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Biomedical subjects

R Nakano

Publications and source records attributed to R Nakano.

At least 91 records · Page 5Linked to original sources

Bronchial artery aneurysm as a cause of atelectasis.

A 54-year-old nonsmoker female developed atelectasis of the anterior basal segment of the right lower lobe. A non-pulsating endobronchial tumor was observed bronchoscopically obstructing the right basal bronchus. The tumor was confirmed on arteriography to be a saccular aneurysm of the right bronchial artery. The aneurysm was treated with bronchial artery embolization. Bronchial artery aneurysm, without a predisposing disease, is quite rare, but should be considered as an etiological factor of atelectasis.

Aneurysm↗

Splanchnic hemodynamic pattern and liver function in patients with cirrhosis and esophageal or gastric varices.

OBJECTIVES: This study was designed to characterize the splanchnic hemodynamic pattern and liver function in patients with cirrhosis and esophageal or gastric varices. METHODS: Forty control subjects and 112 patients with cirrhosis were studied. Portal inflow (the sum of superior mesenteric arterial and splenic arterial flows), portal venous flow, and collateral flow (the difference between portal inflow and portal venous flow) were measured using duplex ultrasonography. Endoscopic examination showed that 45 patients had no varices or small esophageal or gastric varices, 49 had large esophageal varices, and 18 had large gastric varices. Liver function was assessed by Pugh-Child score. RESULTS: Portal inflow was significantly greater in patients with large esophageal varices or large gastric varices than in control subjects and patients with no varices or small esophageal or gastric varices. Portal venous flow was significantly lower in patients with large gastric varices than in the other three groups. Collateral flow was significantly greater in patients with large gastric varices than in patients with large esophageal varices. The Pugh-Child score was significantly higher in patients with large gastric varices than in patients with large esophageal varices. The Pugh-Child score was also inversely correlated with portal venous flow (r = -0.35, p < 0.01) and directly correlated with collateral flow (r = 0.59, p < 0.01). CONCLUSIONS: Both patients with esophageal varices and those with gastric varices have increased portal inflow. However, patients with gastric varices, in contrast to patients with esophageal varices, have a reduced portal venous flow associated with an increased collateral flow. Such a portal outflow pattern may contribute to the worse liver function seen in patients with gastric varices.

Endoscopy, Digestive System↗

Instability of mutant Cu/Zn superoxide dismutase (Ala4Thr) associated with familial amyotrophic lateral sclerosis.

In about 20-25% of cases of familial amyotrophic lateral sclerosis (FALS) patients have mutations in the Cu/Zn superoxide dismutase (SOD1) gene. The mechanism through which the mutations in the SOD1 gene cause ALS still remain unknown. We performed pulse-chase experiments using a system for the transient expression of human SOD1 in COS7 cells to examine whether the Ala4Thr mutation, which we previously reported, decreases the stability of SOD1. The expression vector (pEF-BOS) carrying the wild-type or mutant (Ala4Thr) human SOD1 cDNA was transfected into COS7 cells, and transiently expressed human SOD1 was then metabolically radiolabeled. Half-lives of the wild-type and the Ala4Thr mutant SOD1 were determined to be 78 h and 18 h, respectively. These results suggest that the Ala4Thr mutation in SOD1 decreases the stability of SOD1 and that this instability may play an important role in the pathogenesis of the degeneration of motor neurons in FALS.

Amyotrophic Lateral Sclerosis↗

Conserved Glu318 at the cytochrome P450 1A2 distal site is crucial in the nitric oxide complex stability.

Nitric oxide synthase (NOS) has a thiolate-coordinated heme active site similar to that of cytochrome P450 (P450). Both NOS and P450 form stable nitric oxide (NO)-ferric heme complexes, whereas an NO-ferric heme complex of methemoglobin, that has an imidazole-coordinated heme active site, is easily reduced. The NO complex stability of the thiolate-coordinated hemoproteins, however, appeared irreconcilable with the strong electron-donating capability of the cysteine thiolate. In the present study, NO bindings to cytochrome P450 1A2 (P450 1A2) distal mutants were studied in the presence of various substrates. We found that a mutation at Glu-318 to Ala in the putative distal site of P450 1A2, suggested to be important in the O2 activation of P450 reactions, markedly facilitates the reduction of the NO-ferric complex. Addition of 1,2:3,4-dibenzanthracene or phenanthrene almost abolished the mutation effect on the NO complex. Based on these results, together with other spectral and kinetic data, it is suggested that the NO-ferric complex stability of P450, and perhaps of NOS, is largely ascribed to an ionic bridge between NO and the distal carboxyl group.

Binding Sites↗

Tris(2,2'-bipyridyl)ruthenium(II)-mediated photoinduced electron transfer of engineered cytochrome P450 1A2.

In this study, it is shown that an electron from photoreduced tris(2,2'-bipyridyl)Ru2+ ion reaches the haem iron of engineered wild-type cytochrome P450 1A2 (P450 1A2) with an electron transfer rate of 6.04 x 10(-3) min(-1). The electron transfer rate, 4.05 x 10(-2) min(-1), of a His163Glu mutant, which has a redox potential 40 mV lower than that of the wild type, is more than sixfold faster than that of the wild type. The photoinduced electron transfer rates of the present system are strongly influenced by detergents, cholic acid and Emulgen 913. We discuss the intermolecular and intramolecular electron transfer mechanism of the P450 1A2 system based on the kinetic data.

2,2'-Dipyridyl↗

The multidrug resistance-associated protein gene confers drug resistance in human gastric and colon cancers.

To determine the expression of multidrug resistance-associated protein (MRP) gene and its role in gastric and colon cancers, we analyzed 10 gastric and 10 colon non-drug-selected cell lines and a similar number of tissue samples of these cancers. We compared the expression of MRP and mdrl mRNA in cell lines and tissues using reverse-transcriptase polymerase chain reaction. In mdrl-negative cells, the relationship between the level of MRP gene expression and sensitivity to anticancer drugs was examined. The effect of verapamil, an MRP-modulating agent, was also examined in these cells. The expression of MRP gene in gastric cancer cell lines varied from a low to a high level, but mdrl was not detected in any of these cell lines. Colon cancer cell lines expressed low to intermediate levels of MRP gene, and half of the cells co-expressed low to high levels of mdrl. In tissue samples, the expression pattern of the two multidrug resistance (MDR) genes was broadly similar to that described for the cell lines, except that most of the gastric cancer tissue samples did express low levels of mdrl. No significant correlation was observed between the level of MRP gene expression and sensitivity to anticancer drugs in gastric and colon cell lines. However, verapamil significantly increased the sensitivity to etoposide, doxorubicin and vincristine in cells highly expressing MRP gene. Our results indicate that MRP gene may be important in conferring MDR in gastric and colon cancer cells.

Antineoplastic Agents↗

Increase in the relative level of type V collagen during development and ageing of the placenta.

AIM: To obtain some insight into the extracellular matrix in the placenta, changes in the composition of collagens during placental development were investigated. METHODS: Collagen was extracted from placentas (group 1, 25-30 weeks, n = 21; group 2, 31-36 weeks, n = 32; and group 3, 37-41 weeks of gestation, n = 40) and the relative concentrations of various collagens were evaluated by SDS-PAGE. RESULTS: The ratio of the intensity of the alpha 1 (III) band to that of alpha 1 (I) chain collagen in group 3 placentas were lower than those in group 1 placentas. In contrast, the ratio of the intensity of the alpha 1 (V) band to that of alpha 1 (I) chain collagen in group 3 placentas were higher than those in group 1 and group 2 placentas. CONCLUSIONS: These results suggest that type V collagen might play an important role in the function of the placenta and that an increased relative concentration of type V collagen might be closely associated with the development and ageing of the placenta.

Adult↗

Apoptosis in the human uterine endometrium during the menstrual cycle.

To investigate apoptotic changes, we studied the cleavage of DNA in the uterine endometrium obtained from regularly cycling women by a quantitative end labeling of DNA gel fractionation and in situ analysis. The ladder pattern characteristic of the apoptotic cleavage of DNA into fragments of low mol wt was identified at three different phases of the cycle, namely the early proliferative, late secretory, and menstrual phases. However, DNA of high mol wt was predominant in the endometrium during the late proliferative, early secretory, and midsecretory phases. Our analysis in situ revealed that cells undergoing apoptosis were scattered in the functional layer of the early proliferative endometrium. However, apoptotic cells were no longer detectable during the late proliferative phase, and none was observed until the midsecretory phase. At the beginning of the late secretory phase, apoptosis reappeared in the stromal cells and spread gradually to almost all components of the functional layer. By contrast, cells in the basal layer showed no evidence of apoptosis throughout the menstrual cycle. The present study demonstrates that apoptosis occurs in specific populations of cells during three phases of the human endometrial cycle. Our results indicate, moreover, that apoptosis might have an important role in the regulation of the menstrual cycle in women.

Adult↗

Apoptosis of human corpora lutea during cyclic luteal regression and early pregnancy.

To elucidate the role of apoptotic cell death in human corpus luteum (CL) regression, human CL during the menstrual cycle and early pregnancy were isolated and processed for biochemical (radio-labeling) analysis of DNA integrity. Total DNA extracted from human CL of the early luteal phase contained predominantly high mol wt DNA, whereas CL of the midluteal phase exhibited the appearance of DNA cleavage into low mol wt ladders characteristic of apoptosis. Although apoptotic DNA cleavage of human CL significantly increased from the midluteal phase to the late luteal phase (P < 0.05), CL of early pregnancy did not exhibit apoptotic DNA fragmentation by biochemical analysis. In situ analysis of DNA fragmentation revealed that both large and small luteal cells exhibited DNA cleavage in human CL of the midluteal and late luteal phases and in regressive CL. The present findings suggest that 1) human luteal regression may be mediated by apoptosis; and 2) CL of early pregnancy may be rescued from luteolysis through inhibiting the occurrence of apoptotic luteal cell death.

Adult↗

Decreased type IV collagen expression by human decidual tissues in spontaneous abortion.

To provide some insight into the etiology of spontaneous abortion, the expression of type IV collagen was investigated in human decidual tissues obtained after spontaneous abortion (n = 17) and normal pregnancy (n = 22). Indirect immunofluorescent staining was performed for type I, III, and IV collagen as well as laminin, and Northern blot analysis was conducted to assess the expression of messenger ribonucleic acid for the alpha 1(IV) chain. Immunohistochemical analysis did not reveal any significant differences between normal pregnancy and spontaneous abortion with respect to interstitial collagens (type I and III collagen) and laminin in the decidual tissue. However, although pericellular immunostaining for type IV collagen was recognized around the decidual cells in normal pregnancy, very weak or no staining was observed in spontaneous abortion. Northern blot analysis revealed that the decidual expression of messenger ribonucleic acid for the alpha 1(IV) chain was significantly reduced in spontaneous abortion compared to that in normal pregnancy (P < 0.001). These results suggest that type IV collagen might play an important role in the maintenance of pregnancy and that decreased expression of this collagen could be associated with spontaneous abortion.

Abortion, Spontaneous↗

Presence and localization of endothelin receptor in the rat ovary and its regulation by pituitary gonadotropins.

In the present study we examined the regulation of receptors for endothelin 1 (ET-1) in rat granulosa cells. We examined the localization and regulation of ET receptors in immature rat ovary and the effects of ET-1 on steroidogenesis in cultured rat granulosa cells. The ovaries used in autoradiography were derived from pregnant mare serum gonadotropin and human chorionic gonadotropin-treated immature rats. Granulosa cells were obtained from diethylstilbestrol-treated immature rats and incubated with 125I-ET-1. Granulosa cells were cultured with ET-1 in the presence or absence of ovine follicle-stimulating hormone. The concentrations of sex steroid hormones in conditioned media were measured by radioimmunoassay. The binding site for ET-1 was localized in the granulosa cells, but not in thecal and luteal cells. Follicle-stimulating hormone (FSH) induced a dose-dependent increase in specific binding for ET-1 to cultured rat granulosa cells. In contrast, luteinizing hormone (LH) induced a dose-dependent decrease in specific binding for ET-1 to cultured rat granulosa cells. Conversely, treatment with prolactin and several sex steroid hormones had no effects on the specific binding of ET-1. Treatment with ET-1 inhibited FSH-stimulated accumulation of progesterone and estradiol in cultured rat granulosa cells. The results indicate that both FSH and LH influence the expression of ET-1 receptor, and that ET-1 may play a regulatory role in the ontogeny of the granulosa cell.

Animals↗

Alterations in distribution and composition of the extracellular matrix during decidualization of the human endometrium.

The distribution of the extracellular matrix, including type I, III, IV and VI collagens and laminin, and of prolyl hydroxylase was investigated in the human endometrium by an indirect immunofluorescence method with specific monoclonal antibodies. Collagens were also extracted from the endometrial tissues in the proliferative and secretory phases and from the decidual tissues in the first trimester of pregnancy. Immunohistochemical studies demonstrated that interstitial collagens, such as type I, III, and VI collagens, were localized diffusely in the stroma of the endometrium throughout the menstrual cycle, as well as in the decidua. Type IV collagen and laminin were localized exclusively in the basement membrane of the endometrial glands and in the walls of blood vessels during the proliferative and secretory phases. However, strong staining for type IV collagen and laminin was recognized in the pericellular region of endometrial stromal cells in the decidua. Prolyl hydroxylase was localized in the cytoplasm of endometrial stromal cells and endometrial glandular cells during the menstrual cycle. Intense immunostaining for prolyl hydroxylase was observed in the decidual cells. However, immunoreactivity for prolyl hydroxylase in the endometrial glandular cells disappeared during the process of decidualization. The ratio of type III to type I collagen was significantly decreased (P < 0.05) and the ratio of type V to type I collagen was significantly increased (P < 0.01) in the decidua, as compared with ratios in the endometrium during the proliferative phase. The present results suggest that changes in the extracellular matrix may play an important role in implantation, in invasion of trophoblastic cells and in the maintenance of pregnancy.

Basement Membrane↗

Cytokine modulation of inhibin secretion in cultured rat granulosa cells.

In the present study, we examined the effects of tumour necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) on inhibin secretion by cultured rat granulosa cells using immunoblotting and two-site enzyme immunoassay for inhibin A (alpha-beta A dimer). FSH stimulated the secretion of the inhibin alpha-beta A dimer (32 kDa) by the cells in a dose-dependent manner. In addition to the predominant 32 kDa inhibin alpha-beta A dimer staining, staining of minor immunoreactive bands was also enhanced by FSH. TNF alpha alone did not have any effect on inhibin secretion. Immunoblot analyses using an antiserum against alpha-subunit and an antiserum against beta A-subunit revealed a dose-dependent inhibition by TNF alpha of FSH-stimulated secretion of inhibin by rat granulosa cells. Similarly, TNF alpha inhibited in a dose-dependent manner FSH-stimulated inhibin secretion when measured using a two-site enzyme immunoassay. IL-1 beta alone did not exert any effect on inhibin secretion but it inhibited FSH-stimulated inhibin release in a dose-dependent manner (using both immunoblotting and a two-site assay for inhibin A). The present observations suggest that TNF alpha and IL-1 beta inhibit gonadotrophin-stimulated inhibin production by cultured rat granulosa cells.

Animals↗

Chronic bronchial foreign body mimicking peripheral lung tumor.

We describe a case with chronic bronchial foreign body presenting with recurrent hemoptysis mimicking a peripheral lung tumor, and the outcome of surgical resection. A 61-year-old female with recurrent hemoptysis had a peripheral nodule in the right lower lobe. A right bronchial arteriogram showed dilatation and hypervascularity in the nodule. Surgical removal of the nodule contained a small branch of a white cedar. Chronic bronchial foreign body, while rare in adults, should be considered in the differential diagnosis of peripheral lung tumors associated with recurrent hemoptysis.

Angiography↗

Serial electroencephalograms and somatosensory evoked potentials in a patient with isolated adrenocorticotropic hormone deficiency.

Serial electroencephalograms (EEGs) and somatosensory evoked potentials (SEPs) were carried out in a 36-year-old man with isolated ACTH deficiency. Before treatment with glucocorticoids, the EEGs displayed bilateral diffuse 5-6 Hz theta waves, and SEPs demonstrated a decreased amplitude. Following treatment with glucocorticoids, the EEGs showed gradual improvement; a diffuse alpha pattern was demonstrated on the 11th day after treatment and an occipital dominant alpha pattern was found on the 83rd day after treatment. After treatment, SEPs also showed improvement. The amplitude of N20 increased and N32 became clearly recognizable. The influence of glucocorticoids on EEGs and SEPs was discussed in the context of these observations.

Adrenocorticotropic Hormone↗

A prospective study of bronchoscopy for endotracheobronchial tuberculosis.

To clarify the role of bronchoscopy for endotracheobronchial tuberculosis (EBTB), we performed a prospective study in 45 patients with active pulmonary tuberculosis, in 15 (33%) of whom bronchoscopic findings related to EBTB were seen. The findings were classified into six types:edematous hyperemic, submucosal nodule, ulcerative (shallow and deep), polypoid, cicatrical, and compression type. Each of these types was related to the healing process and outcome after antituberculosis chemotherapy. Serial bronchoscopy revealed that lesions less advanced than the deep ulcerative type responded to chemotherapy; the deep ulcerative and polypoid types progressed to cicatrical bronchostenosis despite chemotherapy. In the follow-up of patients with lesions of the deep ulcerative and polypoid types, serial bronchoscopy after chemotherapy is recommended; these patients also require adjunctive therapy to prevent cicatrical bronchostenosis.

Biopsy↗