Biomedical subjects

A Yoshikawa

Publications and source records attributed to A Yoshikawa.

At least 37 records · Page 2Linked to original sources

PubMed1999

Hepatocyte growth factor supply accelerates compensatory hypertrophy caused by portal branch ligation in normal and jaundiced rats.

BACKGROUND: Hepatocyte growth factor (HGF), first identified as the most potent mitogen for hepatocytes, significantly stimulates liver regeneration after hepatectomy. In this report, we examined whether HGF is also useful in accelerating compensatory hypertrophy caused by portal branch ligation in normal and jaundiced rats. MATERIALS AND METHODS: Normal and reversible obstructive jaundiced rats underwent portal ligation of the left lateral and median branches, which supply approximately 70% of the total volume of the liver. Simultaneously, the animals were continuously treated with either recombinant human HGF (rhHGF) or vehicle alone via an intraperitoneally implanted osmotic pump. Two and four days after portal ligation, the degree of compensatory hypertrophy in unoccluded lobes was examined by measuring the wet weight ratios of the unoccluded lobes to the whole liver and the 5-bromo-2'-deoxyuridine labeling index of hepatocytes in each group. RESULTS: The HGF treatment significantly increased the wet weight ratios and the DNA synthesis in nonoccluded lobes 2 and 4 days after portal ligation in both normal and jaundiced rats. Moreover, rhHGF supply promptly decreased serum total bilirubin level in jaundiced rats. CONCLUSIONS: Continuous rhHGF administration not only accelerates compensatory hypertrophy in normal and jaundiced rats but also ameliorates hyperbilirubinemia in jaundiced rats.

Adaptation, Physiological↗

PubMed1999

Functional magnetic resonance imaging to word generation task in a patient with Broca's aphasia.

We describe the findings of functional magnetic resonance imaging (fMRI) in a patient with Broca's aphasia. The patient was a 45-year-old, right-handed woman who developed Broca's aphasia after infarction in the left frontal lobe. The first fMRI showed no signals in the left frontal lobe during verbal tasks, 2 weeks after the onset of infarction. Four weeks later, when the patient's symptom had improved, the second fMRI showed some increase in the fMRI signals in the left frontal lobe. Seven months later, she had completely recovered the ability to speak. The last fMRI then showed that the increment in signal activity in the left frontal lobe during verbal tasks had recovered to the level seen in normal subjects. There was a good correlation between the increase in task-related signals in Broca's area and the recovery of language function. Our findings show that fMRI has can be important in assessing cognitive functions in patients with Broca's aphasia.

Aphasia, Broca↗

PubMed1999

Amino acid sequences of lysozymes newly purified from invertebrates imply wide distribution of a novel class in the lysozyme family.

Lysozymes were purified from three invertebrates: a marine bivalve, a marine conch, and an earthworm. The purified lysozymes all showed a similar molecular weight of 13 kDa on SDS/PAGE. Their N-terminal sequences up to the 33rd residue determined here were apparently homologous among them; in addition, they had a homology with a partial sequence of a starfish lysozyme which had been reported before. The complete sequence of the bivalve lysozyme was determined by peptide mapping and subsequent sequence analysis. This was composed of 123 amino acids including as many as 14 cysteine residues and did not show a clear homology with the known types of lysozymes. However, the homology search of this protein on the protein or nucleic acid database revealed two homologous proteins. One of them was a gene product, CELF22 A3.6 of C. elegans, which was a functionally unknown protein. The other was an isopeptidase of a medicinal leech, named destabilase. Thus, a new type of lysozyme found in at least four species across the three classes of the invertebrates demonstrates a novel class of protein/lysozyme family in invertebrates. The bivalve lysozyme, first characterized here, showed extremely high protein stability and hen lysozyme-like enzymatic features.

Amino Acid Sequence↗

PubMed1999

Heterotopic nasopharyngeal brain tissue associated with cleft palate.

OBJECTIVE: The occurrence of extracranial brain tissue is rare. Most of the literature describes cases in which it is located around the nose and throat and has been classified as nasal glioma. Even more unusual is heterotopic brain tissue in the nasopharynx. We were able to find only 17 previously reported cases. Of these 17 cases, 6 had heterotopic brain tissue located in a cleft palate. This report comments on the identification and treatment of heterotopic brain tissue associated with cleft palate without connection to the central nervous system. Our case subject is a 10-month-old girl diagnosed with heterotopic nasophranygeal brain tissue associated with cleft palate. RESULTS: Excision and palatoplasty were performed conjunctively with excellent results. CONCLUSIONS: Simultaneous excision of heterotopic nasopharyngeal brain tissue and palatoplasty of the cleft palate is an excellent option for treatment of these cases.

Brain↗

PubMed1999

Pretreatment with soluble thrombomodulin prevents intrasinusoidal coagulation and liver dysfunction following extensive hepatectomy in cirrhotic rats.

The major cause of posthepatectomy liver dysfunction is supposed to be microcirculatory disturbance caused by imbalance of intrasinusoidal coagulation equilibrium. Thrombomodulin (TM) is a potent anticoagulant expressed on the endothelial cell surface that regulates the coagulation system by binding thrombin and accelerating the thrombin-catalyzed activation of protein C. Therefore, we examined the effect of soluble TM purified from human urine (UTM) on intrasinusoidal coagulation in cirrhotic rats. Dimethylnitrosamine-induced cirrhotic rats underwent 70% hepatectomy and received endotoxin 48 h after. UTM or vehicle alone was intravenously administered to each rat 30 min before endotoxin injection. UTM treatment attenuated the increases in cytosolic enzymes and serum hyaluronic acid level. The UTM supply improved the survival rate of the rats at 12 h after endotoxin challenge. Histologically, intrasinusoidal fibrin depositions and massive hepatocellular necrosis observed in control rats were scarcely found in UTM-treated rats. Immunohistochemical examination revealed that marked TM stains in sinusoidal endothelial cells were well preserved in UTM-treated rats. In conclusion, UTM administration prevented intrasinusoidal fibrin depositions and attenuated posthepatectomy liver dysfunction in cirrhotic rats.

Animals↗

PubMed1999

New animal model of glandular stomach carcinogenesis in Mongolian gerbils infected with Helicobacter pylori and treated with a chemical carcinogen.

In 1994 WHO/IARC concluded that "Helicobacter pylori is a definite carcinogen" based on epidemiological studies, but there have been few reports demonstrating a relation between H. pylori and stomach cancer in animal models. We have succeeded in producing adenocarcinomas in the glandular stomachs of Mongolian gerbils with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or N-methyl-N-nitrosourea as carcinogens and hope to establish an experimental stomach carcinogenesis model using H. pylori. Male Mongolian gerbils, 7 weeks old, were infected with H. pylori followed by MNNG administration at a concentration of 100ppm administration or treated with MNNG at a concentration of 300ppm in their drinking water followed by inoculation with H. pylori. They were then killed sequentially, and their excised stomachs underwent microbiological and histopathological examinations. H. pylori were detected in all infected gerbils. Hyperplastic change of pyloric mucosa was observed with high 5-bromo-2'-deoxyuridine incorporation in affected animals. H. pylori infection persists on administration of MMNG and enhances glandular stomach proliferation in Mongolian gerbils. Whether long-term colonization promotes carcinogenesis in the glandular stomach of Mongolian gerbils is a matter of great interest.

Adenocarcinoma↗

PubMed1998

Hepatocyte growth factor promotes liver regeneration with prompt improvement of hyperbilirubinemia in hepatectomized cholestatic rats.

BACKGROUND: In hepatectomy for patients with liver cirrhosis or cholestasis, prolonged postoperative hyperbilirubinemia is a troublesome complication and, if uncontrolled, often leads to life-threatening hepatic failure. Hepatocyte growth factor (HGF), first identified as the most potent mitogen for primary hepatocytes, has been shown to have multiple biological properties on liver, including mitogenic, antifibrotic, and cytoprotective activities. This study investigated the beneficial effects of a perioperative HGF supply to jaundiced liver after hepatectomy in rats. MATERIALS AND METHODS: As a model of jaundiced liver, we used an alpha-naphtylisocyocyanate (ANIT)-induced intrahepatic cholestasis model. Forty-eight hours after intraperitoneal injection of ANIT (75 mg/kg), when the total serum bilirubin level was moderately increased, a 70 % hepatectomy was performed. Human recombinant HGF (250 microgram/kg) (n = 15) or vehicle alone (n = 15) was intermittently administered to the rats 12 h before surgery and every 12 h after that until sacrifice. RESULTS: Perioperative HGF treatment effectively accelerated hepatocellular DNA synthesis of cholestatic liver followed by increase in the regenerated liver weight. Moreover, HGF supply promptly improved hyperbilirubinemia within 24 h after surgery. Histological examination revealed that HGF administration attenuated periportal inflammation and formation of bile duct obstructions. Postoperative serum concentrations of tumor necrosis factor-alpha, a representative inflammatory cytokine, were not altered by HGF treatment. CONCLUSIONS: Perioperative HGF supply not only promotes liver regeneration but also ameliorates hyperbilirubinemia in hepatectomized cholestatic rats. This mode of HGF treatment may be clinically useful for hepatectomy in patients with cholestasis.

Animals↗

PubMed1998

Perioperative continuous hepatocyte growth factor supply prevents postoperative liver failure in rats with liver cirrhosis.

Insufficient regeneration and dysfunction of cirrhotic liver following partial hepatectomy often make the resection extremely vulnerable to postoperative liver failure, which frequently leads to multiple organ failure. Hepatocyte growth factor (HGF), first identified as the most potent mitogen for primary hepatocytes, not only stimulates hepatic regeneration but also accelerates liver function, improves fibrosis, and protects liver cells against injury. Therefore, we investigated the ability of a continuous supply of HGF to cirrhotic livers to prevent postoperative liver failure in rats. After liver cirrhosis was induced in 40 rats by the intraperitoneal injection of dimethylnitrosamine (DMN) for 4 weeks, fibroblasts genetically modified to secret rat HGF or control fibroblasts were implanted in the spleens of 20 syngenic rats per group to supply HGF continuously and directly to the cirrhotic livers. Two weeks after the implantation, all rats underwent a 30% hepatectomy. The HGF administration significantly improved liver fibrosis at the time of operation, attenuated the postoperative hepatic damage on histological examination, markedly accelerated the liver regeneration at 24 h after the hepatectomy. The blood chemical analysis indicated that HGF significantly suppressed postoperative liver failure. Most importantly, the HGF treatment significantly improved the survival rate of the rats at 48 h after the hepatectomy. The perioperative continuous supply of HGF from the spleen effectively prevented liver failure following resection of cirrhotic livers in rats.

Animals↗

PubMed1998

Helicobacter pylori promotes development of pepsinogen-altered pyloric glands, a preneoplastic lesion of glandular stomach of BALB/c mice pretreated with N-methyl-N-nitrosourea.

H. pylori is thought to be a stomach carcinogen. Since no experimental model has hitherto been established to clarify the relationship between H. pylori and stomach carcinogenesis, the effects of infection with the bacteria on experimental carcinogenesis in the glandular stomach of mice were investigated. BALB/c mice were given salty diet or N-methyl-N-nitrosourea (MNU) and administered broth culture of H. pylori. The incidence of pepsinogen-altered pyloric glands, considered as precancerous lesions, was increased in the H. pylori inoculated group pre-treated with MNU. The findings provide the new experimental model demonstrating the relationship between stomach cancer and H. pylori.

Animals↗

PubMed1998

Portal branch ligation with a continuous hepatocyte growth factor supply makes extensive hepatectomy possible in cirrhotic rats.

In a cirrhotic liver, the regenerative ability and specific functions are so impaired that excessive resection easily complicates postoperative liver dysfunction, which frequently leads to life-threatening multiple-organ failure. Hepatocyte growth factor (HGF), first identified as the most potent stimulator of DNA synthesis in primary hepatocytes, not only stimulates liver regeneration, but also accelerates hepatic function, improves fibrosis, and protects liver cells against injury. Therefore, we investigated the efficacy of preoperative portal branch ligation (PBL) (which can induce compensatory hypertrophy of the unaffected lobes) combined with a continuous HGF supply in the performance of extensive hepatectomy in cirrhotic rats. Cirrhosis was induced by intraperitoneal injections of dimethylnitrosamine (DMN) three times per week for 3 weeks. Five days after the last injection, when 70% hepatectomy is lethal, the rats underwent portal ligation of the left lateral and median branches (corresponding to approximately 70% of the total volume of the liver). Simultaneously, they were continuously treated with either recombinant human HGF (rhHGF) or vehicle from an intraperitoneally implanted osmotic pump. Four days after the portal ligation, the occluded lobes were resected. The HGF treatment rapidly increased both the wet weight of the unoccluded lobes and the hepatocellular DNA synthesis. The blood chemical analysis indicated that HGF significantly suppressed the posthepatectomy liver dysfunction. Most importantly, the HGF treatment markedly improved the survival rate of the rats at 48 hours after the major hepatectomy. In conclusion, PBL combined with a continuous HGF supply makes extensive hepatectomy possible in cirrhotic rats, mainly by promoting the hypertrophy of the unaffected lobes.

Animals↗

PubMed1998

Hepatocyte growth factor prevents lipopolysaccharide-induced hepatic sinusoidal endothelial cell injury and intrasinusoidal fibrin deposition in rats.

BACKGROUND: Acute endotoxemia is known to cause activation of Kupffer cells as well as serious injury in parenchymal and nonparenchymal cells in the liver. We have recently shown that a continuous recombinant hepatocyte growth factor (rHGF) supply prevents lipopolysaccharide (LPS)-induced liver injury in rats. As an attempt to elucidate the mechanism, here we investigate the cytoprotective effect of rHGF on sinusoidal endothelial cells (SECs) in LPS-induced liver injury in rats. MATERIALS AND METHODS: In order to supply rHGF continuously to the liver, syngenic rat fibroblasts genetically modified to secret rat rHGF were implanted in the spleen. Fourteen days after cell implantation, we injected LPS intravenously and evaluated SEC damage histologically and blood chemically. RESULTS: Phosphotungstic acid-hematoxylin staining revealed that rHGF treatment greatly attenuated intrasinusoidal LPS-induced fibrin deposition. The ultrastructural changes in SECs caused by LPS administration in control rats were barely detectable in rHGF-treated rats. Blood chemical analyses showed that rHGF potently suppressed the LPS-induced increase in serum hyaluronic acid and transaminase levels. CONCLUSIONS: Our results indicate an important role for HGF in SEC protection in vivo and would suggest a novel therapeutic strategy for liver diseases with SEC injury.

Alanine Transaminase↗

PubMed1998

Peutz-Jeghers syndrome manifesting complete intussusception of the appendix and associated with a focal cancer of the duodenum and a cystadenocarcinoma of the pancreas: report of a case.

The unusual occurrence of an "inside-out" appendix reported here is a case of complete intussusception of the appendix of a 45-year-old woman with Peutz-Jeghers syndrome in whom the diagnosis of intussusception was made preoperatively. At laparotomy, the lead point of intussusceptum was revealed to be a Peutz-Jeghers syndrome polyp of the appendix. There was also a cystic lesion in the pancreas, and subsequent distal pancreatectomy revealed a cystadenocarcinoma of the pancreas. Two jejunal Peutz-Jeghers syndrome polyps and two duodenal Peutz-Jeghers syndrome polyps were found via intraoperative endoscopies. The duodenal polyps were endoscopically removed, whereas a jejunal wedge resection was performed for the adjoining jejunal polyps. One of the two duodenal polyps possessed an adenocarcinoma focus. To our knowledge, this is the first report of complete intussusception of the appendix caused by a Peutz-Jeghers syndrome polyp.

Appendiceal Neoplasms↗

PubMed1998

Induction of glandular stomach cancers in Helicobacter pylori-sensitive Mongolian gerbils treated with N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine in drinking water.

An animal model of stomach carcinogenesis was established using Mongolian gerbils with N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as the carcinogens. In addition, the sensitivity of these gerbils to Helicobacter pylori (H. pylori) was confirmed. One hundred and sixty specific pathogen-free male MGS/Sea animals, 7 weeks old, were treated with MNU in the drinking water (30 ppm for alternate weeks to give 10 weeks exposure, or 10 ppm or 3 ppm for 20 weeks continuous exposure), or given MNNG in the drinking water at 400 ppm or 200 ppm for 20 weeks, or orally inoculated with ATCC43504 H. pylori (1.7 x 10(8) CFUs/animal). Adenocarcinomas in the glandular stomach were found in 2 out of 12 effective animals (2/ 12) treated with 30 ppm MNU at week 20, although all were dead or moribund by week 30 due to MNU toxicity. At week 50, the incidences of gastric adenocarcinomas in groups treated with 10 ppm MNU, 3 ppm MNU, 400 ppm MNNG, and 200 ppm MNNG were 2/21 (9.5%), 1/23 (4.3%), 7/ 11 (63.6%), and 1/10 (10.0%). The lesions were generally well differentiated, although poorly differentiated adenocarcinoma was also found in a single gerbil in each of the 10 ppm MNU and 400 ppm MNNG groups. In control animals no tumors were found. In the infection study, the animals were killed at week 20, and H. pylori was detected in all cases, causing multiple erosions with marked inflammatory cell infiltration in the lamina propria and submucosa, and frequent formation of lymphoid follicles. Thus, MNU and MNNG in the drinking water induced neoplastic lesions in the glandular stomach epithelium of H. pylori-sensitive gerbils.

Adenocarcinoma↗

PubMed1998

Increased expression of sucrase and intestinal-type alkaline phosphatase in human gastric carcinomas with progression.

The activities of sucrase, total alkaline phosphatase (total ALP) and intestinal-type alkaline phosphatase (I-ALP) were assayed in gastric carcinomas and in their surrounding mucosae from 57 patients with advanced cancers, and the localization of sucrase in 203 carcinomas, including 86 early cancers, was examined immunohistochemically using polyclonal anti-sucrase antibody. All three enzymes were active in the 57 carcinomas as well as in their surrounding mucosae, but the levels were fairly low as compared to those in normal jejunum mucosa. A considerable part of the total ALP activity in tumor specimens was assumed to be due to I-ALP itself. Increased sucrase and I-ALP were found with greater depth of invasion by undifferentiated-type carcinomas. The pattern of immunohistochemical localization of sucrase in the 203 carcinomas also clearly indicated increased expression with greater depth of invasion even in differentiated-type carcinomas.

Adenocarcinoma↗

PubMed1998

Application of the human hepatitis B virus core antigen from transgenic tobacco plants for serological diagnosis.

BACKGROUND AND OBJECTIVES: The aim was to produce HBcAg from plants more cheaply than can be done by other currently available means, and to apply such antigen to immunoassay procedures for pretransfusion testing of donor blood. MATERIALS AND METHODS: Transgenic Nicotiana tabacum cv. SR-1 plants expressing the human hepatitis B virus (HBV) core antigen (HBcAg) gene were generated by Agrobacterium-mediated transformation. The recombinant product, called tHBcAg, can assemble itself into a spherical particle with a diameter of 25 to 30 nm, and can maintain two antigenic determinants of HBcAg, namely HBc/alpha and HBc/beta. Partly purified tHBcAg was used in the hemagglutination-inhibition (HI) test, as routinely used by the Japanese Blood Center, to test a panel of 524 blood units taken from HBV-positive donors. RESULTS: In the HI test, tHBcAg showed serologic properties comparable to that from Escherichia coli, the standard antigen used in the Japanese Blood Center. CONCLUSIONS: Transgenic plants can produce reagents for serologic testing and perhaps even such medical materials as oral vaccines.

Agrobacterium tumefaciens↗

PubMed1998

[Experimental study of percutaneous hot ethanol injection therapy (PHEIT) by continuous heating device for hepatocellular carcinoma].

Percutaneous ethanol injection therapy (PEIT) is widely used as a local treatment for hepatocellular carcinoma (HCC). However, because only a small amount of ethanol can be used in one PEIT session and because the antitumor effect is limited, this modality is indicated only when there are three or fewer tumors and when the tumor diameter is < or = 3 cm. To obtain a more potent and certain antitumor effect, we have devised a new treatment called percutaneous hot ethanol injection therapy (PHEIT), and developed a Continuous Heating Device with which ethanol can be heated and locally injected at a specified temperature. The continuous Heating Device is composed of three major components: a syringe heater, a needle thermocontroller, and a needle tip thermosensor. A disposable syringe filled with liquid is inserted into the syringe heater, which heats the liquid to a desired temperature by adjusting the voltage. The needle thermocontroller is a puncture guide needle to which a heating device has been attached. The needle-tip thermosensor constantly measures, displays and records the temperature of the liquid at the needle tip during injection. Also, because the Continuous Heating Device is a closed-circuit system, there is no risk of accidental a fire, which ensures procedural safety. It is also possible to use this device to safely heat and inject a variety of other liquids, such as physiological saline and anticancer agents and thus contribute to the widespread development of ultrasound-guided injection therapy.

Animals↗

PubMed1997

Stomach-partitioning gastrojejunostomy for unresectable gastric carcinoma.

OBJECTIVES: To analyze the results of a new type of bypass procedure, stomach-partitioning gastrojejunostomy (SPGJ), for unresectable gastric carcinoma and to compare these results with those of conventional gastrojejunostomy (GJ). DESIGN: Retrospective review. SETTING: A university hospital in Japan. PATIENTS: Eight patients underwent SPGJ in 1 group, and 13 underwent conventional GJ in the other group. Staging was determined using preoperative diagnostic imagings and intraoperative findings. MAIN OUTCOME MEASURES: Assessment of food intake and mean survival rates. RESULTS: There were no significant differences between the 2 groups regarding male-female ratio, mean age, and histological type of carcinoma. All patients had stage IV cancers according to the classification of the Union Internationale Contre le Cancer. The rates of taking a regular meal at 2 weeks after an operation were 88% in the SPGJ group and 31% in the GJ group (P < .05). The mean 1-year survival rates for SPGJ and GJ groups were 42.9% and 7.7%, respectively (P < .05). The mean survival times were 13.4 months in the SPGJ group and 5.8 months in the GJ group (P < .05). CONCLUSIONS: Stomach-partitioning gastrojejunostomy achieved an improved quality of life and a better prognosis for patients, and it is the preferred bypass procedure for unresectable gastric carcinoma.

Aged↗

PubMed1997

Brain MR imaging in patients with hepatic cirrhosis: relationship between high intensity signal in basal ganglia on T1-weighted images and elemental concentrations in brain.

In patients with hepatic cirrhosis, the globus pallidus and putamen show high intensity on T1-weighted MRI. While the causes of this high signal have been thought to include paramagnetic substances, especially manganese, no evidence for this has been presented. Autopsy in four cases of hepatic cirrhosis permitted measurement of metal concentrations in brain and histopathological examination. In three cases the globus pallidus showed high intensity on T1-weighted images. Mean manganese concentrations in globus pallidus, putamen and frontal white matter were 3.03 +/- 0.38, 2.12 +/- 0.37, and 1.38 +/- 0.24 (micrograms/g wet weight), respectively, being approximately four- to almost ten-fold the normal values. Copper concentrations in globus pallidus and putamen were also high, 50% more than normal. Calcium, iron, zinc and magnesium concentrations were all normal. The fourth case showed no abnormal intensity in the basal ganglia and brain metal concentrations were all normal. Histopathologically, cases with showing high signal remarkable atrophy, necrosis, and deciduation of nerve cells and proliferation of glial cells and microglia in globus pallidus.. These findings were similar to those in chronic manganese poisoning. On T1-weighted images, copper deposition shows no abnormal intensity. It is therefore inferred that deposition of highly concentrations of manganese may caused high signal on T1-weighted images and nerve cell death in the globus pallidus.

Basal Ganglia↗