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Biomedical subjects

Akira Yamada

Publications and source records attributed to Akira Yamada.

At least 91 records · Page 5Linked to original sources

Effect of orally administered shao-yao-gan-cao-tang (Shakuyaku-kanzo-to) on muscle cramps in maintenance hemodialysis patients: a preliminary study.

Muscle cramps are one of the most common complications of hemodialysis (HD), and often are a source of great pain in spite of various clinical measures. The traditional herbal medicine, shao-yao-gan-cao-tang (Japanese name: Shakuyaku-kanzo-to), consists of equal amounts of paeony and licorice roots, and has been used in Japan and China for muscle pain or skeletal muscle tremors. To determine whether this medicine is able to prevent frequent and unendurable muscle cramps in patients undergoing HD, Shakuyaku-kanzo-to at 6 g per day was prospectively administered for 4 weeks to five patients on HD who were suffering from frequent muscle cramps. The frequency and severity of cramping before and after the treatment treatment were carefully observed and compared. Skeletal muscle cramps completely disappeared in two of the treated patients after the start of oral administration of Shakuyaku-kanzo-to. Moreover, the frequency of cramping was significantly decreased in two of the remaining three patients after persistent administration. The severity of muscle cramps was also decreased by this treatment in the responsive patients. No serious side effects were detected during the treatment period. The inhibitory effect of Shakuyaku-kanzo-to on muscle contraction was also experimentally examined by using phrenic nerve-diaphragm preparations from male Wistar rats. Differences between the twitch responses were determined when the diaphragms and the nerves were stimulated in the presence and absence of the extract of Shakuyaku-kanzo-to. The results demonstrated that extracts of paeony and licorice roots inhibit contraction of skeletal muscles in rats. Taken together, we suggest that administration of Shakuyaku-kanzo-to is a safe, effective treatment for preventing muscle cramps in patients undergoing HD.

Administration, Oral↗

[A case of Behçet's disease associated with neuromyopathy induced by combination therapy with colchicine and cyclosporin].

A 61-year-old man with incomplete Behçet's disease was admitted to our hospital because of weakness and muscle pain in August 2001. The patient was diagnosed as having incomplete Behçet's disease because of oral aphtha, genital ulcer and uveitis. He had been administered with colchicine since December 1999. Cyclosporin was added in June 2000, because of repeated ocular attacks. In May 2001, he noticed weakness of proximal limb muscles. In three months, severe generalized muscle pain and numbness in his hands progressed. Laboratory findings showed elevation of muscular enzyme, serum creatinine, and hepatic transaminases. Electromyography and nerve conduction studies indicated myopathy and mild polyneuropathy, respectively. On diagnosis as drug induced neuromyopathy, colchicine administration was stopped. But, severe muscle pain continued. Thus, the cyclosporin dose was also reduced. Seven days later, weakness and muscle pain disappeared and laboratory findings markedly improved. These data indicate that the pathogenesis of neuromyopathy in this case was closely related to colchicine and cyclosporin. Caution will be needed in using these drugs for patients with Behçet's disease.

Behcet Syndrome↗

[Computer simulation of DOI-PET detector (1) -analysis of DOI discrimination accuracy in a detector block-].

A detector proposed by Murayama et al. for detection of depth-of-interaction (DOI) in PET consists of three-dimensionally arranged crystal elements with proper optical reflectors and is coupled to an array of photomultiplier tubes. This detector has a great advantage in easiness and cost in fabrication. We implemented a simulator of this detector that allows us to find appropriate values of parameters such as optical properties of crystal or detector unit geometry before making detectors. The simulator is based on the Monte Carlo method that traces the migration of optical photons generated by interaction of a gamma ray with crystal. First, the simulator performance was validated by comparing with the experimental data obtained with some prototype detectors. Then, on some parameters including refractive index of inter-crystal material, reflectance of optical reflector and detector geometry, appropriate values were investigated for accurate discrimination of crystal element of interaction.

Computer Simulation↗

[Hemophagocytic syndrome associated with hypercytokinemia in a patients with rheumatoid arthritis].

A 65-year old female, who had been suffered from rheumatoid arthritis, was admitted to our hospital because of fever, oral ulcers, perianal skin ulcers, petechiae in the both legs, hepatosplenomegaly and cervical lymphadenopathy. Her laboratory data showed severe anemia, leukocytopenia, and thrombocytopenia as well as low PT activity, prolonged APTT, decreased fibrinegen and elevated FDP. In addition to raised values of liver enzymes and triglyceride, marked elevation of several cytokines were found. IgM and IgG class antibodies to cytomegalovirus were demonstrated positive and their titers were 2.60 and 938.0, respectively. The study for the aspiration of bone marrow revealed hemophagocytosis of erythrocytes, leukocytes and thrombocytes. Based upon these findings, she was diagnosed as having hemophagocytic syndrome associated with cytomegalovirus infection. Steroid treatment inducing mini-pulse therapy was introduced to her and bought full recovery from the illness. The association of hemophagocytic syndrome to rheumatoid arthritis was reviewed in the literature and five cases were documented to have good prognosis with steroid treatment.

Aged↗

[Current status and prospect of T cell costimulatory blockade in transplantation].

Organ transplantation has been widely accepted as a routine medical treatment in Japan. The recent introduction of new immunosuppressive reagents may improve outcome after transplantation. However, further investigations are required to achieve the prevention of chronic rejection and the induction of donor-specific tolerance in clinical transplantation. The potential of costimulatory blockade in controlling allograft rejection is now extensively under investigation. Although costimulatory blockade can prevent rejection and induce tolerance experimentally, there are several issues that need to be clarified before its clinical application. Recently, several novel costimulatory pathways have also been reported. Each costimulatory pathway has distinct and unique immunological roles in T cell activation and down-regulation. Upon the perception of underlying mechanisms, the theoretical and effective use of costimulatory blockade in combination with conventional immunosuppression and/or novel molecular targeting therapies might make a major breakthrough in clinical transplantation.

Animals↗

Physiological mechanisms of regulating alloimmunity: cytokines, CTLA-4, CD25+ cells, and the alloreactive T cell clone size.

The mechanisms underlying physiological regulation of alloimmune responses remain poorly defined. We investigated the roles of cytokines, CTLA-4, CD25(+) T cells, and apoptosis in regulating alloimmune responses in vivo. Two murine cardiac transplant models were used, B10.D2 (minor mismatch) and C57BL/6 (major mismatch), into BALB/c recipients. Recipients were wild type, STAT4(-/-) (Th1 deficient), or STAT6(-/-) (Th2 deficient) mice. Minor mismatched allografts were accepted spontaneously in approximately 70% of wild type and STAT4(-/-) mice. By contrast, there was significantly shorter graft survival in minor mismatched STAT6(-/-) mice. Either the adoptive transfer of STAT4(-/-) splenocytes or the administration of IL-4Fc fusion protein into STAT6(-/-) mice resulted in long term graft survival. Blocking CTLA-4 signaling accelerated the rejection in all recipients, but was more pronounced in the minor combination. This was accompanied by an increased frequency of alloreactive T cells. Furthermore, CTLA-4 blockade regulated CD4(+) or CD8(+) as well as Th1 or Th2 alloreactive T cells. Finally, while anti-CD25 treatment prolonged graft survival in the major mismatched combination, the same treatment accelerated graft rejection in the minor mismatched group. The latter was associated with an increased frequency of alloreactive T cells and inhibition of T cell apoptosis. These data demonstrate that cytokine regulation, CTLA-4 negative signaling, and T cell apoptosis play critical roles in regulating alloimmunity, especially under conditions where the alloreactive T cell clone size is relatively small.

Abatacept↗

Synthesis and antibacterial evaluation of novel 2-[N-Imidoylpyrrolidinyl] carbapenems.

The synthesis, antibacterial activity and DHP-susceptibility of a series of novel carbapenems, directly linked with heterocyclic moiety are described. Especially, the compounds linked pyrrolidine-carbapenem exhibited to have a good antibacterial activity against Staphylococcus aureus (MRSA) as well as Pseudomonas aeruginosa to maintain a good stability towards DHP-I.

Animals↗

Combined intraarterial 5-fluorouracil and subcutaneous interferon-alpha therapy for advanced hepatocellular carcinoma with tumor thrombi in the major portal branches.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) invading into the major branches of the portal vein (Vp3) is extremely poor. METHODS: Eleven consecutive patients with HCC and Vp3 were treated with 2-6 cycles of a "basic" combination therapy consisting of continuous arterial infusion of 5-fluorouracil (450-500 mg/day, for the initial 2 weeks) and subcutaneous injection of interferon-alpha (5 million international units, 3 times/week, 4 weeks). In the first 3 patients, methotrexate (90 mg/day 1 of every week), cisplatin (10 mg/day), and leucovorin (30 mg/days 2 and 3 of every week) also were administered for the initial 2 weeks ("full" regimen). RESULTS: In 8 (73%) of 11 patients, an objective response (complete response [CR] or partial response [PR]) was observed with marked regression of tumor and decrease in tumor markers. The use of the full regimen was associated with objective response in all patients; instead, they developed thrombocytopenia or leukopenia. In the subsequent 8 patients with basic regimen, 5 patients showed CR (2 cases) or PR (3 cases; objective response rate, 63%), and leukopenia was observed only in 1 patient. CONCLUSIONS: Simple combination therapy with subcutaneous interferon-alpha and intraarterial 5-fluorouracil therefore is a promising treatment modality for intractable HCC with Vp3.

Adult↗

Simple assay for antitumour immunoactive glycoprotein derived from Chlorella vulgaris strain CK22 using ELISA.

A quantitative ELISA system was developed using a monoclonal antibody (MAb) specific for an antitumour immunoactive glycoprotein (CVS) derived from C. vulgaris strain CK22. The full measuring range of the assay extends from 0.63 to 10.0 ng/mL of CVS. Although no cross-reaction was observed to proteins tested or other biological response modifiers (BRMs) derived from different sources, cross-reactions were found with culture supernatants from two other strains of C. vulgaris having a strong antitumour immunoactivity. Treatment of CVS with protease, acid or alkali weakened or completely eliminated the reactivity against the MAb and also its antitumour immunoactivities. This ELISA system is suitable for the biologically active form of CVS derived from C. vulgaris strain CK22 and related immunoactive strains.

Algal Proteins↗

Less-invasive thoracic aortic aneurysm repair.

To minimize surgical trauma, we performed graft replacement of a descending aortic aneurysm through a minithoracotomy (12 cm) with the use of thoracoscopy and special vascular clamps. Contrast magnetic resonance angiography can be useful for preventing postoperative paraplegia by revealing the Adamkiewicz artery. The patient was satisfied with the postoperative comfort and good cosmetic result. Further refinement of the technique and instrumentation would make this technique a valuable adjunct to conventional thoracic aortic surgery.

Aged↗

Activation of signal transducer and activator transcription 3 and expression of suppressor of cytokine signal 1 during liver regeneration in rats.

BACKGROUND/AIMS: Recent work has shown that the signal transducer and activator of transcription (STAT) 3 activation is important for the initiation of the proliferative response following partial hepatectomy (PH). However, the issue of where STAT3 is activated and how it is regulated is unclear. The aims of this study were to identify STAT3-activated cells and to clarify the expression of suppressor of cytokine signal (SOCS), a negative feedback molecule of STAT3, after PH. METHODS: STAT3-activated cells and SOCS1-positive cells were identified by immunohistochemistry after a two-thirds PH in rats. SOCS mRNA was examined by Northern analysis. RESULTS: STAT3 was activated in hepatocytes from those localized in the periportal zones of hepatic lobules after PH. STAT3 activation was also detected in Kupffer cells and sinusoidal endothelial cells prior to its detection in hepatocytes. After STAT3 activation, SOCS1 protein in response to PH was detected immunohistochemically in regenerating liver. SOCS1 and SOCS3 mRNA were induced in regenerating liver after PH. CONCLUSIONS: STAT3 signaling can occur in Kupffer cells and sinusoidal endothelial cells prior to in hepatocytes from those localized in the periportal zones. SOCS1 as well as SOCS3 may regulate STAT3 signaling negatively after PH.

Animals↗

NF-kappaB activation in non-parenchymal liver cells after partial hepatectomy in rats: possible involvement in expression of heparin-binding epidermal growth factor-like growth factor.

BACKGROUND/AIMS: Nuclear factor (NF) B activation plays a critical role in the initiation of liver growth after partial hepatectomy (PH). However, the issue of where specifically NF-B is activated is unclear. We previously reported that heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a hepatotrophic factor. The aims of this study were to identify NF-B-activated cells and to clarify their involvement in HB-EGF expression after PH. METHODS: Using rats, a two-thirds PH was performed, after which NF-B-activated cells and HB-EGF-positive cells were identified by Southwestern histochemistry or immunohistochemistry. NF-B binding activity and HB-EGF gene expression were analyzed in rat hepatocytes and non-parenchymal cells (NPC) in primary culture. RESULTS: NF-B was activated in Kupffer cells and sinusoidal endothelial cells prior to activation in hepatocytes. HB-EGF immunoreactivity was detected after NF-B activation in the sinusoidal cells from those localized in the periportal zones of hepatic lobules. HB-EGF gene expression by tumor necrosis factor was accompanied by an increase in NF-B binding activity in NPC but not in hepatocytes in primary culture, which was abolished by pyrrolidine dithiocarbamate, an inhibitor of NF-B activation. CONCLUSIONS; NF-B was activated in NPC prior to activation in hepatocytes. NF-B activation may be involved in HB-EGF expression in NPC after PH.

Animals↗

The relative contribution of direct and indirect antigen recognition pathways to the alloresponse and graft rejection depends upon the nature of the transplant.

In this study, we measured direct and indirect T-cell alloresponses mediated by CD4(+) and CD8(+) T cells in three mouse transplantation models: skin, cornea, and retina. We show that the contribution of direct and indirect antigen recognition pathways to the alloresponse to fully allogeneic grafts varies depending upon the nature of the tissue/organ transplanted. The implications of this finding for understanding the cellular mechanisms by which rejection is mediated in different transplant models are discussed.

Animals↗

Thoracoabdominal or descending aortic aneurysm repair after preoperative demonstration of the Adamkiewicz artery by magnetic resonance angiography.

OBJECTIVE: The outcome of thoracoabdominal or descending aortic aneurysm repair after preoperative demonstration of the artery of Adamkiewicz (ARM) by magnetic resonance angiography (MRA) was investigated. METHODS: Between January 2000 and December 2001, 40 consecutive patients who had aneurysms of the thoracoabdominal or descending aorta underwent preoperative MRA to visualize the ARM. Thirty-two patients underwent replacement of the aneurysms, and 25 patients (TAAA, 11; TAA, 14) underwent replacement of the aneurysms with preoperative detection of the ARM. Only intercostal or lumbar arteries in aneurysms, which were detected as the origin of the ARM, were reattached to the graft. The results of thoracoabdominal aortic aneurysm operations in 11 patients in whom the ARM was preoperatively detected (group I) were compared with the results of TAAA operations in 26 patients in whom the ARM was not preoperatively detected (group II). RESULTS: MRA demonstrated the ARM in 29 (73%) of the 40 patients. The laterality of the arteries originated from the left side in 29 (100%) and between Th9 and Th12 in 25 (86%), between Th9 and L1 in 28 (97%) of the 29 patients. No spinal cord injury occurred in patients (TAAA and TAA) in whom the ARM had been preoperatively detected. Major complications following TAAA operations included paraplegia (0% in group I and 8% in group II), respiratory failure (9% in group I and 23% in group II), and renal failure requiring hemodialysis (18% in group I and 22% in group II). Operation times were 439+/-99 min in group I and 620+/-200 min in group II (P=0.008). CONCLUSIONS: Preoperative detection of the ARM is possible by MRA and is very useful for reducing the incidence of ischemic injury of the spinal cord and for reducing the time of an operation for repair of an aneurysm of the thoracoabdominal or descending aorta.

Aged↗

Transarterial embolization for large hepatocellular carcinoma with use of superabsorbent polymer microspheres: initial experience.

The authors report the initial experience with transarterial embolization of large hepatocellular carcinoma (HCC) with use of superabsorbent polymer microsphere (SAP-MS) particles. Six patients with nine HCCs (mean diameter, 8.2 cm) underwent 10 embolization procedures. Two patients underwent surgery later. In follow-up, tumor necrosis, postembolization syndrome, and laboratory data were assessed. Complete necrosis in three nodules, nearly complete necrosis in three nodules, and partial necrosis in three nodules were observed. Histologically, SAP-MS occluded intratumoral vessels tightly without ischemic damage of normal hepatic tissue. Postprocedural pain was minimal. No deterioration of liver function occurred. Our initial experience suggests that embolization with use of SAP-MS leads to extensive tumor necrosis of large nodular HCC, sparing use of chemotherapeutic agents.

Aged↗

Combination treatment with FTY720 and CTLA4IgG preserves the respiratory epithelium and prevents obliterative disease in a murine airway model.

BACKGROUND: Mouse heterotopic tracheal transplantation offers a reproducible model of obliterative bronchiolitis after lung transplantation. CTLA4IgG inhibits signaling of the CD28/B7 pathway and induces antigen-specific T-cell unresponsiveness. FTY720 induces T-cell apoptosis and sequestration of circulating mature lymphocytes. We previously found that CTLA4IgG could prevent the development of obliterative airway disease but could not preserve the respiratory epithelium of grafted tracheae. We evaluated whether treatment with either FTY720 or CTLA4IgG, or with combination FTY720 and CTLA4IgG could preserve the respiratory epithelium and inhibit the development of obliterative airway disease. METHODS: Tracheae with main bronchi from C3H/He mice were transplanted heterotopically into BALB/C mice and harvested on Day 35. Recipient mice received either no treatment or treatment with intraperitoneal FTY720, CTLA4IgG, or the combination of the 2. RESULTS: Either FTY720 or CTLA4IgG alone significantly inhibited the development of obliterative airway disease. However, normal ciliated columnar respiratory epithelial cells were lost in the allografts. In contrast, combination therapy preserved the respiratory epithelium of the allografted tracheae. FTY720 concentration in the tissue was very high; treatment with FTY720 inhibited mixed lymphocyte reactions and augmented T-cell apoptosis. CONCLUSION: Combination treatment with FTY720 and CTLA4IgG may prevent obliterative airway disease.

Abatacept↗

Renal contraction therapy for enlarged polycystic kidneys by transcatheter arterial embolization in hemodialysis patients.

Kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) usually continue to increase in size, even after patients begin dialysis therapy, and the mass effects may lead to severe complications. Such external conventional therapies as surgical and laparoscopic procedures have not yielded satisfactory results. Because kidneys in patients with ADPKD usually are supplied by well-developed arteries, we attempted renal contraction therapy in patients with ADPKD by renal transcatheter arterial embolization (TAE) using intravascular coils. After obtaining informed consent, we selected anuric patients on dialysis therapy with markedly distended abdomens or macroscopic hematuria. Between October 1996 and December 2000, a total of 64 patients were treated. Renal size, abdominal circumference, dry weight, hematocrit, and insulin-like growth factor-I were measured before TAE and 3, 6, and 12 months after TAE. Renal sizes decreased to 73.8% +/- 12.0%, 61.7% +/- 14.7%, and 53.4% +/- 11.6% of preinterventional values at 3, 6, and 12 months after therapy, respectively (P < 0.0001). Abdominal circumference and dry weight were significantly decreased at 3, 6, and 12 months (P < 0.0001) compared with baseline values before therapy. Hematocrits increased sequentially after 3, 6, and 12 months (P < 0.0001). Levels of insulin-like growth factor-I an index of nutritional status, significantly increased at 3, 6, and 12 months compared with the baseline value (P < 0.001). This therapy was effective for all patients. Serious complications were not seen after this treatment, although such minor complications as fever and flank pain were observed within the first week after the procedure. Our internal treatment with TAE is a safe and effective procedure that has resulted in improvement in the quality of life and nutritional status of patients with ADPKD.

Aged↗