Biomedical subjects

K Fukuda

Publications and source records attributed to K Fukuda.

At least 451 records · Page 25Linked to original sources

PubMed1996

[Combination of intra-hepatic arterial infusion of low-dose cisplatin and oral administration of high-dose doxyfluridine for patients with liver metastases of gastric cancer].

Three cases of gastric cancer with multiple liver metastases were treated with low-dose CDDP and high-dose 5'-DFUR after surgery. The regimen was 20 mg CDDP intra-hepatic arterial infusion per week and 1,200 mg 5'-DFUR oral treatment per day. The liver metastases of two cases responded to this chemotherapy with a reduction of more than 90%, and two cases lived more than 2 years. All of them lived more than one year. This therapy had few side effects and was performed ambulatorily once per week, so patients were able to maintain their quality of life. This combination therapy may well assure a better prognosis for patients with liver metastases of gastric cancer.

Administration, Oral↗

PubMed1996

Hyaluronic acid increases proteoglycan synthesis in bovine articular cartilage in the presence of interleukin-1.

Osteoarthritis is a common joint disorder in humans. Although intra-articular injection of hyaluronic acid (HA) is in widespread clinical use, there are limited data on the effect of HA on degenerated cartilage. When bovine articular cartilage is degraded with interleukin-1, HA penetrates the cartilage and accumulates in the pericellular matrix of chondrocytes. HA also enhances proteoglycan synthesis that has been reduced by interleukin-1. Thus HA seems to have anabolic effects on degraded cartilage.

Animals↗

PubMed1996

[A case of occult AVM diagnosed 17 years after subdural hematoma in the neonatal period].

There have been few reports on cerebral arteriovenous malformation (AVM) of newborns. We present here an interesting case of occult AVM diagnosed 17 years after an episode of acute subdural hematoma in the neonatal period. The cause of subdural hematoma had remained unclear and the patient had suffered from an intractable epilepsy of 17 years duration. Seizures were mainly characterized by drop attacks and included other seizure types such as complex partial seizure and generalized tonic clonic seizure. The symptoms had gradually become worse and the intervals between the occurrences of symptoms had become shorter. An interictal scalp EEG showed a focal spike in the left temporoparietal lobe. CT and MRI of that region demonstrated a porencephalic cyst which was supposed to have resulted from an old hematoma. There were no vascular abnormalities in angiography. Temporoparietal craniotomy and a corticogram were performed. The cortex with a focus was resected and the disappearance of a focal spike in the corticogram was confirmed during operation. Microscopically the cortex included AVM with gliosis. The initial postoperative course was good and seizures disappeared immediately after the operation. However, the symptoms of drop attacks observed before operation began to occur again 3 months later. The fact of postoperative recurrence suggests that the long history of the patient's seizures originating from AVM may have produced secondary epileptic foci.

Adolescent↗

PubMed1996

Strategy for breast conserving treatment--analysis of recurrence and prognosis after breast cosnserving treatment.

Two hundred and four patients with small breast cancer (T < or = 3.0 cm. N0 or N1a) were given breast conserving treatment (radiation group: 101, non-radiation group: 103) during the period from Feb. 1988 to Jan. 1995. Survival analysis of breast conserving treatment radiation group versus non-radiation group revealed the following: 1) Breast conserving treatment had a good prognosis, and a 5-year overall survival rate of 96.2%. 2) There was no significant difference of 5-year overall, disease-free and ipsilateral breast disease-free survival rate between the radiation group and non-radiation group. 3) Surgical margin involvement was the most significant risk factor in local recurrence after breast conserving treatment, and non-radiation was a possible risk factor. 4) Local recurrence was a significant risk factor for distant metastases after breast conserving treatment the same as node positive. These results suggested as follows: 1) Lumpectomy with a clear margin and radiation is the best choice for small breast cancer (T < or = 3.0 cm, N0 or N1a). 2) Adjuvant therapy after surgical treatment is necessary for local recurrence.

Axilla↗

PubMed1996

Retroviral risk factors in patients with autoimmune disease.

OBJECTIVE: Retroviruses can cause immunoregulatory disturbances and may play a role in the pathogenesis of autoimmune disorders. Little is known about the frequency of behavioral risk factors for exogenous retroviral infections in patients with autoimmune diseases. We compare the frequency of recognized risk factors for retroviral infections among patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and controls. METHODS: Patients with SLE and RA from a university rheumatology clinic and control patients were enrolled in this study. The presence of retroviral risk factors (intravenous drug use, prostitution, increased number of sex partners, sexually transmitted diseases, high risk sex partners, blood transfusion) was determined by a self-administered questionnaire. RESULTS: We surveyed 81 patients with SLE and 117 with RA and 100 healthy controls. Patients in all groups reported similar exposure to all risk factors surveyed for retroviral infection except sexually transmitted disease, which was reported more often in patients with SLE (25% of SLE versus 11% of RA and 11% of controls, p = 0.013). CONCLUSION: Self-reported retroviral risk factors were generally not increased in patients with autoimmune disease compared to healthy controls; the role of exogenous retroviruses in the pathogenesis of SLE and RA remains unclear.

Adolescent↗

PubMed1996

[Evaluation of prophylactic hepatic arterial infusion chemotherapy after hepatectomy for metastases from colorectal cancer--the second report].

We followed 18 patients who underwent curative hepatectomy for metastatic carcinoma of the colon from March 1993 to March 1995, and investigated their survival and the effect of treatment on recurrence. The patients were randomly divided into two groups. Group A (n = 9) was given continuous 5-FU (500 mg x 4 days/week) for six weeks from 2 weeks after surgery via the hepatic artery and Group B (n = 9) was given 5-FU orally from 2 weeks after surgery. The cumulative one-, two-, and three-year survival was 88.9, 88.9, and 76.2% in Group A, while the one- and two-year survival was 100 and 80% in Group B. The one-, two-, and three-year disease-free survival was 77.8% in Group A, while the one- and two-year disease-free survival was 55.6 and 29.6% in Group B (p = 0.0369: Mantel-Cox). These findings suggest that continuous hepatic artery infusion of 5-FU is effective against post-hepatectomy recurrence of metastatic carcinoma of the colon.

Colorectal Neoplasms↗

PubMed1996

[Molecular biological study on structure and function of the opioid receptor].

Pharmacological actions of opioid analgesics are mediated by the mu-, delta- and kappa-opioid receptors in the nervous system. To understand the molecular basis of the opioid receptor functions, experiments using molecular biological methods have been performed. Amino acid sequences elucidated by cDNA cloning revealed that the opioid receptor possesses characteristic structural features of the G-protein-coupled receptor family, including the presence of seven transmembrane segments. Furthermore, molecular mechanism for the ligand selectivity of the mu- and delta-opioid receptors was investigated by analyzing chimeric receptors between the mu- and delta-receptors and mutant receptors with one amino acid replacement.

Amino Acid Sequence↗

PubMed1996

[A case-control study of ovarian cancer to identify its risk factors].

To analyze the association between the potential risk factors and ovarian cancer, we conducted a case-control study from October, 1994 to January, 1996 in northern Kyushu. We interviewed 78 patients whose ovarian cancer was histologically confirmed, and 346 controls, selected from women at mass screening, who had not ever suffered from a cancer or an ovarian disorder. An odds ratio (OR) and its 95% confidence interval (95% CI) were estimated by the conditional logistic regression method. As a result, it was found that the risk was significantly increased for a family history of ovarian cancer in a mother or a sister (OR = 2.85, 95% CI 1.01-8.08), for heavier maximum body weight in the past (trend, OR = 1.31, 95% CI 1.06-1.63), and for larger maximum body mass index (trend, OR = 1.30, 95% CI 1.06-1.60). Conversely, the risk was significantly decreased with the number of parities (trend, OR = 0.57, 95% CI 0.39-0.83), and with experience in having ever taken oral contraceptive pills (OR could not be calculated, p < 0.05). The positive relationship of maximum body weight or maximum body mass index to the ovarian cancer risk may in part explain the recent increase in the incidence of ovarian cancer in Japan.

Alcohol Drinking↗

PubMed1996

[Helical CT for lumbosacral spinal].

PURPOSE: The aim of this study was to investigate the efficacy of helical CT for lumbosacral pathology. MATERIALS AND METHODS: We performed helical CT with multiplanar reconstruction, including the formation of oblique transaxial and coronal images, in 62 patients with various lumboscral disorders, including 32 non-enhanced CT and 36 CT after myelography. We correlated the appearance of the stenotic spinal canal and neoplastic disease with the findings on MRI obtained at nearly the same time. RESULTS: We obtained helical CT images in all cases in about 30 seconds. The diagnostic ability of helical CT was roughly equal to that of MRI in patients with spondylosis deformans, spondylolisthesis and herniated nucleus pulposus. There was no significant difference in diagnostic value for degenerative lumbosacral disease with canal and foramnial stenosis between non-enhanced and post-myelography helical CT. However, non-enhanced helical CT could not clearly demonstrate neoplastic disease because of the poor contrast resolution. CONCLUSION: Helical CT was useful in evaluating degenerative disorder and its diagnostic value was nearly equal to that of MRI. We considered that helical CT may be suitable for the assessment of patients with severe lumbago owing to the markedly shortened examination time. However, if helical CT is used as a screening method for lumbosacral disease, one must be careful of its limitations, for example, poor detectability of neoplastic disease, vascular anomalies and so on.

Adult↗

PubMed1996

Direct evidence of the production of IgA by tonsillar lymphocytes and the binding of IgA to the glomerular mesangium of IgA nephropathy patients.

Tonsils were obtained by tonsillectomy from a 33-year-old woman with IgA nephropathy. Hetero-hybridoma cells of human tonsillar B-lymphocytes with mouse myeloma cells (NS-1) were made, and cultured in HAT medium supplemented with 10% fetus bovine serum and hybridoma cloning factor. The culture medium was analyzed by Western blot analysis using anti-human IgA antibody, and both IgA1 and IgA2 were demonstrated to be produced. The specimens of the biopsied kidney tissue of IgA nephropathy were washed with 0.02 M citrate buffer (pH 3.2) to remove deposited IgA from glomerulus. The specimens were then incubated with the culture media of hybridoma cells, and immuno-fluorescence analysis using FITC-conjugated anti-human IgA antibody was performed. IgA deposit was efficiently removed by washing with citrate buffer and was recovered after incubation with the culture medium of hybridoma cells. Direct evidence of binding of IgA produced by tonsillar B-lymphocytes to the glomerular mesangium of IgA nephropathy was demonstrated.

Adult↗

PubMed1995

Induction of HSP-70 after hyperosmotic opening of the blood-brain barrier in the rat.

The cellular response resulting from breakdown of the blood-brain barrier was evaluated 24 h after hyperosomotic infusion of mannitol into the internal carotid artery in the rat. Heat shock protein (HSP-70), a marker of cellular stress and/or injury, was induced in scattered patches of neurons and glia in regions of barrier breakdown. These findings suggest that osmotically induced breakdown of the blood-brain barrier may result in cell injury.

Animals↗

PubMed1995

Induction of heme oxygenase-1 (HO-1) after traumatic brain injury in the rat.

The induction of heme oxygenase-1 (HO-1), the 32 kDa heat shock protein, was examined in the traumatized rat brain. At 24 h after either mild or severe brain injury or sham surgery, HO-1 was immunolocalized in fixed sections of brain. After mild brain injury, hemorrhage was apparent in the subarachnoid space, external capsule and cerebellum. HO-1 was induced in similar areas in macrophages in the subarachnoid space and in glia in the cortex adjacent to the site of impact, the ipsilateral hippocampus, external capsule and cerebellum. After severe brain injury, extensive hemorrhage occurred in the external capsule, hippocampus and cerebellum. HO-1 was induced in glia in these areas of hemorrhage but was more extensive than that seen after mild injury and included the contralateral external capsule and hippocampus. These findings demonstrate remarkable induction of HO-1 in glia in the injured brain. Since heme is a potent inducer of HO-1, it is likely that the subarachnoid and/or intraparenchymal blood induced HO-1 in the glia where the heme was metabolized to biliverdin, iron, and carbon monoxide.

Animals↗

PubMed1995

Localization of rat endothelin-converting enzyme to vascular endothelial cells and some secretory cells.

Endothelin is a potent vasoconstrictive peptide that is produced by vascular endothelial cells; it is formed from its precursor, big endothelin, by endothelin-converting enzyme (ECE). In this work, ECE was studied using specific monoclonal antibodies. In immunoblotting, ECE was estimated to be a 300 kDa protein on SDS/PAGE under non-reducing conditions, and 130 kDa under reducing conditions. Cross-linking experiments revealed that ECE is composed of two disulphide-linked subunits. Localization of ECE was studied at the cellular and subcellular levels in various rat tissues and cells. High-level expression of ECE was observed in membrane fractions of simian virus 40-transformed rat endothelial cells by immunoblotting, but the immunoreactive band was absent form aortic smooth muscle cells and cytosolic fractions of endothelial cells. In immunohistochemical analysis, ECE was found to be localized in the endothelial cells of the aorta, lung, kidney, liver and heart. Confocal immunofluorescent microscopy showed that most of the ECE in endothelial cells and cells transfected with ECE cDNA was clustered along the plasma membrane. Intact COS or CHO cells transfected with ECE cDNA rapidly and efficiently cleaved big endothelin-1 added to the culture medium. Thus endothelial cells express ECE on the plasma membrane and the active site of the enzyme faces outside the cells, i.e. it is an ectoenzyme. Other than endothelial cells, ECE was also present in some secretory cells. The enzyme was abundant in the adrenal gland, and localized in chromaffin cells. ECE was also highly condensed in pancreatic islet beta cells. It is concluded that ECE and endothelin may be involved in the regulated secretion of hormones.

Adrenal Glands↗

PubMed1995

Identification of the amino acid residues involved in selective agonist binding in the first extracellular loop of the delta- and mu-opioid receptors.

Effects of amino acid substitutions in the first extracellular loop region of the delta- and mu-opioid receptors were examined. Substitution of lysine-108 of the delta-receptor (delta K108) with asparagine improved affinity to [D-Ala2,MePhe4,Gly-ol5]enk ephalin (DAGO), a mu-selective peptide agonist, to be comparable with that of the mu-receptor. On the other hand, replacement of mN127 with lysine decreased the affinity to DAGO by approximately 15-fold. These results suggest that dK108 and mN127, which correspond to each other in the aligned amino acid sequences, mainly determine the difference in DAGO binding affinity between the delta- and mu-receptors.

Amino Acid Sequence↗

PubMed1995

Structure-function relationship of the eukaryotic DNA replication factor, proliferating cell nuclear antigen.

Proliferating cell nuclear antigen (PCNA) is essential for eukaryotic DNA replication and functions as a processivity factor of DNA polymerase delta (pol delta). Due to the functional and structural similarity with the beta-subunit of Escherichia coli DNA polymerase III, it has been proposed that PCNA would act as a molecular clamp during DNA synthesis. By site-directed mutagenesis and biochemical analyses, we have studied the functional domains of human PCNA required for stimulation of replication factor C (RF-C) ATPase and DNA synthesis by pol delta. Short deletions from either the N or C termini caused drastic changes in extraction and chromatographic behaviors, suggesting that both of these terminal regions are crucial to fold the tertiary structure of PCNA. The short C-terminal stretch from Lys254 to Glu256 is necessary for stimulation of RF-C ATPase activity, but not for stimulation of DNA synthesis by pol delta. Nine basic amino acids that are essential for activating DNA synthesis by pol delta are positioned at the internal alpha-helices of PCNA. This result is in good agreement with the observation that PCNA has a ring structure similar to the beta-subunit and clamps a template DNA through this positively charged internal surface. Several other charged amino acids are also required to stimulate either RF-C ATPase or pol delta DNA synthesis. Some of them are positioned at loops which are exposed on one of the side surface of PCNA adjacent to the C-terminal loop. In addition, the beta-sheets composing the intermolecular interface of the trimeric PCNA are important for interaction with pol delta. Therefore, the outer surface of PCNA has multiple functional surfaces which are responsible for the interaction with multiple factors. Furthermore, the two side surfaces seem to be functionally distinguishable, and this may determine the orientation of tracking PCNA along the DNA.

Adenosine Triphosphatases↗

PubMed1995

Intrathecal administration of endothelin-1 in the rat: impact on spinal cord blood flow and the blood-spinal cord barrier.

The purpose of this study was to examine the integrity of the blood-spinal cord barrier after intrathecal administration of endothelin-1 (ET-1) in the rat spinal cord. A laser Doppler probe was positioned in the exposed subarachnoid space at the T8 vertebral level. In the first experiment, horseradish peroxidase (HRP), a marker of barrier integrity, was given intravenously prior to the intrathecal application of ET-1. Blood flow was then recorded for 3 h, after which the anesthetized animals were euthanized. In the second experiment, animals exposed to endothelin were recovered after confirming a 50% reduction in blood flow. HRP was given 10 min prior to euthanasia at 24 h post infusion. The intensity of staining for HRP was quantified by optical density in fixed sections of spinal cord. There was a significant sustained reduction in spinal cord blood flow and significant barrier breakdown to HRP at both 3 and 24 h after administration of the peptide. Based upon these results we conclude that intrathecal infusion of ET-1 reduces spinal cord blood flow and results in prolonged breakdown of the blood-spinal cord barrier.

Animals↗

PubMed1995

Location of regions of the opioid receptor involved in selective agonist binding.

To elucidate which portions of the opioid receptor molecules are involved in the ligand selectivity, we have expressed chimeric receptors between the rat delta- and mu-opioid receptors from cDNAs and analysed their ligand binding properties. We demonstrate that the major binding determinant for the delta-selective enkephalin-related peptide, [D-Pen2,D-Pen5]enkephalin, resides within the region comprising the transmembrane segments V-VII and the intervening loop regions. On the other hand, the region spanning from the intracellular loop I to the amino-terminal half of the transmembrane segment III is shown to be involved in determining high-affinity binding of the mu-selective enkephalin-related peptides, [D-Ala2, MePhe4,Gly-ol5]enkephalin and [D-Ala2,MePhe4,Met-ol5]enkephalin, whereas the major determinant for binding of the mu-selective alkaloids, morphine and codeine, is demonstrated to exist in the region spanning the transmembrane segments V-VII. These results indicate that distinct regions of the opioid receptor determine the selectivity for the delta- and the mu-selective enkephalin-related peptides and that the binding determinant for the mu-selective alkaloids is distinct from that for the mu-selective enkephalin-related peptides.

Animals↗

PubMed1995

Effective production of the hepatitis C virus core antigen having high purity in Escherichia coli.

The amino-terminal half of putative nucleocapsid (core) protein (amino acids 1-115) of hepatitis C virus (HCV) was directly overproduced in Escherichia coli under the control of the tac promoter. Overproduction of core antigen was achieved by inserting several target genes and by optimizing the culture conditions, whereas a large amount of directly expressed and purified core antigen has not yet been reported. Although the level of expression was comparable to that of the conventional E. coli fused expression system, our recombinant proteins contain only HCV amino acid sequence. Using recombinant E. coli, overproduced large-scale culture system was achieved in jar-fermenter. A highly purified sample of the expressed protein was obtained by ion-exchange and gel permeation column chromatography in the presence of 8 M urea. From a 3.5 l culture, approximately 440 mg of recombinant core protein was obtained after a two-step purification procedure. An enzyme-linked immunosorbent assay developed using the highly purified antigen satisfactorily diagnosed hepatitis C.

Base Sequence↗