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Biomedical subjects

H Mishima

Publications and source records attributed to H Mishima.

At least 55 records · Page 3Linked to original sources

[Efficacy of combination therapy (hepatectomy and prophylactic arterial chemoinfusion) for liver metastases of colorectal cancer].

From 1979 to 1997, 146 patients had hepatectomy for metastases of colorectal cancer (curative B: 122; curative C: 24). We categorized the severity of liver metastases as follows, H1: one lobe; H2: bilateral but less than five, and H3: bilateral with five or more lesions. In H1 and H2 patients, we compared the survival rate after resection alone (including repeat hepatectomy) with that after combination therapy (resection and prophylactic arterial chemoinfusion of 12-24 g of 5-FU). In H1 patients, the 3-year survival rate of the resected group (n = 74) and combination group (n = 6) was 47.2 and 53.3, respectively. In H2 patients, the resected group (n = 16) and combination group (n = 7) had survival rates of 34.5 and 100%, respectively. In H1 cases, the 3-year recurrence rate in the remnant liver was 63.4 versus 16.7% and in H2 cases it was 58.0 versus 0%. H3 patients received one week of continuous prophylactic arterial chemoinfusion [total dose of 5-FU = 6 g]. All four patients in the H3 combination group are alive at 20, 13, 13, and 12 months after resection, while the median survival of the resection only group (n = 4) was 12.5 months. We suggest that our combination therapy may be applicable to all patients with liver metastases of colorectal cancer.

Antimetabolites, Antineoplastic↗

[Features of colorectal cancer with fecal-occult-blood tests--comparison with colorectal cancer with no screening].

BACKGROUND: There is now evidence from three randomized controlled trials (from Minnesota, Nottingham and Funen) that screening average-risk individuals for colorectal cancer (CRC) with fecal-occult-blood tests (FOBT) can reduce mortality from CRC. In Japan, mortality rates from CRC have increased and mass screening with FOBT has been performed since 1992. Although there is growing proportion of CRC with FOBT, there is no conclusive evidence that they reduce mortality from this cause. We evaluated the feature of CRC with FOBT, as one of the methods for evaluation of the efficacy of screening with this test. METHODS: Between January, 1982 and December, 1996, 2071 cases with CRC resected in our hospital were considered. We evaluated the clinicopathological findings about age, sex, location of tumor, size depth, incidence of lymph node metastasis, stage and prognosis of CRC with FOBT (376) compared with CRC with no screening (controls; 1695). RESULTS: CRC with FOBT were earlier stage and smaller-sized cancers than controls. No significant difference was found in the incidence of lymph node metastasis at each depth and prognosis in each stage. CONCLUSIONS: By screening with FOBT, we can detect at an earlier stage and with a smaller cancer, with the same biological behavior as controls. Now, we must encourage colon screening, continuing to research ways to improve identification of high-risk subgroups and increase complicance.

Colorectal Neoplasms↗

SPARC from corneal epithelial cells modulates collagen contraction by keratocytes.

PURPOSE: Contraction of the scar tissue during corneal wound healing changes the shape of the cornea and corneal refraction. In a previous study, it was found that corneal epithelial cells secrete the factor that stimulates collagen gel contraction by keratocytes in vitro. The purpose of the present study was to purify and identify the contraction-stimulating factor derived from corneal epithelial cells. METHODS: The cultured medium of rabbit corneal epithelial cells was collected and used as an epithelial cell-conditioned medium (ECCM). Subcultured rabbit keratocytes were embedded in a collagen gel, and collagen gel contraction was investigated. The contraction-stimulating factor in the ECCM was purified through acetone precipitation, affinity chromatography (heparin Sepharose), gel filtration, and reversed-phase chromatography. The amino acid sequence of a contraction-stimulating factor was analyzed. RESULTS: Collagen gel contraction by keratocytes was enhanced by the addition of ECCM in a dose-dependent manner. The amino acids sequence of the contraction-stimulating factor was homologous to a 32-kDa glycoprotein, a secreted protein that is acidic and rich in cysteine (SPARC). Western blot analysis confirmed that SPARC was contained in the ECCM. Collagen gel contraction by keratocytes was enhanced by the addition of purified SPARC in a dose-dependent manner. SPARC was found in the basal layer of the migrating epithelium and activated keratocytes adjacent to the wound 3 days and 1 week after perforating injury in rabbit corneas. CONCLUSIONS: Epithelial cells secrete SPARC, which modulates the contraction of scar tissue in the corneal stroma.

Animals↗

Adoptively transferred late allergic airway responses are associated with Th2-type cytokines in the rat.

Late allergic airway responses can be transferred by CD4+ T cells in the rat. To investigate the role of T-cell cytokines in these responses, we examined the expression of mRNA for Th2 (interleukin [IL]-4 and IL-5) and Th1 (IL-2 and interferon gamma [INF-gamma])-type cytokines in Brown Norway rats that were administered either antigen-primed W3/25(CD4)+ or OX8(CD8)+ T cells. Donors were actively sensitized by subcutaneous injection of ovalbumin (OVA) in the neck and T cells were obtained from the cervical lymph nodes by immunomagnetic cell sorting for administration to unsensitized rats. Control rats received bovine serum albumin (BSA)-primed CD4+ and CD8+ T cells. Two days later, recipient rats were challenged with aerosolized OVA, and bronchoalveolar lavage (BAL) was performed 8 h after challenge. BAL cells expressing mRNA for IL-2, IL-4, IL-5, and INF-gamma were analyzed using the technique of in situ hybridization. Recipients of OVA-primed CD4+ T cells had an increase in the fraction of BAL cells expressing mRNA for IL-4 and IL-5 compared with BSA-primed CD4+ or OVA-primed CD8+ cells (P < 0.001). Recipients of CD8+ T cells had an increase in INF-gamma mRNA expression after OVA challenge compared with recipients of BSA-primed-CD8+ or OVA-primed CD4+ T cells (P < 0.001). In conclusion, T-cell-dependent allergen-induced late responses are associated with the expression of mRNA for IL-4 and IL-5, indicating Th2 cell activation. Furthermore, the increased expression of INF-gamma in allergen challenge recipients of antigen-primed CD8+ T cells suggests that CD8+ T cells may be important in modulating allergic responses.

Adoptive Transfer↗

Capnometry as a tool to unmask silent pulmonary embolism.

Because pulmonary embolism is often silent, simple clinical procedures are desirable to identify patients with a low to intermediate probability of pulmonary embolism. Among 19,467 patients managed under general anesthesia, we had one bile tract surgery case and three neurosurgical cases whose silent pulmonary embolism was initially suggested by an increase in the arterial to end-tidal CO2 gradient (from 17 to 27 mmHg) after general anesthesia was induced or their trachea was intubated. During the preoperative assessment, the patients presented no clinical manifestations suggestive of pulmonary embolism. Our initial diagnosis was confirmed by scintigraphy and/or angiography done immediately after the operations. Because capnometry has been shown to be applicable to non-intubated, spontaneously breathing patients, we suggest that measuring the gradient may serve as an additional method for unmasking silent pulmonary embolism in patients at risk or with disturbed consciousness, whether they are scheduled for operations or not.

Aged↗

[High resolution MR imaging of the hip using pelvic phased-array coil].

A pelvic phased-array coil was applied to obtain high resolution MR images of the hip. Three-mm-thick fast spinecho images were obtained in seven hips. Images with a pelvic coil enhanced delineation of acetabular labrum and articular cartilage more clearly than those with a body coil or flexible-surface coil. The use of a pelvic coil in imaging of the hip may be of diagnostic value because of its superior delineation.

Adult↗

Possible role of neurointerventional techniques in the diagnosis of hemifacial spasm.

We used neurointerventional techniques to conduct a functional investigation of the artery responsible for hemifacial spasm in a 48-year-old woman. Insertion of a microcatheter into the posterior inferior cerebellar artery stopped the hemifacial spasm immediately and completely. The artery was verified intraoperatively as the vessel compressing the root exit zone of the facial nerve.

Arteries↗

[A new two-part therapy for multiple bilobar liver metastases of colorectal cancer--treatment of one lobe with partial hepatectomy and the other with arterial chemotherapy].

We studied a new two-part therapy for patients of multiple (more than five) bilobar liver metastases from colorectal cancer, in which one lobe is treated with partial hepatectomy and the other with arterial chemotherapy. The patient was a 72-year-old woman who had undergone sigmoidectomy and partial hepatectomy on March 9, 1995, for advanced sigmoid cancer with liver metastasis. In December 1995, new foci were detected in the remaining liver. Intraoperative echography during reoperation revealed 6 foci in the right lobe, 2 in the left lobe and 1 in the caudate lobe. During reoperation, we performed partial hepatectomy at the left lobe metastases and microwave coagulation in the caudate lobe. A catheter was inserted into the right hepatic artery, and the right hepatic artery was ligated with the catheter. From 2 weeks after operation, CDDP (20 mg) and 5-FU (1,500 mg) were given weekly by infusion from the arterial root. As a result, the serum CEA level fell to 3.6 ng/ml on June 26, 1996, and 1.9 mg/ml on August 14, 1996. A right lobectomy would have been performed if no metastasis appeared in the remainder of the left lobe over a one-year period. However, no foci were detected on a CT scan on March 26, 1997. This new two-part therapy warrants detailed investigation for bilobar bilateral liver metastases of colorectal cancer.

Aged↗

Entactin modulates the attachment of rabbit corneal epithelial cells.

PURPOSE: To understand the biological activity of entactin, a component of the basement membrane of the corneal epithelium, we investigated the ability of rabbit corneal epithelial cells to attach to an entactin matrix and the effect of entactin on the cells' attachment to other corneal basement proteins. METHODS: Multiwell plastic plates were coated with bovine serum albumin (BSA), alone or with BSA and entactin, laminin, fibronectin or collagen type IV. Cultured rabbit corneal epithelial cells were seeded on the plates. After incubation (usually 90 min), the cells were fixed and stained with 1% crystal violet. The number of attached cells was counted under a light microscope. RESULTS: The numbers of attached cells increased in proportion to both the incubation period and the concentration of entactin coated. Furthermore, the number of cells attached to the entactin-coated plate was greater than the number attached to the BSA-coated plate for each incubation period (30 to 120 min). Likewise, when laminin-coated plates were treated with entactin, the number of the attached cells increased in proportion to the concentration of entactin. However, entactin did not affect the cellular attachment of fibronectin or type IV collagen. Cellular attachment to entactin was partially inhibited by the cells' preincubation with the synthetic peptide (GRGDSP). CONCLUSIONS: The present results showed that cultured corneal epithelial cells adhere to entactin and that entactin stimulated the attachment of these cells to the laminin matrix. These findings suggest that entactin plays a specific role in maintaining the normal integrity of the corneal epithelium.

Amino Acid Sequence↗

[Combination of intra-hepatic arterial infusion of low-dose cisplatin and oral administration of high-dose doxyfluridine for patients with liver metastases of gastric cancer].

Three cases of gastric cancer with multiple liver metastases were treated with low-dose CDDP and high-dose 5'-DFUR after surgery. The regimen was 20 mg CDDP intra-hepatic arterial infusion per week and 1,200 mg 5'-DFUR oral treatment per day. The liver metastases of two cases responded to this chemotherapy with a reduction of more than 90%, and two cases lived more than 2 years. All of them lived more than one year. This therapy had few side effects and was performed ambulatorily once per week, so patients were able to maintain their quality of life. This combination therapy may well assure a better prognosis for patients with liver metastases of gastric cancer.

Administration, Oral↗

Strategy for breast conserving treatment--analysis of recurrence and prognosis after breast cosnserving treatment.

Two hundred and four patients with small breast cancer (T < or = 3.0 cm. N0 or N1a) were given breast conserving treatment (radiation group: 101, non-radiation group: 103) during the period from Feb. 1988 to Jan. 1995. Survival analysis of breast conserving treatment radiation group versus non-radiation group revealed the following: 1) Breast conserving treatment had a good prognosis, and a 5-year overall survival rate of 96.2%. 2) There was no significant difference of 5-year overall, disease-free and ipsilateral breast disease-free survival rate between the radiation group and non-radiation group. 3) Surgical margin involvement was the most significant risk factor in local recurrence after breast conserving treatment, and non-radiation was a possible risk factor. 4) Local recurrence was a significant risk factor for distant metastases after breast conserving treatment the same as node positive. These results suggested as follows: 1) Lumpectomy with a clear margin and radiation is the best choice for small breast cancer (T < or = 3.0 cm, N0 or N1a). 2) Adjuvant therapy after surgical treatment is necessary for local recurrence.

Axilla↗

[Evaluation of prophylactic hepatic arterial infusion chemotherapy after hepatectomy for metastases from colorectal cancer--the second report].

We followed 18 patients who underwent curative hepatectomy for metastatic carcinoma of the colon from March 1993 to March 1995, and investigated their survival and the effect of treatment on recurrence. The patients were randomly divided into two groups. Group A (n = 9) was given continuous 5-FU (500 mg x 4 days/week) for six weeks from 2 weeks after surgery via the hepatic artery and Group B (n = 9) was given 5-FU orally from 2 weeks after surgery. The cumulative one-, two-, and three-year survival was 88.9, 88.9, and 76.2% in Group A, while the one- and two-year survival was 100 and 80% in Group B. The one-, two-, and three-year disease-free survival was 77.8% in Group A, while the one- and two-year disease-free survival was 55.6 and 29.6% in Group B (p = 0.0369: Mantel-Cox). These findings suggest that continuous hepatic artery infusion of 5-FU is effective against post-hepatectomy recurrence of metastatic carcinoma of the colon.

Colorectal Neoplasms↗

[Effects of beta-adrenergic blockers on retinal circulation].

We evaluated the effects of 0.5% betaxolol hydrochloride and 0.5% timolol maleate on retinal blood flow. We measured the diameter of the retinal artery (Da) and vein (Dv), and retinal venous blood flow rate (V) in 8 healthy young volunteers by laser speckle velocimetry before and after the application of betaxolol or timolol topically to both eyes daily for one week. There were no any significant changes. Da before and after the application of betaxolol was 114.2 +/- 6.3 (mean +/- standard deviation) microns and 115.6 +/- 6.7 microns and before and after the application of timolol, 117.5 +/- 12.7 microns and 101.3 +/- 9.5 microns. Dv before and after the application of betaxolol was 149.5 +/- 11.1 microns and 148.4 +/- 13.3 microns, and before and after the application of timolol 148.5 +/- 9.2 microns and 146.2 +/- 10.3 microns. V before and after the application of timolol was 12.3 +/- 2.6 mm/s and 12.6 +/- 2.4 mm/s, and before and after the application of betaxolol, 11.6 +/- 1.5 mm/s and 11.4 +/- 2.1 mm/s. Thus one-week application of the beta-blockers, betaxolol and timolol did not change the retinal arterial or venous blood flow.

Adolescent↗

Morphological and biochemical characterization of mineralizing primary cultures of avian growth plate chondrocytes: evidence for cellular processing of Ca2+ and Pi prior to matrix mineralization.

Advances in the culture of mineralizing growth plate chondrocytes provided an opportunity to study endochondral calcification under controlled conditions. Here we report that these cultures synthesize large amounts of proteins characteristically associated with mineralization: type II and X collagens, sulfated proteoglycans, alkaline phosphatase, and the bone-related proteins, osteonectin and osteopontin. Certain chondrocytes appeared to accumulate large amounts of Ca2+ and Pi during the mineralization process: laser confocal imaging revealed high levels of intracellular Ca2+ in their periphery and X-ray microanalytical mapping revealed the presence of many Ca(2+)- and Pi-rich cell surface structures ranging from filamentous processes 0.14 +/- 0.02 microns by 0.5-2.0 microns, to spherical globules 0.70 +/- 0.27 microns in diameter. Removal of organic matter with alkaline sodium hypochlorite revealed numerous deposits of globular (0.77 +/- 0.19 micron) mineral (calcospherites) in the lacunae around these cells. The size and spatial distribution of these mineral deposits closely corresponded to the Ca(2+)-rich cell surface blebs. The globular mineral progressively transformed into clusters of crystallites. Taken with earlier studies, these findings indicate that cellular uptake of Ca2+ and Pi leads to formation of complexes of amorphous calcium phosphate, membrane lipids, and proteins that are released as cell surface blebs analogous to matrix vesicles. These structures initiate development of crystalline mineral. Thus, the current findings support the concept that the peripheral intracellular accumulation of Ca2+ and Pi is directly involved in endochondral calcification.

Animals↗

Up-regulation of integrin alpha 5 beta 1 expression by interleukin-6 in rabbit corneal epithelial cells.

Interleukin-6 (IL-6) has been shown to promote the attachment of rabbit corneal epithelial cells to fibronectin-coated substratum and ex vivo migration of the cells on the corneal stroma. To examine whether IL-6 promotes cell attachment through up-regulation of expression of integrin alpha 5 beta 1, i.e., the major cell surface fibronectin receptor, we quantified the levels of both alpha 5 and beta 1 subunit transcripts by reverse transcription-polymerase chain reaction in cultured rabbit corneal epithelial cells pretreated with various concentrations of IL-6. The levels of both alpha 5 and beta 1 mRNAs were dose-dependently elevated by IL-6, attaining 1.5- and 1.8-fold increases, respectively, at 10 ng/ml. The stimulatory effect of IL-6 was transient; the levels of both subunit mRNAs reached a maximum 1 h after the addition of IL-6 and returned to the basal levels after 6 h. The IL-6-induced up-regulation of integrin alpha 5 and beta 1 mRNAs was also confirmed by Northern blot analysis. These results indicate that the increased attachment of corneal epithelial cells to fibronectin and enhanced ex vivo migration on corneal stroma by IL-6 is, at least in part, due to the temporal up-regulation of integrin alpha 5 beta 1 expression in corneal epithelial cells.

Amino Acid Sequence↗

Transfer of allergic airway responses with antigen-primed CD4+ but not CD8+ T cells in brown Norway rats.

Activated CD4+ helper T cells have been demonstrated in asthmatic airways and postulated to play a central role in eliciting allergic inflammation; direct evidence of their involvement seems to be lacking. We hypothesized that CD4+ T cells have the potential to induce allergic responses to antigen challenge, and tested this hypothesis in a model of allergic bronchoconstriction, the Brown Norway rat, using the approach of adoptive transfer. Animals were actively sensitized to either ovalbumin (OVA) or BSA and were used as donors of T cells. W3/25(CD4)+ or OX8(CD8)+ T cells were isolated from the cervical lymph nodes of sensitized donors and transferred to naive BN rats. 2 d after adoptive transfer recipient rats were challenged by OVA inhalation, and changes in lung resistance (RL), bronchoalveolar lavage (BAL) cells, and serum levels of antigen-specific IgE were studied. After OVA challenge recipients of OVA-primed W3/25+ T cells exhibited sustained increases in RL throughout the entire 8-h observation period and had significant bronchoalveolar lavage eosinophilia, which was detected by immunocytochemistry using an antimajor basic protein mAb. Recipients of BSA-primed W3/25+ T cells or OVA-primed OX8+ T cells failed to respond to inhaled OVA. OVA-specific immunoglobulin E was undetectable by ELISA or skin testing in any of the recipient rats after adoptive transfer. In conclusion, antigen-induced airway bronchoconstriction and eosinophilia were successfully transferred by antigen-specific W3/25+ T cells in Brown Norway rats. These responses were dependent on antigen-primed W3/25+ T cells and appeared to be independent of IgE-mediated mast cell activation. This study provides clear evidence for T cell mediated immune mechanisms in allergic airway responses in this experimental model.

Allergens↗

Thermal stability of mineralized and demineralized dentin: a differential scanning calorimetric study.

The purpose of this study was to determine the difference, if any, in the thermal stability of collagen in mineralized and demineralized dentine compared to that in unmineralized tissues, using differential scanning calorimetry, DSC. Human tooth dentin blocks, about 1 x 1 x 2 mm in size, were used in this study. Some dentin blocks were demineralized using a Plank Rychlo solution; others, using EDTA solution. The mineralized dentin showed an exothermic peak at about 310 degrees C and the combustion of organic materials was completed at about 450 degrees C. For the demineralized dentin, the combustion was completed at higher temperature range and showed a strong exothermic peak at about 470 degrees C. An exotherm at the temperature between 450 degrees C and 470 degrees C was also observed in DSC pattern of native type I collagen from calf skin and rat tail tendon. DSC pattern of rat tail collagen showed a close similarity to that of the demineralized dentin. Statistically, the same heat flow value was obtained both from the mineralized dentin and the demineralized dentin and from the native type I collagen. These findings indicated that the thermal stability of collagen in dentin is lower than collagen in uncalcified connective tissue. It is suggested that in calcified collagen, the apatite crystallites may have intruded into spaces of the crosslinks of intra- and inter-fibrils, and in so doing, destroyed the crosslinks.

Animals↗