Search PubMed⌕ Search

Biomedical subjects

M Kojima

Publications and source records attributed to M Kojima.

At least 451 records · Page 25Linked to original sources
PubMed1994

Immunohistochemical analysis of cyclin D1 protein in hematopoietic neoplasms with special reference to mantle cell lymphoma.

Immunohistochemical expression of PRAD1/cyclin D1 protein has been investigated in 106 tissue specimens of 104 cases of lymphoma, non-neoplastic lymphoid disorders and other hematologic malignancies by employing the monoclonal antibody 5D4 with formalin-fixed paraffin-embedded sections, using the microwave oven heating method. Positive neoplastic cells were found in 60 (74%) of 81 cases of non-Hodgkin's lymphoma. The positivity pattern was nuclear in 17 (85%) of 20 cases of mantle cell lymphoma in which cytoplasmic staining was also seen. This pattern of cyclin D1 positivity was in contrast to the negative staining of normal reactive mantle zones. In the other cases, positivity appeared to lie within the cell cytoplasm without nuclear staining, and most of the nodal follicular and diffuse B-cell lymphomas variously expressed PRAD1/cyclin D1. In contrast, the reaction was absent in a significant number of T-cell and extranodal B-cell lymphomas. Immunolocalization of PRAD1/cyclin D1 expression appears to be a useful diagnostic adjunct to discriminate mantle cell lymphoma from other non-Hodgkin's lymphomas.

Antigens, CD↗
PubMed1994

Myxoid leiomyoma of the vulva mimicking aggressive angiomyxoma.

A case of vulvar leiomyoma with extensive myxoid change in a 40 year old female is described. The tumor had a unique connection with a non-degenerative leiomyoma that compressed the rectum and the bladder. Scattered smooth muscle cells in a loose myxoid stroma were immunoreactive for desmin. Fibroblast-like spindle cells were immunoreactive for vimentin but not for desmin. The initial, although incorrect, pathological diagnosis of the tumor was aggressive angiomyxoma based on the similarity in both clinical and pathological aspects with this more invasive tumor. Myxoid vulvar leiomyoma should also be differentiated from angiomyofibroblastoma. The key to the differential diagnosis is the presence of interlacing smooth muscle cells and an awareness of tendency toward myxoid change in vulvar leiomyomas.

Adult↗
PubMed1994

Vasorelaxant effect of mexiletine in mesenteric resistance arteries of rats.

1. The vascular action of mexiletine, a class Ib antiarrhythmic agent, was investigated in the mesenteric resistance arteries of rats. 2. The second order branch of the mesenteric artery was cut into rings and changes in isometric tension were recorded. 3. Mexiletine (10(-6) -10(-3) M) evoked concentration-dependent, endothelium-independent relaxations in arteries contracted with noradrenaline. 4. Mexiletine (10(-4) M) did not affect the contraction induced by noradrenaline in Ca(2+)-free solution, while the compound inhibited the contraction induced by CaCl2 in noradrenaline-activated arteries. 5. The relaxation induced by mexiletine was less pronounced in arteries contracted with high KCl than in those contracted with noradrenaline. 6. Mexiletine induced identical relaxations in arteries contracted with noradrenaline in high KCl solution containing verapamil and in Krebs solution. 7. Thus, mexiletine induces relaxations by inhibiting transmembrane Ca2+ movement, but not Ca2+ release from the intracellular store site in mesenteric resistance arteries of rats. It is speculated that mexiletine possesses greater inhibitory effects against noradrenaline-activated, verapamil-insensitive (receptor-operated) Ca2+ channels than against verapamil-sensitive (voltage-dependent) channels.

Animals↗
PubMed1994

Recurrence of epithelial ovarian carcinoma after clinical remission.

One hundred and eighty-eight patients with epithelial ovarian carcinoma were treated with primary cytoreductive surgery and subsequent combination chemotherapy. The first recurrent findings such as sites and disease-free interval were analyzed in 141 patients who were clinically remitted 6 months after operation or chemotherapy. Fifty-seven cases had a recurrence. Five-year disease-free survival rates were 75, 72, 29, and 0% in stage I, II, III, and IV, respectively. Twenty-one of 22 patients with > 2 cm maximum residual tumor died, although they once achieved clinical remission. Significant differences were observed between histologic types, and the disease-free survival rate was lowest for serous cystadenocarcinoma. Nine of 15 stage IV patients with serous histology experienced remission, but none of the 8 in stage IV with other histologies did so, suggesting that serous adenocarcinoma is sensitive to chemotherapy and conducive to clinical remission. However, all stage IV patients in remission encountered a recurrence. Intra-abdominal cavity and lymph node were frequently the initial recurrent sites (38 and 27%, respectively). On the other hand, the incidence of distant recurrence was as high as 27%, and 8 of 16 cases with distant recurrence were stage I. Survival time after recurrence was not different among initial sites of recurrence and mean survival time was 15 months.

Female↗
PubMed1994

Angiotensin II receptor antagonist TCV-116 induces regression of hypertensive left ventricular hypertrophy in vivo and inhibits the intracellular signaling pathway of stretch-mediated cardiomyocyte hypertrophy in vitro.

BACKGROUND: Previous studies have demonstrated that angiotensin II (Ang II) acts as a growth-promoting factor directly on cardiac myocytes and that angiotensin-converting enzyme inhibitor induces regression of hypertrophied hearts both in experimental animals and in humans. These results suggest that the renin-angiotensin system (RAS) is involved in the formation of left ventricular hypertrophy (LVH). To elucidate the role of RAS in the progression of cardiac hypertrophy, we evaluated the effect of an Ang II receptor antagonist on LVH in spontaneously hypertensive rats (SHRs) and investigated the molecular mechanisms by which antagonizing Ang II receptors reduces cell hypertrophy of myocytes using the in vitro model of mechanical stretch. METHODS AND RESULTS: In the in vivo study, we treated SHRs with the nonpeptide Ang II receptor antagonist TCV-116 (0.1, 1, or 10 mg/kg per day) or hydralazine (10 mg/kg per day). Blood pressure was measured by the tail-cuff method, and wall thickness of left ventricle was serially monitored using M-mode echocardiography. Rats were killed at the age of 13, 17, 21, or 25 weeks, and left ventricular (LV) weight, transverse diameter of cardiomyocytes, relative amount of V3 myosin heavy chain (MHC), and degree of interstitial collagen accumulation were examined. Untreated SHRs progressively developed severe hypertension, but treatment with TCV-116 or hydralazine inhibited the increase in blood pressure. Treatment with TCV-116 reduced LV weight, LV wall thickness, transverse diameter of myocytes, relative amount of V3 MHC, and interstitial fibrosis, whereas treatment with hydralazine slightly prevented an increase in LV wall thickness but did not exert significant reduction in other parameters. In the in vitro study, neonatal rat cardiomyocytes were cultured on deformable silicone dishes and mechanically stretched with or without pretreatment of CV-11974 (an active metabolite of TCV-116), and [3H]phenylalanine incorporation, activity of mitogen-activated protein (MAP) kinase, and c-fos mRNA expression were analyzed. Pretreatment of cultured cardiomyocytes with 10(-7) mol/L CV-11974 inhibited an increase in [3H]phenylalanine incorporation, MAP kinase activity, and c-fos gene expression induced by stretch of cardiomyocytes. CONCLUSIONS: The Ang II receptor antagonist TCV-116 induced regression of cardiac hypertrophy and had cardioprotective effects on hypertrophied myocardium in vivo, and antagonizing Ang II receptors inhibited intracellular signaling of stretch-mediated cardiomyocyte hypertrophy in vitro. These results suggest a crucial role of the cardiac RAS in the development of LVH produced by pressure overload.

Angiotensin II↗
PubMed1994

Effect of KCA-098, a new benzofuroquinoline derivative, on bone mineral metabolism.

The effect of 3,9-bis(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2-c]quinoli ne-6-one designated as KCA-098) on the bone mineral metabolism of chick embryonic bone was examined. KCA-098 dose-dependently inhibited bone resorption of cultured chick embryonic femora and calvariae. It increased the length, dry weight, and calcium and phosphorus contents of 9-d-old chick embryonic femurs cultivated for 6 d, indicating that it stimulated bone formation. These results show that KCA-098 has the unique effects of inhibiting bone resorption and stimulating bone formation of chick embryo. In addition, in an in vivo experiment, oral administration of KCA-098 (3.0 mg/kg/d) for 16 weeks led to an increase in calcium and phosphorus content as well as an increase in the amount of force required to break the femur from ovariectomized rats, suggesting that it may be useful for the treatment of bone diseases.

Animals↗
PubMed1994

Induction of osteopenia in confined rats.

We have developed a simple model of osteopenia in rats which is induced by confinement without requiring surgical operation. Each rat was maintained for 8 weeks in a compartment of a commercially-available wire netting cage subdivided into 10 areas (compartment size, 9 x 16 x 14 cm) to restrict exercise. The femora isolated from the confined rats showed significant decreases in mineral (calcium and phosphorus) content, compared with the level in normal rats, 2 weeks after the start of their confinement. Confined rats showed significantly lower values for the physical properties of bones such as breaking energy and breaking force and also density composed with normal rats 4 weeks after the start of confinement. KCA-098 (1 mg/kg), a new benzofuroquinoline derivative that inhibits bone resorption and at the same time stimulates bone mineralization in organ culture, protected against these decreases when given orally for 8 weeks. All these results show that confinement of rats offers a simple and useful animal model of osteopenia.

Animals↗
PubMed1994

Effects of KCA-098 on bone metabolism: comparison with those of ipriflavone.

We previously found that 3,9-bis(N,N-dimethylcarbamoyloxy)-5H- benzofuro[3,2-c]quinoline-6-one (KCA-098) inhibited bone resorption in organ culture. In this study, to determine if KCA-098 is therapeutically applicable for the treatment of osteoporosis, we compared the effect of KCA-098 on bone tissues with that of ipriflavone, a drug that is clinically used for the treatment of osteoporosis. Both KCA-098 and ipriflavone inhibited parathyroid hormone-, prostaglandin E2-, 1 alpha,25-dihydroxyvitamin D3- and interleukin 1 beta-induced bone resorption of fetal rat bones, but the inhibitory activity of KCA-098 was more potent than that of ipriflavone. In fact, the effective concentrations of KCA-098 were 10 to 100 times lower than those of ipriflavone. Oral administration of KCA-098 (1 and 3 mg/kg) or ipriflavone (100 mg/kg) to ovariectomized rats on a low-calcium diet increased the breaking force and bone density of the femora, indicating that KCA-098 is an effective on the whole animal as ipriflavone. Furthermore, KCA-098 increased the length and calcium content of 9-day chick embryonic femora cultured in vitro, whereas ipriflavone did not, suggesting that KCA-098 had a direct stimulatory effect on bone mineralization. Therefore, KCA-098 seems to be more potent than ipriflavone in stimulating bone tissue formation and may thus be expected to become a useful agent for the treatment of osteoporosis.

24,25-Dihydroxyvitamin D 3↗
PubMed1994

Cellular localization and functional analysis of the protein encoded by the chromosomal virulence gene(acvB) of Agrobacterium tumefaciens.

A chromosomal virulence gene, acvB, of Agrobacterium tumefaciens [J. Bacteriol., 175, 3208-3212 (1993)] was over-expressed in Escherichia coli. A 47-kDa protein was produced and localized in the periplasmic space of E. coli. Amino acid sequence analysis of its N-terminal demonstrated that a signal peptide of 24 amino acids was cleaved from the pre AcvB protein to produce the mature 47-kDa protein. Western-blot analysis using the antiserum against the AcvB protein detected a 47-kDa protein in the periplasmic space only with strain A208 (acvB+). The amount of AcvB protein synthesized was not increased in strain A208 by induction with acetosyringone (100 microM). There was observed no significant difference in induction by acetosyringone of virB::lacZ, virD::lacZ, and virE::lacZ fusion genes regardless of the presence or absence of the acvB gene. The T-strand (lower strand of T-DNA) was detected in strains A208 as well as B119 (acvB-) which were cultured in induction medium containing acetosyringone. AcvB protein bound to single-stranded DNAs with no apparent sequence specificity. The results suggest that AcvB protein binds to the T-strand in periplasm and mediates the transfer of the T-strand from A. tumefaciens to the host plant cell.

Acetophenones↗
PubMed1994

DNA adducts in target and nontarget tissues of 3,2'-dimethyl-4-aminobiphenyl in rats.

3,2'-Dimethyl-4-aminobiphenyl (DMAB) is a potent carcinogenic aromatic amine which demonstrates multiorgan tropism in rats. Using polyclonal antibodies against DMAB-DNA adducts, an immunohistochemical procedure as well as an ELISA were applied to investigate the relationship between DMAB-DNA adduct formation and tumorigenicity. Dose-related nuclear staining was observed 24 hr after application of the carcinogen but specificity in terms of sites of tumor development was lacking. No observable decrease in staining intensity was evident in most organs by 168 hr after administration of DMAB. Specific DNA lesions which could be responsible for carcinogenesis were not detected by the 32P-postlabeling method. The tumorigenic response of the ventral prostate in five strains of rats was roughly paralleled by DMAB-DNA adduct levels generated in the tissue. Strong enhancement of bladder tumor development by combined administration of the antioxidants, butylated hydroxyanisole, or butylated hydroxytoluene, with DMAB, was well correlated with an increase in DNA adducts. Our findings so far suggest that DNA adduct formation itself does not determine the carcinogenic organotropism of DMAB. Other factors (including cell proliferation and promotion by exogenous agents) may play important additional roles. For individual target organs or tissues, however, there seems to be a correlation between adduct levels and carcinogenic potential.

Aminobiphenyl Compounds↗
PubMed1994

The carcinogenicity of methoxyl derivatives of 4-aminoazobenzene: correlation between DNA adducts and genotoxicity.

To elucidate the cause of the difference in genotoxic activity between carcinogenic 3-methoxy-4-aminoazobenzene (3-MeO-AAB) and noncarcinogenic 2-methoxy-4-aminoazobenzene (2-MeO-AAB), we analyzed DNA adducts in the livers of rats exposed to either of these chemicals and studied the resulting biologic potential with the aid of in vitro modified M13 phage DNA. 32P-Postalbeling analysis revealed that the carcinogen 3-MeO-AAB produced 20-fold higher amounts of adducts than did 2-MeO-AAB. Five adducts were formed in the 3-MeO-AAB case whereas only one adduct was apparent in 2-MeO-AAB-treated rat. Studies of in vitro DNA replication using N-hydroxy (N-OH)-aminoazo dye-modified M13 phage DNA as a template demonstrated inhibition by 3-MeO-AAB adducts to be substantially greater than in the 2-MeO-AAB-adducts. The specificity of mutagenesis induced in M13mp9 phage DNA by these chemicals also was analyzed after transfection into SOS-induced Escherichia coli JM103, mutation frequencies being higher with N-OH-3-MeO-AAB- than N-OH-2-MeO-AAB-modified DNA. The mutation spectra differed in each case. Our data suggest that the difference in hepatocarcinogenic activity between the two chemicals depends not only on qualitative and quantitative variation in adduct formation but also on conformation changes in modified DNA.

Animals↗
PubMed1994

Percutaneous biopsy for adrenal tumors using ultrasonically guided puncture.

Percutaneous biopsy for adrenal tumors was performed on 12 patients using ultrasonically guided puncture. Of the 12 tumors, 11 were detected incidentally by ultrasonography or computed tomography. In 11 cases, cytological or pathological diagnosis was obtained without any complication. Among these, surgical operation was carried out in 4 cases, in which biopsy findings were confirmed by the examination of the surgical specimens. The other 7 cases were being followed up without surgery. The rate of correct discrimination between benign and malignant adrenal tumors by biopsy was 91% (10/11 cases) in this series. It is accordingly considered that adrenal biopsy is the choice to confirm the diagnosis of nonfunctioning adrenal tumors because of its efficacy and ease of use.

Adrenal Gland Neoplasms↗
PubMed1994

Antihypertensive treatment in patients with a history of accelerated malignant hypertension, with special reference to clinical decision-making in changing treatment.

Conditions under which patients with hypertension controlled by combined therapy may be able to be switched to monotherapy were investigated. Eleven patients with benign phase accelerated malignant hypertension had their long-term combination antihypertensive treatment withdrawn for 1 day in an attempt to determine factors contributing to individual variability in the extent of BP increase. Patients were divided into two groups according to BP on day 1: patients with DBP above 130 mmHg formed group A, and those with DBP below 130 mmHg formed group B. Group A patients were not controlled by monotherapy with manidipine, even at the maximal dose of 60 mg/day, while group B patients were satisfactorily controlled by manidipine 20 mg/day. Group A patients had renal dysfunction whereas those in group B did not. Thus, renal dysfunction appears to be the most important single factor in predicting whether long-term combination therapy may be reduced in patients with a history of accelerated malignant hypertension.

Aged↗
PubMed1994

[A case of malignant pheochromocytoma treated with 131I-metaiodobenzylguanidine and CVD regimen].

A 44-year-old male had multiple metastasis to the lung, liver, kidney and paraaortic lymph node from primary adrenal malignant pheochromocytoma. Radiation therapy with 131I-metaiodobenzylguanidine (131I-MIBG), was first performed, which was followed by chemotherapy with cyclophosphamide, vincristine and dacarbazine (CVD). A total amount of 4810 MBq of 131I-MIBG was administered then 7 cycles of CVD regimen were added. He was survived for sixteen months with tumor response in primary tumor, paraaortic lymph node and liver metastasis tumors, in addition to hormonal response. It was considered that the survival was prolonged in spite of advanced case with inoperative primary tumor.

3-Iodobenzylguanidine↗
PubMed1994

Changes in the endothelial cyclooxygenase pathway in resistance arteries of spontaneously hypertensive rats.

Vasodilator responses to adenosine and acetylcholine (ACh) were studied in ring preparations of mesenteric resistance arteries of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Adenosine (10(-7)-3 x 10(-4) M) caused relaxations in rings with endothelium. The relaxation was more pronounced in WKY than in SHR. Removal of the endothelium in WKY, but not in SHR, reduced the relaxation. In rings without endothelium, the relaxation was identical in the two strains. In WKY, the cyclooxygenase inhibitor meclofenamic acid attenuated the relaxation to adenosine in rings with endothelium but not in rings without endothelium. With meclofenamic acid, the relaxation was identical in WKY arteries with and without endothelium. ACh (10(-9)-10(-4) M) evoked endothelium-dependent relaxations in WKY. In contrast, in SHR the muscarinic agonist evoked contractions at higher concentrations (10(-6)-10(-4) M), whereas lower concentrations of ACh caused relaxations similar to those observed in WKY. The contraction in SHR was completely inhibited by meclofenamic acid, and with meclofenamic acid the relaxation to ACh was identical in WKY and SHR. Thus, adenosine evokes endothelium-dependent (through release of cyclooxygenase product) and endothelium-independent relaxations and ACh evokes endothelium-dependent relaxations in rat mesenteric resistance arteries. In SHR, the endothelium-dependent responses to the agonists are altered owing to the changes in the endothelial cyclooxygenase pathway.

Acetylcholine↗
PubMed1994

A model study of time- and voltage-dependent effects of class I antiarrhythmic drugs in guinea-pig papillary muscles as related to external potassium concentration.

1. A piecewise exponential three-state model previously introduced by the authors in 5.4 mmol/l was intended to apply to states with different [K+]o and with a different drug. Using the conventional microelectrode technique the effects of 20 mumol/l mexiletine (MEX), 5 mumol/l aprindine (APR), 20 mumol/l quinidine (QUI), 5 mumol/l flecainide (FLE), 5 mumol/l E-0747 (dl-6-chloro-2,2'-dimethyl-1'-[3-(4-hydroxypiperizino)propyl]spiro [chroman-4,4'-imidazolidine]-2',5'-dione hydrochloride and 100 mumol/l QX-222, a quaternary derivative of lidocaine, on action potentials (APs) in guinea-pig papillary muscles were studied. Specific objects of the study were (1) steady state Vmax values at various frequencies (all drugs), (2) the recovery process of Vmax in premature responses (MEX) and (3) Vmax changes during a train of stimulation at 1 Hz after a rest period (all other drugs) in 2.7 and 10 mmol/l [K+]o. Further, those of APR alone and APR plus 1 mmol/l nicorandil (NIC), which shortened action potential durations (APDs) specifically, were investigated on the above items (1) and (3) in 5.4 mmol/l [K+]o. 2. All the drugs reduced the Vmax of APs frequency-dependently and, except QX-222, more markedly in 10 mmol/l [K+]o than in 2.7 mmol/l [K+]o at 1 Hz. 3. The rate constants estimated from the model fitting characterized MEX and APR and the other drugs as predominantly inactivated and activated channel blockers, respectively. The calculated rate of onset of block, lambda T, does not differ much between the three [K+]o levels. lambda T shows that APR belongs to class Ia rather than class Ib.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1994

[Eye complications in atopic dermatitis].

Eye complications were studied in 240 cases of atopic dermatitis (age distribution 9 months to 40 years) hospitalized in the dermatology ward of our hospital. One hundred and thirty-four patients (55.8%) had at least one eye complication. Allergic conjunctivitis, cataracts, vernal conjunctivitis, retinal detachment, keratoconus, and retinal tears were detected in 28.3%, 17.9%, 2.1%, 1.3%, 1.3%, and 0.8%, respectively. Serum IgE levels and eye complications did not correlate. Routine ophthalmological examinations are recommended for patients with atopic dermatitis.

Adolescent↗