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Biomedical subjects

K Okuda

Publications and source records attributed to K Okuda.

At least 109 records · Page 6Linked to original sources
PubMed2000

Successful surgical treatment for implanted intraperitoneal metastases of hepatocellular carcinoma.

We report here two patients with hepatocellular carcinoma who experienced implanted metastases in the abdominal cavity after hepatectomy or microwave coagulo-necrotic therapy. Hepatic resection and microwave coagulo-necrotic therapy were successful for these tumors, and the postoperative status was satisfactory in both patients. Implanted metastases were discovered in the abdominal cavity of each of these two patients 6 months after surgery. It is necessary to look not only for the presence of liver metastasis but also for the recurrence of the tumor in the abdominal cavity during the follow-up period. Generally, surgical resection for intraabdominal implanted tumors arising from any other abdominal organs is not indicated for improving the patient's quality of life. However, resection of metastatic tumors that occur in the abdominal cavity, arising from hepatocellular carcinoma may be of value in improving patient survival.

Aged↗
PubMed2000

Resectable carcinoma of the pancreatic head developing 7 years and 4 months after distal pancreatectomy for carcinoma of the pancreatic tail.

A 67-year-old woman was referred with an abnormal finding on an abdominal echogram but presented with no symptoms; a pancreatic tail tumor was detected by ultrasonography. Biochemical examinations showed slight elevation of serum carcinoembryonic antigen level. The lesion was resected by tail and body pancreatectomy and her postoperative course was uneventful. Seven years and 4 months after the initial operation, however, her serum level of carbohydrate antigen 19-9 was found to be elevated, and a recurrence of pancreatic cancer was suspected. Examinations revealed a mass in the head of the remnant pancreas. The lesion was radically resected by total remnant pancreatectomy. Histological examinations showed that the initial tumor was a well differentiated tubular adenocarcinoma, while the second tumor was characterized as a moderately differentiated tubular adenocarcinoma. The surgical margins of the distal pancreatectomy specimen were free of atypical cells. Therefore, the position of the second lesion diminished the likelihood that it had developed by intrapancreatic metastasis. This suggests that the second carcinoma in the head of the pancreas may have been a second primary lesion.

Adenocarcinoma↗
PubMed2000

Insulinoma occurring in association with fatty replacement of unknown etiology in the pancreas: report of a case.

A 66-year-old woman with a 10-year-history of diabetes mellitus was admitted to our hospital for investigation of several recent attacks of hypoglycemia. Her fasting blood glucose level was very low, at 30-40 mg/dl, and abdominal ultrasonography and computed tomography revealed a tumor in the pancreatic tail with fatty changes. Endoscopic retrograde cholangiopancreatography revealed absence of the main pancreatic duct from the body to tail of the pancreas. Abdominal angiography showed a hypervascular tumor stain in the pancreas, and percutaneous transhepatic portal vein sampling demonstrated a step-up of immunoreactive insulin levels in the splenic vein. Based on these clinical findings, we made a preoperative diagnosis of an insulinoma accompanied by fatty changes in the pancreatic body and tail. During laparotomy for the insulinoma, fat tissue was identified in the anatomic location of the pancreatic body and tail, and resected. Pathological examination of the resected specimen revealed a number of Langerhans islets in the adipose tissue, and an islet cell tumor with fatty replacement of the pancreatic tissue around the tumor. The insulinoma was found not to have caused obstruction of the main pancreatic duct. We present herein a rare case of an insulinoma that developed in the pancreas, and was associated with fatty replacement of unknown etiology.

Adipose Tissue↗
PubMed2000

Synchronous or metachronous double cancers of the pancreas and other organs: report on 12 cases.

Pancreatic carcinoma carries a poor prognosis, especially invasive ductal carcinoma of the pancreas. This retrospective study describes the results of the treatment and prognosis for double cancers in which cancer of the pancreas was associated with malignancies in other organs in 12 patients who were diagnosed and treated at Kurume University Hospital. The patients included 4 women and 8 men, with an average age of 67 years. Of the 12 tumors, 7 were metachronous pancreatic cancers which occurred after resections of other organ malignancies. Five patients had synchronous double cancers, one of whom was diagnosed to have gastric cancer on admission. Two other patients of this group were diagnosed to have lung cancer, while the remaining 2 patients suffered from colon cancer. By the time pancreatic cancer was diagnosed, gastrectomies had been performed in 7 patients for either gastric cancer or ulcers. In addition, one patient underwent a hysterectomy for uterine carcinoma and another received a low anterior resection for rectal carcinoma. Four of 5 patients in the synchronous group had nonresectable tumors and a palliative bypass operation was performed in 2 of these patients. Six patients who had metachronous double cancers died because of pancreatic cancer recurrence or metastases. We conclude that the prognosis of double cancers, where cancer of the pancreas is associated with other organ malignancies, primarily depends on the prognosis of the pancreatic carcinoma, and the present study suggests the necessity of long-term follow-up examinations for gastrectomy patients in order to make an early diagnosis of pancreatic cancer.

Aged↗
PubMed2000

Telomere attrition of the human abdominal aorta: relationships with age and atherosclerosis.

Little is known about the turnover rate (i.e. the rate of replication and death) of cells in the intima and media of human arteries as a function of age and atherosclerosis. One indicator of the replicative history of cells is telomere length. In this work we explored the rate of telomere attrition as a function of age and atherosclerosis in cells of the human abdominal aorta. Telomere length, measured by the terminal restriction fragment using Southern analysis, was determined in the intima and media of the distal (infrarenal) versus proximal (suprarenal) segments of the abdominal aorta. Telomere length was then correlated with age and atherosclerotic grade. The rate of age-dependent telomere attrition was higher in both the intima and media of the distal versus proximal abdominal aorta. In addition, telomere length was negatively correlated with atherosclerotic grade. However, after adjustment for age, this relationship was not statistically significant. The high rate of age-dependent telomere attrition in the distal abdominal aorta probably reflects enhanced cellular turnover rate due to local factors such as an increase in shear wall stress in this vascular segment.

Adolescent↗
PubMed2000

Different actions of noradrenaline and nitric oxide on the output of prostaglandins and progesterone in cultured bovine luteal cells.

The effects of noradrenaline (NA) and nitric oxide (NO) on prostaglandins (PGs) and progesterone (P4) secretion during the development of the bovine corpus luteum (CL) were investigated. Bovine luteal cells of early and mid-cycle CL were cultured for 20 to 24 h in medium containing 10% calf serum, washed, and treated with NA or nitrergic agents for an additional 16 h in a serum-free medium. NA (10(-5) M) stimulated P4 from early and mid-cycle CL by 238% and 154% (P < 0.01), respectively. Moreover, although NA induced a twofold increase in PGE2 secretion (P < 0.01) in both examined periods, the effect of NA on PGF2alpha secretion was approximately 1.5 times higher (P < 0.05) in early than in mid-cycle CL. Two NO synthase inhibitors, L-NAME and L-NOARG (both 10(-4) M), stimulated P4 secretion only in mid-luteal cells (P < 0.01), although they did not affect the cells from early CL. Although a NO donor, S-NAP (10(-4) M) inhibited P4 secretion from mid-cycle luteal cells (P < 0.05), it strongly stimulated PGE2 in both examined phases (P < 0.001). On the other hand, the output of PGF2alpha was stimulated by S-NAP only in the cells of the mid-cycle CL (P < 0.01). The overall results suggest that adrenergic and nitrergic agents play opposite roles in the regulation of bovine CL functions. Whereas NA may play a supporting role in luteal development, NO may participate in the functional regression of the bovine CL by inhibiting steroidogenesis.

Animals↗
PubMed2000

Hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is increasing in many countries as a result of an increase in hepatitis C virus (HCV) infection since World War II. The epidemiology of HCC varies with the global region. There have been conflicting observations from different parts of the world concerning the frequency of HCC in patients who in the distant past had post-transfusion non-A, non-B hepatitis. The genetic basis of hepatocarcinogenesis is still poorly understood. In hepatitis B virus (HVB) associated HCC, codon 249 mutation in the p 53 gene seems more related to exposure to aflatoxin B1 than to hepatocarcinogenesis itself. HCC that occurs in children in high HBV endemic regions could be associated with germ-line mutations, but little information is available; not much is known about chemical hepatocarcinogens in the environment other than aflatoxins. The X gene of HBV seems to play an important role in HBV-associated hepatocarcinogenesis. There are preliminary observations on the molecular mechanism of HCV-associated HCC, such as HCV core protein inducing HCC in transgenic mice and the NS3 genome transforming NIH 3T3 cells. Pathological distinction between preneoplastic and very early transformed lesions still depends on classical morphology, and a more genetically oriented differential diagnosis is required. Clinical diagnosis based on modern imaging has improved greatly, but is still unsatisfactory in the differential diagnosis of preneoplastic and early transformed nodules, because the vasculature changes that occur within the nodule are not accurately discerned with the current imaging. Use of sensitive des-gamma-carboxy prothrombin (PIVKA II) assay, and lectin affinity chromatography separating HCC specific subspecies of AFP molecules with a more practical biochemical technique will further improve diagnosis. Early diagnosis and transplantation are the best treatment at the moment, but transplantation is not widely available because of the donor shortage. Despite successful resection, the remnant cirrhotic liver frequently develops new HCC lesions, seriously curtailing long-term survival. All-out efforts should be directed to the prevention of HCC, through prevention of viral hepatitis, prevention of acute hepatitis from becoming chronic, prevention of chronic hepatitis from progressing to cirrhosis, and prevention of the cirrhotic liver from developing HCC (chemoprevention). At the moment, very few such studies exist.

Animals↗
PubMed2000

Successful control with bromide of two patients with malignant migrating partial seizures in infancy.

A 3-month-old male and a 4-month-old female infant with intractable seizures were diagnosed as having malignant migrating partial seizures in infancy (MMPSI) with developmental arrest on the basis of characteristics of symptoms, clinical courses and EEGs. We treated these two patients with potassium bromide (80 mg/kg) after conventional antiepileptic drugs failed to adequately control the seizures. The potassium bromide therapy resulted in complete control of seizures in one patient, and more than 95% reduction in seizure frequency in the other.

Bromides↗
PubMed2000

Immunochemical analysis of a photoreceptor protein using anti-IP3 receptor antibody in the unicellular organism, Blepharisma.

The blepharismin-200 kD protein complex of the ciliated protozoan Blepharisma is a novel type of photosensor responsible for the step-up photophobic response of the cell. In immunoblotting assays, the 200 kD protein is weakly cross-reacted with anti-inositol triphosphate receptor antibody (anti-IP3 R antibody). Indirect immunofluorescence assays show that the pigment granules in which the blepharismin-200 kD protein complex is localized are labelled by anti-IP3 R antibody. When the anti-IP3 R antibody or antisense oligonucleotide for IP3 receptor is introduced into the living cells of Blepharisma, both the photosensitivity of the cells and content of blepharismin-200 kD protein are reduced. The results suggest that the photoreceptor 200 kD protein is possibly an IP3 receptor-like protein.

Amino Acid Sequence↗
PubMed2000

Relationships between the onset of pustulosis palmaris et plantaris, periodontitis and bacterial heat shock proteins.

Relationships between the onset of pustulosis palmaris et plantaris, periodontitis and heat shock proteins were studied by using enzyme-linked immunosorbent assay to examine levels of immunoglobulin G (IgG) against Escherichia coli GroEL, a recombinant DnaJ of Actinobacillus actinomycetemcomitans heat shock protein, a synthetic peptide made from the 180th to the 188th amino acids of Mycobacterium bovis BCG Hsp65, and a recombinant human Hsp60, in sera obtained from 43 pustulosis palmaris et plantaris patients judged to have chronic infectious diseases of the oral cavity. We found that the titers of IgG against E. coli GroEL and A. actinomycetemcomitans DnaJ in the sera from pustulosis palmaris et plantaris patients were significantly higher than those in the control group, whereas the titers of IgG against the synthetic M. bovis Hsp65 and the recombinant Hsp60 did not differ significantly. Periodontal therapy and extraction of teeth with periapical infectious resulted in remission of pustulosis palmaris et plantaris and a statistically significant reduction in the levels of IgG against E. coli GroEL in 9 of the 22 patients (41%) examined. We also found that the IgG levels against A. actinomycetemcomitans DnaJ in 6 serum samples of 16 (37%) were reduced, but not significantly, after the treatment. These results suggest that the IgG responses to heat shock proteins partially induced by oral bacteria may be related to the onset of pustulosis palmaris et plantaris in some patients.

Adult↗
PubMed2000

Histatin 5 inhibits inflammatory cytokine induction from human gingival fibroblasts by Porphyromonas gingivalis.

Porphyromonas gingivalis is a gram-negative rod associated with the progression of human periodontal disease. It has been demonstrated that outer-membrane proteins as well as lipopolysaccharides from P. gingivalis ATCC 53977 can induce interleukin 6 (IL-6) and IL-8 from the cells of the periodontium in vitro. But, they cannot induce IL-1 and tumor necrosis factor-alpha from the cells. In the present study, we studied the effects of salivary protein on cytokine induction from human gingival fibroblasts by P. gingivalis outer-membrane protein. Histatin 5 suppressed the IL-6 and IL-8 induction by P. gingivalis outer-membrane protein. This activity was more effective when outer-membrane protein was incubated with histatin 5 before addition to the cell culture. The present study indicates that histatin 5 restrains induction of inflammatory cytokines by periodontal pathogens and that histatin is one of the salivary proteins responsible for this activity.

Bacterial Outer Membrane Proteins↗
PubMed2000

Cytostatic action of enamel matrix derivative (EMDOGAIN) on human oral squamous cell carcinoma-derived SCC25 epithelial cells.

During surgical treatment of periodontal disease, enamel matrix derivative (EMD) is topically applied as a substitute for extracellular matrix in order to facilitate regeneration of damaged periodontal tissue. However, the mechanism for EMD action is poorly understood. We have now examined the effects of EMD on the proliferation of oral epithelial (SCC25) cells in vitro. After 3 days of treatments, EMD (25 100 microg/ml) dose-dependently inhibited cell division and concomitantly arrested cell cycle at the G1 phase. Prior to this inhibition, EMD significantly up-regulated p21WAF1/cip1, a cyclin-dependent kinase inhibitor, induced G1-arrest, and inhibited DNA synthesis. In addition, EMD down-regulated expression of cytokeratin-18 (CK18) protein, which was most due to decreased production, but less to increased degradation. However, EMD did not discernibly increase the number of apoptotic cells over 8 days of treatment. These findings indicate (1) that EMD acts as a cytostatic agent, rather than a cytotoxic agent, on epithelial cells, and (2) that this anti-proliferative action is probably due to p21WAF1/cip1-mediated G1-arrest. Furthermore, our in vitro cellular data clearly verify and provide an explanation for the clinical observation that EMD application suppresses the down-growth of junctional epithelium onto dental root surfaces, a process that frequently interferes with the formation of new connective tissue attachments.

Adolescent↗
PubMed2000

8 Br-cAMP enhances both humoral and cell-mediated immune responses induced by an HIV-1 DNA vaccine.

From a series of preclinical studies and animal experiments, we have been able to demonstrate that DNA vaccines are a promising tool in strategies for protecting hosts from a variety of infectious diseases. Since the promoter activity of the human cytomegalovirus immediate-early promoter/ enhancer (CMV promoter) is known to be responsive to an elevation in the level of intracellular cAMP, we hypothesized that use of cAMP analogue (8-Bromo adenosine 3'5'-cyclic monophosphate, 8 Br-cAMP) would increase the level of transgene expression supported by the CMV, and enhance the ability of DNA vaccines to evoke an immune response against the transgene product in vivo. To evaluate this hypothesis, immune responses against HIV-1 envelope protein, gp160, an immunogenic HIV-1 component expressed under the control of the CMV promoter, were evaluated in BALB/c mice with or without stimulation by 8 Br-cAMP. DNA vaccine with 8 Br-cAMP was intramuscularly (i.m.) or intranasally (i.n.) administered to BALB/c mice twice on days 0 and 14. Regardless of which route was used, the combination increased the serum IgG antibody (Ab) titer, HIV-1-specific cytotoxic T lymphocyte (CTL) activity and the delayed-type hypersensitivity (DTH) response, compared with the effect of using the vaccine alone. When administered via the i.n. route, the combination also remarkably increased the titer of secretory IgA (sIgA). Moreover, it induced increased production of interferon-gamma with reduction in IL-4 synthesis, and decreased the ratio of serum IgG1/IgG2a. However, these enhancements were not observed when 8 Br-cAMP was coadministered with peptide vaccine or protein antigen. These data suggest that 8 Br-cAMP is able to enhance both humoral and cellular immune responses induced by the DNA vaccine. The induction of T helper type 1 (Th1) immunity against HIV-1 was also enhanced by coadministration of 8 Br-cAMP. A CAT assay study demonstrated that the adjuvant effect of 8 Br-cAMP may be due to the activation of the CMV promoter in the DNA vaccine. The virus challenge experiment in a mouse influenza model also proved our hypothesis.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Interleukin 6 receptor expression by human cord blood- or peripheral blood-derived primitive haematopoietic progenitors implies acquisition of different functional properties.

The significance of interleukin 6 receptor (IL-6R) expression by cord blood (CB)- and peripheral blood (PB)-derived primitive haematopoietic progenitors was investigated. IL-6R was preferentially expressed by PB-derived myeloid progenitors. Most PB-derived erythroid bursts (BFU-E) and mixed colony-forming cells (CFU-Mix) did not express this receptor. However, CB-derived primitive progenitor cells possessed multipotentiality, irrespective of IL-6R expression. Interestingly, the long-term culture-initiating cell (LTC-IC) population was enriched in PB-derived CD34+ IL-6R+ cells, but the extended LTC-IC (ELTC-IC) population, which represents a less mature class of haematopoietic progenitors, seemed to be equally distributed in the IL-6R+ and IL-6R- cell populations. In contrast, the number of LTC-ICs and ELTC-ICs was similar in CB-derived CD34+ IL-6R+ or IL-6R- cells. It is noteworthy that the number of LTC-ICs and ELTC-ICs in CB-derived CD34+ cells was markedly higher than that in PB-derived CD34+ cells regardless of IL-6R expression. Telomerase activity was consistently lower in PB-derived CD34+ IL-6R- cells than in CD34+ IL-6R+ cells. In contrast, telomerase activity was similar in CB-derived CD34+ IL-6R+ or IL-6R- cells. The pattern of telomerase induction upon cytokine stimulation differed between CB- and PB-derived CD34+ IL-6R+ or IL-6R- cells. However, overall telomerase activity per dish was well correlated with the proliferative potential of both cell populations, suggesting that induction of telomerase plays an important role in the escape from replicative senescence of primitive haematopoietic progenitors. Collectively, these results suggest that CB-derived primitive progenitors are less mature than PB-derived progenitors and that the expression of IL-6R by primitive haematopoietic progenitors may have different implications for PB- and CB-derived CD34+ cells.

Antigens, CD↗
PubMed2000

Th1-biased immune responses induced by DNA-based immunizations are mediated via action on professional antigen-presenting cells to up-regulate IL-12 production.

The efficacy of DNA-based immunization in conferring protective immunity against certain microbial pathogens including human immunodeficiency virus type 1 (HIV-1) has been described. The potential advantage of DNA-based immunization over the traditional vaccines largely results from its capacity to efficiently induce Th1-biased immune responses against an encoded antigen. We describe how Th1-biased immune responses are induced by DNA-based immunization, using a DNA vaccine construct encoding HIV-1 gp160 cDNA and an eukaryotic expression plasmid carrying murine IFN-gamma cDNA. Transfection of an eukaryotic expression plasmid carrying immunostimulatory sequences (ISS) as well as a gene of interest (DNA vaccine) into professional antigen presenting cells (APC) induced transactivation of IL-12 mRNA, which resulted in antigen-specific Th1-biased immune responses against the encoded antigen. Th1-biased immune responses induced by DNA-based immunization were substantially upregulated by a codelivery of an ectopic IFN-gamma expression system, and this augmentation was mediated via action on professional antigen presenting cells to upregulate IL-12 production. Taken together, it appears likely that Th1-biased immune responses induced by DNA-based immunization are mediated via action on professional antigen-presenting cells to produce IL-12. Interestingly, the model provided strikingly resembles that previously described in infection with Listeria monocytogenes, an intracellular Gram-positive bacterium that induces strong Th1-biased immune responses. The result suggests that DNA-based immunization mimics certain aspects of natural infection with microbial organisms like attenuated vaccines, which in turn provides a rationale to the question of why DNA-based immunization so efficiently induces protective immunity against these microbial pathogens.

AIDS Vaccines↗