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Biomedical subjects

T Ikegami

Publications and source records attributed to T Ikegami.

At least 37 records · Page 2Linked to original sources

Experimental study of a type 3 phosphodiesterase inhibitor on liver graft function.

BACKGROUND: The number of liver transplant recipients is increasing but donor organ shortages have become more severe. The effect of milrinone, a type 3 phosphodiesterase inhibitor (PDEI), on non-heart-beating donor grafts was evaluated using an orthotopic liver transplantation model in rats. METHODS: Type 3 PDEI or normal saline (control group) was given intravenously to the donor animals for 60 min continuously (50 microg kg-1 min-1 ) before 60 min of warm ischaemia followed by cold preservation and subsequent transplantation. Survival, serum chemistry, bile output, histopathological findings and tissue cyclic 3',5'-adenosine monophosphate (cAMP) concentrations were then compared. RESULTS: Five of seven animals in the PDEI group were alive at 7 days, compared with only one of seven rats in the control group (P < 0.01). Serum levels of alanine aminotransferase 2 and 6 h after reperfusion, and hyaluronic acid levels 6 h after reperfusion, were significantly lower in the PDEI group than in the control group. Bile output from the transplanted graft was significantly greater in the PDEI group than in controls 2 h after reperfusion (P < 0.01). The mean necrotic area 6 h after reperfusion was also reduced in the PDEI-treated grafts (P < 0.01). cAMP levels in liver tissue at the end of both warm and cold ischaemia, and 2 and 6 h after reperfusion, were significantly higher in the PDEI group compared with those in the control group. CONCLUSION: Type 3 PDEI attenuated the graft injury caused by warm and cold ischaemia and subsequent reperfusion injury via an increase in intracellular cAMP levels. This treatment may be a novel pharmacological intervention for safe and efficient usage of liver grafts from non-heart-beating donors.

Animals↗

Changes in the caudate lobe that is transplanted with extended left lobe liver graft from living donors.

BACKGROUND: Caudate lobe transplantation with an extended left lobe graft is an innovative and promising method for increasing the graft volume in living donor liver transplantation. However, little is known about the fate of the caudate lobe after transplantation. METHODS: Eight extended left lobe grafts with the caudate lobe were included in this study. No attempt was made to reconstruct the short hepatic veins. On the basis of the computed tomography scans that were obtained before the operation and 1 month after the transplantation, the increase in the graft volume by the addition of the caudate lobe and the changes in the transplanted caudate lobe were evaluated. RESULTS: The addition of the caudate lobe increased the graft volume by 25 +/- 2 g, corresponding to a 2% increase in graft volume/standard liver volume ratio. One month after the transplantation, the caudate lobe volume increased in all patients but 1. The regeneration rate of the caudate lobe and other segments (segments II-IV) 1 month after transplantation was 62% +/- 24% (24 +/- 4 mL- 37 +/- 4 mL) and 152% +/- 35% (374 +/- 45 mL-930 +/- 65 mL), respectively (P <.01). CONCLUSIONS: This technique affords a modest increase in liver volume with living donor left liver procurement.

Humans↗

Small graft for living donor liver transplantation.

OBJECTIVE: To evaluate the impact of graft size on recipients in living donor liver transplantation (LDLT) to establish a clinical guideline for the minimum requirement. SUMMARY BACKGROUND DATA: Although the minimum graft size required for LDLT has been reported to be 30% to 40% of graft volume (GV)/standard liver volume (SLV), the safety limit of the graft size was unknown. METHODS: A total of 33 cases of LDLT, excluding auxiliary transplantation, were reviewed with a minimum observation period of 4 months. The 33 patients were divided into three groups according to GV/SLV: medium-size graft group, small-size graft group, and extra-small graft group. The effect of GV/SLV on graft function, graft regeneration, and survival was evaluated. RESULTS: The overall patient survival rate was 94% at a mean follow-up of 15 months with a minimum observation period of 4 months. There were no statistically significant differences in postoperative bilirubin clearance, alanine aminotransferase, prothrombin time, and frequency of postoperative complications among the three groups. One week after transplantation, the regeneration rate (GV at 1 week/harvested GV) in the extra-small and small groups was significantly higher than that of the medium group. The graft and patient survival rates were both 100% in the extra-small group, 75% and 88% in the small group, and 90% and 95% in the medium group. CONCLUSIONS: Small-for-size grafts less than 30% of SLV can be used with careful intraoperative and postoperative management until the grafts regenerate.

Adult↗

A study of factors influencing prognosis after resection of hepatic metastases from colorectal and gastric carcinoma.

OBJECTIVE: The aim of this study is to determine the absolute contraindication for hepatic resection for colorectal metastases and investigate the value of hepatectomy for gastric metastases by comparing it with the results of colorectal metastases performed with the same criteria. METHODS: A retrospective cohort study was conducted in patients undergoing hepatic resection for metastatic colorectal (n = 64) and gastric (n = 17) carcinomas. Common predictive factors for both metastases were analyzed by the stratified Cox proportional hazard model. In this model, the different baseline hazard was set for each disease, whereas the risk of each covariate was assumed to be equal in both gastric and colorectal metastases. RESULTS: Overall 1-, 2-, and 5-yr survival rates after hepatectomy for colorectal and gastric metastases were 90%, 73%, 42%, and 47%, 22%, 0%, respectively. Factors controlling prognosis were as follows: age > or = 60, extrahepatic metastases, serosal invasion, grade of lymph node metastases, tumor cell differentiation of the primary lesion(s), carcinoembryonic antigen level, tumor-exposed surgical margin, and blood transfusion. In particular, presence of extrahepatic metastases showed the markedly high-risk ratio among these eight variables. CONCLUSIONS: Hepatectomy, if possible, is indicated in patients with hepatic metastases from colorectal carcinoma if there are no extrahepatic metastases and if the primary disease is controlled. It is indicated only in carefully selected patients with metastases from gastric carcinoma.

Adult↗

Detection of Ebola viral antigen by enzyme-linked immunosorbent assay using a novel monoclonal antibody to nucleoprotein.

With the increase in international traffic, the risk of introducing rare but severe infectious diseases like Ebola hemorrhagic fever is increasing all over the world. However, the system for the diagnosis of Ebola virus infection is available in a limited number of countries. In the present study, we developed an Ebola virus antigen-detection enzyme-linked immunosorbent assay (ELISA) system using a novel monoclonal antibody (MAb) to the nucleoprotein (NP). This antibody recognized an epitope defined by a 26-amino-acid stretch near the C terminus of NP. In a sandwich ELISA system with the MAb, as little as 30 ng of purified recombinant NP (rNP) was detected. Although this MAb was prepared by immunization with rNP of subtype Zaire, it also reacted to the corresponding region of NP derived from the Reston and Sudan subtypes. These results suggest that our ELISA system should work with three of four Ebola subtypes. Furthermore, our ELISA system detected the NP in subtype Reston-infected monkey specimens, while the background level in noninfected specimens was very low, suggesting the usefulness of the ELISA for laboratory diagnosis with clinical specimens.

Animals↗

Type II (adult onset) citrullinaemia: clinical pictures and the therapeutic effect of liver transplantation.

OBJECTIVE: Adult onset type II citrullinemia is an inherited disorder of amino acid metabolism caused by a deficiency of liver specific argininosuccinate synthetase activity. Most of the patients with this disease were reported in Japan and therefore, this disease has not been well recognised outside this country. The detailed clinical pictures of the patients with type II citrullinaemia are reported and their outcomes after liver transplantation referred to. METHODS: Ten patients with this disease were evaluated. Seven of them underwent liver transplants using a graft obtained from a healthy family member. RESULTS: There were six men and four women; the age of onset of encephalopathy ranged from 17 to 51 years. The initial symptom in nine patients was sudden onset disturbance of consciousness, and one patient had long been regarded as having a chronic progressive psychotic illness. High concentrations of plasma citrulline and ammonia were commonly seen on admission. Although brain CT or MRI lacked any consistent findings, the EEG was abnormal in all patients, showing diffuse slow waves. Additionally, in five patients chronic pancreatitis preceded the onset of encephalopathy. After liver transplantation the metabolic abnormalities, including abnormal plasma concentrations of citrulline and ammonia, were immediately corrected and all neuropsychic symptoms soon disappeared, except for impaired cognitive function in one patient. Six out of these seven patients returned to their previous social lives, including work. CONCLUSIONS: The clinical concept of adult onset type II citrullinaemia coincides well with the range of hepatic encephalopathy, and liver transplantation is a very promising therapeutic approach.

Adolescent↗

Modulation of glucagon receptor expression and response in transfected human embryonic kidney cells.

The modulation of glucagon receptor (GR) expression and biological response was investigated in human embryonic kidney cell (HEK-293) clones permanently expressing the GR with different densities. The GR mRNA expression level in these clones was upregulated by cellular cAMP accumulation and presented a good correlation with both the protein expression level and the maximum number of glucagon binding sites. However, the determination of glucagon-induced cAMP accumulation in these cell lines revealed that the enhancement of receptor expression did not lead to a proportional increase in cAMP formation. Under these conditions, the maximum cAMP production induced by NaF and forskolin was not significantly different among selected clones, regardless of the receptor expression level. High receptor-expressing clones showed the greatest susceptibility for agonist-induced desensitization compared with clones with lower GR expression levels. The results of the present study suggest that the GR can recruit non-GR-specific desensitization mechanism(s). Furthermore, the partial inhibition or alteration of the overall cAMP synthesis pathway at the receptor level may be a necessary adaptive step for a cell in response to a massive increase in membrane receptor expression level.

8-Bromo Cyclic Adenosine Monophosphate↗

Primary sclerosing cholangitis complicated with idiopathic thrombocytopenic purpura.

We present a 66-year-old woman with primary sclerosing cholangitis (PSC) complicated with idiopathic thrombocytopenic purpura (ITP). Both PSC and ITP are considered to reflect an immunological disturbance. However, their coexistence is very rare and to the best of our knowledge this is only the second reported case. In Japan, PSC patients are rarely treated with liver transplantation. Fortunately, the present patient underwent successful hepatic transplantation from a brain-dead donor and simultaneous splenectomy. This case emphasizes the importance of liver transplantation as an effective treatment for primary sclerosing cholangitis.

Aged↗

[An autopsy case of idiopathic interstitial pneumonia with diffuse alveolar hemorrhage due to acute exacerbation].

There has hitherto been no report describing idiopathic interstitial pneumonia associated with diffuse alveolar hemorrhage, but we herein report one such rare case. A 75-year-old man who had received a diagnosis of idiopathic interstitial pneumonia had been followed in our hospital since 1995, and had been treated with cyclophosphamide since September 1999. He discontinued taking cyclophosphamide without informing us, and two months later he was admitted to our hospital with deterioration of dyspnea on September 13, 2000. Since chest radiography and CT findings demonstrated alveolar infiltrates in the right middle lung field, he was treated with antibiotic agents. Although no deterioration of symptoms occurred, on September 14 he began to suffer rapidly progressive dyspnea accompanied with production of bloody sputum, which eventually developed into full-blown hemoptysis in the evening of September 15. He died of respiratory failure early the next morning. The autopsy findings demonstrated diffuse alveolar hemorrhage, diffuse alveolar damage, interstitial pneumonia, and pulmonary fibrosis.

Aged↗

The impact of donor age on living donor liver transplantation.

BACKGROUND: The impact of the age of the donor on the outcome of living related liver transplantation is yet to be clarified. METHODS: During October 14, 1996 and December 20, 1999, 34 living related liver transplantations were performed. Of these, 26 cases were performed using the extended left lobe graft, which were classified into three groups; younger donor group (group Y, donor age < 30, n = 7), middle-aged donor group (group M, 30 < or = donor age <50, n=13), and older donor group (group O, donor age < 50, n = 6). Early allograft function and regeneration were compared between these groups. RESULTS: There was no difference in standard liver volume, and predicted or harvested graft size between the three groups. Although serum transaminase and total bilirubin levels within postoperative day 7 were not different between the groups, the prothrombin time on postoperative day 3 was significantly longer in group O than in group Y. One week after transplantation, group Y had significantly greater graft/standard liver volume ratio than group O, and greater graft volume than group M and O. One month after transplantation, however, there was no significant difference in such graft size parameters between the groups. Graft and patient survival were comparable between the three groups. CONCLUSION: Although function and regeneration of the allografts from older donors in living donor liver transplantation is worse than those of their younger counterparts, the outcome is not affected by the age of the liver.

Adult↗

Beneficial effect of FR167653 on cold ischemia/reperfusion injury in rat liver transplantation.

BACKGROUND: Proinflammatory cytokines such as interleukin 1-beta (IL-1beta) and tumor necrosis factor-a (TNF-alpha) play an important role in the development of hepatic ischemia/reperfusion injury. FR167653 has been characterized as a potent suppressant of IL-1beta and TNF-alpha production. The aim of this study was to evaluate the effect of FR167653 on cold ischemia/ reperfusion injury in rat liver transplantation. METHODS: Donor livers were preserved with cold University of Wisconsin solution for 48 hr and transplanted orthotopically. Immediately after reperfusion, FR167653 (1 mg/kg, FR-treated group) or normal saline solution (control group) was administered i.v.. The severity of liver injury was determined by hepatic enzyme levels as well as by histological findings. The accumulation of IL-1beta and TNF-alpha mRNA in the liver was analyzed by semi-quantitative reverse transcription-polymerase chain reaction. Tissue factor expression was subjected to immunohistochemical analysis. RESULTS: In the FR-treated group, release of aspartate aminotransferase and alanine aminotransferase after reperfusion was significantly lower (P<0.05 and P<0.02, respectively), and histological liver injury was less prominent, than in the control group. Accumulation of IL-1beta and TNF-alpha mRNA was suppressed in the FR-treated liver. Tissue factor expression on Kupffer cells and sinusoidal endothelial cells, marked in the control group, was almost absent in the FR-treated group. Seven-day survival in the FR-treated group (75%) was significantly better than that in the control group (12.5%) (P<0.01). CONCLUSIONS: These results indicate that treatment with FR167653 ameliorates cold ischemia/reperfusion injury in liver transplantation.

Animals↗

Domino liver transplantation from a living related donor.

BACKGROUND: Although domino liver transplantations (OLT) from cadaveric donors have been performed in about 50 cases since 1995, only one case in the Japanese literature has been reported on a domino OLT from a living related donor. The difficulties of the later surgery lie in the small size of the graft volume and the short length of the vascular cuffs in the graft. METHODS: The left lobe graft was procured from a 43-year-old younger brother of a familial amyloidotic polyneuropathy (FAP) patient. Next, the left lobe graft (510 g, 44% of the estimated standard liver volume of the FAP patient) was implanted into the 48-year-old female FAP patient. At surgery for the FAP patient, a sufficient length of the vascular cuffs was secured by an extended left lobe resection, although the right lobe graft was able to maintain sufficient vascular cuffs. The right lobe graft (720 g, 54% of the recipient's estimated standard liver volume) was then implanted in the 43-year-old male patient with liver cirrhosis and hepatocellular carcinoma (stage IV-A). RESULTS: The two recipients were discharged from the hospital 1 month after OLT. At 7 months after OLT, they are both doing well and the domino recipient is free of any tumor recurrence. CONCLUSION: A domino OLT from the living related donor can therefore be done safely when careful attention is paid to the graft volume and the length of the vascular cuffs for anastomosis.

Amyloid Neuropathies↗

Self-maintenance and self-reproduction in an abstract cell model.

Living cells must maintain their membranes by active metabolism. The membrane is not static but a dynamic structure that has evolved along with its internal reactions. When we reflect on the emergence and evolution of primitive cells, we should not forget the mutual dependency between membranes and metabolic cycles inside the cell. In this paper, we present a simple abstract model of the self-maintaining cell. A metabolic cycle will produce a self-assembling membrane that will enclose the metabolic cycle. We show that a self-maintaining cell has the potential to reproduce itself spontaneously. Further, we have demonstrated two different ways of cellular reproduction depending on the mobility of chemicals. In the first case, a cell releases autocatalytic chemicals that create new cells outside the mother cell. In the second case, a cell grows larger and divides itself into daughter cells by creating a new internal dividing membrane.

Animals↗

An alternative method of arterial reconstruction after hepatic arterial thrombosis following living-related liver transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) remains an important cause of graft loss after liver transplantation. Emergency rearterialization methods are limited in cases of living-related liver transplantation in which the graft hepatic artery is thin and short. CASE: A 19-year-old woman who underwent living-related liver transplantation for biliary atresia developed HAT on the 4th postoperative day. During the emergency laparotomy the recipient hepatic artery was found to be too short to anastomose, so the recipient's right gastroepiploic artery was anastomosed to the graft hepatic artery. The patient is now alive and well 6 months after reoperation, and she has experienced no further episode of HAT. CONCLUSION: The right gastroepiploic artery can be used easily and safely for hepatic graft revascularization without causing ischemia of the stomach. An additional skin incision is not required, and the artery is long enough to anastomose to the graft artery directly. The method of hepatic graft rearterialization described here is an important option for patients who undergo living-related or split liver transplantation.

Adult↗

Solution structure of the chitin-binding domain of Bacillus circulans WL-12 chitinase A1.

The three-dimensional structure of the chitin-binding domain (ChBD) of chitinase A1 (ChiA1) from a Gram-positive bacterium, Bacillus circulans WL-12, was determined by means of multidimensional heteronuclear NMR methods. ChiA1 is a glycosidase that hydrolyzes chitin and is composed of an N-terminal catalytic domain, two fibronectin type III-like domains, and C-terminal ChBD(ChiA1) (45 residues, Ala(655)-Gln(699)), which binds specifically to insoluble chitin. ChBD(ChiA1) has a compact and globular structure with the topology of a twisted beta-sandwich. This domain contains two antiparallel beta-sheets, one composed of three strands and the other of two strands. The core region formed by the hydrophobic and aromatic residues makes the overall structure rigid and compact. The overall topology of ChBD(ChiA1) is similar to that of the cellulose-binding domain (CBD) of Erwinia chrysanthemi endoglucanase Z (CBD(EGZ)). However, ChBD(ChiA1) lacks the three aromatic residues aligned linearly and exposed to the solvent, which probably interact with cellulose in CBDs. Therefore, the binding mechanism of a group of ChBDs including ChBD(ChiA1) may be different from that proposed for CBDs.

Amino Acid Sequence↗

Evolution of specificity in an immune network.

A dynamic antigen response of the immune network is discussed, based on shape-space modelling. The present model extends the shape-space modelling by introducing the evolution of specificity of idiotypes. When the amount of external antigen increases, a measure of stability of the immune network is lost and thus the network can respond to the antigen. It is shown that specific and non-specific responses emerge as a function of antigen amounts. A specific response is observed with a fixed-point attractor, and a non-specific response is observed with a chaotic attractor for the lymphocyte population dynamics. The network topology also changes between fixed-point and chaotic attractors. For some antigen amounts, chaotic attractors will vanish or become long-lived super-transient states. A dynamic bell-shaped response function will thus emerge. The relevance of long-lived chaotic transient states embedded in fixed-point attractors is discussed with respect to immune functions.

Animals↗

The correlation between P300 alterations and regional cerebral blood flow in non-demented Parkinson's disease.

P300 was evoked by a visual oddball and an S1-S2 task in 22 non-demented Parkinson's disease (PD) patients (13 in the early stage, nine in the late stage) and 18 normal controls. Reaction time was also measured. All patients undertook the (99)Tc-ECD SPECT examination. Quantitative regional cerebral blood flow (rCBF) was obtained by overlying SPECT image on the 3D-magnetic resonance image. In the PD patients in the late stage, P300 latency to S2-same and reaction time were significantly prolonged, while rCBF at bilateral frontal, temporal, and the right parietal lobes was decreased. P300 latency to S2-same was significantly correlated with the rCBF at bilateral temporal lobes. Reaction time was significantly correlated with the rCBF at the right frontal and parietal lobes, as well as the temporal and occipital lobes. The results suggest that P300 changes in non-demented PD in the late stage could be related to the temporal lobe dysfunction.

Aged↗