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Biomedical subjects

H Kuroda

Publications and source records attributed to H Kuroda.

At least 109 records · Page 6Linked to original sources

Heterogeneous distribution of K-ras-mutated epithelia in mucinous ovarian tumors with special reference to histopathology.

The carcinogenic process of epithelial ovarian carcinomas is still unknown, and both pathways of de novo carcinogenesis from the surface epithelium and malignant transformation of benign cystadenoma have been suggested. Especially in mucinous ovarian tumors, the transition from benign cystadenomas to tumors of low malignant potential (LMP) or carcinomas has been implicated. To elucidate this possibility, we analyzed the presence or absence of heterogeneity of the K-ras mutation corresponding to the histological heterogeneity in 71 epithelial ovarian tumors, including 31 mucinous tumors. K-ras mutation was identified in nine mucinous tumors (4 of 10 carcinomas, 4 of 14 LMP tumors, and 1 of 7 cystadenomas) and in two nonmucinous carcinomas. Microdissection of multiple sites with reference to their histological appearance showed the heterogeneous distribution of K-ras-mutated epithelia in two of the nine mucinous tumors. One mucinous carcinoma showed K-ras mutation in all of the histologically LMP and malignant portions, but not in benign portions. In another LMP tumor, all of the LMP portions and one of the benign portions showed K-ras mutation, whereas the other two benign portions had no mutation. In the remaining seven mucinous tumors with K-ras mutation, however, there was a homogeneous distribution of K-ras-mutated epithelia irrespective of their histological appearance. These findings suggest that the K-ras mutation occurs during the transformation from benign cystadenomas to LMP or malignant lesions, providing molecular genetic support for the hypothesis of the "adenoma-carcinoma sequence" in some mucinous ovarian tumors, but in other cases an alternative pathway may also be possible.

Adenocarcinoma, Mucinous↗

Expression of abnormal transcripts of the FHIT (fragile histidine triad) gene in ovarian carcinoma.

To elucidate the role of the FHIT (fragile histidine triad) gene in ovarian carcinogenesis, the expression of the gene was analysed by reverse transcription-polymerase chain reaction (RT-PCR) in 51 cases of ovarian carcinoma, 6 cases of borderline tumour and 4 cases of benign ovarian tumour. The concomitant expressions of normal and abnormal FHIT transcripts were detected in 39% of carcinomas and in 83% of borderline tumours, while benign tumours and normal ovarian tissues expressed only normal transcript. In addition, there were 4 (8%) cases of carcinoma lacking expression of normal FHIT transcript, all of which were in advanced stages (stage III-IV) and poorly differentiated. These results suggest that the expression of abnormal transcripts of the FHIT gene is a feature of ovarian malignant/borderline tumours and that the complete loss of normal FHIT expression is related to the progression of ovarian carcinoma in a subset of the cases. However, abnormal FHIT transcripts themselves were not associated with any clinicopathological parameters, such as clinical stage, histological subtype of tumour, grade of differentiation or outcome of the patient. Additionally, abnormal FHIT expression was not associated with the presence of loss of heterozygosity (LOH) at this locus, suggesting that abnormal FHIT transcripts are not derived from genetic alteration or that genetic alteration at this locus is complicated.

Acid Anhydride Hydrolases↗

Prognostic significance of heat shock proteins HSP70 and HSP90 in endometrial carcinomas.

Heat shock proteins HSP70 and HSP90 are sex steroid receptor-associated proteins, and HSP90 expression has reportedly been correlated with sex steroid receptor status in endometrial carcinomas. HSP70 is also known to associate with several oncogene products such as p53 protein, and expression of HSP70 has been reported to be a prognostic factor in several malignant neoplasms. In endometrial carcinomas, however, little is known about the prognostic significance of these proteins. Therefore, we analyzed the survival of 44 endometrial carcinoma patients treated in our hospital with reference to the immunohistochemical expressions of HSP70 and HSP90, as well as the clinicopathological factors such as age, menstrual status, FIGO stage, histologic grade, p53 protein overexpression, and sex steroid receptor status. The expression of HSP70 was observed in 50% (22 cases), and strong HSP90 expression in 30% (13 cases) of the 44 carcinomas. The patients with HSP70-positive tumors showed significantly poorer survival than the patients with HSP70-negative tumors (p = 0.045), although multivariate analysis did not reveal HSP70 expression to be an independent prognostic factor. In contrast, the strong expression of HSP90 in the tumor was significantly correlated with a favorable prognosis of the patient (p = 0.026). Other prognostic indicators were FIGO stage (p = 0.0086) and the expression of progesterone receptor (p = 0.042). Accordingly, expressions of HSP70 and HSP90 each have different prognostic significance in endometrial carcinoma and may be useful for prediction of patient survival.

Adult↗

Expression of the TCL1 gene at 14q32 in B-cell malignancies but not in adult T-cell leukemia.

The TCL1 gene was recently cloned as a candidate target within the 14q32.1 breakpoint cluster region observed in T-cell malignancies. We examined the TCL1 gene expression in 21 patients with adult T-cell leukemia (ATL) and 5 cell lines, because ATL is reported to have frequent chromosome 14 band q32 aberrations. However, 20 of the ATL patients and all 5 cell lines lacked any TCL1 expression on northern blot analysis, and TCL1 transcripts were only very faintly detected in the remaining one patient. Expansion of our analysis to include other types of hematopoietic malignancies revealed strong expression of the TCL1 gene in almost all tumor cells of B-cell lineage except myelomas. However, no TCL1 signals were encountered in cells of T-cell or myeloid lineages. In normal human tissues TCL1 was found to be expressed in the spleen, lymph nodes and B-lymphocytes of peripheral blood. These results indicate that TCL1 is not a major target gene for ATL, but that it may play a role in B-cell differentiation and proliferation.

Adult↗

Early invasive adenocarcinoma of the fallopian tube: a case report and review of the literature.

We present an early invasive adenocarcinoma of the fallopian tube, which was incidentally found in a 45-year-old woman undergoing a laparotomy for uterine myoma. Histological examination of the hydropic tubes revealed widespread endosalpingeal hyperplasia without atypia in both tubes. In addition, the left tube contained 3 scattered lesions of carcinoma in situ, one of which was accompanied by a microfocus of definite stromal invasion confined within the endosalpingeal mucosa. Such a case seems extremely rare, and it might represent the histological appearance of an early invasive feature of tubal carcinoma. We reviewed previously reported cases of in situ and/or early invasive carcinomas of the fallopian tube with respect to the pathological diagnosis and histogenesis of primary tubal adenocarcinomas.

Adenocarcinoma↗

Transvenous dual chamber pacing via a unilateral left superior vena cava.

A 74-year-old woman with a unilateral left superior vena cava required dual chamber permanent pacing after a radical cardiac operation for an incomplete from of endocardial cushion defect. An active fixation ventricular lead was used to prevent the instability induced by the strange course of the electrode. For atrial pacing, a ventricular passive fixation lead was used. A transvenous dual chamber pacemaker was successfully inserted via a unilateral left superior vena cava.

Aged↗

[Leydig cell tumor of the testis: a case report].

A 63-year-old male visited our hospital with a complaint of painless swelling of the left scrotum. Left high orchiectomy was performed since ultrasonography suggested a testicular tumor. Histologically, this testicular mass was a Leydig cell tumor. We reviewed 47 cases of this tumor previously reported in Japan.

Humans↗

[Primary carcinoma in situ of the ureter: a case report].

A 55-year-old male visited our hospital with a complaint of gross hematuria and right lower abdominal pain. Cytological findings of voided urine suggested the presence of malignant cells. Cystoscopic examination revealed bloody urine discharge from the right ureteral orifice and no abnormality in the bladder wall. The retrograde pyelogram showed no tumor masses. However, malignant cells were detected cytologically in the right ureteral catheteral urine twice. Under the preoperative diagnosis of primary urothelial tumor of the right upper urinary tract, right total nephroureterectomy was performed. A histological study revealed transitional cell carcinoma in situ in the lower portion of the ureter. We reviewed 46 cases of primary carcinoma in situ of the upper urinary tract previously reported in Japan.

Carcinoma in Situ↗

[A case of constrictive pericarditis reoperated 13 years after pericardiectomy by left thoracotomy approach].

A 48-year-old male with constrictive pericarditis was reoperated through median sternotomy 13 years after pericardiectomy through left thoracotomy. Extensive pericardiectomy is the most important point for constrictive pericarditis. Therefore, we have recently chosen the median sternotomy approach which has advantages over the left thoracotomy approach. Namely, the cardiopulmonary bypass is performed in the former approach immediately if the posterior pericardiectomy is difficult or the coronary arterial injury happens during decortication.

Humans↗

[SLE with interstitial pneumonia during cyclophosphamide pulse therapy].

A 49 year-old man was admitted for edema and renal impairment due to SLE. Since he did not improve with predonisolone and methylprednisolone pulse therapy, cyclophosphamide pulse therapy (300 mg div.) was administered. The patient subsequently developed a fever, dyspnea and cough, and interstitial regions of the lungs exhibited shadows on X-ray and CT. The patient also suffered hypoxemia and poor lung function. Since several culture tests and viral antibody tests were negative for infection, antibiotics were not effective, and TBLB indicated interstitial pneumonia, which we speculated was induced by cyclophosphamide. However, this was such a severe case of interstitial pneumonia that it could not be cured merely by discontinuing the cyclophosphamide, but it did improve immediately after starting methylprednisolone pulse therapy. The incidence of cyclophosphamide-induced interstitial pneumonia is very low, but the mortality rate is high. Since cyclophosphamide pulse therapy is often used to treat SLE, attention should be focused on the incidence of interstitial pneumonia.

Cyclophosphamide↗

Individual pineal cells in chick possess photoreceptive, circadian clock and melatonin-synthesizing capacities in vitro.

Chick pineal cells express a circadian rhythm of melatonin release under light-dark (LD) cycles, with an increase during the dark period and a decrease during the light period, and this rhythm persists under constant darkness (DD). We cultured individual single pineal cells with 15 microl of medium per well in a Terasaki plate and measured melatonin secretion every 12 h under LD, DL and DD. Individual cells secreted more melatonin during the dark period than during the light period under both LD and DL conditions, and those rhythmic secretions persisted under DD. These results suggest that individual pineal cells in chick have photoreceptive, circadian clock and melatonin-synthesizing capacities.

Animals↗

Fibronectin fragment-facilitated retroviral transfer of the glutathione-S-transferase pi gene into CD34+ cells to protect them against alkylating agents.

To protect bone marrow cells from the toxicity of chemotherapy, a multidrug resistant gene or a dihydrofolate reductase gene has been introduced into stem cells. These genes, however, are not capable of conferring refractoriness to alkylating agents (AA), which are some of the most commonly used agents in chemotherapy regimens. In the present study, an attempt was made to endow human stem cell (CD34+ cells) with resistance to cyclophosphamide, a well-known AA, and adriamycin (ADM) by transducing the glutathione-S-transferase pi (GST-pi) gene whose product is thought to detoxify AA by conjugating them with glutathione and to remove a toxic peroxide formed by ADM. The gene transduction was carried out retrovirally with a virus titer of 1 x 10(5) FFU/ml, employing a recombinant fibronectin fragment; transduction efficiency was extremely low without the fragment. Incubation with interleukin-6 and stem cell factor enhanced the expression of fibronectin ligands VLA4 and VLA5 on CD34+ cells. This enhanced expression of VLA4 and VLA5 was considered to facilitate a close contact of the CD34+ cell to the retroviral vector via fibronectin fragments and the subsequent transduction process. The GST-pi gene-transduced CD34+ cells formed almost 3- and 2.5-fold more CFU-GM than neo gene-transduced CD34+ cells in the presence of 2.5 microg/ml of 4-hydroperoxycyclophosphamide (4-HC), an active form of cyclophosphamide, and 30 ng/ml ADM, respectively. The transfectants formed an appreciable number of colonies, even at higher concentrations of these drugs (5.0 microg/ml of 4-HC, 50 ng/ml of ADM) whereas neo gene-transduced or nontransduced CD34+ cells formed no colonies at all, indicating the possibility of selecting out the transfectants by exposing them to these anticancer drugs. Thus, we were able to demonstrate that transduction of the GST-pi gene confers resistance to cyclophosphamide as well as to ADM, and therefore this approach can be applied clinically for high-dose chemotherapy.

Alkylating Agents↗

Characteristics of 161 patients with cardiac tumors diagnosed during 1993 and 1994 in Japan.

We investigated clinical and pathologic characteristics of 161 patients with primary or secondary cardiac tumors diagnosed between 1993 and 1994 in Japan. The increased use of cardiovascular imaging, especially echocardiography, contributed to the early identification of small cardiac tumors, resulting in a reduction of the serious complications such as embolization.

Adolescent↗

Studies on the mechanism for Cai-transients in sea urchin zygotes caused by refertilization and external application of sperm extract.

Sea urchin zygotes can be refertilized when they are deprived of the fertilization membrane and the hyaline layer. We have earlier reported that a transient increase of the intracellular Ca2+ concentration (Cai-transient) is induced in zygotes refertilized by sperm or treated with a sperm extract (spex) (M. Osawa et al., 1994, Dev. Biol. 166, 268-276). We investigated quantitative characteristics of the Cai-transient induced by sperm and spex, using a Ca2+ indicator, Indo-1. When sperm or spex was applied to zygotes, the peak value of the Cai-transient was 1.16 or 0.69 microM, respectively. Although these values were lower than the peak value of 1.95 microM measured during normal fertilization, the entire time courses of the three types of Cai-transients were similar. The Cai-transients during fertilization is known to be caused both by the IP3-induced Ca2+ release (IICR) and by a mechanism independent of IICR. The Cai-transients during refertilization and fertilization were not inhibited by an IP3 receptor inhibitor, heparin or by a G-protein inhibitor, GDPbetaS. However, heparin delayed the time courses of both Cai-transients. These results suggest that there may be two signal transduction pathways operating during refertilization, one dependent and the other independent of IICR. By contrast, both heparin and GDPbetaS inhibited the spex-induced Cai-transient. The IP3 content in spex-treated zygotes increased, and the spex-induced Cai-transient occurred even in the absence of external Ca2+. Cai-transient was not observed when spex was injected into zygotes. These data suggest that spex induces IICR in zygotes by activating certain cell surface receptors coupled to G-proteins.

Animals↗

Increased expression of LH/hCG receptors in endometrial hyperplasia and carcinoma in anovulatory women.

Endometrial hyperplasias and carcinomas are well documented to occur in anovulatory women with or without polycystic ovarian syndrome (PCO), which is characterized by hypersecretion of luteinizing hormone (LH). Although overexpression of LH/human chorionic gonadotropin (hCG) receptors has been demonstrated in endometrial carcinomas, whether LH/hCG receptors are also expressed in the endometrial hyperplasias is not known. In this study, the expression of LH/hCG receptors as well as that of progesterone receptors (PR) was analyzed by immunohistochemistry in 20 cases of normal endometria and 24 cases of endometrial hyperplasia and carcinoma (9 simple hyperplasias, 6 complex hyperplasias, 6 atypical hyperplasias, and 3 well-differentiated carcinomas). Fifteen of the 24 patients were 40 years old or younger, presumably anovulatory by BBT chart. Serum levels of LH, follicular stimulating hormone (FSH), prolactin, estradiol, and testosterone were measured by radioimmunoassay. Expression of LH/hCG receptors was detected in 19 of the 21 hyperplasias with a relatively stronger staining intensity in the glandular cells of complex or atypical hyperplasia as compared with normal endometrial glands or simple hyperplasia. In addition, all of the 3 carcinoma specimens showed stronger expression of LH/hCG receptors compared with normal endometria. The expression of LH/hCG receptors was well correlated with the staining for PR. Hormonal assay revealed 3 women to have the typical endocrinological profile of PCO. These findings suggest that the increased expression of LH/hCG receptors is a feature of endometrial hyperplasia and carcinoma developing in younger anovulatory women including those with PCO.

Adult↗

Daily wheel running activity modifies the period of free-running rhythm in rats via intergeniculate leaflet.

The period of free-running rhythms (tau) in rats, as measured using a running wheel, is different from that measured using an Automex. The aim of this work was to examine the effects of lesions of the intergeniculate leaflet (IGL) on the tau of these two activity rhythms. When blind rats were transferred from a cage with a running wheel to a cage without a running wheel, the tau lengthened. The tau of the wheel-running activity was associated with the number of wheel revolutions per day. A complete lesion of the IGL lengthened the tau of the wheel-running activity, and caused a reduction in the number of wheel revolutions per day in all rats. In rats housed in cages without a running wheel, locomotor activity was reduced by IGL lesions, although the tau was unaffected. When IGL-lesioned rats were transferred from a cage with a running wheel to a cage without a running wheel, no further change was observed. These results indicate that the tau is modified by the daily activity of wheel-running, but not by general locomotor activity, and that the IGL may be involved in this modification.

Animals↗