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Biomedical subjects

T Okuda

Publications and source records attributed to T Okuda.

At least 163 records · Page 9Linked to original sources
PubMed1996

Acceleration of wound healing in diabetic mice by basic fibroblast growth factor.

We studied the effect of recombinant human basic fibroblast growth factor (bFGF) on wound healing in genetically diabetic mice. Wound closure after full-thickness excision of skin was markedly delayed in diabetic mice compared to normoglycemic mice. A single application of bFGF caused a marked acceleration of wound healing in a dose-dependent manner. There were no hypertrophic scars or unlimited granulation tissue formation in regenerated tissues treated with any doses of bFGF under histological examination. The repeated application of bFGF for 7 d showed a bell-shaped dose-response in the rate of wound closure, and the optimal dose was as small as 0.2-2 mu g per wound. Reduced angiogenesis and granulation tissue formation were observed in diabetic mice compared to normal mice, and bFGF treatment restored both responses to significant levels. The beneficial effect of bFGF on wound healing would be largely explained by enhanced angiogenesis and granulation tissue formation.

Animals↗
PubMed1996

[FAM as a palliative chemotherapy for gastric cancer with bone metastasis].

A 50-year-old male was admitted to our hospital with severe malaise and lumbar pain. He suffered from diffuse bone metastasis of gastric cancer (mod. tub. adenocarcinoma) and DIC. In order to palliate his severe bone pain and bleeding tendency, FAM (5-fluorouracil 600 mg/body day 1, 7, 29, 36; doxorubicin 40 mg/body day 1, 29; and mitomycin C 12 mg/body day 1) combination chemotherapy was used. After administration of FAM therapy, bone pain and bleeding tendency due to DIC disappeared. For three months after initiation of chemotherapy, the patient's quality of life was maintained fairly well. Adverse reactions of FAM therapy were only appetite loss for several days. FAM therapy might be a useful regimen for palliation of bone pain and DIC due to diffuse bone metastasis of gastric cancer.

Adenocarcinoma↗
PubMed1996

[Primary myelofibrosis with positive coombs' test responding to prednisolone].

Primary myelofibrosis was diagnosed in a 43-year-old female in 1991, who gradually became transfusion dependent. There was no evidence suggesting connective tissue diseases except for biological false positive STS. Because her direct Coombs' test was positive and serum haptoglobin level was extremely low (< 6mg/dl), intermediate dose (30mg/day) prednisolone therapy was started. Her hemoglobin level and platelet count increased dramatically to a normal level within 3 weeks after the initiation of prednisolone therapy. Bone marrow biopsy performed 6 months later revealed marked recovery of hematopoiesis. Though the effects of corticosteroid therapy in primary myelofibrosis still remain unclear, this therapy might be useful in the treatment of some groups of patients via the correction of immunological aberrations and/or the decrease of bone marrow fiber.

Adult↗
PubMed1996

[Multiple myeloma presenting as parasellar syndrome and cranial nerve palsies].

Cranial and intracranial locations have been rarely reported in multiple myeloma. Their occurrence as a harbinger of multiple myeloma seems to have a particular significance. In this report, we discuss a case of multiple myeloma presenting as parasellar syndrome and cranial nerve palsies. A 75-year-old woman was admitted to the hospital in June, 1994, with a 3-month history of headache and a 3-week history of diplopia and photophobia. Physical examination revealed right third, fourth and sixth cranial nerve palsies. MRI scan demonstrated a homogeneous, voluminous mass, isointense in T1-weighted images with the cerebral parenchyma and hyperintense in T2-weighted images, occupying the sphenoid sinus and extending within the sella turcica and right cavernous sinus. Lying above the mass and apparently separated from it by a thin rim of hypointensity was a normal pituitary gland. X rays revealed destructive changes of the sella turcica. A minimal disturbance of endocrine function together with a radiologically abnormal pituitary fossa indicated that the primary lesion might lie outside the pituitary fossa. A diagnosis of IgG-kappa type multiple myeloma was made by pertinent laboratory studies. She received local radiation to the intracranial mass (50 Gy) and conventional chemotherapy. Sixteen months after the therapy she is in good health.

Aged↗
PubMed1996

Effect of basic fibroblast growth factor on wound healing in healing-impaired animal models.

The effect of basic fibroblast growth factor (bFGF) on wound healing was studied in healing-impaired animal models such as metabolic diseases (obesity and diabetes), infection, steroid treatment, malnutrition and chronic liver failure. bFGF treatment resulted in an acceleration of wound healing in an almost same dose range regardless of impairment causes or animal species used. The beneficial effects of bFGF on wound healing were suggested to be due to its potent angiogenesis and granulation tissue formation activities, leading to a rapid reepitherialization of the wound. In addition, the findings that bFGF promoted healing in infection wound and burn wound of diabetic mice, and burn wound of dietary-restricted rats indicated its ability to accelerate wound contraction, another important process of wound closure.

Animals↗
PubMed1996

[Prolonged antinociceptive effect after epidural injection of polyethylene glycol-morphine composites in rats].

Epidurally administered morphine is useful in the management of postoperative or cancer pain, and a reliable method which can produce prolongation of analgesia with a single dose may be very useful. We synthesized a polyethylene glycol-morphine (PEG-morphine) composites and examined the duration of analgesia after a single epidural administration dose of this agent in the rat. The molecular weight of PEG was functionally evaluated. PEG-morphine was injected surgically along the epidural space. Morphine in doses of 2.5, 5.0 and 7.5 mg and PEG only were administered. A second group of animals received intramuscular injections of PEG-morphine (5.0mg). Animals were then tested for analgesia using the tail-flick test. The antinociceptive effect of 7.5mg was significantly longer than that of 2.5mg or 5.0mg. Neither PEG alone nor intramuscular administration of PEG-morphine induced antinociceptive effect. Sensory blockade was reversible and the animal appeared to have normal sensory perception. We conclude that the antinociceptive effect of morphine is dose-dependent and its duration can be prolonged when administered as a PEG-morphine composite in the epidural space.

Analgesics, Opioid↗
PubMed1996

[Role of peritoneal lavage smears and gastric wall brushing smears in gastric cancer surgery].

Examinations of peritoneal lavage smears (LC) and gastric wall brushing smear cytology (BC) appear to be important for determining accurately the stage of gastric cancer. We have been carrying out such examinations during gastric cancer surgery for 7 years. In the present study, we evaluated the results obtained from 287 patients with gastric cancer. Tumor invasion and peritoneal dissemination were correlated with a positive incidence of cancer cells in LC and/or BC. Gastric cancer showing serosal invasion was classified into positive for LC and/or BC and negative for LC and/or BC. Patients positive for LC and/or BC had a poorer prognosis. For future gastric cancer treatment, patients positive for peritoneal cytology are expected to be targeted for intensive treatment during or before surgery.

Adenocarcinoma↗
PubMed1996

[Primary amyloidosis complicated with chronic myelomonocytic leukemia].

A 79-year-old male was admitted to our hospital because of abnormal shadows in both lungs on chest X-ray film. He had a 5-year history of repeated bleeding episodes of unknown etiology before admission. Transbronchial lung biopsy revealed the alveolar septal type of lung amyloidosis. His serum contained a monoclonal IgA-lambda type protein but there was no evidence of multiple myeloma. A diagnosis of primary amyloidosis was made. On admission, his hematological findings revealed the coexistence of chronic myelomonocytic leukemia (CMML). Coexistence of primary amyloidosis and CMML is extremely rare. Because monocytes are known to play an essential role in the degenerative processes of serum amyloid precursor, it was suggested that his amyloidosis was accelerated by the onset of CMML through certain dysfunctions of pathological monocytes.

Aged↗
PubMed1996

Enhanced angiogenesis and granulation tissue formation by basic fibroblast growth factor in healing-impaired animals.

The effect of basic fibroblast growth factor (bFGF) on angiogenesis and granulation tissue formation in normal and healing-impaired animals was studied. bFGF showed a dose-dependent enhancement of granulation tissue formation in the subcutaneous implantation of a paper disk in normal rats. Application of bFGF restored the formation in healing-impaired rat models treated with steroid, chemotherapy and X-ray irradiation. The angiogenic activity of bFGF was also demonstrated in the micro-pocket assay using the cornea of rabbits. Repeated applications of bFGF accelerated closure of full-thickness excisional wounds in diabetic mice, but the high doses showed rather diminished response. In contrast histological and gross evaluation of wound tissues revealed enhanced angiogenesis and granulation tissue formation in a dose-dependent manner. The findings suggested that the topical application of excess amounts of bFGF might reduce its ability to promote wound closure because of the prolonged responses in both neovascular and granulation tissue formation.

Animals↗
PubMed1995

Molecular cloning, expression pattern, and chromosomal localization of human CDKN2D/INK4d, an inhibitor of cyclin D-dependent kinases.

Progression through the G1 phase of the cell cycle is dependent on the activity of holoenzymes formed between D-type cyclins and their catalytic partners, the cyclin-dependent kinases cdk4 and cdk6. p16INK4a, p15INK4b, and p18INK4c, a group of structurally related proteins, function as specific inhibitors of the cyclin D-dependent kinases and are likely to play physiologic roles as specific regulators of these kinases in vivo. A new member of the INK4 gene family, murine INK4d, has recently been identified. Here we report the isolation of human INK4d (gene symbol CDKN2D), which is 86% identical at the amino acid level to the murine clone and approximately 44% identical to each of the other human INK4 family members. The INK4d gene is ubiquitously expressed as a single 1.4-kb mRNA with the highest levels detected in thymus, spleen, peripheral blood leukocytes, fetal liver, brain, and testes. The abundance of INK4d mRNA oscillates in a cell-cycle-dependent manner with expression lowest at mid G1 and maximal during S phase. Using a P1-phage genomic clone of INK4d for fluorescence in situ hybridization analysis, the location of this gene was mapped to chromosome 19p13. No rearrangements or deletions of the INK4d gene were observed in Southern blot analysis of selected cases of pediatric acute lymphoblastic leukemia (ALL) containing a variant (1;19)(q23;p13) translocation that lacks rearrangement of either E2A or PBX1, or in ALL cases containing homozygous or hemizygous deletions of the related genes, INK4a and INK4b.

Amino Acid Sequence↗
PubMed1995

Involvement of rho in GTP gamma S-induced enhancement of phosphorylation of 20 kDa myosin light chain in vascular smooth muscle cells: inhibition of phosphatase activity.

In beta-escin-permeabilized cultured pig aortic smooth muscle cells GTP gamma S dose-dependently enhances Ca(2+)-induced, wortmannin-sensitive phosphorylation of 20 kDa myosin light chain (MLC20). GTP gamma S does not potentiate thiophosphorylation of MLC20, but does inhibit its dephosphorylation. Pretreatment with C. botulinum exotoxin C3, which specifically ADP-ribosylates and inactivates the rho family of the small molecular weight G proteins, completely abolishes the effects of GTP gamma S. These results indicate that rho is involved in the GTP gamma S-induced enhancement of Ca(2+)-dependent MLC20 phosphorylation in aortic smooth muscle cells, and strongly suggest that this effect of rho is due to inhibition of protein phosphatase activity toward MLC20.

Animals↗
PubMed1995

Frequent deletion of p16INK4a/MTS1 and p15INK4b/MTS2 in pediatric acute lymphoblastic leukemia.

The tandemly linked p16INK4aMTS1 and p15INK4b/MTS2 genes on chromosome 9, band p21 encode proteins that function as specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. This locus undergoes frequent bi-allelic deletion in human cancer cell lines, suggesting that the encoded proteins may function as tumor suppressors. However, more recent analysis of primary tumor samples has shown a much lower frequency of abnormalities affecting this region, raising doubt over the importance of these proteins in human malignancies. Hemizygous deletions and rearrangements of chromosome 9, band p21, are among the most frequent cytogenetic abnormalities detected in pediatric acute lymphoblastic leukemia (ALL), occurring in approximately 10% of cases. To determine if the p16INK4a/p15INK4b locus might be the target of these chromosomal lesions, we analyzed both genes in primary clinical samples from 43 pediatric ALL patients using interphase fluorescence in situ hybridization, Southern blot analysis, and the polymerase chain reaction. Deletions of p16INK4a/p15INK4b were identified in 18 of 20 cases with cytogenetically observed abnormalities of 9p and 5 of 23 with apparently normal chromosomes 9p, with the majority containing bi-allelic deletions (16 homozygous/7 hemizygous). Although most homozygous deletions involved both genes, Southern blot analysis showed an interstitial deletion in a single case that was confined to p16INK4a, suggesting that p15INK4b was not the critical target gene in this case. Sequence analysis of both p16INK4a and p15INK4b in all seven cases with hemizygous deletions failed to show mutations within the coding regions of the retained alleles. In this select group of patients, deletion of p16INK4a/p15INK4b was associated with T-cell phenotype, nonhyperdiploid karyotype (< 50 chromosomes), and poor event-free survival. These findings indicate that deletion of the p16INK4a/p15INK4b locus is one of the most common genetic abnormalities so far detected in pediatric ALL, and that loss of one or more of these cell cycle kinase inhibitors is important in leukemogenesis.

Adolescent↗
PubMed1995

Clinical significance of epidermal growth factor (EGF), EGF receptor, and c-erbB-2 in human gastric cancer.

The EGF stimulation system for growth regulation is implicated in normal and neoplastic cell proliferation. The role of EGF, the EGF receptor, and c-erbB-2 in human gastric cancer is reviewed on the basis of several reports, which have been mainly oriented toward their clinical significance. EGF has been shown immunohistochemically to be present in 26% of gastric cancers (n = 395). The presence of EGF in gastric cancer is correlated with the degree of gastric wall invasion and lymph node metastasis. The 5-year survival of patients with EGF-positive tumors is worse than that of patients with EGF-negative tumors. The presence of EGF in human gastric cancer may therefore represent a higher malignant potential. Fifteen percent of gastric cancers (n = 352) were also shown to be positive for both EGF and the EGF receptor immunohistochemically, and the simultaneous occurrence of EGF and the EGF receptor suggests that these tumors grow in an autocrine fashion. Tumors exhibiting EGF and the EGF receptor simultaneously show a greater degree of local invasion and lymph node metastasis. Increased expression of EGF receptor protein in gastric cancer appears to be related to biologic aggressiveness, although gene amplification has occurred only to a small extent. Twelve percent of gastric cancers (n = 486) were found to be positive for c-erbB-2. This type of tumor has a frequent metastasis, and patients with c-erbB-2-positive cancer have a poorer prognosis than those with c-erbB-2-negative tumors. Selective blockade of the EGF receptor and c-erbB-2 from their ligands with monoclonal antibodies (MoAbs) inhibits the growth of human gastric cancer xenografts. These MoAbs may therefore be effective antitumor agents against gastric cancer showing overexpression of EGF receptors or c-erbB-2.

Epidermal Growth Factor↗
PubMed1995

Hyperventilation activation on EEG recording in children with epilepsy.

In 20 patients with epilepsy, electroencephalography (EEG) slowing was quantitatively characterized during standardized hyperventilation activation (respiratory rate: 30/min, threefold elevation of total expiratory volume, duration: 4 min) and changes in cerebral blood flow and velocity in the right common carotid artery were monitored with the Doppler ultrasonic method. Thirteen age-matched normal children served as controls. The results were as follows: (1) EEG slowing in the epilepsy group was greater compared with controls. (2) There was a significant decrease in mean frequency (decrease in alpha power and increase in delta power) during hyperventilation in the epilepsy group, but no significant change in the controls. (3) The decrease in cerebral blood flow (CBF) was greater in the epilepsy group at the beginning of hyperventilation, possibly related to the greater EEG slowing. (4) The percentage of CBF at the end of hyperventilation was similar in the epilepsy and control groups. The difference in EEG response to hyperventilation between the 2 groups may be due to differences in the decrease in CBF volume and the sensitivity of the change in CBF.

Blood Flow Velocity↗
PubMed1995

Insulin nonattenuation of vasoactive agent-induced responses in mesangial cells from spontaneously hypertensive rats.

We recently found that insulin attenuates intracellular calcium transients and cell contraction caused by vasoactive agents in cultured rat mesangial cells. Because altered glomerular function may be causally related to the evolution of hypertension, we examined in the present study the effects of insulin on the functions of mesangial cells derived from spontaneously hypertensive rats (SHR) of 4- and 8-weeks of age. Age-matched Wistar Kyoto rats (WKY) were used as controls. Intracellular calcium concentration ([Ca2+]i) was measured with Fura-2 method in suspended mesangial cells. Pretreatment of mesangial cells with 5 micrograms/ml insulin for 120 minutes did not affect basal [Ca2+]i in either WKY or SHR mesangial cells. However, insulin pretreatment significantly attenuated [Ca2+]i transients to vasoactive agents in WKY mesangial cells. In contrast, [Ca2+]i transients to these agents were not attenuated by insulin in SHR mesangial cells. Additionally, SHR mesangial cell contraction in response to angiotensin II (Ang II) was not altered by insulin, while WKY mesangial cell contraction to Ang II was, as in normal Wistar rats, significantly reduced by insulin. Since we previously showed the possibility that the attenuation of calcium signal by insulin is via insulin-like growth factor I (IGF-I) receptor, we also examined the effect of IGF-I. In contrast to WKY mesangial cells, IGF-I-induced attenuation of [Ca2+]i responses to platelet activating factor was absent in SHR mesangial cells. [125I]-IGF-I binding in SHR mesangial cells was not significantly different from that in WKY mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Effects of sevoflurane on the middle latency auditory evoked response and the electroencephalographic power spectrum.

We investigated the effects of sevoflurane on the middle latency auditory evoked response (MLR) and the power spectrum of the electroencephalogram (EEG) in 10 elective surgical patients. The MLR and the EEG power spectrum were recorded with a surface electrode placed at the central (Cz) scalp location. End-tidal sevoflurane concentrations of 0%, 0.25%, 0.5%, 0.75%, 1.0%, and 1.5% in 50% nitrous oxide and oxygen were studied. The Na, Pa, and Nb components of the MLR increased in latency and decreased in amplitude in a dose-dependent manner at increasing concentrations of sevoflurane. The latencies for Na, Pa, and Nb increased in a linear fashion (correlation coefficients: r = 0.81, r = 0.81, and r = 0.89, respectively). The EEG delta power was dominant with increasing sevoflurane concentration, and was significantly increased at sevoflurane concentrations of 1.0%-1.5%. The beta power, median power frequency (MPF), and 95% spectral edge frequency (SEF) decreased significantly according to the increases by 0.5% sevoflurane. Regarding the changes evoked by 0.25% sevoflurane, the Nb latency of the MLR responded significantly under 0.75% of sevoflurane. At these low concentrations of sevoflurane, the MLR seemed to be more sensitive to changes in anesthetic concentration than the various EEG variables.

Anesthetics↗