Biomedical subjects

Hiroto Ishikawa

Publications and source records attributed to Hiroto Ishikawa.

11 recordsLinked to original sources

PubMed2006

Effects of bone marrow stromal cell injection in an experimental glaucoma model.

We investigated if bone marrow stromal cells (BMSCs) transplanted into the vitreous body of a glaucoma model eye could be integrated in the host retina and also whether they could rescue the retinal ganglion cells (RGCs) from death induced by the elevated intraocular pressure. Glaucoma was induced in the right eye of adult Wistar rats by ligating the episcleral veins. The GFP-expressing BMSCs (GFP-BMSCs) were injected into the vitreous body of both the control and the glaucomatous eyes. After transplantation, GFP-BMSCs were mostly present along with the inner limiting membrane and only a few cells were integrated into the ganglion cell layer. At 2 or 4 weeks after transplantation, GFP-BMSCs were observed to express various trophic factors. The BMSCs injected glaucoma model eyes showed less reduction in the number of RGCs compared to the glaucomatous eyes with PBS injection. This study suggests that BMSC transplantation may be worthy as a neuroprotective tool to treat glaucoma.

Animals↗

PubMed2005

Bone marrow stromal cells generate muscle cells and repair muscle degeneration.

Bone marrow stromal cells (MSCs) have great potential as therapeutic agents. We report a method for inducing skeletal muscle lineage cells from human and rat general adherent MSCs with an efficiency of 89%. Induced cells differentiated into muscle fibers upon transplantation into degenerated muscles of rats and mdx-nude mice. The induced population contained Pax7-positive cells that contributed to subsequent regeneration of muscle upon repetitive damage without additional transplantation of cells. These MSCs represent a more ready supply of myogenic cells than do the rare myogenic stem cells normally found in muscle and bone marrow.

Animals↗

PubMed2005

[A study of recurrent pancreatic cancer with metastatic liver tumors after pancreatectomy].

BACKGROUND: Pancreatectomy is the best treatment for pancreatic cancer. However, there is a high risk of post-operative complications, such as local recurrence, metastatic lymphadenopathy, carcinomatosa peritonitis and liver metastasis. Presently, there is no significant treatment that has yet had a strong impact on recurrent pancreatic cancer. This study was conducted concerning recurrent pancreatic cancer with metastatic liver tumors after pancreatectomy. SUBJECTS AND METHODS: Between April 1998 and March 2005, our institute treated recurrent pancreatic cancer patients with liver metastasis. This study consisted of groups who received therapy and those who did not, and their subsequent survival rate was also studied. RESULTS: Nine cases had a recurrent pancreatic cancer with metastatic liver tumors. According to the treatment modality, the study population was classified into two groups: one group consisted of 4 patients with no treatment and the other group consisted of 5 patients who received treatment with gemcitabine (GEM). The mean survival rate for the group who received no treatment was 6.6 months. The mean survival rate for the group who received the treatment was 22.3 months. In addition, one year survival rate for those who received no treatment was 0%. The one year survival rate for those who received the treatment was 75%. The group with treatment showed better results in overall mean survival rates, as well as a higher one-year survival rate than the group with no treatment. The GEM administration included both intraarterial infusion and intravenous infusion. CONCLUSIONS: Prolongation of the survival period was obtained by administration of GEM for recurrent pancreatic cancer with metastatic liver tumors and inoperable advanced pancreatic cancer. We attempted to utilize the active treatment for recurrent pancreatic cancer with metastatic liver tumors. Thus, it was indicated that the therapy can be effective against recurrent pancreatic cancer with metastatic liver tumors.

Aged↗

PubMed2005

[The hepatic artery injection chemotherapy and prostaglandin E1 administration for hepatocellular carcinoma invading the biliary tract with jaundice].

A 69-year-old man had radiofrequency ablation therapy (following RFA) for type C cirrhosis with hepatoma (following HCC) of S7 in November 2001. Afterward the patient was followed as an outpatient, but he had been admitted to our hospital due to jaundice confirmed in March 2004. His abdominal wall appeared to be soft and flat, and we could not detect a tumor mass by palpating either. Even though he exhibited no actual symptom of anemia, jaundice was found in the bulbar conjunctiva at the time of admission. Laboratory findings showed a mild inflammation and anemia on his admission, and biochemical data showed a rise of hepatobiliary enzyme with jaundice. A rise of tumor marker (AFP, PIVKA-II) was recognized, too. We performed percutaneous transhepatic bile duct drainage (following PTBD) to decrease jaundice because abdominal echography and CT showed an extension of tumor thrombosis in bile duct and right hepatic duct by HCC of S8. However, a check of T-Bil. was 7.29 mg/dl and showed some slight decrease. Therefore, we administered prostaglandin E1 (following PGE1) at first with an intra-arterial injection catheter aiming to protect the hepatocyte. One week later, we performed hepatic artery injection chemotherapy (CDDP+5-FU) for four weeks. We confirmed a manifested improvement in T-Bil to be 1.92 mg/dl at the end of hepatic artery injections as well as a manifested decrease in hepatobiliary enzyme. We confirmed a decrease of HCC of S8 by abdominal CT, and the response rate was PR. Afterward the patient was conservatively treated even though pancytopenia was present, and was discharged from the hospital in June 2004. The hepatic artery injection chemotherapy used together with PGE1 was effective for the HCC patient with jaundice.

Aged↗

PubMed2004

Study of drug effects of calcium channel blockers on retinal degeneration of rd mouse.

In the present study, we studied drug effects of Ca(2+) antagonists on the retinal degeneration of rd mouse to evaluate their efficacy. Several kinds of Ca(2+) antagonists, diltiazem, nicardipine, nilvadipine or nifedipine were administrated intraperitoneally and thereafter retinal morphology and functions were analyzed. In addition, we performed DNA microarray analysis both in nilvadipine treated and control retinas to understand their drug effects at molecular levels. We found that nilvadipine caused significant preservation of retinal thickness in rd mouse during the initial stage of the retinal degeneration, and nicardipine showed also significant but lesser preservation than nilvadipine. However, we recognized no preservation effects of diltiazem and nifedipine. In the total 3774 genes, the expressions of 27 genes were altered upon administration of nilvadipine, including several genes related to the apoptotic pathway, neuro-survival factor, Ca(2+) metabolisms, and other mechanisms. It is suggested that some types of Ca(2+) channel blockers, such as nilvadipine and nicardipine, are able to preserve photoreceptor cells in rd mouse and can potentially be used to treat some RP patients.

Animals↗

PubMed2004

Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation.

Bone marrow stromal cells (MSCs) have the capability under specific conditions of differentiating into various cell types such as osteocytes, chondrocytes, and adipocytes. Here we demonstrate a highly efficient and specific induction of cells with neuronal characteristics, without glial differentiation, from both rat and human MSCs using gene transfection with Notch intracellular domain (NICD) and subsequent treatment with bFGF, forskolin, and ciliary neurotrophic factor. MSCs expressed markers related to neural stem cells after transfection with NICD, and subsequent trophic factor administration induced neuronal cells. Some of them showed voltage-gated fast sodium and delayed rectifier potassium currents and action potentials compatible with characteristics of functional neurons. Further treatment of the induced neuronal cells with glial cell line-derived neurotrophic factor (GDNF) increased the proportion of tyrosine hydroxylase-positive and dopamine-producing cells. Transplantation of these GDNF-treated cells showed improvement in apomorphine-induced rotational behavior and adjusting step and paw-reaching tests following intrastriatal implantation in a 6-hydroxy dopamine rat model of Parkinson disease. This study shows that a population of neuronal cells can be specifically generated from MSCs and that induced cells may allow for a neuroreconstructive approach.

Animals↗

PubMed2003

[Chemoradiation therapy for stage IV pancreatic cancer].

BACKGROUND: Pancreatic cancer is a malignant tumor with a poor prognosis. It frequently presents with locally advanced and distant metastasis at the time of diagnosis. Favorable results were obtained by performing intraoperative radiation therapy (IORT) and chemotherapy (administration of GEM) for the treatment of inoperable pancreatic cancer. A study was conducted on its efficacy as an adjuvant therapy for inoperable and advanced pancreatic cancer. SUBJECTS AND METHODS: Between May 1998 and December 2002, 40 patients with stage IV pancreatic cancer were treated at our institution. The study comprised background factors, adjuvant therapy and survival rate. RESULTS: According to the treatment modality, the study population was classified into four groups: group A, consisting of 3 patients with localized unresectable tumors who had been treated with IORT: group B, 5 patients who underwent curative resection of primary tumor combined with IORT: group C, 6 patients who were administered GEM combined with IORT: group D, 26 patients not falling into groups A, B or C. The mean survival for group A, B, C and D was 10.3 months, 6.7 months, 16.8 months and 9.4 months, respectively. The 1-year survival rates were 0%, 0%, 80.0% and 19.3%, respectively. The mean survival and the 1-year survival rate were significantly better in group C than in the other groups. In group C, the tumor decreased in size, invasion of large vessels and pancreatic posterior evolution was suppressed, and 4 patients survived for 17 months or more. CONCLUSIONS: Prolongation of the survival period was shown by concomitant IORT and administration of GEM for inoperable advanced pancreatic cancer. Thus, attempting to combine chemotherapy with IORT and giving additional consideration to the administration method was shown to provide adjuvant therapy that can be expected to be effective against stage IV inoperable pancreatic cancer.

Adult↗

PubMed2002

Superconductivity in compressed lithium at 20 K.

Superconductivity at high temperatures is expected in elements with low atomic numbers, based in part on conventional BCS (Bardeen-Cooper-Schrieffer) theory. For example, it has been predicted that when hydrogen is compressed to its dense metallic phase (at pressures exceeding 400 GPa), it will become superconducting with a transition temperature above room temperature. Such pressures are difficult to produce in a laboratory setting, so the predictions are not easily confirmed. Under normal conditions lithium is the lightest metal of all the elements, and may become superconducting at lower pressures; a tentative observation of a superconducting transition in Li has been previously reported. Here we show that Li becomes superconducting at pressures greater than 30 GPa, with a pressure-dependent transition temperature (T(c)) of 20 K at 48 GPa. This is the highest observed T(c) of any element; it confirms the expectation that elements with low atomic numbers will have high transition temperatures, and suggests that metallic hydrogen will have a very high T(c). Our results confirm that the earlier tentative claim of superconductivity in Li was correct.

Journal Article↗

PubMed2002

Role of cyclic nucleotides in ischemia and reperfusion injury of canine livers.

BACKGROUND: In a series of canine liver ischemia experiments, we have shown that amelioration of hepatic injury is achievable by the inhibition of vasoconstriction, cytokine production, platelet aggregation, and neutrophil infiltration. Cyclic adenosine diphosphate (cAMP) was considered to be involved in most of these events. In our study, we tested our hypothesis that augmentation of endogenous cAMP by phosphodiesterase (PDE) 3 inhibitor, amrinone (AM), or adenylate cyclase stimulator, NKH477 (NKH), could attenuate ischemia and reperfusion injury of the liver. METHODS: Thirty-six beagle dogs were used. They were divided into group CT (untreated control), group AM, group NKH, and group CB (treated by both agents). AM or NKH were administered i.v. 1 hr before ischemia (group preAM and group preNKH) or 15 min before reperfusion (pos-AM and postNKH). Combination group animals were treated only before ischemia. Animal survival, hepatic tissue blood flow, liver enzymes, platelet counts, energy metabolism, hepatic cAMP and cyclic guanosine 3',5'-cyclic monophosphate levels, and histopathology were analyzed. RESULTS: Two-week animal survival was significantly improved by pre- or posttreatment with either agent. After reperfusion, hepatic tissue blood flow, liver enzyme release, platelet counts, energy metabolism, tissue cAMP levels, and histological architecture were also ameliorated markedly. Combination of both agents induced severe liver damage and lethal hypotension. AM treatment exhibited more protective effects than NKH, particularly when it was given before ischemia. Interestingly, not only cyclic guanosine 3',5'-cyclic monophosphate, were also restored at higher levels after reperfusion by preischemia treatment. CONCLUSIONS: Administration of amrinone or NKH477 maintained hepatic tissue concentrations of cyclic nucleotides, and attenuated ischemia and reperfusion injury of the liver. Thus, regulation of hepatic tissue cyclic nucleotides is an important alternative for prevention of hepatic damage in liver preservation and surgery.

Adenosine Triphosphate↗

PubMed2002

Nonparasitic solitary huge liver cysts causing intracystic hemorrhage or obstructive jaundice.

We report two cases of a nonparasitic solitary huge liver cyst. The first case, that of a 42-year-old woman, was admitted with a chief complaint of upper abdominal pain. Computed tomography (CT) scans revealed a huge cyst, 10 cm in diameter, in segments 4 and 5 of the liver, and spontaneous rupture of the cyst with intracystic hemorrhage. Her general condition was improved by transcatheter arterial embolization (TAE). Percutaneous cystic needle aspiration cytological examination revealed no malignant cells, so she was discharged. After 3 weeks, however, the cyst had increased in size, and simple cystectomy was performed. Histological examination proved the cyst to be benign. The patient in the second case, a 70-year-old man, was admitted with epigastric discomfort and obstructive jaundice. CT scans revealed a huge liver cyst, 18 x 15 cm, in the right lobe of the liver, with dilation of the bile duct in the lateral segment. Magnetic resonance cholangiopancreatography showed compression of the left hepatic duct by the cyst and dilation of the bile duct in the lateral segment. Endoscopic retrograde cholangiopancreatography disclosed no communication between the bile duct and the cyst. Percutaneous transhepatic cyst drainage was performed, and minocycline hydrochloride was infused. The cyst was reduced in size, and the reduction has been maintained for 20 months since treatment.

Adult↗

PubMed2002

[Intra-arterial chemotherapy with gemcitabine (GEM) for unresectable pancreatic cancer].

PURPOSE: Most patients with pancreatic cancer are unresectable because of local invasion and liver metastasis at the time of diagnosis. To date, no treatment has had a significant impact on this disease. To deliver a high concentration of drug to the cancer, intra-arterial chemotherapy with GEM was performed in two patients with unresectable advanced cancer. PATIENTS AND METHODS: One patient, a 70-year-old man with liver metastasis, was treated with arterial infusion of GEM 1,000 mg/body. Another patient, a 55-year-old woman with local invasion and distant metastatic lymphadenopathy, was given intra-arterial infusion of GEM 400 mg and intra-venous infusion of GEM 1,000 mg/body. The patients were given GEM weekly for 3 weeks followed by a week of rest. RESULTS: In the first patient, the pain went away and CEA was decreased for 6 months. After that, the patient died due to intra-abdominal dissemination within 4 months. In the other patient, the pain went away. Tumor markers, such as CEA and CA19-9, were normalized and primary pancreatic cancer was reduced locally. The patient currently has a metastatic liver tumor, but she has had a significant improvement in performance status. CONCLUSION: Intra-arterial chemotherapy with GEM may be tolerated in patients with unresectable pancreatic cancer.

Aged↗