisplatin, and 4'-epirubicin in the treatment of advanced solid cancers.

This phase II study was designed to assess the therapeutic potential of intensive course treatment with three anticancer agents: 50 mg of cisplatin on day 1, 40 mg/m2 of epirubicin on day 2, and 250 mg of 5-fluorouracil on days 2 through 5. Drug courses were repeated every 2 weeks and most patients received between 4 and 6 courses. Thirty-five patients with measurable advanced solid cancers entered the study. They consisted of 16 gastric, 5 colorectal, 4 gallbladder, 3 pancreatic, 3 lung, 2 esophageal, 1 uterine, and 1 ovarian cancers. Of the 35 patients, 29 were evaluated for therapeutic effect of the regimen, and the overall response rate was 31.0% (5 CR + 4 PR/29). A 33.3% rate of tumor regression, consisting of 2 complete responses (CR) and 3 partial responses (PR) out of 15 patients (2 CR + 3 PR/15), was seen for gastric cancers. For the other types of tumors the responses were achieved in 2 lung cancers (1 CR + 1 PR/3). 1 uterine cancer (1 CR/1), and 1 ovarian cancer (1 CR/1). The esophageal, colorectal, pancreatic, and gallbladder cancers were unresponsive to this regimen. Toxicities of the drug treatment were clinically tolerable and consisted of general malaise, nausea, vomiting, stomatitis, alopecia, and leucopenia. However, two patients died of uncontrollable metabolic acidosis after 1 and 2 courses, respectively. This intensive course treatment appears to promote the regression of gastric, lung, and gynecologic cancers.

Adult↗

PubMed1993

Concomitant enhancement of the response to Mls-1a antigens and the induction of post-thymectomy autoimmune gastritis in BALB/c mice.

We examined the role of Mls antigens in the induction of autoimmune gastritis (AIG) in BALB/c and DBA/2 mice subjected to thymectomy. The prevalence of AIG in Mls-1b mice which underwent thymectomy on day 3 after birth (3d-Tx) was 78% (mean), while in Mls-1a DBA/2 mice it was < 6%. Whereas AIG-negative 3d-Tx DBA/2 mice produced 2-mercaptoethanol (2-ME)-sensitive antiparietal cell autoantibody, AIG-positive BALB/c mice made 2-ME-resistant anti-parietal cell autoantibody. In addition, the prevalence of AIG in 3d-Tx BALB/c mice which were rendered tolerant to MIs-1a antigens by injection of bone marrow cells from (BALB/c x DBA/2)F1 mice within 24 h after birth was decreased compared with the non-tolerant control mice; the prevalence being 80% in the controls and 30% in the tolerant animals. Thus, the activation of helper T cells, including T cells responding to Mls-1a antigens and including immunoglobulin class switch, appeared to be closely associated with the induction of AIG. Flowcytometric analysis confirmed that CD4- V beta 6 T cells had increased in the regional lymph nodes of the stomach in AIG mice. However, an increase in the number of V beta 11 T cells, which are known to increase in 3d-Tx mice, occurred in the CD8, but not in the CD4 T cell population. Injection of MoAb to L3T4, but not Lyt2, V beta 6- or V beta 8-TCR, into 3d-Tx BALB/c and syngeneic nude mice which had received spleen cells of 3d-Tx BALB/c mice bearing AIG completely abrogated the development of AIG, despite there being remarkable decreases in T cells expressing relevant markers to the injected antibodies in all the mice. These findings suggest that the increase of V beta 6+ L3T4+ T cells in AIG mice was concomitant with the activation of AIG-inducing V beta 6- L3T4+ T cells.

Animals↗

PubMed1993

Interspecies-specific ovarian autoantigens involved in neonatal thymectomy-induced murine autoimmune oophoritis.

PROBLEM: Thymectomy of mice on day 3 after birth (3d-Tx) gives rise to the appearance of a particular type of ovarian lesion known as experimental autoimmune oophoritis (AIO). METHOD: In the present study, the spleen cells from BALB/c mice having undergone 3 day-Tx AIO were fused with X63-Ag8-6.5.3 myeloma cells, and a number of hybridoma clones producing autoantibodies against ovarian tissue were established. RESULTS: On the basis of immunohistochemical and protein-chemical analysis, two independent clones, designated at T2.2 and S1.6, were found to react with interstitial tissues surrounding the follicles. These monoclonal antibodies showed broad cross-species reactivity, in that they recognized similar antigenic macromolecules in the rat, pig, human, and mouse. The antigenic determinants were strongly resistant to heat and acid, especially to the treatment of periodic acid, indicating that the antigenic determinants had no relation with carbohydrate components. CONCLUSIONS: By antibody affinity chromatography, two kinds of autoantigens were identified. SDS-PAGE, under reduced or nonreduced conditions, revealed an 80/85 kDa protein for T2.2, and an 82 kDa for S1.6, respectively.

Animals↗

PubMed1993

[A basic study for estimating the level of exposure to a nasal inhalant containing a stimulant].

Criminal cases involving stimulant abuse have increased since 1970 but have now leveled off. Some of the offenders claimed to have used the Vicks Inhaler containing a stimulant (1-methamphetamine) which is used for the treatment of nasal obstruction. The aim of this experiment was to measure the amount of 1-methamphetamine contained in the Vicks Inhaler by stimulating the human respiratory system. The results are as follows: 1) The data from the stimulation experiment showed that the inhalation level of 1-methamphetamine was estimated to be 320.4ng. From this value, the level of 1-methamphetamine absorbed per one respiration was calculated to be 21ng. 2) The data from quantitative and qualitative analysis by gas-chromatography showed that menthol interfered with the methamphetamine. 3) A qualitative test for the stimulant in urine was negative when the subject inhaled the Vicks Inhaler only once. However, this test turned positive when the subject inhaled it more than 17 times.

Chromatography, Gas↗

PubMed1993

Delayed-type skin allergic reaction in guinea pigs induced by anti-rheumatic compounds with sulfhydryl groups.

Delayed-type skin allergic (DTA) reactions induced by various sulfhydryl compounds were investigated. Sulfhydryl compounds investigated were bucillamine and D-penicillamine: antirheumatic agents, SA981: an intramolecular cyclic disulfide of bucillamine, tiopronin: a hepatoprotective and potent antirheumatic agent and captopril: antihypertensive and potent antirheumatic agent. Guinea pigs were sensitized on day 1 by subcutaneous injection and day 7 by subcutaneous and intramuscular injection of emulsions of these compounds (3 mg/animal) with Freund's complete adjuvant. Two weeks after the second sensitization, 0.3 mg/animal of each compound was intradermally challenged and the 24 hr DTA reaction was evaluated. A large number of sulfhydril compounds showed positive in the DTA reactions and the intensity of these reactions had a good correlation with the frequency of the skin rashes referred to by the adverse effects in clinical reports of anti-rheumatic drugs. It is suggested that guinea pig DTA reaction may provide a good screening way to find new sulfhydryl or disulfide compounds with low incidence of skin rash. A novel sulfhydryl compound N-(2,2-dimethyl-3-mercaptopropionyl)-L-cysteine (SA3441) and its intramolecular cyclic disulfide (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4-carboxylic acid (SA3443), which show no DTA activity in guinea pigs, were found using the above-mentioned DTA reaction.

Animals↗

PubMed1992

Thrombocytosis in patients with tumors producing colony-stimulating factor.

We investigated the cause of thrombocytosis in 14 patients with tumors producing colony-stimulating factor (CSF). Of the 14 patients, 10 had tumors producing granulocyte-CSF (G-CSF) and 4 had tumors producing granulocyte-macrophage--CSF (GM-CSF). Thrombocytosis of greater than 400 x 10(9)/L was noted in 8 of 10 patients with G-CSF-producing tumors and all 4 patients with GM-CSF-producing tumors. Median peak platelet counts were, respectively, 511 x 10(9)/L (range, 384 to 694 x 10(9)/L) and 579 x 10(9)/L (range, 526 to 910 x 10(9)/L) in patients with tumors producing G-CSF and GM-CSF. In most patients, thrombocytosis declined towards the terminal stage. High interleukin-1 (IL-1) and IL-6 levels were found in addition to CSFs in the plasma or culture supernatants of tumor cells obtained from most patients. In patients with GM-CSF-producing tumors, these specimens had megakaryocyte-CSF (Meg-CSF) activity, which was abolished by anti-GM-CSF antibody. These specimens also had megakaryocyte potentiating (Meg-Pot) activity attributable to both GM-CSF and IL-6. In patients with G-CSF-producing tumors, only Meg-Pot activity due to IL-6 was detected. These results indicate that the thrombocytosis in GM-CSF-producing tumors was caused by both the Meg-CSF activity of GM-CSF and the Meg-Pot activity of IL-6 plus GM-CSF, while that in G-CSF-producing tumors was due to the Meg-Pot activity of IL-6.

Adult↗

PubMed1992

c-myc over-expression in human primary ovarian tumours: its relevance to tumour progression.

Expression of the c-myc gene was analyzed in 56 human primary ovarian cancer tissues, including 51 common epithelial and 5 non-epithelial tumours to determine molecular events in the carcinogenic process in ovaries. Over-expression of the c-myc gene was found in 37.3% of all ovarian tumour tissues, and in 63.5% of serous adenocarcinoma tissues. Significant over-expression of the c-myc gene at Stage III compared with other stages, and one remarkable case of over-expression in a serous tumour of low malignant potential suggest that c-myc expression is temporarily activated at some stage(s) during tumorigenesis of ovarian cancer, especially of serous tumours.

Female↗

PubMed1992

Effects of bacillus Calmette-Guerin on cytotoxic activities of peripheral blood lymphocytes against human T24 lined and freshly isolated autologous urinary bladder transitional carcinoma cells in patients with urinary bladder cancer.

The effects of bacillus Calmette-Guerin (BCG) on the cytotoxic activities of peripheral blood lymphocytes against human T24 lined and freshly separated autologous urinary bladder transitional carcinoma cells in patients with urinary bladder cancer were analyzed in a 12-hour chromium 51 (51Cr) release assay. The results of this study indicate that BCG activates the tumor killing system through stimulation of effector cells and elevation of target cell susceptibility in patients with urinary bladder cancer, suggesting that BCG-augmented cytotoxicity may be oriented specifically to urinary bladder cancer cells. This could explain the remarkable clinical benefits of intravesical instillation of BCG against urinary bladder cancer.

Aged↗