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Biomedical subjects

M Kawakami

Publications and source records attributed to M Kawakami.

At least 145 records · Page 8Linked to original sources
PubMed1999

[Diabetic retinopathy--the mechanisms of the ocular neovascularization and the development of anti-angiogenic drugs].

Ocular neovascularization contributes to severe visual loss of the patients with diabetic retinopathy (DR) which is the leading cause of blindness on adults of working age. The mechanisms of ocular neovascularization are not fully understood. Several growth factors, particularly vascular endothelial growth factor (VEGF), vasoactive peptides such as angiotensin II and adhesion molecules such as integrins are considered to contribute to the ocular neovascularization. VEGF is believed to play the key role in the development of DR. Ischemic hypoxia of retina is well known to be the potent stimulus for the production of VEGF. In addition, we have reported that reactive oxygen intermediates, advanced glycation end products and insulin-like growth factor-1, also all, may participate in the pathogenesis of DR through their ability to increase VEGF production. The trials for anti-angiogenic drugs is developing now for the treatment of DR. VEGF may be the most suitable target for the inhibition of the ocular neovascularization.

Adult↗
PubMed1999

[Giant metastatic neck tumor responding to oral administration of UFT--a case report].

A 63-(correction of 65) year old female with giant neck tumor was admitted to our hospital. The pathological diagnosis was metastatic neck carcinoma of unknown origin. General and local examinations could not clarify the origin of her neck tumor. Computed tomography was performed, and her tumor was diagnosed as unresectable. She was treated by oral administration of UFT (400 mg/day). About four months later, her neck tumor showed a shrinking tendency and the clinical symptoms were improved. This case shows a remarkable response to the oral administration of UFT even in a case of terminal neck cancer.

Administration, Oral↗
PubMed1999

[Venous and arterial thrombotic events induced by synthetic-steroid hormones or oral contraceptives].

Most users of synthetic-steroid hormones for postmenopausal hormone replacement or contraception, are healthy with a low background incidence of major diseases. Since they take these medicines for a long time, serious or frequent adverse effects should not be occurred. By changing content and reducing dose of both estrogen and progestagen, the incidences of venous and arterial thrombotic events by combined low dose oral contraceptives, is low in women who have not major risk factors. Although postmenopausal hormone replacement therapy decreases risk for coronary heart diseases, it seems to increases for venous thromboembolic events according to several clinical trials. In this article, the recent data on both the risk and the mechanisms of venous and arterial thrombotic events associated with use of oral contraceptives or with postmenopausal hormone replacement, is reviewed.

Adult↗
PubMed1999

Detection of anti-annexin IV and V antibodies in patients with antiphospholipid syndrome and systemic lupus erythematosus.

OBJECTIVE: Annexins (Anx) are a family of structurally related proteins that bind to phospholipids in a calcium dependent manner. It has been reported that antibodies to Anx V, which acts as an antithrombotic protein, are associated with thrombosis in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). Homology between the primary structures of Anx IV and Anx V is the highest among members of the Anx family. We investigated whether anti-Anx IV autoantibodies can be detected in the sera of patients with SLE and/or APS. METHODS: Seventy-four patients with SLE/APS were divided into 3 groups: Group A, patients with SLE but no clinical or serological features of APS; Group B, patients with SLE having only serological signs of APS; and Group C, patients with clinical symptoms and serological signs of APS. Anx IV and Anx V were prepared by recombinant technique. Anti-Anx IV, Anx V, cardiolipin (CL), and CL beta2-glycoprotein I were detected by ELISA. RESULTS: Anti-Anx IV was found in 15.4% of Group A, 20.0% of Group B, and 21.7% of Group C. Anti-Anx V was found in 3.8% of Group A, 28.0% of Group B, and 30.4% of Group C. Significant correlations were noted between anti-Anx IV titer and anti-Anx V titer (p<0.001), and between anti-Anx IV titer and aCL titer (p<0.01). CONCLUSION: Anti-Anx IV and V antibodies were characterized in the sera of patients with SLE/APS. Significantly higher frequency of arterial or venous thrombosis was found in patients with anti-Anx V.

Adolescent↗
PubMed1999

Three-dimensional image analysis of the hepatic restructuring process in chronic active hepatitis.

OBJECTIVE: To elucidate the process of hepatic restructuring in the course of chronic hepatitis from a morphologic viewpoint. STUDY DESIGN: The three-dimensional (3-D) liver structure was investigated by computer-aided reconstruction in five cases (one autopsy and four surgical cases) of chronic active hepatitis (type C), including early to late stages of restructuring. RESULTS: Our 3-D reconstruction revealed the following. At an early stage, portal and periportal inflammation and fibrosis widened the portal tracts, giving rise to the formation of portal-to-portal and portal-to-hepatic venous connections, although most central veins were still located at an almost normal site in the hepatic lobules. In a middle stage, bridging fibrosis developed to create a network of interstitium where the central veins were rather decreased in number, with regenerative nodules multiplying in the parenchyma. At the late stage, the lobular structure was destroyed, and the parenchyma consisted uniformly of regenerative nodules, with remaining but rearranged lobules among them. CONCLUSION: The above changes of liver structure suggest that in cirrhogenesis from chronic hepatitis, a combination of nodular regeneration and formation of an interstitial network come to replace the normal lobular structure, hastening the development of liver cirrhosis.

Adult↗
PubMed1999

True small lymphocytic T-cell chronic lymphocytic leukemia lacking the CD3 molecule and TCR-alpha beta on its cell surface.

We report a case of T-cell chronic lymphocytic leukemia (T-CLL) in which the lymphocytes were small and mature, did not have cytoplasmic granulation, and appeared to be similar to those of B-cell chronic lymphocytic leukemia (B-CLL). Immunophenotyping of the lymphocytes revealed CD2+, CD4+, CD5+, and CD25+ on the cell surface, but expression of the CD3 and TCR-alpha beta molecules was localized only in the cytoplasm. The clinical course was as indolent as that of B-CLL, and the patient was able to undergo open-heart surgery. Thus, we confirmed that true T-CLL is able to exist as a counterpart of B-CLL.

Aged↗
PubMed1999

[Home chemotherapy in the Department of surgery, Higashi Sapporo Hospital].

It is widely accepted that home chemotherapy improves the quality of life (QOL) of patients. Its purpose is to prevent the growth of the tumor rather than to reduce it is size, that is long NC, and to lessen the symptoms. The most important thing is side-effect-free treatment, because the patient is usually in the home. For this reason, the patient him/herself must be familiar with the side effects and emergency situations. Evaluation of home chemotherapy is very difficult, because the amount of anticancer drug is reduced or optimized for the individual patient. Thus, evaluation depends not only on tumor size, but also on QOL, lessening of symptoms, satisfaction or dissatisfaction with the treatment, and the philosophy of life of patients. This approach is being put to greater and greater use to maintain the QOL of patients, and to reduce the hospital costs. In the future, new anticancer drugs that have fewer side effects and stronger anticancer action are desirable.

Adult↗
PubMed1999

Non-traumatic aneurysms of the cavernous sinus causing massive epistaxis--report of three cases.

Three cases of non-traumatic intracavernous aneurysms that gave rise to massive epistaxis and required operative intervention, are reported. This is a rare but serious cause of epistaxis, because delayed diagnosis and management can lead to repeated bleedings and even to death. It is important, therefore, to diagnose the source of epistaxis and treat it as soon as possible. In our three patients, an emergency angiography enabled us to diagnose an aneurysm in the cavernous sinus. These aneurysms were located in the C3 or C4 portion of the internal carotid artery and were 3-5 mm in diameter. The projections of these aneurysms were infero-medial, antero-inferior, and lateral, respectively. All three patients underwent emergent surgery. Neck clipping of the aneurysm was performed in two patients, and gradual occlusion of the internal carotid artery in the third patient. Emergency surgery successfully prevented further episodes of epistaxis in all three patients.

Aneurysm↗
PubMed1998

Indication and clinical results of laminoplasty for cervical myelopathy caused by disc herniation with developmental canal stenosis.

STUDY DESIGN: The outcome of a herniated disc in patients with cervical myelopathy treated by laminoplasty without discectomy and in those treated conservatively was studied by magnetic resonance imaging. OBJECTIVES: To compare the surgical results of laminoplasty with those of anterior spinal fusion in patients with myelopathy caused by to cervical disc herniation and to make a treatment strategy for cervical disc herniation depending on these results. SUMMARY OF BACKGROUND DATA: Anterior discectomy and spinal fusion have had acceptable surgical results, but many complications have been reported, especially adjacent segment degeneration and bone graft complications. METHODS: Forty-seven patients with cervical disc herniation were examined in this study. Of them, 32 patients (mean age, 56 years) underwent laminoplasty without resection of the herniated disc. Seven patients with mild cervical myelopathy and 8 patients with radiculopathy (mean age, 53 years) were treated conservatively. As a control group, 44 patients (mean age, 50.3 years) who underwent anterior spinal fusion were examined. All patients in the laminoplasty group also had congenital spinal canal stenosis in which the ventrodorsal canal diameter was less than 13 mm. The association between the outcome of a herniated disc and clinical features was investigated. The severity of myelopathy was evaluated according to the Japanese Orthopaedic Association's scoring system. Surgical outcomes were evaluated by the system of Hirabayashi for determining recovery rate. RESULTS: The recovery rate averaged 67.9% in laminoplasty and 68.8% in anterior spinal fusion. There were no significant differences between the groups. No patients underwent anterior spinal fusion after laminoplasty. Follow-up magnetic resonance imaging showed regression of the size of the herniated disc in 15 of the 20 patients in the laminoplasty group and in 12 of 15 patients treated conservatively. In the MRI studies of the natural course of disc herniation, the size of the herniated disc decreased to almost half in 1 to 2 months and almost disappeared within 3 months after surgery. CONCLUSIONS: The size of the herniated disc in cervical lesions regressed as it does in the lumbar lesions. Laminoplasty for patients with narrowed spinal canals showed favorable surgical results. Therefore, the therapeutic method for cervical disc herniation should be chosen after taking the natural history of the disc herniation into consideration.

Case-Control Studies↗
PubMed1998

An ion channel of the degenerin/epithelial sodium channel superfamily controls the defecation rhythm in Caenorhabditis elegans.

Ultradian rhythms are widespread phenomena found in various biological organisms. A typical example is the defecation behavior of the nematode Caenorhabditis elegans, which repeats at about 45-sec intervals. To elucidate the mechanism, we studied flr-1 mutants, which show very short defecation cycle periods. The mutations also affect some food-related functions, including growth rate, the expulsion step of defecation behavior, and the regulation of the dauer larva (a nonfeeding, special third-stage larva) formation in the unc-3 (Olf-1/EBF homolog) background. The flr-1 gene encodes a novel ion channel belonging to the DEG/ENaC (C. elegans degenerin and mammalian epithelial sodium channel) superfamily. A flr-1::GFP (green fluorescent protein) fusion gene that can rescue the flr-1 mutant phenotypes is expressed only in the intestine from embryos to adults. These results suggest that FLR-1 may be a component of an intestinal regulatory system that controls the defecation rhythm as well as other functions.

Activity Cycles↗
PubMed1998

Mammalian mitochondrial methionyl-tRNA transformylase from bovine liver. Purification, characterization, and gene structure.

The mammalian mitochondrial methionyl-tRNA transformylase (MTFmt) was partially purified 2,200-fold from bovine liver mitochondria using column chromatography. The polypeptide responsible for MTFmt activity was excised from a sodium dodecyl sulfate-polyacrylamide gel and the amino acid sequences of several peptides were determined. The cDNA encoding bovine MTFmt was obtained and its nucleotide sequence was determined. The deduced amino acid sequence of the mature form of MTFmt consists of 357 amino acid residues. This sequence is about 30% identical to the corresponding Escherichia coli and yeast mitochondrial MTFs. Kinetic parameters governing the formylation of various tRNAs were obtained. Bovine MTFmt formylates its homologous mitochondrial methionyl-tRNA and the E. coli initiator methionyl-tRNA (Met-tRNAfMet) with essentially equal efficiency. The E. coli elongator methionyl-tRNA (Met-tRNAmMet) was also formylated although with somewhat less favorable kinetics. These results suggest that the substrate specificity of MTFmt is not as rigid as that of the E. coli MTF which clearly discriminates between the bacterial initiator and elongator Met-tRNAs. These observations are discussed in terms of the presence of a single tRNAMet gene in mammalian mitochondria.

Amino Acid Sequence↗
PubMed1998

Effects of steroid and lipopolysaccharide on spontaneous resorption of herniated intervertebral discs. An experimental study in the rabbit.

STUDY DESIGN: Histologic examination was performed on autografted intervertebral disc materials of rabbit models, which were partially incised through a retroperitoneal approach at L1-L2 and grafted within the posterior epidural space at L4. OBJECTIVE: To evaluate whether the resorption process of the herniated intervertebral disc is influenced and controlled by treatments with medications. SUMMARY OF BACKGROUND DATA: Regarding resorption of herniated intervertebral discs, recent studies of magnetic resonance images and histologic investigations of surgically resected specimens in lumber disc herniation patients have been reported. It has been shown that inflammatory factors may play an important role in the mechanism of resorption of the herniated intervertebral disc. However, little is known about the origin of newly formed vessels and inflammatory cells detected in herniated disc specimens from patients. In this study, The resorption process of disc material grafted into the epidural space was observed in a rabbit model. METHODS: Thirty-six adult rabbits were used. The L1-L2 intervertebral disc was partially incised through a retroperitoneal approach. The harvested disc material, which contains the nucleus pulposus and the anulus fibrosus were placed into the posterior epidural space at L4 of the same rabbit. The animals were divided into control, and steroid groups. The control group received no treatment after surgery. In the lipopolysaccharide group, rabbits were injected 1 mg/kg into the peritoneum immediately and at 7 days after surgery. In the steroid group, rabbits were injected with 1 mg/kg betamethasone into the epidural space daily from 1 to 7 days after surgery. Rabbits of each group were killed for histologic examination at 1, 2, 4, and 8 weeks after surgery. RESULTS: At 1 and 2 weeks after surgery, inflammatory cells and newly formed vessels were more frequently observed in the lipopolysaccharide group than in the control and steroid groups. At 4 weeks after surgery, derangement and loosening of collagen fibers were also observed in the lipopolysaccharide group. At 8 weeks after surgery, fragmentation and partial disappearance of matrix were observed in the control and lipopolysaccharide groups. Most of the intervertebral discs were replaced by fibrous tissues in the lipopolysaccharide group. However, the matrix of the intervertebral disc almost remained. CONCLUSIONS: Autologous intervertebral disc material grafted into the epidural space was penetrated by newly formed vessels produced from the epidural fat tissue and resolved as the result of inflammatory reaction. Lipopolysaccharide accelerated the replacement of grafted intervertebral disc by fibrous tissue, which suggests the resorption of the disc in the epidural space of the rabbit, whereas high-dose steroid suppressed the replacement.

Animals↗
PubMed1998

Wilms' tumor gene (WT1) competes with differentiation-inducing signal in hematopoietic progenitor cells.

The WT1 gene is a tumor-suppressor gene that was isolated as a gene responsible for Wilms' tumor, a childhood kidney neoplasm. We have previously reported that the WT1 gene is strongly expressed in leukemia cells with an increase in its expression levels at relapse and an inverse correlation between its expression levels and prognosis, thus making it a novel tumor marker for leukemic blast cells. Furthermore, WT1 antisense oligomers have been found to inhibit the growth of leukemic cells. These results strongly suggested the involvement of the WT1 gene in human leukemogenesis. The present study was performed to prove our hypothesis that the WT1 gene plays a key role in leukemogenesis and performs an oncogenic function in hematopoietic progenitor cells, rather than a tumor-suppressor gene function. 32D cl3, an interleukin-3-dependent myeloid progenitor cell line, differentiates into mature neutrophils in response to granulocyte colony-stimulating factor (G-CSF). However, when transfected wild-type WT1 gene was constitutively expressed in 32D cl3, the cells stopped differentiating and continued to proliferate in response to G-CSF. As for signal transduction mediated by G-CSF receptor (G-CSFR), Stat3alpha was constitutively activated in wild-type WT1-infected 32D cl3 in response to G-CSF, whereas, in WT1-uninfected 32D cl3, activation of Stat3alpha was only transient. However, most interesting was the fact that G-CSF stimulation resulted in constitutive activation of Stat3beta only in wild-type WT1-infected 32D cl3, but not in WT1-uninfected 32D cl3. Thus, WT1 expression constitutively activated both Stat3alpha and Stat3beta. A transient activation of Stat1 was detected in both wild-type WT1-infected and uninfected 32D cl3 after G-CSF stimulation, but no difference in its activation was found. No activation of MAP kinase was detected in both wild-type WT1-infected and uninfected 32D cl3 after G-CSF stimulation. These results demonstrated that WT1 expression competed with the differentiation-inducing signal mediated by G-CSFR and constitutively activated Stat3, resulting in the blocking of differentiation and subsequent proliferation. Therefore, the data presented here support our hypothesis that the WT1 gene plays an essential role in leukemogenesis and performs an oncogenic function in hematopoietic progenitor cells and represent the first demonstration of an important role of the WT1 gene in signal transduction in hematopoietic progenitor cells.

Animals↗
PubMed1998

Structure-activity of novel rhodacyanine dyes as antitumor agents.

We have previously reported that rhodacyanine dyes, such as 1 and 2, exhibited a potent inhibitory effect on the growth of several tumor cells and that 4-oxothiazolidine (rhodanine) was an essential moiety for antitumor activity. On the basis of our foregoing work, two types of rhodacyanine dyes, which categorized into class I and II depending on the methine length, were synthesized and evaluated as a novel antitumor agent. Attention was particularly focused on the structure-activity study of two heteroaromatic rings. In class I, where the A rings were conjugated to rhodanine via two methine groups, compounds 1, 20, 23, and 24 were found to be efficacious in tumor-bearing nude mice model study, but they did not have the chemical properties (stability, solubility) suitable for clinical use. In contrast, in class II, where the A rings were directly conjugated to rhodanine, compounds 13 and 25, which possessed a benzothiazole moiety for the A ring, exhibited the favorable biological and chemical properties. Therefore, we decided to have a benzothiazole moiety as the A ring and introduce various heterocyclic groups for the B ring. As a result, the pyridinium ring was selected as the optimal moiety for the B ring (compound 13). Further, the variation of counteranion had a profound effect on solubility in water without influence on antitumor activity. Chloride anion was selected as the favorable anion with respect to synthetic method as well as solubility in water. Our study finally led us to the identification of compound 3 (MKT 077, 1-ethyl-2-[[3-ethyl-5-(methylbenzothiazolin-2-ylidene)-4-oxothi azolidin-2 -ylidene]methyl]pyridinium chloride) as the candidate for clinical trials and is currently subjected to further investigation as a potent antitumor agent in phase I clinical trial for the treatment of solid tumors.

Animals↗
PubMed1998

Adsorption of anaphylatoxins from the plasma of systemic lupus erythematosus patients using dextran sulfate cellulose columns.

Complement-derived anaphylatoxin may be one of the causes of vascular injury and an indicator of activity in systemic lupus erythematosus (SLE). The present study examines the effectiveness of dextran sulfate (DS) column immunoadsorption treatment to remove anaphylatoxins (C3a, C4a, and C5a) from the blood of patients with SLE. Seven SLE patients were subjected to immunoadsorption using DS-bound cellulose columns (Selesorb, Kaneka). Blood samples were taken both before and after the immunoadsorption session. Specimens were also obtained from both the inlets and outlets of the DS columns every 1,000 ml of treated plasma volume. The DS columns removed anaphylatoxins C3a and C4a from the separated plasma (from 775+/-334 ng/ml to 640+/-252 ng/ml, and from 1,303+/-847 ng/ml to 619+/-578 ng/ml, respectively) during the clinical anti-DNA apheresis procedure. In these study, the C5a levels in the circulating plasma of SLE patients were not elevated. To confirm whether DS-bound cellulose beads adsorbs anaphylatoxins in vitro, zymosan-activated plasma (ZAP) containing high levels of anaphylatoxins was incubated with DS-bound cellulose beads. The levels of C3a, C4a and C5a in the ZAP significantly decreased by mixing with DS-bound cellulose beads (P<0.05). Nevertheless, C3a and C4a in the peripheral blood were not significantly decreased after the immunoadsorption, suggesting that these anaphylatoxins bypass the DS columns in apheresis and return to the patient via the cell-rich fraction.

Adult↗
PubMed1998

Idiopathic mediastinal fibrosis: report of a case.

We report herein the case of a 28-year-old woman who presented with a mediastinal mass, subsequently confirmed to be idiopathic mediastinal fibrosis. Preoperative chest computed tomography (CT) showed a noncalcified mediastinal mass and surgery was performed to exclude malignancy. The mass was hard and dense, involved the left phrenic nerve, vagus nerve, and left upper lobe, and surrounded the subclavian artery, subclavian vein, superior vena cava, and left pulmonary artery. Pathologic examination showed the findings of mediastinal fibrosis and the mass was partially excised. Postoperative medical treatment was performed with prednisolone and tranilast, and a 3-year follow-up has not demonstrated any complications.

Adult↗
PubMed1998

Plasma activated clotting time as an indicator of dangerous hypocoagulability in warfarin-treated trauma patients: a preliminary study.

This study was conducted to determine the possibility of detecting dangerous hypocoagulability in trauma victims given warfarin by measuring plasma activated clotting time (ACT). Sensitivity of the plasma ACT to warfarin was tested using lyophilized plasmas and plasma samples from nontraumatized but anticoagulated patients. Lyophilized plasmas were also used to evaluate the effect of defects in the intrinsic coagulation system on the plasma ACT. The plasma ACT, measured using a 4.4-mM calcium solution, showed satisfactory prolongation when the thrombotest of matched samples was within the therapeutic range for warfarin therapy. Conversely, the plasma ACT was not prolonged when the only abnormality of matched samples was mild to moderate prolongation of the activated partial thromboplastin time (APTT). These findings suggest that the plasma ACT could be a reliable indicator of dangerous hypocoagulability in trauma patients receiving warfarin therapy during the immediate postinjury period.

Anticoagulants↗