Biomedical subjects
Publications and source records attributed to K Okamoto.
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About 90% of the soluble amyloid beta (sA beta) that circulates in normal human plasma is associated with lipoprotein particles. In sporadic Alzheimer's disease patients, free sA beta42 but not sA beta40 is increased approximately 2.3-fold compared with age-matched controls, although a more marked elevation (approximately 8-fold for free sA beta40 and about 20-fold for sA beta42) is found in Down's syndrome patients. The data suggest that lipoprotein-sA beta dissociation may contribute to the influx of sA beta into the brain as a result of decreased plasma clearance.
Cicatricial fibromatoses usually occur in the anterior abdominal wall or in the extremities, but rarely in the scalp or the soft tissues of the neck. We report a case of desmoid fibromatosis that developed in a 15-year-old boy 8 months after surgery for cerebellar medulloblastoma.
Carcinomatous peritonitis is the most frequent type of recurrence observed after surgery for cancer of the digestive tract. Most patients with carcinomatous peritonitis present with bowel obstruction and/or ascites. Surgical treatment including colostomy and intestinal anastomosis and chemotherapy have been attempted in patients with carcinomatous peritonitis, although the results have not been satisfactory. New drug delivery systems, such as mitomycin C-adsorbed charcoal, anticancer drugs entrapped in microspheres, and immunoconjugates composed of anticancer drugs and antibodies, will be powerful new tools for the treatment of metastatic cancer.
We hypothesized that patients who have undergone hypothermic cardiopulmonary bypass may have abnormal oxygen metabolism after cardiac surgery because of oxygen debts that occurred during cardiopulmonary bypass. A prospective study was designed to determine oxygen consumption and carbon dioxide production using an indirect calorimeter in 45 adult patients who underwent hypothermic cardiopulmonary bypass. Inspiratory and expiratory gases were analyzed and the respiratory exchange ratio (carbon dioxide production/ oxygen consumption) was obtained every 6 hours up to 24 hours after surgery. The respiratory exchange ratio immediately following cardiopulmonary bypass was abnormally high then gradually decreased. The respiratory exchange ratio at 18 or 24 hours after surgery was significantly lower than the one on admission to the intensive care unit. Duration of cardiopulmonary bypass was the most significant parameter which correlated to the respiratory exchange ratio on admission to the intensive care unit (r = 0.82, p < 0.001). We conclude that the respiratory exchange ratio can be used to monitor systemic metabolism, especially during the recovery phase from metabolic abnormality following hypothermic cardiopulmonary bypass.
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Before and after treatment with methylprednisolone-pulse therapy (MPT), we investigated the superoxide production from the neutrophils of 10 patients stimulated by phorbol myristate acetate, N-formyl-methionyl-leucyl-phenylalanine or opsonized zymosan. Effects of pre-treatment with patient serum on neutrophils from control subjects were also examined. Patient neutrophils produced significantly less superoxide after MPT than before MPT. The superoxide production was significantly less in normal neutrophils from control subjects pre-treated with patient serum after MPT than in those before MPT. Neutrophils pre-treated with control serum-supplemented with or without methylprednisolone secreted essentially the same amount of superoxide. These findings indicate that MPT suppresses superoxide production by neutrophils, which is not a direct effect of methylprednisolone on neutrophils. We assume that MPT may reduce some factors from lymphocytes which stimulate not only neutrophils but also macrophages producing superoxide. This effect on the macrophages which present in the pathologic lesion may be the origin of medicinal effects of MPT.
The antitumor activity of etoposide (ETP) against human uterine cancer cell lines were investigated in vitro and in vivo. The cytotoxic activity of ETP against HeLa S3, a human cervical cancer cell line, depended on exposure time. The survival rate with 24 h prolonged exposure was reduced to about 1/200 that with 6 h exposure. The time dependency of antitumor activity of ETP against HeLa S3 subcutaneously transplanted in nude mice was studied. The effect of 21 or 28 consecutive days oral administration was greater than that of 5 or 14 consecutive days. Furthermore, a longer administration schedule was less toxic. The antitumor activity of ETP administered orally for 21 consecutive days was compared with that of CDDP, CPT-11 and 5'-DFUR using both human uterine cancer cell lines (TCO-1, SIHA, UCC08JCK) transplanted subcutaneously in nude mice and human uterine cancer cell lines (HeLa S3, UCC08JCK) transplanted into the uterus of nude mice. ETP showed the same antitumor activity as CPT-11 and 5'-DFUR against TCO-1 and UCC08JCK, human uterine cancer cell lines transplanted subcutaneously in nude mice. ETP also showed anticancer activity against two cell lines transplanted into the uterus. The growth inhibition caused by ETP administered orally at 50 mg/kg against HeLa S3 transplanted subcutaneously was 36.7% while that against the same cell line transplanted into the uterus was 58.5%. 5'-DFUR also showed the same antitumor activity as ETP. These results suggest that long term oral administration of ETP is clinically useful for cervical cancer patients.
Photoinduced electron transfer from tetrakis(4-carboxy-phenyl porphyrin)-zinc complex (Zn-TCPP) to an acceptor molecule (methyl viologen; MV2+) has been found to be controlled by the complex formation of monoclonal antibody 03-1 for the porphyrin (TCPP) and Zn-TCPP. Although there are no ground-state interactions between Zn-TCPP and MV2+ for a 2:1 complex of antibody 03-1 and Zn-TCPP, the fluorescence of Zn-TCPP is quenched by the addition of MV2+. The Stern-Volmer plots and emission lifetime studies show that there is a long-range electron transfer through the antibody 03-1.
The adherence of Fusobacterium necrophorum subsp. necrophorum to the surfaces of animal cells was studied in order to elucidate the differences between the bacterial appearance in clinical specimens from various animals. The bacterial cells had a strong affinity for murine and rabbit cheek cell surfaces. The bacterium showed a moderate affinity for goat cells, whereas it adhered not so well to canine, feline, human or porcine cells. Treatment of the bacterial cells with haemagglutinin antiserum prior to the binding assay reduced the degree of attachment to murine and rabbit cells. Scanning electron microscopy revealed that the adherent fusobacteria often penetrated into murine and rabbit cell membranes. These observations indicate that the bacterial attachment contributes to the establishment of the infection in mice and rabbits. It is suggested that the weak binding ability resulted in a low incidence of the bacterium in canine, feline and porcine lesions.
Twenty-five cases with unresectable metastatic liver cancers were experienced in our hospital over the past five years who underwent weekly 24-hour continuous hepatic arterial infusion chemotherapy using 5-FU and CBDCA. The response rate was 20%, the median survival was 23 months, and the one/two year overall survival rates averaged 81.3/45.5%. In 77% of patients, this therapy prevented death from hepatic metastases. Moreover, since adverse effects were limited compared with bolus infusion, weekly 24-hour continuous hepatic arterial infusion chemotherapy was thought to be a favorable method.
Pseudomyxoma peritonei, which is the seeding of the peritoneum by mucin-secreting metastatic deposits and the filling of the peritoneal cavity by these secretions, is a malignancy that even after excision of the metastatic areas has a poor prognosis, since no effective therapy has yet been established. Herein, we report five cases of pseudomyxoma peritonei that responded to a combined postsurgical therapy consisting of CDDP, 5-FU and MMC. A 59-year-old women had a complete response who underwent an appendectomy, a right ovariectomy, and an omentectomy due to pseudomyxoma peritonei, and was postoperatively given a 50 mg intraperitoneal administration of CDDP. Further, a subcutaneous implant-type reservoir was positioned intraperitoneally for postoperative chemotherapy. At 14 days after surgery, therapy was begun which consisted of CDDP (70 mg/m2/day 1), 5-FU (350 mg/m2/day 1) and MMC (6 mg/m2/day 1) administered intraperitoneally, and 5-FU (350 mg/m2/day 1-3) that was continuously infused by an intravenous drip. She received 4 courses of postoperative chemotherapy. As a result of this therapy, the serum CEA values, which had elevated postoperatively, fell to within their respective normal ranges, and at 44 months postoperatively, this patient remains alive. Given the results above, intraperitoneal administrations of this combined CDDP, 5-FU, MMC therapy may be effective for patients with pseudomyxoma peritonei.
The combination effect of cisplatin (CDDP) and methotrexate (MTX) on the cytotoxicity against normal fibroblast and malignant cell line were investigated utilizing MTT assay. In case of normal fibroblast, the optical density (OD) value in CDDP + MTX was significantly higher and remained at a consistently higher value in various mixture rates than that in CDDP alone. Such low cytotoxicity may be due to MTX because the addition of Leucovorin resulted in an apparent decrease in the OD value. The combination of the two drugs was thought to alleviate the toxicity of CDDP on fibroblast, in contrast to its increase on cancer cells.
We report serial cerebral computed tomography (CT) and magnetic resonance imaging (MRI) in a case of hemolytic uremic syndrome (HUS) with the complication of the central nervous system due to Escherichia coli O157:H7. Although initial brain CT was normal, follow-up CT and MRI revealed lesions in the white matter and bilateral basal ganglia, representing brain edema and infarcts, respectively. Especially, lesions in the bilateral basal ganglia were very unique. Serial CT and MRI findings are useful to understand the mechanism of the complications of the central nervous system associated with HUS.
Against enterohemorrhagic Escherichia coli (EHEC) O157 clinically isolated, the effects of faropenem (FRPM), a novel oral penem antibiotic, on the MICs, bactericidal activity, verotoxin (VT)-release, and lipopolysaccharide (LPS)-release were investigated in vitro and compared with those of other types of antibacterial agents. The MICs of FRPM in aerobic and anaerobic culture condition, were 0.78 and 0.39 microgram/ml, respectively. In aerobic condition, FRPM was more active than ampicillin, amoxicillin (AMPC), fosfomycin (FOM), kanamycin (KM), minocycline (MINO), and clarithromycin (CAM), but was slightly less active than cefdinir (CFDN), cefditoren (CDTR), and norfloxacin (NFLX) against O157 clinical isolates. In anaerobic condition, however, FRPM showed as strong activity as CFDN, CDTR, and NFLX. FOM, NFLX, and KM as well as the beta-lactams including FRPM indicated the powerful bactericidal activity against one strain of O157 clinical isolates. The effects of MINO and CAM were bacteriostatic. FOM and the beta-lactams including FRPM promoted verotoxin type 1 (VT1)-release, but rather suppressed verotoxin type 2 (VT2)-release from the same isolate. NFLX, however, promoted VT1-release and vast amount of VT2-release. In the case of KM, MINO, and CAM, the release suppression of both VT1 and VT2 was observed. FRPM, AMPC, and FOM had very weak activity on LPS-release, while CFDN, CDTR, and NFLX released a large amount of LPS from the strain. KM, MINO, and CAM had relatively weak activity. In these in vitro experiments, FRPM demonstrated the effective profile to the treatment for EHEC infection, except for the effect on VT1-release. These results suggest the possibility that FRPM shows good clinical efficacy for EHEC infection.
We report a simultaneous operated case of a 73-year-old man with aortic arch aneurysm and squamous cell carcinoma of the lung. Via median sternotomy, aneurysmectomy and graft replacement was performed under hypothermic circulatory arrest and selective brain perfusion. After changing the position, left upper lobectomy with lymph node dissection was performed via left posterolateral thoracotomy. In spite of using cardiopulmonary bypass, hemostasis was easy, and there was no complication through intra-operative to post-operative course. The cases of simultaneous operation of thoracic aortic aneurysm and lung cancer are rare, and only 3 cases have been reported in Japan. Under careful selection of the patients, simultaneous operations can be performed safely.
We reported a 41-year-old woman with severe rheumatoid arthritis who developed chronic sensory ataxic neuropathy and anti-a-fodrin antibody. Neurological examinations, electrophysiological studies and sural nerve biopsy findings suggested dorsal root ganglioneuronopathy. T2*-weighted MRIs showed high signal intensities in the posterior column of the cervical and thoracic spinal cord, suggesting the degeneration of the posterior column of the spinal cord caused by ganglioneuronopathy. She showed xerophthalmia but no other manifestations indicating Sjögren's syndrome including sialography and salivary gland biopsy findings. In serological studies, although anti-SS-A/SS-B antibodies and anti-ganglioside antibodies were negative, her serum reacted to a-fodrin, a 120kD protein degraded from a chain of fodrin. As a-fodrin has been recently regarded as an autoantigen highly specific to Sjögren's syndrome and its antibody is likely to appear preclinically, she may develop Sjögren's syndrome in the future. It is essential to accumulate clinical and pathological findings of cases like ours in order to elucidate an etiological relationship between anti-a-fodrin antibody and dorsal root ganglioneuronopathy.
A 16-year-old boy with acute respiratory distress syndrome (ARDS) due to near-drowning was admitted to our hospital. ARDS was treated with low-level nitric oxide (NO) inhalation (ranging from 4 ppm to 1 ppm) for 24 days. Oxygenation was improved and pulmonary hypertension was reduced after NO inhalation, but systemic blood pressure, heart rate, and cardiac output were not affected. PaO2 improved from 153 Torr to 354 Torr under identical ventilating conditions (F1O2 1.0), and mean pulmonary arterial pressure fell from 40 mm Hg to 27 mmHg. It has been reported that NO inhalation alleviates ventilation-flow mismatch and pulmonary hypertension. It is unclear, however, whether this therapy improves the prognosis for ARDS. In our patient, NO inhalation was effective in alleviating the oxygenation impairment and pulmonary hypertension associated with ARDS.