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Biomedical subjects

S Hatakeyama

Publications and source records attributed to S Hatakeyama.

At least 19 recordsLinked to original sources
PubMed1998

Accelerated neutrophil apoptosis in mice lacking A1-a, a subtype of the bcl-2-related A1 gene.

To elucidate the role of A1, a new member of the Bcl-2 family of apoptosis regulators active in hematopoietic cell apoptosis, we established mice lacking A1-a, a subtype of the A1 gene in mice (A1-a-/- mice). Spontaneous apoptosis of peripheral blood neutrophils of A1-a-/- mice was enhanced compared with that of either wild-type mice or heterozygous mutants (A1-a+/- mice). Neutrophil apoptosis inhibition induced by lipopolysaccharide treatment in vitro or transendothelial migration in vivo observed in wild-type mice was abolished in both A1-a-/- and A1-a+/- animals. On the other hand, the extent of tumor necrosis factor alpha-induced acceleration of neutrophil apoptosis did not differ among A1-a-/-, A1-a+/-, and wild-type mice. The descending order of A1 mRNA expression was wild-type, A1-a+/-, and A1-a-/-. Taken together, these results suggest that A1 is involved in inhibition of certain types of neutrophil apoptosis.

Animals↗
PubMed1998

Shortened telomeres involved in a case with a jumping translocation at 1q21.

The jumping translocation (JT) is a rare chromosomal abnormality in which a specific chromosomal segment translocates onto the ends of various chromosomes (jumps). In most cases, the region distal to 1q21 jumps onto numerous different telomeres. Here we report a molecular study of the JT involving 1q21 found in a patient with acute myelomonocytic leukemia that had transformed from myelodysplastic syndrome (MDS). This is the first report describing the analysis of the molecular structure of the JT. We demonstrated the presence of a stretch of telomeric repeats at the breakpoint by means of a fluorescence in situ hybridization experiment, molecular cloning, and nucleotide sequencing of the fused region. A significant amount of variant telomeric repeats (a telomeric sequence having one-base mismatch within the authentic telomeric repeat TTAGGG) was found in this region. The variant telomeric repeat has been shown to be present in the proximal region of telomeres and does not perform telomeric functions by itself. Therefore, these results indicated that the telomeres had already been critically shortened when the jumps occurred. We suggest that the extended proliferation of cancer cells during the premalignant stage, such as MDS, results in chromosomal instability due to the loss of telomeric functions.

Base Sequence↗
PubMed1998

Cloning and characterization of the yeast RAD1 homolog gene (mus-38) from Neurospora crassa: evidence for involvement in nucleotide excision repair.

A Neurospora crassa gene encoding a product with homology to the Saccharomyces cerevisiae Rad1 nucleotide excision repair (NER) protein was isolated by degenerate PCR. The predicted protein consists of 892 amino acids with a molecular weight of 100.4 kDa, and 32-37% identity to the XPF/ERCC4 protein family. The homolog was mapped to the left arm of linkage group I, the location of the mus-38 gene. Subsequently, gene inactivation and complementation studies identified the RAD1 homolog as mus-38. Immunological assays showed that the mus-18 (UV-specific endonuclease) and mus-38 strains have partial and normal UV-damage excision activities, respectively, but removal of thymine dimers and TC (6-4) photoproducts is abolished in the mus-18 mus-38 double mutant. The double mutant also was synergistically more sensitive to UV than either single mutant. The data suggest that mus-38 may participate in a different NER pathway from that involving the mus-18 gene.

Amino Acid Sequence↗
PubMed1998

Prenatally diagnosed cystic lymphangioma in infants.

BACKGROUND/PURPOSE: Prenatally diagnosed cystic lymphangioma (CL) is often associated with chromosomal anomalies, hydrops fetalis, and, in the case of cervical CL, occasionally respiratory distress just after birth. Often it is difficult to treat prenatally diagnosed CL because of the large size and associated symptoms. METHODS: Between 1988 and 1997, 11 cases of prenatally diagnosed CL were treated. Five pregnancies were terminated electively and one aborted spontaneously (nondelivered, non-D group), and another five delivered (delivered, D group). Thirteen infants nondiagnosed prenatally were also seen in the same period (prenatally nondiagnosed, without pre-D group). RESULTS: In the non-D group, massive CLs were diagnosed by ultrasound scan between 16 and 20 weeks' gestation. They occurred in the head and neck in all six cases, and four had associated pleural effusions or hydrops. In the D group, CL occurred in the face and neck in four cases. Three were born by cesarean section with neonatologists and surgeons standing by, then transferred to our hospital immediately after birth. Respiratory distress appeared in two cases; tracheostomy was carried out in one case. One patient with a huge CL in the chest and abdominal wall necessitated partial resection after OK-432 sclerotherapy. In the without pre-D group, there was CL in the face or neck in 10 cases, abdominal wall in two cases, and chest wall in one case. Respiratory distress was observed in three cases of cervical CL, and tracheostomy was required in two cases. One patient with hypoxic brain damage sequela died of pneumonia afterward. CONCLUSIONS: Prenatal diagnosis permits planned delivery, prompt postnatal resuscitation, and improve prognosis. Infants with massive CL diagnosed early in pregnancy have other associated anomalies as well as hydrops fetalis, and a poor outcome or difficult management can be expected.

Diagnosis, Differential↗
PubMed1998

Effects of the agrochemicals butachlor, pretilachlor and isoprothiolane on rat liver xenobiotic-metabolizing enzymes.

1. The herbicides butachlor (2-chloro-2',6',diethyl-N-[buthoxymethyl] acetanilide) and pretilachlor (2-chloro-2',6'-diethyl-N-[2-propoxyethyl] acetanilide) are widely used in Asia, South America, Europe and Africa. Isoprothiolane (diisopropyl-1,3-dithiolan-2-ylidenemalonate) is used as a fungicide and an insecticide in rice paddies. We administered these agrochemicals to the male rat and examined their effects on cytochrome P450 (P450), glutathione S-transferase (GST), UDP-glucuronosyltransferase (UDPGT), and NAD(P)H-quinone oxidoreductase 1 (NQO1)-related metabolism in the liver. 2. Administration of isoprothiolane, butachlor or pretilachlor to rat induced hepatic P4502B subfamily-dependent enzyme activities (pentoxyresorufin O-depentylation and testosterone 16 beta-hydroxylation) up to 271-413% of control, which coincided with the increase in expression levels of the P4502B apoprotein. 3. Activities of GST toward 1-chloro-2,4-nitrobenzene and 3,4-dichloronitrobenzene were slightly induced (127-133% of control) in the liver of the rat treated with these pesticides. On the other hand, marked elevations of UDPGT activities toward p-nitrophenol (164-281% of control) were observed. NQO1-related metabolism (menadione reductase activity) was also induced (123-176% of control) in the liver of rat treated with these agrochemicals. 4. These results indicate that some of the agrochemicals currently in use are capable of inducing phase I and II xenobiotic-metabolizing enzyme activities in an isozyme selective manner. The induction of these activities may disrupt normal physiologic functions related to these enzymes in exposed animals.

Acetanilides↗
PubMed1998

Multiple gene duplication and expression of mouse bcl-2-related genes, A1.

Here we report the genomic cloning and characterization of the murine A1 genes, which belong to the bcl-2 gene family. Southern analysis indicated the existence of at least four A1 genes in the murine genome and four different A1 genes, designated A1-a, -b, -c and -d, were cloned from the murine genomic library. The A1-a, -b and -d genes consisted of two exons, whereas the A1-c gene contained 1 bp insertion in the coding region which may result in an aberrant and truncated protein by frame-shift. With the exception of A1-c, the coding regions among A1 genes are highly conserved at >97% at the nucleotide level and at >96% at the amino acid level. A1-a, -b and -d genes appeared to be expressed specifically in organs containing many neutrophils. In neutrophils, A1-a, -b and -d transcripts were detected at a comparable level. Our data suggest that the multiple A1 genes in mice were generated by gene duplication and each of them may function as anti-apoptotic molecules in neutrophils.

Amino Acid Sequence↗
PubMed1998

Induction of endometriosis and adenomyosis by transvaginal pituitary transplantation in mice with and without natural killer cell activity.

PROBLEM: The aims of this study were to establish a mouse model of endometriosis and adenomyosis and to elucidate the necessity of reduced natural killer (NK)-cell and T-cell activities in the establishment of endometriosis and adenomyosis. METHOD OF STUDY: Pituitary glands, submandibular glands, a hypothalami were transvaginally inoculated into the uteri of syngeneic female mice. Twenty weeks later, the recipient mice were sacrificed and examined. RESULTS: Cysts, adhesion of the uteri to surrounding tissues, and adenomyosis had formed in the uteri of 7 (29.2%), 14 (58.3%), and 22 (91.7%) mice, respectively, out of 24 BALB/c mice after the transplantation of pituitary glands. Similar findings were obtained by experiments with C3H/He and C57BL/6 mice. In NK-cell-deficient C57BL/6-bgJ and T-cell-deficient BALB/c nu/nu mice, an increase in the formation of cysts, adhesion, and adenomyosis was not observed. CONCLUSIONS: These findings indicate that transvaginal pituitary transplantation specifically induces cysts, adhesion, and adenomyosis. Reduced NK-cell activities may not be necessary in the primary development of endometriosis and adenomyosis.

Animals↗
PubMed1998

Effect of L-carnitine and palmitoyl-L-carnitine on erythroid colony formation in fetal mouse liver cell culture.

The administration of L-carnitine to patients undergoing hemodialysis increases hematocrit and improves the response to recombinant human erythropoietin (rhEPO). This suggests a contribution by carnitine to erythrocyte membrane function or erythropoiesis. We investigated the effect of L-carnitine and palmitoyl-L-carnitine on erythropoiesis by assessing erythroid colony formation in in vitro fetal mouse liver cell cultures. L-Carnitine or palmitoyl-L-carnitine was added with rhEPO to fetal mouse liver cell cultures. Doses of L-carnitine of up to 200 micromol/l to the culture had no effect on colony formation. In contrast, the addition of above 12.5 micromol/l palmitoyl-L-carnitine into the culture increased colony formation significantly. These results suggest that long-chain acyl carnitine may have an effect on erythropoiesis.

Animals↗
PubMed1998

[Effects of mesalazine on liver carcinogenesis in medium-term bioassay using rats].

A two stage carcinogenesis promotion test using phenobarbital (PB) as a positive control was performed on mesalazine in rats (F344,male). Pathological and immunohistological examinations were performed to examine the cell damage and proliferation in the liver and kidneys. As the initiation treatment, groups 1,2,3 and 5 were administered 300 mg/kg diethylnitrosamine (DEN)dissolved in 0.9% physiological saline, and group 4 was administered 5 ml/kg 0.9% physiological saline once intraperitoneally. Then group 1 was orally administered a water solution (5 ml/kg) containing 0.5% CMC-Na, and groups 2,3 and 4 similar water solution but containing 150, 300 and 300 mg/kg mesalazine, respectively. Group 5 was administered 0.05% PB mixed in feed from weeks 2 to 8. Partial (2/3) hepatectomy was performed in all 5 groups at week 3 after DEN administration. NO clear differences between the groups were observed in general conditions, body weight or amount of food consumption. The number or area-size of hepatic GST-P positive altered cell foci revealed no significant differences between groups 1,2 and 3, but a significant increase in number and area-size was observed in group 5. No GST-P positive cell foci were detected in group 4. The number of altered cell foci (H.E. staining) in the DENgroups administered mesalazine was the same as that in group 1. Thus, mesalazine did not promote hepatocarcinogenesis in the present experimental system. Statistically insignificant appearances of basophilic and acidophilic changes were observed in the renal tubular epithelium and mineral deposits in the renal papillary region and cortical margin region. The PCNA labeling rate was significantly lower in group 4, corresponding with the histological finding showing no proliferation of the renal tubular epithelium. Judging from the above test results, mesalazine was likely to show neither a promotion effect on the initiation induced by DEN nor cell proliferative activity on the kidneys by administration for this experimental period.

Administration, Oral↗
PubMed1998

[Chromosome rearrangement involving telomeres in cancers].

Stable maintenance of chromosomes needs the functional telomeres at the chromosomal ends. It has been proposed that the loss of telomeric function (LTF) plays a major role in the production of abnormal chromosomes, such as the telomere association (TA) and the jumping translocation (JT). We analyzed TA and JT to evaluate the involvement of LTF in chromosomal instability. A shortened telomeres was identified at the fusion point of the JT. We also developed a method to examine TA based on PCR and found relationships between telomere shortening and products of PCR. Our findings strongly suggest that LTF may cause chromosomal instability and contribute to cancer cell evolution.

Chromosome Aberrations↗
PubMed1998

[Isoniazid-induced pneumonitis].

An 82-year-old man was treated with isoniazid (INH) because of a low-grade fever. On the 9th day of treatment, dry coughing and general malaise developed. On the 30th day, he was admitted to our hospital. A chest-X ray film showed infiltrative shadows in the right middle and lower lung fields, but a chest CT scan showed an abnormal lung density in the right lower lobe. Abnormal laboratory findings included leucocytosis, liver dysfunction, hypoxemia, low vital capacity, low diffusing capacity and a high level of C-reactive protein. A differential cell count of the bronchoalveolar lavage fluid (BALF) showed many neutrophils and lymphocytes; examination of a specimen obtained by transbronchial lung biopsy (TBLB) revealed edema of alveolar walls, lymphocyte infiltration, and proliferation of type II alveolar epithelial cells. A drug lymphocyte stimulation test (DLST) against INH was positive. After discontinuation of INH, symptoms resolved, laboratory findings became normal, and the infiltrative shadows in the right middle and lower lung fields disappeared. The clinical course and the findings of BALF, TBLB, and DLST suggested the diagnosis of pneumonitis caused by INH.

Aged↗
PubMed1998

[Efficacy of granisetron as anti-emetic agent for emesis induced by intra-arterial injection therapy for hepatocellular carcinoma].

The effect of granisetron in preventing nausea and emesis induced by intraarterial chemotherapy was comparatively studied with a historical control group (46 cases) in 50 patients with hepatocellular carcinoma receiving intraarterial anti-tumor drugs such as cisplatin and doxorubicin. Emesis was perfectly controlled in 39 out of 50 patients in the treatment group (78%), in comparison to 33 out of 46 patients (71.7%) in the historical control group. This represented no statistical significance between the two groups. In terms of the severity of nausea, however, the granisetron group demonstrated significant superiority to the control group with 27 out of 50 patients (54%) being free of symptoms compared with 16 out of 46 patients (34.8%) in the control group. A stratified analysis of the data also demonstrated significant superiority of the granisetron group over the historical group in the number of emetic episodes and the severity of nausea in female patients, who are more predisposed to emesis. The above results confirm the usefulness of granisetron as an antiemetic agent used for the prevention of acute nausea and emesis induced by intraarterial chemotherapy.

Adult↗
PubMed1997

Fluorometric determination of serum and urinary aluminium with 8-quinolinol by kinetic-differentiation-mode micellar chromatography.

A new fluorometric method has been developed for the determination of aluminium with 8-quinolinol by kinetic-differentiation-mode micellar chromatography. The proposed method enabled the determination of aluminium down to 1 microgram/l in human serum and urine without preliminary deproteinization. The most remarkable point of this method is that only aluminium ion selectively responds among metal ions. The complex formation of aluminium in serum with 8-quinolinol was completed within a few minutes at room temperature. The serum matrix and aluminium chelate were separated on a reversed-phase column with an eluent containing acetonitrile, sodium dodecylsulfate, and Triton X-100, and aluminium chelate was detected at Ex 370 nm, Em 504 nm. The values obtained by this method were in good agreement with those of Zeeman graphite-furnace atomic absorption spectrometry. The proposed method will provide a simple and rapid technique for the determination aluminium in medical fields.

Aluminum↗
PubMed1997

Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases.

In most instances, the transfer of ubiquitin to target proteins is catalyzed by the action of ubiquitin protein ligases (E3s). Full-length cDNAs encoding murine E6-associated protein (mE6-AP) as well as Nedd-4, a protein that is homologous to E6-AP in its C terminus, were cloned. Nedd-4 and mouse E6-AP are both enzymatically active E3s and function with members of the UbcH5 family of E2s. Mouse E6-AP, like its human counterpart, ubiquitinates p53 in the presence of human papilloma virus E6 protein, while Nedd-4 does not. Consistent with its role in p53 ubiquitination, mE6-AP was found both in the nucleus and cytosol, while Nedd-4 was found only in the cytosol. Binding studies implicate a 150-amino acid region that is 40% identical between mE6-AP and Nedd-4 as a binding site for the C-terminal portion of an E2 enzyme (UbcH5B). Nedd-4 was determined to have a second nonoverlapping E2 binding site that recognizes the first 67 amino acids of UbcH5B but not the more C-terminal portion of this E2. These findings provide the first demonstration of physical interactions between mammalian E2s and E3s and establish that these interactions occur independently of ubiquitin and an intact E3 catalytic domain. Furthermore, the presence of two E2 binding sites within Nedd-4 suggests models for ubiquitination involving multiple E2 enzymes associated with E3s.

Amino Acid Sequence↗
PubMed1997

Csk overexpression reduces several monokines and nitric oxide productions but enhances prostaglandin E2 production in response to lipopolysaccharide in the macrophage cell line J774A.1.

The catalytic activity of src-family protein tyrosine kinases (src-PTK) is suppressed when a C-terminal tyrosine is phosphorylated by an intracellular PTK, C-terminal Src kinase (Csk). In the present report, to study the regulatory functions of the Csk in cells of monocyte/macrophage lineage, we transfected a eukaryotic expression vector containing rat csk cDNA in a macrophage cell line, J774A.1, and examined alterations of the response to lipopolysaccharide (LPS) in the transfectants which overexpressed Csk. Csk overexpression resulted primarily in a down-regulation of Fgr activity, an src-PTK expressed in J774A.1, and hyperphosphorylation of several cellular proteins of 35, 57, 66, 97 and 120-130 kDa. Furthermore, in these Csk transfectants, production of interleukin (IL)-1alpha, IL-6, tumor necrosis factor-alpha, and nitric oxide (NO) following LPS stimulation were reduced compared with those in parental J774A.1 or J774A.1 transfected with the vector alone. The extent of reduction paralleled the amounts of Csk proteins expressed in the Csk-transfected J774A.1. The reduced NO production in these cells was associated with low levels of mRNA of inducible NO synthetase. On the other hand, an enhancement of prostaglandin E2 production was observed in the Csk-transfected J774A.1 cells upon stimulation with LPS, which appeared to result from the high level of prostaglandin-H synthetase in the transfectants. The present findings indicate that overexpression of Csk has differential effects on the regulation of production of chemical mediators and monokines, probably via modulation of signal transduction downstream of LPS-mediated signals.

Animals↗
PubMed1997

Correlation between overall pesticide effects monitored by shrimp mortality test and change in macrobenthic fauna in a river.

The relationship between change in benthic fauna in the Suna River and shrimp mortality in the river water samples (test was conducted two times per week from May to September) was investigated to assess the insecticide impact on the benthic community. The river was selected because pesticide application had been restricted for a long time in the upper reaches, while aerial insecticide spraying had been done four times on paddy fields in the lower reaches in summer. Species richness and density of benthos were high at the stations in the upper reaches. High shrimp mortality was measured in the water samples collected from a downstream station during the pesticide spraying period, from late July to late August. Species richness and density of benthos markedly decreased at the stations in the lower reaches in that period. However, several species of chironomids, Cheumatopsyche (Trichoptera), which demonstrated tremendous insecticide resistance, and Baetis sahoensis (Ephemeroptera), which has a high recovery potential, were not affected, even in the insecticide spraying period. The benthic fauna in the lower reaches tended to recover from autumn to spring, although not sufficiently. It is considered that the temporal recovery of the benthic community was brought about through recruitment from the benthic community in the 5-km upper reaches. A close correlation was found between the high mortality of shrimp in the water samples and the deterioration in the benthic fauna in this river which was contaminated with insecticides during the summer.

Animals↗
PubMed1997

Right hepatectomy for pyogenic liver abscesses with true multiloculation.

We report the case of 61-year-old woman with cryptogenic liver abscesses who had been profoundly ill with severe upper abdominal pain, impaired consciousness, prostration, continuous high fever secondary to sepsis, and thrombocytopenia (platelets, 1-5 x 10(4)/mm3) since admission. Ultrasonograms and computed tomograms revealed two separate multiloculated lesions in the right lobe of the liver, consistent with the liver abscesses. Immediately after diagnosis, percutaneous abscess drainage was performed under ultrasonographic guidance; however, only a small amount of pus was drained, prompting continuous irrigation of the abscess cavity. Four days later, transcatheter hepatic arterial infusion of antibiotics was attempted. However, the abscesses had enlarged and her general condition had worsened. On hospital day 8, she underwent right hepatectomy because the multiloculated lesions were refractory to drainage. The operation was successful in terms of hepatectomy, although she continued to suffer from sepsis, secondary right subphrenic abscess formation, and prolonged thrombocytopenia with associated coagulation disorders for two months. Examination of multiple cross sections of the resected specimen disclosed that the lesions consisted of aggregations of multiple small locules. There was no communication between the locules and there were true septations, rather than multiloculated lesions with pseudoseptations. The patient has been well for 2 years without recurrent abscess of the liver or any infectious disease.

Drainage↗