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Biomedical subjects

M Yasunaga

Publications and source records attributed to M Yasunaga.

At least 19 recordsLinked to original sources
PubMed1998

Ultrastructural study of development of hepatic necrosis induced by TNF-alpha and D-galactosamine.

Recent studies have suggested an association between tumor necrosis factor-alpha (TNF-alpha) and the development and progression of acute liver failure. To investigate the role of TNF-alpha in the mechanism of massive hepatic necrosis, we studied a mouse model of TNF-alpha and D-galactosamine (GalN) -induced hepatic necrosis by ultrastructural analysis. Administration of GalN caused edema of hepatocellular microvilli and widening of sinusoidal endothelial fenestrae (SEF); administration of TNF-alpha caused only a widening of the SEF. Massive hepatic necrosis with hemorrhage was seen 6 hr after concomitant administration of TNF-alpha and GalN. In the ultrastructural analysis, edema of the hepatocellular microvilli, widening of the SEF, and transmigration of red blood cells (RBC) and platelets to the space of Disse without exfoliation and necrosis of the sinusoidal endothelial cells were observed. Fibrin deposits were seen in areas adjacent to injured hepatocytes. The diameter of the SEF was significantly greater than in the nontreated group and the groups treated with TNF-alpha or GalN alone. These results suggest that as a consequence of the increase in diameter of the SEF, transmigration of RBCs and platelets to the space of Disse may have resulted in massive hepatic necrosis due to occlusion of the microcirculation.

Animals↗
PubMed1998

Clinical aspects of total colectomy--laparoscopic versus open technique for familial adenomatous polyposis and ulcerative colitis.

Clinical aspects of laparoscopy combined total colectomy (LTC) (n = 10) and open total colectomy (OTC) (n = 29) with ileorectal anastomosis for familial adenomatous polyposis and ulcerative colitis are compared in a retrospective study. The mean operative time was 282 (range, 169 to 420) minutes in the LTC group and 274 (range, 139 to 570) minutes in the OTC group. The mean volume of operative blood loss was 321 (range, 52 to 728) ml and 471 (range, 48 to 1040) ml for the LTC and OTC groups, respectively. Nasogastoric tube could be removed after POD 1.2 vs. 5.8 (p < 0.05), the mean time to passage of stool was 1.9 (range, 1 to 3) vs. 5.2 (range, 3 to 7) days (p < 0.01), and in the LTC group watery stool was soon made solidification after POD 23.4 vs. 84.1 (p < 0.01). Laparoscopy combined total colectomy may prove to have one-stage restorative total colectomy without a temporary ileostomy due to early solidification of watery stool and more benefits than conventional open surgery.

Adenomatous Polyposis Coli↗
PubMed1998

Functional outcome of double-stapled and transanal ileal pouch-anal anastomosis after proctocolectomy.

Improvement of functional outcome after proctocolectomy for ulcerative colitis and familial adenomatous polyposis was compared between transanal ileal pouch-anal anastomosis (T-IAA group, n = 29) and double-stapled ileal pouch-anal anastomosis (DS-IAA group, n = 8). Clinical functions were evaluated using a functional scoring system, and physiologic functions by anorectal manometry after one year postoperatively. Although in the T-IAA group 4 of the 29 patients (13.8%) displayed partial incontinence (< 9 points), all of 8 patients in the DS-IAA group showed good results referring to continence (> 10 points). The maximum resting pressure was 44.3 +/- 5.2 cmH2O in the T-IAA group vs. 56.6 +/- 5.8 cmH2O in the DS-IAA group, and postoperatively the maximum squeezing pressure was 96.8 +/- 9.2 cmH2O in the T-IAA group vs. 106.3 +/- 8.1 cmH2O in the DS-IAA group. There was a significant difference of maximum resting pressure and no significant difference of maximum squeezing pressure between the two groups. The length of the high pressure zone in the anal canal was significantly shorter in patients of the T-IAA group (2.1 +/- 0.8 cm) than in those of the DS-IAA group (3.5 +/- 1.1 cm) (p < 0.05). The DS-IAA is associated with excellent objective physiologic and subjective functional results. This reflects the sacrifice of the internal anal sphincter 1.5 cm cephalad necessary to effect this anastomosis at a mean of 1.4 cm from the dentate line.

Adolescent↗
PubMed1998

Transsacral rectopexy for complete rectal prolapse.

A prospective study was carried out to analyze the clinical and functional results of transsacral rectopexy with a DEXON mesh in the elderly or poor risk patients with complete rectal prolapse. Six patients with complete rectal prolapse were operated from 1994 to 1996. All patients could be traced for examination with anorectal manometry and defecography. None of the patients had recurrence for the longest three years. In postoperative clinical symptoms, fecal incontinence score recovered from the preoperative mean score of 3.8 to the postoperative 1.2 and constipation was improved in 4 out of 5 cases (80.0%). Straining anorectal angle (S-ARA) by defecography improved from the preoperative value of 120.6 +/- 6.9 degrees to the postoperative value of 98.5 +/- 3.5 degrees (p < 0.05) and the perineal descent (PD) improved from the preoperative value of 16.2 +/- 2.5 cm to the postoperative value 8.1 +/- 1.3 cm (p < 0.05). Maximal resting pressure (MRP) increased from the preoperative value of 20.5 +/- 3.7 cmH2O to the postoperative value of 40.5 +/- 4.8 cmH2O (p < 0.05). Transsacral rectopexy with DEXON mesh for complete rectal prolapse is useful as this technique is simple to conduct, can be applied to the elderly or poor risk patients, replaces rectal prolapse, improves defecation troubles and recovers fecal incontinence.

Aged↗
PubMed1998

Intraductal ultrasonography for treatment of Tis and T1 colorectal cancer.

The aim of the study was to determine the treatment for Tis and T1 colorectal cancer and the depth of cancer invasion which was examined preoperatively by intraductal ultrasonography (IDUS) using a 20 MHz high frequency thin sonoprobe. IDUS was performed on 62 patients with Tis and T1 colorectal cancer using 20 MHz radial images. The tumors imaged by IDUS were classified into 3 groups according to the degree of lesions in the 5 layers of the large intestinal wall: Tis showing no changes in the third layer, T1 with slight invasion in which the ruptured region in the third layer occupied less than 50% of the tumor diameter, and T1 with massive invasion in which the ruptured region in the third layer occupied more than 50% of the tumor diameter. The correct preoperative diagnosis of the depth of the lesions was obtained in 21 of the 23 patients with Tis (91.3%), in 18 of the 21 patients with T1 with slight invasion (85.7%), and in 8 of the 11 patients with T1 with massive invasion (72.7%). In conclusion, IDUS can be used for endoscopic examination of the large intestinal cancer to judge whether local treatment or not.

Colonoscopy↗
PubMed1998

Endoscopic removal with clipping for colonic lipomas.

Endoscopic removal of colonic lipoma of 2 cm in size or more is not widely used because of the risk of complications which are a hemorrhage and a perforation associated with endoscopic resection. We report here safety endoscopic removal using a bipolar snare and clipping the mucosa of the defective region in three cases with large colonic lipoma. We consider that this technique enhanced the safety of the endoscopic procedure.

Aged↗
PubMed1997

The effect of wedged insoles on the thrust of osteoarthritic knees.

We describe a method of quantifying the lateral/medial thrust of the knee which occurs in the early phase of walking. We have used this method to evaluate the effects of wedged insoles on the lateral and medial thrust for normal knees and knees with unicompartment osteoarthritis (OA). A laterally elevated (valgus) insole decreased the lateral thrust of both normal and osteoarthritic knees. A medially elevated (varus) insole increased the lateral thrust. In 50 symptomatic knees with medial compartment OA, decreasing the lateral thrust with a valgus insole reduced pain on walking in 27. Patients whose pain was reduced by valgus insoles tended to have earlier OA and to have a significantly greater reduction in the lateral thrust than in the 23 remaining unaffected knees. A varus insole was effective in decreasing the medial thrust and reducing pain in all ten knees with lateral compartment OA. We recommend the use of valgus insoles for patients with painful early medial compartment OA and the use of varus insoles for lateral compartment OA.

Acceleration↗
PubMed1996

Electron microscopic evidence of impaired intramembrane particles and instability of the cytoskeletal network in band 4.2 deficiency in human red cells.

To obtain direct evidence of impaired intramembrane particles (IMPs) and a deranged cytoskeletal network in situ in human red cells of band 4.2 deficiency, electron microscopic studies were performed utilizing the freeze fracture method for IMPs and the quick-freeze deep-etching method for the cytoskeletal network. Three patients with three different previously identified mutations of the band 4.2 gene, i.e., band 4.2 Komatsu (homozygous; codon 175 GAT --> TAT), band 4.2 Nippon (homozygous; codon 142 GCT --> ACT), and band 4.2 Shiga (compound heterozygous; codon 317 CGC --> TGC and codon 142 GCT --> ACT), were selected for this study. The decrease in the number of IMPs with increase in their size was most marked in band 4.2 Komatsu, which was clinically most severe with no band 4.2 protein. In this regard, in band 4.2 Nippon, which showed moderate severity in clinical hematology with a nearly missing band 4.2 protein, increased sizing was less marked. The abnormalities in IMPs were the least in band 4.2 Shiga, which demonstrated compensated hemolysis with band 4.2 protein in a trace amount. The extent of the impairment of IMPs may be reflected by the total absence or the presence of band 4.2 protein even in a trace amount and/or by the specific site(s) of the mutation of the band 4.2 gene. Derangement of the cytoskeletal network was also observed in these three patients. It was most abnormal in band 4.2 Komatsu, and less so in band 4.2 Nippon and in band 4.2 Shiga. These results clearly indicate that 1) band 4.2 plays an important role not only in its binding to band 3 but also to the skeletal network (mostly to spectrins) vertically, and 2) its deficiency produces critical abnormality in maintenance of the structural and functional integrity of the integral proteins (such as band 3), as well as the cytoskeletal network.

Amino Acid Sequence↗
PubMed1996

Hepatocyte proliferation induced in rats by lead nitrate is suppressed by several tumor necrosis factor alpha inhibitors.

Lead nitrate induces liver cell proliferation in rats without accompanying liver cell necrosis. However, the mechanism of this proliferation and its effect on hepatocytes remain unknown. Therefore, we examined the liver and blood level of hepatocyte growth factor and tumor necrosis factor alpha (TNF-alpha) at various intervals to determine whether lead nitrate modifies hepatocyte proliferation by altering the production of these cytokines. We also administered several TNF-alpha inhibitors, dexamethasone, adenosine, (2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2- propenoic acid (E 3330), and pentoxifylline, to rats to clarify whether pretreatment with these inhibitors suppresses the increase of TNF-alpha messenger RNA (mRNA) in the liver and prevents the hepatocyte proliferation induced by lead nitrate. Hepatocyte proliferation occurred by 24 hours and reached a peak 48 hours after a single intravenous injection of lead nitrate (100 mumol/kg). TNF-alpha mRNA expression in the liver was increased 1, 6, and 12 hours after the injection, whereas no alteration was observed in liver or blood level of hepatocyte growth factor. Pretreatment with dexamethasone (4.0 mg/kg), E3330 (100 mg/kg) adenosine (0.3 mmol/kg), and pentoxifylline (100 mg/kg), inhibited both TNF-alpha mRNA expression and hepatocyte proliferation 48 hours after the injection. These experimental results strongly support the hypothesis that TNF-alpha positively regulates the hepatocyte proliferation induced in rats by the mitogen, lead nitrate.

Adenosine↗
PubMed1996

Expression of hepatocyte growth factor, transforming growth factor alpha, and transforming growth factor beta 1 messenger RNA in various human liver diseases and correlation with hepatocyte proliferation.

Hepatocyte growth factor (HGF) and transforming growth factor alpha (TGF-alpha) stimulate liver regeneration, whereas transforming growth factor beta 1 (TGF-beta 1) inhibits it in rats. However their significance in human liver diseases, especially in severe acute liver injury, remains unclear. We studied HGF, TGF-alpha, and TGF-beta 1 messenger RNA (mRNA) expression in the livers of patients with live diseases using a competitive reverse transcriptase polymerase chain reaction. As little as a twofold difference in mRNA expression could be detected from minute liver biopsy samples. We then examined cell proliferation using proliferating cell nuclear antigen (PCNA) staining. HGF mRNA levels were significantly higher (approximately threefold) in acute hepatitis (AH) than in exacerbation of chronic liver disease (EX) (P < .05). TGF-alpha mRNA levels were significantly greater in AH (approximately twofold) than EX (P < .05), and the levels were significantly higher (approximately threefold) in chronic hepatitis (CH) than in EX (P < .05). The TGF-beta 1 mRNA levels in all the groups were not significantly different. In acute liver injury (AH and EX), there was a significant correlation between HGF mRNA expression and the PCNA labeling index (LI) in the liver (r = .87, P < .005). TGF-alpha mRNA expression also correlated with the PCNA LI (r = .92,P < .0001). There was no significant correlation between the serum HGF and the PCNA LI in the liver. In conclusion, HGF and TGF-alpha produced in the liver stimulate hepatocyte proliferation in response to acute liver injury in humans.

Base Sequence↗
PubMed1996

Involvement of Fyn tyrosine kinase in progression of cytokinesis of B lymphocyte progenitor.

We analyzed the role of Fyn tyrosine kinase in cell cycle progression of B lymphocyte progenitor (pro B cell). Whereas there were no substantial defects in the intramarrow B cell genesis in the fyn(-) mouse, and long-term proliferation of fyn(-) pro B cells was maintained in vitro under a serum containing culture condition, the cell cycle was arrested at G2/M upon serum deprivation. Morphological analyses demonstrated that the cytokinesis of fyn(-) pro B cells was retarded in the presence of serum and that the entry of fyn(-) pro B cells into late telophase was completely blocked under the serum-free condition. In contrast, the earlier phases of mitosis of fyn(-) pro B cells proceeded normally without FCS. This failure to initiate late telophase resulted in the accumulation of elliptical binucleated cells that might be the outcome of the nuclear division without cytokinesis. Consistent with this defect in the progression of cytokinesis, Fyn was localized in the midspace of dividing pro B cells at anaphase. These results suggested that Fyn localizes at the midspace of dividing pro B cells and regulates the progression of cytokinesis.

Animals↗
PubMed1996

Role of IL-7 and KL in activating molecules controlling the G1/S transition of B precursor cells.

While chemically defined conditions for culturing normal tissue have been attained for only a few cell types, the sustained proliferation of B precursor cells expressing IL-7 receptor and c-Kit can be supported under chemically defined conditions containing recombinant IL-7 and the ligand for c-Kit (KL). To understand the biochemical basis of the cell cycle progression of B precursor cells proliferating under these conditions, we investigated the correlation between growth factor stimulation and CDK4 activity. Consistent with our findings that IL-7 regulates the G1/S transition, while KL has only a little role in this process, the kinase activity of CDK4 was related closely with IL-7 stimulation but not KL stimulation. We investigated the mechanism underlying CDK4 activation in the IL-7 stimulated B precursor cells. Our results showed that (i) CDK4 and cyclin D3 are the G1/S regulators in B precursor cells; (ii) their expression levels are unchanged between the cells in G1 arrest and cycling cells; and (iii) they are present in an associated form even when the cell cycle stage is arrested at G1. Thus, the regulation of the expression of CDK4 and cyclin D3 or regulation of their assembly are not the mechanisms for activating CDK4 in the B precursor cells. On the other hand, a number of molecules co-immunoprecipitated with CDK4 were enhanced in the lysate of IL-7-stimulated B precursor cells. Thus, we present a possibility that CDK4 activation might be regulated by molecules associated with the CDK4-cyclin D3 complex in IL-7-dependent manner.

B-Lymphocytes↗
PubMed1996

[Mechanisms of enhanced erythrocyte destruction in patients with erythrocyte membrane disorders].

Factors causing erythrocyte destruction in patients with congenital erythrocyte membrane disorders include 1) decreased cell deformability, 2) increased cell viscosity, 3) decreased membrane stability, 4) increased intracellular Ca2+ concentrations, 5) changes in membrane permeability, 6) extracellular conditions such as hypoxia and acidic pH, or 7) hypersplenism. erythrocytes with shape changes due to abnormality of membrane skeleton lose deformability to negotiate the interendothelial slits into the splenic venous sinus, and stagnate within the cordal space where metabolic stress reduces membrane stability. Thereafter, erythrocytes are ingested by cordal macrophages, resulting in extravascular hemolysis.

Anemia, Hemolytic, Congenital↗
PubMed1996

[The study of lateral thrust of the knee in normal and osteoarthritic knees--evaluation with an accelerometric technique].

An accelerometric method was performed on 30 normal and 148 osteoarthritic (OA) knees to clarify sideways movement of the knee (lateral thrust) which occurs suddenly in the early stance phase of walking. Three thrust patterns were observed: (1) lateral thrust (LT) pattern, (2) medial thrust (MT) pattern, (3) unclassifiable (U) pattern. LT, MT and U patterns were observed in 66.7, 26.6, 6.7% respectively of the 30 normal knees; 76.6, 0, 23.4% of the 137 medial compartmental OA knees, and 0, 45.5, 54.5% of the 11 lateral compartmental OA knees. Descending steps and slope, increased walking speed, and walking with a heavy (20 Kg) object on the shoulders, all significantly increased the first peak of acceleration compared with the usual level walking in both normal and OA knees. However, the rate of increase was significantly greater in OA than in normal knees. A laterally elevated wedged-insole (LWI) decreased the first peak of lateral acceleration, whereas a medially elevated wedged-insole (MWI) increased it. In OA knees, effectiveness of the insole was well correlated with a degree of a reduction in the first peak value of acceleration. Although the LWI caused changes in the magnitude of the lateral acceleration, none of the insoles changed the accelerographic patterns, suggesting their limited effects on the lateral thrust. Clinically properly performed high tibial osteotomy (HTO) showed much greater restraining effects on the lateral thrust of the knee than any insoles, since HTO changed the LT pattern of the 25 medial OA knees to either the MT pattern (72%) or U pattern (28%).

Acceleration↗
PubMed1995

Cell cycle control of c-kit+IL-7R+ B precursor cells by two distinct signals derived from IL-7 receptor and c-kit in a fully defined medium.

An important goal for the investigation of the proliferation of mammalian cells is to establish a fully defined condition for culturing them in vitro. Here, we report establishment of a fully defined culture condition that supports the primary culture of normal c-kit+IL-7 receptor (IL-7R)+ B precursor cells without the aid of stromal cell lines. This defined culture condition contains IL-7, the ligand for c-kit, transferrin, insulin, and bovine serum albumin as protein components. By using the cell lines derived from RAG2(-/-) mice, which do not differentiate into c-kit- stage, we have evaluated the role of each protein in the cell cycle progression of c-kit+IL-7R+ B precursor cells. Since B precursor cells can grow without insulin, c-kit remains a sole functional receptor tyrosine kinase for their growth. While both c-kit ligand (KL) and IL-7 are the requisite molecules for sustained proliferation of B precursor cells, each molecule plays distinct roles. IL-7 starvation results in prompt arrest of the cells at G1. An accumulation of the cells in the mitotic phase was also detected. Thus, the major role of IL-7 is to regulate the G1/S transition and the process of cytokinesis of B precursor cells. Although prolonged KL starvation over 48 h resulted in accumulation of G1 cells, its effect could not be detected within 24 h, which is long enough for all the cells to complete one cell cycle. This suggests that KL might be involved in the cell cycle progression of B precursor cells in a manner that its signal could still be effective in the one or two cell cycles that follow. Although molecular nature of the signals underlying the present observation awaits future investigation, the method described in this report would provide a useful model system for investigating the signaling pathways that are involved in the cell cycle progression of B precursor cells.

Animals↗
PubMed1995

Making the in-vitro model closer to actual B lymphopoiesis in the bone marrow.

After more than a decade since Whitlock and Witte established an in-vitro long-term culture of bone marrow B lineage cells, c-kit+IL-7-receptor(R)+B precursor cells in fresh bone marrow are now able to be grown under a fully defined culture condition containing only BSA, transferrin, IL-7 and the ligand for c-kit(Kit-ligand;KL) as protein components. On the other hand, previous studies indicated that the actual intramarrow B-cell-genesis is a complex process involving multiple stromal cell-derived molecules. Thus, the next step for the culture of B-cell genesis is to develop this simple culture into a new defined culture of B-cell-genesis that is closer to the actual process. In this article, we will describe how this defined culture condition has developed from the original Whitlock-Witte type culture, how the B precursors under this culture-condition are different from that in the bone marrow, and finally our biased view on the future direction to which this defined culture should develop.

Animals↗