Biomedical subjects
Publications and source records attributed to M Endo.
Carotid endarterectomy (CEA) clearly benefits high stroke-risk patients with coronary or peripheral vascular disease, but its value of procedures is not still recognized for thoracic surgeons in Japan. Therefore we reviewed our technique of CEA and presented its usefulness and necessity.
Therapeutic hypothermia may improve outcome after severe head injury, but its efficacy has not been established in children with a severe head injury. The authors evaluated the effects of hypothemia (33-34 degrees C) in 9 severely closed head-injured children (under 16 years old). The cooling period was 3 to 21 days (mean 9.3). Hypothermia significantly reduced ICP when it reached 33-34 degrees C. From 3 to 6 months after injury, 6 (67%) of the 9 patients had good outcome (good recovery in 2 and moderate disability in 4), but 3 (33%) had poor outcome (severe disability in 2 and vegetative state in one). Complications, including infectious disorders (pneumonia, meningitis, sepsis), cardio-vascular system dysfunction (cardiac arrhythmia, hypotension), decreased platelet counts, hypokalemia, diabetes insipidus, acute pancreatitis occurred during hypothermia in 7 patients (78%). The results of this study suggest that treatment with hypothermia in children with severe head injury is often accompanied complications, but it is an effective method to control intracranial hypertension and may have improved the outcome.
Focal nodular hyperplasia of the liver is a lesion characterized by a well-circumscribed region of hyperplastic liver parenchyma and contains a stellate fibrous scar. The lesion is thought to be because of liver-cell hyperplasia that is caused by focal circulatory disturbances. We describe here a pediatric case of this lesion that provided direct histopathologic evidence of circulatory disturbances. We identified arterial and portal thrombi, as well as recanalization of arteries in the nodule. Hepatic necrosis was also seen in the lesion. We speculate that thrombosis of the hepatic artery and/or portal vein was the cause of hepatic necrosis and that reperfusion following hepatic arterial recanalization resulted in nodule formation. Although there was no stellate scar present in our case, the presence of bile ductular proliferation at the periphery of the nodule was helpful in distinguishing this lesion from adenoma and hepatocellular carcinoma. The early stage of nodular formation may explain the lack of a stellate scar in our case. The patient was treated earlier with actinomycin D and vincristine following surgical excision of Wilms' tumor. It is possible that such chemotherapy contributed to thrombosis in our case.
It is nearly 40 years since the introduction of coronary artery bypass grafting (CABG) in humans. A. Carrel (1910) attempted the first CABG in animals and G. Murray (1954) succeeded in performing experimental CABG using the internal mammary artery (IMA). The first reported CABG using the IMA in humans was performed by R. Goetz using the sutureless technique in 1960. V. Kolessov (1964) performed the first sutured bypass grafting using the IMA. From 1962 to 1967, human CABG using autogenous saphenous vein grafts was performed by D. Sabiston (1962). H. Garrett (1964), D. Kahn (1966), and R. Favaloro (1967). Saphenous vein grafting became the most common CABG technique for the next two decades. In Japan, Y. Sezai et al. performed CABG using the free femoral artery, we performed CABG using the IMA, and S. Asada et al. performed CABG using the saphenous vein in 1970. In 1986, F. Loop et al. reported that the long-term survival rate of CABG was significantly higher when the IMA rather than the saphenous vein was used. IMA grafting, supplemented by the gastroepiploic artery, inferior epigastric artery, and radial artery, has enabled complete arterial revascularization to be performed in almost all patients. In the graft selection for CABG, the first choice is the left IMA and the second choice is the right IMA. The third choice is the gastroepiploic artery and/or radial artery, depending on the target anastomotic site, degree of stenosis, size of the distal graft, and in situ or free use.
Leiomyosarcoma of the scrotum is a rare tumor. Up to 1999, only 29 cases have been reported in the literature worldwide. A 27-year-old man presented with a mass on the left side of the scrotum which had been painless and had gradually enlarged over the previous 10 years. During the following 3 months, however, it became painful and he was then referred to our hospital. Physical examination revealed a solid mass on the left side of the scrotum, measuring 7 cm in diameter, which was not adhering to the testis or to the vas deferens. The tumor was surgically resected. The histological examination confirmed the diagnosis of well differentiated leiomyosarcoma. Adjuvant therapy was considered unnecessary. The follow-up at 41 months revealed no local recurrence or distant metastasis.
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The antitumor activity of a novel nucleoside, 1-(2-deoxy-2-fluoro-4-thio-beta-D arabinofuranosyl)cytosine (4'-thio-FAC) was compared with that of 2'-deoxy-2',2'-difluorocytidine (gemcitabine). 4'-Thio-FAC showed potent antitumor effects against various solid cancer cell lines in vitro. Also, gemcitabine showed remarkable in vitro antitumor effects, even more potent than 4'-thio-FAC. However, 4'-thio-FAC inhibited tumor growth more strongly than gemcitabine did at the same dose against human cancer cells implanted s.c. in nude mice. In addition, 4'-thio-FAC suppressed the tumor growth by oral administration. The toxicity of 4'-thio-FAC was weaker than that of gemcitabine in nude mice in both consecutive and intermittent administration. Accordingly, clinical usefulness of 4'-thio-FAC is expected.
Thymidine phosphorylase (dThdPase) is an essential enzyme for the activation of the oral cytostatic drugs capecitabine (N(4)-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine, Xeloda(trade mark)) and its intermediate metabolite doxifluridine [5'-deoxy-5-fluorouridine (5'-dFUrd, Furtulon((R)))] to 5-fluorouracil (5-FUra) in tumors. In a previous study, we found that several cytostatics were able to up-regulate tumor levels of dThdPase in a human colon cancer xenograft model. In the present study, we confirmed that the administration of cytostatics used for breast cancer treatment, such as taxanes and cyclophosphamide (CPA), up-regulated the tumor level of dThdPase in mammary tumor models as well. Because the dThdPase up-regulation was observed even when CPA was given orally, we investigated further the usefulness of combination therapy with the 2 oral drugs, 5'-dFUrd/capecitabine and CPA in mammary tumor models. Daily oral administration of CPA up-regulated human dThdPase levels in the tumor tissue of mice bearing a human mammary tumor xenograft, MX-1, whereas in the small intestine and liver, it did not affect levels of pyrimidine nucleoside phosphorylases (PyNPase) including dThdPase and uridine phosphorylase. The preferential up-regulation of PyNPase activity in the tumor by CPA administration was also confirmed in mice bearing a syngeneic murine mammary adenocarcinoma, A755. In both models, combination therapy of 5'-dFUrd/capecitabine with CPA showed synergistic antitumor activity, without significant potentiation of toxicity. In contrast, treatment with CPA and either 5-FUra or UFT (a mixture of tegafur and uracil) in combination showed only additive activity. Our results suggest that CPA and capecitabine/5'-dFUrd, both available for oral administration, would be good partners, and that clinical trials with this drug combination against breast cancer are warranted.
Bisphenol A, an environmental oestrogenic chemical, was found to conjugate highly with glucuronic acid in male rat liver microsomes studied in vitro. In the various isoforms tested (1A1, 1A3, 1A5, 1A6, 1A7 and 2B1), glucuronidation of bisphenol A and of diethylstilboestrol, a synthetic crystalline compound possessing oestrogenic activity and known to be glucuronidated by liver microsomes, was catalysed by an isoform of UDP-glucuronosyltransferase (UGT), namely UGT2B1, which glucuronidates some endogenous androgens. UGT activity towards bisphenol A in liver microsomes and in UGT2B1 expressed in yeast AH22 cells (22.9 and 0.58 nmol/min per mg of microsomal proteins respectively) was higher than that towards diethylstilboestrol (75.0 and 4.66 pmol/min per mg of microsomal proteins respectively). UGT activities towards both bisphenol A and diethylstilboestrol were distributed mainly in the liver but were also observed at substantial levels in the kidney and testis. Northern blot analysis disclosed the presence of UGT2B1 solely in the liver, and about 65% of the male rat liver microsomal UGT activities towards bisphenol A were absorbed by the anti-UGT2B1 antibody. These results indicate that bisphenol A, in male rat liver, is glucuronidated by UGT2B1, an isoform of UGT.
Using the transglycosylation reaction of testicular hyaluronidase, reconstructions of hybrid glycosaminoglycans (GAGs) containing 6-sulfated (GalNAc6S), 4-sulfated (GalNAcS) and unsulfated N-acetylgalactosamine (GalNAc) were investigated. First, chondroitin 4-sulfate (Ch4S) as a donor containing GalNAc4S and the pyridylaminated (PA) chondroitin 6-sulfate (Ch6S) hexasaccharide as an acceptor containing GalNAc6S were subjected to transglycosylation reaction. Second, when the resulting PA-Ch6S(hexa-)-Ch4S(di-)octasaccharide and chondroitin (Ch) were used as an acceptor and as a donor containing GalNAc, respectively, a new decasaccharide having a hybrid structure composed of disaccharide units derived from Ch6S, Ch4S and Ch was reconstructed. Using a systematic combination of each donor and acceptor molecule, it was possible to reconstruct various types of hybrid GAGs.
PURPOSE: The irradiation system and biophysical characteristics of carbon beams are examined regarding radiation therapy. METHODS AND MATERIALS: An irradiation system was developed for heavy-ion radiotherapy. Wobbler magnets and a scatterer were used for flattening the radiation field. A patient-positioning system using X ray and image intensifiers was also installed in the irradiation system. The depth-dose distributions of the carbon beams were modified to make a spread-out Bragg peak, which was designed based on the biophysical characteristics of monoenergetic beams. A dosimetry system for heavy-ion radiotherapy was established to deliver heavy-ion doses safely to the patients according to the treatment planning. A carbon beam of 80 keV/microm in the spread-out Bragg peak was found to be equivalent in biological responses to the neutron beam that is produced at cyclotron facility in National Institute Radiological Sciences (NIRS) by bombarding 30-MeV deuteron beam on beryllium target. The fractionation schedule of the NIRS neutron therapy was adapted for the first clinical trials using carbon beams. RESULTS: Carbon beams, 290, 350, and 400 MeV/u, were used for a clinical trial from June of 1994. Over 300 patients have already been treated by this irradiation system by the end of 1997.
We investigated the existence and possible role of cytosolic phospholipase A2 (cPLA2) in rat decidualized uteri. PLA2 activity in the cytosol of a decidualized uterine horn, induced by intraluminal oil infusion, was significantly higher than that in contralateral intact horn. The activity was almost completely depressed by cPLA2 inhibitors including arachidonyl trifluoromethyl ketone (ATK). The immunoreactive signals for cPLA2 were intense in decidua and glandular epithelial cells. In vivo administration of ATK (0.1-100 microg) caused a dose-dependent inhibition of decidualization. These results show the presence of cPLA2 and its probable implication in decidualization in rat uterus.
In urethane-chloralose anesthetized rats, the role of GABA(B) receptor in the commissural subnucleus of the nucleus tractus solitarii (commNTS) on the carotid chemoreceptor reflex was investigated. Microinjection of a GABA(B) agonist baclofen into the commNTS did not have any effects on arterial blood pressure (BP) or respiration (RP), while it attenuated the increases in BP and RP elicited by carotid chemoreceptor stimulation. These effects were blocked by microinjection of a GABA(B) antagonist 2-OH-saclofen into the same site. Prior microinjection of 2-OH-saclofen did not have any effects on the chemoreflex or on resting BP or RP, while the effects of baclofen on the chemoreflex were completely blocked. These results suggest that GABAB receptors are present in the carotid chemoreceptor reflex pathway in commNTS and modulate the chemoreceptor reflex.
alpha1-Syntrophin is a member of the family of dystrophin-associated proteins and is strongly expressed in the sarcolemma and the neuromuscular junctions. All three syntrophin isoforms have a PDZ domain that appears to participate in protein-protein interactions at the plasma membrane. alpha1-Syntrophin has additionally been shown to associate with neuronal nitric-oxide synthase (nNOS) through PDZ domains in vitro. These observations suggest that alpha1-syntrophin may work as a modular adaptor protein that can link nNOS or other signaling enzyme to the sarcolemmal dystrophin complex. In the sarcolemma, nNOS regulates the homeostasis of reactive free radical species and may contribute to the oxidative damage to muscle protein in muscle disease such as Duchenne muscular dystrophy. In this study, we generated alpha1-syntrophin knock-out mice to clarify the interaction between alpha1-syntrophin and nNOS in the skeletal muscle. We observed that nNOS, normally expressed in the sarcolemma, was largely absent from the sarcolemma, but considerably remained in the cytosol of the knock-out mice. Even though the distribution of nNOS was altered, the knock-out mice displayed no gross histological changes in the skeletal muscle. We also discovered that muscle contractile properties have not been influenced in the knock-out mice.
Of 40 Wilms tumors with chromosome abnormalities, 6 were hypodiploid, 10 were pseudodiploid, 7 were hyperdiploid with 47 to 49 chromosomes, and 17 were hyperdiploid with 50 or more chromosomes, mostly including +12. WT1 deletions/mutations were found in one hypodiploid, eight pseudodiploid, and one hyperdiploid (47-49 chromosomes) tumor, but in none of the hyperdiploid (> or =50 chromosomes) tumors. Of the 10 tumors with WT1 abnormalities, 6 had a homozygous WT1 deletion, 1 had a nonsense WT1 mutation and loss of heterozygosity at 11p, 1 had an intragenic hemizygous WT1 deletion without detectable WT1 mutation, and 2, which occurred in Wilms tumor-aniridia-genitourinary abnormalities-mental retardation syndrome patients, had a hemizygous deletion and a missense or frameshift mutation of WT1. Six of the nine tumors with homozygous or hemizygous WT1 deletions had chromosome aberrations involving chromosome band 11p13 in one of the two chromosomes 11. While one hypodiploid and one pseudodiploid patient died of the disease, and one hyperdiploid (47-49 chromosomes) patient was alive in nonremission, all hyperdiploid (> or =50 chromosomes) patients had no evidence of disease at the last follow-up. Our data show that chromosome aberrations are closely correlated to WT1 abnormalities and suggest that hyperdiploid (> or =50 chromosomes) Wilms tumors may be characterized by the absence of WT1 abnormalities and possibly also by a favorable prognosis.
The role of sialidase in complement activation and in development of hypocomplementemia in patients with postinfectious acute glomerulonephritis (AGN) was investigated. In sera from 17 patients with AGN and 14 healthy controls, sialidase activity and serum levels of free and total sialic acid were measured by previously established methods. Circulating sialidase activity and serum levels of free and total sialic acid and haptoglobin were increased, and the C3 level was decreased in the acute phase of AGN. There was no correlation between free sialic acid and total sialic acid, which increased in parallel with serum levels of haptoglobin, one of the acute-phase reactants. A follow-up study of these parameters in a typical case reflected this tendency and suggested that increased sialidase after infection, in addition to complement activation by the infectious substance, could play a role in development of hypocomplementemia. To clarify this mechanism, purified neuraminidase was incubated with normal human serum under various conditions. Complement breakdown products were measured in the incubation mixture by enzyme-linked immunosorbent assay using monoclonal antibodies against iC3b, Bb, and C4d neoantigens. iC3b was generated dose-dependently in the presence of neuraminidase. Further examination revealed that iC3b and Bb were generated in the incubation mixture with neuraminidase and NHS and that C4d was not detected in the same mixture. These findings indicate that neuraminidase activates the alternative complement pathway. These in vitro data, together with the former in vivo data led us to conclude that increased sialidase after infection could accelerate the complement amplification system, resulting in hypocomplementemia in the acute phase of postinfectious AGN.
The aquaporins represent a family of transmembrane water channel proteins that are widely distributed in various tissues throughout the body and play a major role in transcellular and transepithelial water movement. Most tumors have been shown to exhibit high vascular permeability and high interstitial fluid pressure, but the transport pathways for water within tumors remain unknown. In this study, we examined the distribution of the aquaporin 1 (AQP1) water channel protein in several types of transplanted tumor. Two mammary carcinomas, MCaIV and R3230AC, and three glioblastomas, HGL21, U87, and F98, were implanted in rats and mice. Two sites of implantation in rodents were chosen: a cranial window (CW) region and a subcutaneous (SC) region. Tissues were studied using immunoblot analysis and immunofluorescence staining. In the mammary carcinomas, AQP1 was localized in vascular structures; no differences between CW and SC regions were observed. Among the three glioblastomas, HGL21 and U87 exhibited similar AQP1 localization in vascular structures, whereas the center of F98 did not show vascular staining. Cell membranes of normal epithelial cells did not show AQP1 expression, while membranes of most tumor cells exhibited significant AQP1 expression. Interestingly, however, HGL21 and F98 in the CW locations showed no AQP1 expression on tumor cell membranes. These results show that the AQP1 water channel is heterogeneously expressed in tumor cells and their vasculature, and that the level of expression is determined not only by the specific cellular origin of the tumor, but also by the location of the tumor in the host animal.
Pedicled pericardium is a useful viable material for cardiac surgery. In an adolescent case, the extracardiac lateral tunnel of a Fontan connection was successfully constructed with pedicled pericardium. This procedure is expected to allow the growth of the tunnel and to need no anti-coagulant therapy, while careful long-term follow-up is necessary.