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Biomedical subjects

M Mano

Publications and source records attributed to M Mano.

At least 37 records · Page 2Linked to original sources

[Diagnosis and treatment of small peripheral lung cancer].

Recently, routine clinical use of CT scan has enabled the detection of many small pulmonary nodules. Concurrently, high-resolution CT(HRCT) has made great advances in the diagnosis of small peripheral lung cancer. In the tumor of adenocarcinoma, non-invasive bronchioloalveolar carcinoma(BAC) component having a replacement growth pattern of alveolar lining cells shows ground-glass opacity(GGO) on HRCT. On the basis of analysis of small peripheral adenocarcinoma (= < 2 cm), patients with tumors showing > = 50% GGO had no metastatic tendency. Therefore, simple wedge resection may be acceptable as a radical operation. On the other hand, since patients with tumors < 50% GGO had slight metastatic tendency depending upon the tumor size, segmentectomy with mediastinal lymph node sampling should be considered only for tumors = < 15 mm.

Adenocarcinoma↗

Incidence rate of satellite tumors in renal cell carcinoma.

BACKGROUND: Nephron-sparing surgery for incidentally detected small renal tumors has been performed. The main objection to such surgery concerns the incidence rate of satellite renal tumors. In this study, the authors analyzed the rate of incidence and proliferative potential of satellite renal tumors. METHODS: The tumors of 124 renal cell carcinoma patients with a clinically identified unilateral and single tumor measuring </=90 mm who were examined between November 1991 and May 1997 were analyzed prospectively. The authors determined whether these specimens obtained by radical nephrectomy had satellite tumors, and whether the satellite tumors were reactive with a monoclonal antibody (MoAb), MIB-1, to assess their proliferative potential. RESULTS: Satellite renal cell carcinomas were detected in 8 of the 124 patients (6.5%). None of the pathologic variables examined (tumor grade, tumor stage, main tumor size, cell pattern, and vascular invasion) were found to be predictive of the presence of satellite tumors. Of these eight tumors, two main tumor specimens and three satellite tumor specimens reacted with the MIB-1 MoAb. The reactivity of MIB-1 correlated with the tumor grade. The satellite tumors were observed to have a proliferative potential compared with the main tumors. Among 86 kidney specimens from patients with urothelial tumors after total nephroureterectomy, 2 (2.3%) contained small renal cell carcinoma but did not show positive staining with the MoAb MIB-1. CONCLUSIONS: The incidence rate of satellite tumors among 124 renal cell carcinoma patients was 6.5% and the presence of satellite tumors was not predictable. Some of these satellite tumors showed positive staining with the MIB-1 MoAb, but small renal tumors detected in kidney specimens with urothelial tumors did not.

Adult↗

Chromosome rearrangement at 17q25 and xp11.2 in alveolar soft-part sarcoma: A case report and review of the literature.

BACKGROUND: Despite the characteristic histopathologic appearance of alveolar soft-part sarcoma (ASPS), its histogenesis remains unclear, and cytogenetic analysis of ASPS is limited to eight cases so far because of the extreme rarity of this disease. METHODS: The authors document a cytogenetic study of a primary case of ASPS in which a modern spectral karyotyping technique was used. RESULTS: A standard cytogenetic analysis of the primary tumor cells with G-banding revealed 46,XY, add(17)(q25) in 23 of 25 metaphases analyzed. This structural rearrangement of chromosome 17, involving band q25, was also present in 5 of 8 ASPS cases in the literature. Moreover, with the spectral karyotyping technique, the additional part of the long arm of chromosome 17 in the current case was found to originate from chromosome X, resulting in a final tumor karyotype of 46, XY, add(17)(q25).ish der(17)t(X;17) (p11.2;q25)(wcpX+). CONCLUSIONS: This case report documents a clonal chromosome abnormality of der(17)t(X;17)(p11.2;q25) in ASPS. The results of the current study indicate that further molecular analyses focused on 17q25 and Xp11.2 are of interest and could help to elucidate the pathogenesis of ASPS.

Child↗

Prognostic value of bronchiolo-alveolar carcinoma component of small lung adenocarcinoma.

BACKGROUND: Bronchiolo-alveolar carcinoma (BAC) is often observed in lung adenocarcinoma, but its clinicopathological and prognostic significance, especially in small peripheral lung adenocarcinoma, remains undetermined. METHODS: We assessed 206 consecutive cases of surgically resected small peripheral lung adenocarcinoma (less than 2 cm in diameter) recorded between 1973 and 1997. According to the component area of well differentiated BAC within maximally cut surface specimens of tumor tissue, we semiquantitatively classified the tumors into four types: those in which the BAC component comprised 0% (type I), 1% to 49% (type II), 50% to 99% (type III), and 100% (type IV) of the tumor tissue. RESULTS: Forty tumors were classified as type I, 75 as type II, 74 as type III, and 17 as type IV. The tumors with less BAC, especially type I and II, showed a significantly more aggressive nodal involvement and tumor stage, and consequently a worse prognosis, while type IV tumors had no nodal involvement and the most favorable prognosis. The patients with type III showed clinicopathological characteristics somewhere between those of type II and type IV patients. Among stage I patients, however, those with type II had the worst prognosis, while those with type I showed as good a prognosis as the other two groups. CONCLUSIONS: This novel classification based on the degree of BAC involvement in small peripheral lung adenocarcinoma may reflect clinicopathological and prognostic characteristics. This classification may prove practical for planning therapeutic strategies, in particular surgical treatment.

Adenocarcinoma↗

Methylcobalamin decreases mRNA levels of androgen-induced growth factor in androgen-dependent Shionogi carcinoma 115 cells.

Methylcobalamin (MeCbl) is an important enzyme cofactor required for methionine synthase activity. It also inhibits, in a dose-dependent manner, the proliferation of an androgen-dependent cell line, SC-3, derived from an androgen-dependent mouse mammary tumor (Shionogi carcinoma 115). In SC-3 cells, androgen induces the production of androgen-induced growth factor (AIGF), an autocrine growth factor increasing the proliferation of SC-3 cells. MeCbl treatment suppressed the androgen-induced, AIGF-mediated growth of SC-3 cells, as well as the androgen-induced increase of AIGF mRNA. In SC-3 cells, androgen receptors linked with androgen form complexes that tightly bind DNA and act as transcription factors in the nucleus to regulate the expression of specific genes such as AIGF. The number and dissociation constants of androgen receptors in control and MeCbl-treated SC-3 cells were the same. Similarly, the extent of binding of normal androgen receptors in nuclei from control and MeCbl-treated cells was virtually identical. The androgen receptors from control and MeCbl-treated cells showed similar capacities for conversion to a form that tightly binds to DNA on heat activation. These results suggest that the reduction of AIGF mRNA, subsequent to the nuclear binding of androgen receptors, may be a partial cause of the growth-inhibitory activity of MeCbl in SC-3 cells.

Androgens↗

Induction of apoptosis by hinokitiol, a potent iron chelator, in teratocarcinoma F9 cells is mediated through the activation of caspase-3.

Hinokitiol, a potent iron chelator, has been reported to induce differentiation in teratocarcinoma F9 cells with a reduction of viable cells. In this study, we examined the steps leading to eventual cell death by hinokitiol during differentiation. Hinokitiol induced DNA fragmentation of F9 cells in a concentration- and time-dependent manner. This effect was also observed in a cell-free system using the nuclei from intact cells and the cytosols from hinokitiol-treated cells. In contrast, hinokitiol methyl ether and hinokitiol-Fe (III) complex, which are deficient in iron-chelating activity, showed no DNA fragmentation activity in both cell culture and cell-free systems. These results suggest that iron deprivation by hinokitiol may be involved in the induction of apoptosis of F9 cells. Caspase-3, one of the key enzymes in the apoptotic cascade, was specifically activated by hinokitiol treatment, but not by the other two derivatives. In addition, its specific inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, strongly blocked hinokitiol-induced DNA fragmentation. These results indicate that iron deprivation by hinokitiol can induce apoptosis of F9 cells through the activation of caspase-3.

Amino Acid Chloromethyl Ketones↗

Myoepithelioma of the lung: report of two cases and review of the literature.

Myoepithelial tumors occur mainly in the salivary glands, the sweat glands or the breast, but uncommonly in the lung. Herein, we describe two cases of myoepithelioma of the lung. Both patients were 58-year-old men, in whom the tumors were located in the right-upper bronchus and in the left-upper bronchus, respectively, with endobronchial growth pattern. Surgery was performed, but metastasis occurred into the forearm and hip muscles in the former case, and into the liver in the latter. Histologically, the tumor in the former was a spindle-plasmacytoid type, and that in the latter was a plasmacytoid type in part with squamous differentiation. Based on histochemical, immunohistochemical and ultrastructural analyses, both were compatible with myoepithelioma. The clinicopathological uniqueness of this neoplasm is discussed, together with a review of reports of this disease in the literature.

Fatal Outcome↗

Myeloperoxidase antineutrophil cytoplasmic autoantibody-associated glomerulonephritis in a very elderly patient with generalized vasculitis at autopsy.

An 86-year-old woman was admitted with hemoptysis and rapid deterioration of renal function. Renal biopsy disclosed necrotizing crescentic glomerulonephritis. Based on positivity for serum myeloperoxidase antineutrophil cytoplasmic autoantibody (MPO-ANCA), MPO-ANCA-associated glomerulonephritis was diagnosed. Steroid pulse therapy was performed, but the patient died after the second course. Autopsy revealed renal vasculitis with fibrinoid necrosis extending to the level of the arcuate arteries. Vasculitis was also observed in the liver, adrenal gland, uterus, and spleen, suggesting the presence of microscopic polyarteritis. This case demonstrates the broad spectrum of MPO-ANCA-positive vasculitis and suggests the need for a more effective therapy suitable for very elderly patients.

Aged↗

The cardiovascular protective role of docosahexaenoic acid.

Dietary fish oils rich in n-3 polyunsaturated fatty acids can modulate a diverse range of factors contributing to cardiovascular disease. This study examined the relative roles of eicosapentaenoic acid (20:5 n-3; EPA) and docosahexaenoic acid (22:6 n-3; DHA) which are the principal n-3 polyunsaturated fatty acids regarded as candidates for cardioprotective actions. At low dietary intakes (0.4-1.1% of energy (%en)), docosahexaenoic acid but not eicosapentaenoic acid inhibited ischaemia-induced cardiac arrhythmias. At intakes of 3.9-10.0%en, docosahexaenoic acid was more effective than eicosapentaenoic acid at retarding hypertension development in spontaneously hypertensive rats (SHR) and inhibiting thromboxane-like vasoconstrictor responses in aortas from SHR. In stroke-prone SHR with established hypertension, docosahexaenoic acid (3.9-10.0%en) retarded the development of salt-loading induced proteinuria but eicosapentaenoic acid alone was ineffective. The results demonstrate that purified n-3 polyunsaturated fatty acids mimic the cardiovascular actions of fish oils and imply that docosahexaenoic acid may be the principal active component conferring cardiovascular protection.

Animals↗

[Argatroban, a selective thrombin inhibitor, for anticoagulant therapy during and following vascular surgery].

We administered argatroban, a selective thrombin inhibitor, as an anti-coagulant during and following vascular surgery. Activated coagulation time was controlled easily by its continuous intravenous infusion. No abnormal bleeding tendency and thrombus formation in graft and blood vessel were observed. The activity of thrombin was inhibited under the infusion of argatroban. We conclude that argatroban is effective for anti-coagulant therapy during and following vascular surgery.

Aged↗

Comparison of salt sensitivity of male and female F2 progeny from crosses between WKY and SHRSP rats.

1. The present study compared the salt sensitivity of male and female F2 progeny obtained from crosses between Wistar-Kyoto/Izumo rats and stroke-prone spontaneously hypertensive rats (SHRSP A3b/Izm) after salt loading for 7 months. 2. Average systolic blood pressure in male F2 progeny was 10 mmHg higher than that of female F2 progeny at 5 months without salt loading. 3. The blood pressure in male F2 progeny was raised significantly 2 months after salt loading, but there was no further significant change in blood pressure even though salt loading was continued for 5 months. 4. In female F2 progeny, however, a significant change in systolic blood pressure was observed 1 month after salt loading and there was a further significant rise in blood pressure over 6 months. 5. Angiotensin I-converting enzyme and RR1023 loci were strongly linked to systolic and diastolic blood pressures in the male but not the female F2 progeny after salt loading for 7 months. 6. We therefore speculate that the hormonal difference between sexes might influence salt sensitivity in the SHRSP.

Animals↗

Effect of dietary magnesium supplementation on intralymphocytic free calcium and magnesium in stroke-prone spontaneously hypertensive rats.

The effects of dietary magnesium (Mg) supplementation on intralymphocytic free Ca2+ ([Ca2+]i) and Mg2+ ([Mg2+]i) were examined in the stroke-prone spontaneously hypertensive rats (SHRSP) at the age of 10 weeks. After 40 day Mg supplementation (0.8% Mg in the diet), systolic blood pressure (SBP) was significantly lower in Mg supplemented group (Mg group) than the control group (0.2% Mg). [Ca2+]i was significantly lower and [Mg2+]i was significantly higher in Mg group than in the control group. Further, [Ca2+]i was positively and [Mg2+]i was negatively correlated with SBP. These results suggest that dietary Mg supplementation modifies [Ca2+]i and [Mg2+]i, and modulates the development of hypertension.

Animals↗

Basal high blood pressure cosegregates with the loci on chromosome 1 in the F2 generation from crosses between normotensive Wistar Kyoto rats and stroke-prone spontaneously hypertensive rats.

We investigated the linkage between high blood pressure (BP) and microsatellite genotypes in the independently produced F2 progenies between Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) at the age of 2.5, 3 and 5 months before salt loading and after 2 month salt loading. In 2.5, 3 and 5 month-old male and female F2 progenies, blood pressure was significantly higher in homozygotes of the SHRSP allele at the two loci on rat chromosome 1, leukosianine (LSN) and myosin light chain (MYL2), than those of heterozygotes or WKY homozygotes. However, this strong cosegregation was attenuated after salt loading for 2 months. Basal (non salt-loaded) blood pressure strongly cosegregates with the loci on rat chromosome 1 and, therefore, putative gene(s) in this region contribute to the development of basal high blood pressure in SHRSP.

Aging↗

Cerebrovascular protection by sequential bilateral carotid artery ligation in aged spontaneously hypertensive rats.

1. Sequential bilateral carotid artery ligation (BCL) separated by a 1 week interval was performed on 5 month spontaneously hypertensive rats (SHR) (i.e. SHRSR-B1/Izm) and the developmental course of hypertension and cerebrovascular lesions in advanced age were analysed as compared with those in age-matched sham-operated controls. 2. Behavioural activity and behavioural reaction to light were also investigated in the above-mentioned SHR, young and adult stroke-prone SHR (i.e. SHRSP-A3/Izm), SHR (i.e. B1/Izm) and Wistar-Kyoto rats (i.e. WKY/Izm). 3. All of the control SHR developed severe hypertension resulting in cerebral stroke with focal oedema due to cerebral haemorrhage and infarction as a result of arterionecrosis 18 months after birth. 4. SHR usually die within a few days of BCL. In the present study, however, they successfully survived without cerebrovascular damage for a long time, although they developed a similar severe hypertension in a significantly shorter period of time (P < 0.05) and showed behavioural abnormalities that were probably due to severe cerebral ischaemia. 5. These experimental results suggest an ischaemic tolerance phenomenon in a hypertensive model that was exposed to mild ischaemic stress by unilateral carotid artery ligation (UCL) before the subsequent induction of severe ischaemia by BCL. The results also suggest that an aggravation of hypertensive cerebrovascular changes due to long-lasting ischaemia after BCL was prevented through a possible cumulative effect of ischaemic stress.

Aging↗

Intralymphocytic free calcium and magnesium in stroke-prone spontaneously hypertensive rats and effects of blood pressure and various antihypertensive agents.

1. Free Ca2+ ([Ca2+]i) and Mg2+ ([Mg2+]i) were measured in peripheral lymphocytes from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) at the age of 5, 7 and 17 weeks, from various antihypertensive agents-treated SHRSP, and from secondary hypertensive WKY. 2. At the age of 5 weeks, no difference was observed in systolic blood pressure (SBP), or lymphocyte [Ca2+]i and [Mg2+]i between SHRSP and WKY. At the age of 7 or 17 weeks, SBP and [Ca2+]i of SHRSP were significantly higher than in WKY, and at the age of 17 weeks, [Mg2+]i of SHRSP was significantly lower than in WKY. Further, [Ca2+]i or [Mg2+]i was positively or negatively correlated to SBP, and [Mg2+]i was negatively correlated to [Ca2+]i. 3. SBP of SHRSP fell significantly after antihypertensive treatment with calcium antagonist, angiotensin-converting enzyme (ACE) inhibitor or hydralazine for 40 days. [Ca2+]i was significantly lower in calcium antagonist and hydralazine groups, and tended to be low in ACE inhibitor group. These four groups showed no difference in [Mg2+]i. 4. After 40-day administration of NG-nitro-L-arginine (L-NNA), WKY developed severe hypertension, but there were no significant differences in lymphocyte [Ca2+]i and [Mg2+]i between the L-NNA treated and non-treated groups. 5. These results suggested that increased lymphocyte [Ca2+]i and decreased [Mg2+]i observed in SHRSP are not only secondary to hypertension but possibly related to a basic genetic abnormality of divalent cation handling.

Animals↗

[Effects of ascorbic acid on trace element metabolism in the choroid-retina of streptozotocin-induced diabetic guinea pigs].

In order to investigate the effect of ascorbic acid on trace element metabolism in the choroid-retina, experimental diabetes mellitus was induced in Hartley guinea pigs with intraperitoneal injection of streptozotocin. After 4 weeks, ascorbic acid-deficient feed was given for 3 weeks. Trace elements of the choroid-retina were measured with inductively-coupled plasma emission spectrometry. The activity of superoxide dismutase and lipid peroxide content also were measured. The results indicated that zinc and magnesium increased in diabetes mellitus. However, with ascorbic acid deficiency in diabetes mellitus, zinc and magnesium significantly decreased. On the other hand, the activity of superoxide dismutase showed no change between either condition and lipid peroxide content decreased under ascorbic acid deficiency in diabetes mellitus. These findings suggested that ascorbic acid played an important role in chorioretinal damage of diabetes mellitus. However, it was also suggested that lipid peroxide has little influence on the choroid-retina under these conditions.

Animals↗

A protective role for nitric oxide in the oxidative modification of low density lipoproteins by mouse macrophages.

Low density lipoproteins (LDL) oxidatively modified by macrophages have been shown to be atherogenic in ex vivo studies. We studied the potential role of nitric oxide (NO), a free radical produced by macrophages, in LDL modification. Human LDL (1 mg/ml) were incubated with mouse peritoneal macrophages in Ham's F-10 medium. The cells were then stimulated by interferon-gamma and tumor necrosis factor-alpha to increase their production of NO from 1.3 to 12.2 microM in 24 h, as measured by nitrite. Lipid peroxidation of LDL, as measured by thiobarbituric acid-reactive materials (TBARS), was reduced in stimulated cells in a time-dependent manner. At 24 h, the decrease was about 27%. In the presence of an NO synthase inhibitor (NG-aminophomoarginine), the generation of NO was diminished and the protection against LDL lipid peroxidation was reversed. The extent of LDL protein modification was also assessed by examining its electrophoretic mobility. It was found that macrophage NO reduced the change in LDL electromobility. These data indicate that the production of NO may inhibit the oxidative modification of LDL with cytokine-stimulated macrophages. We suggest that NO plays a protective role in limiting macrophage-induced LDL modification.

Animals↗