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Biomedical subjects

Osamu Kobayashi

Publications and source records attributed to Osamu Kobayashi.

At least 19 recordsLinked to original sources
PubMed2006

Clinicopathological features of nonpolypoid colorectal tumors as viewed from the patients' background.

BACKGROUND: This study was performed to characterize the clinicopathological features of colorectal tumors with flat-, depressed-, or protruded-type morphology (hereafter referred to simply as flat, depressed, or protruded lesions). METHODS: There are two major types of colorectal tumor: polypoid (protruded) and nonpolypoid (flat and depressed). A total of 130 lesions from 130 patients with colorectal submucosal invasive cancer were classified into three groups according to their macromorphology seen during endoscopy: flat (laterally spreading) and depressed nonpolypoid tumors and protruded polypoid tumors. The following factors in the patients' background were evaluated: indication for colonoscopy, age, and family history of colorectal cancer in first-degree relatives (i.e., parents, siblings, children). We also compared the following characteristics of the tumors: size, location, depth of submucosal invasion, vascular invasion, and frequency of synchronous and metachronous tumor lesions. RESULTS: The incidence of abnormal findings on follow-up studies after polypectomy as an indication for colonoscopy was significantly higher among patients with flat lesions (4/24, 16.7%) and depressed lesions (3/22, 13.6%) than among those with protruded lesions (1/84, 1.2%) (P < 0.01, P < 0.01). Patients with flat lesions (65.8 +/- 7.6 years old) were significantly older than those with protruded lesions (P < 0.05). The patients with flat tumors had a significantly higher rate of a family history of colorectal cancer (6/24, 25.0%) than patients with protruded or depressed lesions (P < 0.01, P < 0.05). The protruded lesions were significantly larger than the depressed lesions (size 13.3 +/- 6.7 mm) (P < 0.05), and the flat lesions (24.1 +/- 10.1 mm) were significantly larger than either the protruded or depressed lesions (P < 0.01, P < 0.01). Seventy-five percent (18/24) of the flat lesions were located in the right colon, and this proportion was significantly higher than that among the protruded or depressed lesions (P < 0.01, P < 0.01). The mean +/- SD depth of submucosal invasion was 1218 +/- 1034 microm in the flat lesions, 2392 +/- 1869 microm in the depressed lesions, and 2761 +/- 1929 microm in the protruded lesions, representing a significant difference (P < 0.05, P < 0.0001). Of the 24 patients with flat lesions, 9 (37.5%) showed vascular invasion; this proportion was significantly lower than that among patients with the depressed or protruded lesions (P < 0.01, P < 0.01). Patients with depressed lesions tended to have higher incidence of synchronous and metachronous malignant polyps than those with protruded or flat lesions. CONCLUSION: It is important to examine the morphology of colorectal tumors when diagnosing them and planning the treatment strategy, including follow-up, after resection of nonpolypoid tumors. It is useful to know the patient's family history so nonpolypoid tumors can be accurately diagnosed.

Aged↗
PubMed2006

Protein levels of tissue inhibitor of metalloproteinase-1 in tumor extracts as a marker for prognosis and recurrence in patients with gastric cancer.

BACKGROUND: Tissue inhibitor of metalloproteinase-1 (TIMP-1) correlates with tumor progression in patients with gastric cancer; however, the clinical significance of TIMP-1 as a marker for prognosis and recurrence has not been fully clarified. METHODS: TIMP-1 protein was measured by an enzyme-linked immunosorbent assay in tumor samples from 86 patients who had undergone surgical resection. An intratumoral TIMP-1 value of 10.0 ng/mg protein or more was defined as positive. Patients were followed up for more than 5 years prospectively. RESULTS: Thirty-one of the 86 patients (36.0%) were positive for TIMP-1. Kaplan-Meier curves for overall survival were significantly different between patients who were positive and those who were negative for TIMP-1. Univariate analysis of factors affecting overall survival showed that depth of tumor invasion; lymph node metastasis; peritoneal dissemination; lymphatic invasion; venous invasion; Lauren classification of histology; curability; and TIMP-1 were statistically significant. Stepwise multivariate analysis for overall survival demonstrated that depth of tumor invasion, nodal metastasis, peritoneal dissemination, and TIMP-1 remained independent prognostic factors. Kaplan-Meier curves for disease-free survival were significantly different between patients who were positive and those who were negative for TIMP-1. The incidence of recurrence was significantly higher in patients positive for TIMP-1 than in those who were negative for TIMP-1. The frequency at each site of recurrence was higher in patients positive for TIMP-1. CONCLUSION: These results suggested that the protein concentration of TIMP-1 in the tumor extracts was a useful marker for overall survival, disease-free survival, and disease recurrence in patients with gastric cancer. Thus, tumor TIMP-1 may serve to identify a high-risk group, for whom optimal surgical and medical treatment can be given.

Biomarkers, Tumor↗
PubMed2006

The efficacy of gastrectomy for large gastric cancer.

BACKGROUND: Large gastric cancer (LGC) is frequently associated with extended disease, and the role of surgical resection has been debated. We investigated the efficacy of surgical treatment for LGC. METHODS: The size of LGC was defined as 8 cm or greater. Four hundred and fifteen patients with LGC who underwent gastrectomy were included. The clinicopathological features, the status of the residual tumor, the incidence and patterns of relapse, and the survival were analyzed. RESULTS: Macroscopically, diffuse-type tumors were dominant (60%). The numbers of patients with tumors of T3 or greater, lymph node involvement, and peritoneal metastases were 356 (86%), 359 (87%), and 126 (30%), respectively. One hundred and eighty-eight patients (45%) underwent incomplete tumor resection (R2). The R2/R0 (no residual tumor) ratio was greater than 1 in patients with type 4 tumors and N1 or greater metastasis and in those with type 3 tumors and N2 or greater metastasis. In contrast, T2, type 2, and type 5 tumors were more likely to be completely resected. The 5-year survival for all 415 patients was 26%. The survival rates were inversely related to the tumor type, size, and lymph node metastasis. In the 216 patients with R0, the 5-year survivals of those with pN (International Union Against Cancer [UICC] classification) 0, 1, 2, and 3 were 66%, 56%, 36%, and 5%, respectively (P = 0.001). In 96 of these 216 patients (44%) the tumor recurred, and peritoneal metastasis was the most frequent mode of recurrence (48%). By Cox's proportional hazard model, the tumor size was an independent prognostic factor. CONCLUSION: The chance of achieving R0 resection for LGC is low, except for T2, type 2, or type 5 tumors. Primary resection should be avoided for other types of LGC.

Gastrectomy↗
PubMed2006

Effect of ciprofloxacin on levels of lipopolysaccharide and cytokines in experimentally induced gram-negative bacterial pneumonia in mice.

This study was performed to examine the ability of ciprofloxacin (CPFX) to suppress the inflammation associated with lipopolysaccharide (LPS) and an inflammatory cytokine in gram-negative bacterial pneumonia. For this purpose we measured viable cell counts in bronchoalveolar lavage fluid (BALF), LPS concentrations in BALF, and BALF levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in mice exposed to Klebsiella pneumoniae. We used three groups of mice: controls, treated with physiological saline; mice treated with CPFX; and mice treated with ceftadizime (CAZ). The viable cell count in BALF was low in both the CAZ and CPFX groups. LPS values in BALF were significantly lower in the CPFX group than in the CAZ group at 48 and 72 h after K. pneumoniae exposure (48 h, P < 0.001; 72 h, P < 0.05). The BALF TNF-alpha level was significantly higher in the CAZ group at 24, 48, and 72 h compared to levels in the control and CPFX groups (P < 0.05). In conclusion, these results suggest that CPFX inhibited increases of LPS and TNF-alpha in gram-negative bacterial pneumonia, thereby suppressing the lung inflammation that accompanies pneumonia.

Animals↗
PubMed2006

Olfactory neuroblastoma in a horse.

An 11-year-old thoroughbred gelding was euthanatized because of right nasal cavity tumor. The tumor consisted of round to oval cells with a scanty cytoplasm and hyperchromatic nuclei. Homer-Wright rosettes and pseudorosettes, as well as microcysts were seen. Neoplastic cells were immunoreactive to vimentin, S-100 protein, and neuron-specific enolase, glial fibrillary acidic protein and microtube-associated protein in varying degrees, indicating neurogenic nature. Based on these findings, this tumor was diagnosed as an olfactory neuroblastoma. Since this type is an uncommon tumor showing histological variety, the nature is discussed.

Animals↗
PubMed2006

Rapid and simple detection of hot spot point mutations of epidermal growth factor receptor, BRAF, and NRAS in cancers using the loop-hybrid mobility shift assay.

A simple and rapid method to detect the epidermal growth factor receptor hot spot mutation L858R in lung adenocarcinoma was developed based on principles similar to the universal heteroduplex generator technology. A single-stranded oligonucleotide with an internal deletion was used to generate heteroduplexes (loop-hybrids) bearing a loop in the complementary strand derived from the polymerase chain reaction product of the normal or mutant allele. By placing deletion in the oligonucleotide adjacent to the mutational site, difference in electrophoretic mobility between loop-hybrids with normal and mutated DNA was distinguishable in a native polyacrylamide gel. The method was also modified to detect in-frame deletion mutations of epidermal growth factor receptor in lung adenocarcinomas. In addition, the method was adapted to detect hot spot mutations in the B-type Raf kinase (BRAF) at V600 and in a Ras-oncogene (NRAS) at Q61, the mutations commonly found in thyroid carcinomas. Our mutation detection system, designated the loop-hybrid mobility shift assay was sensitive enough to detect mutant DNA comprising 7.5% of the total DNA. As a simple and straightforward mutation detection technique, loop-hybrid mobility shift assay may be useful for the molecular diagnosis of certain types of clinical cancers. Other applications are also discussed.

Adenocarcinoma↗
PubMed2006

[Cardiac failure in a child during anesthetic induction with sevoflurane].

A five-year-old boy with recurring tonsillitis and sleep apnea was admitted for tonsillectomy and tympanic membrane tubing. He presented with a history of bronchial asthma and hereditary spherocytosis without obvious cardiac failure symptoms. Anesthetic agents for induction included nitrous oxide, oxygen, and sevoflurane. Because oxygen saturation decreased immediately to 90%, tracheal intubation was performed. The patient began to wheeze. Sevoflurane concentration was increased but cardiac murmur (gallop), cold limbs and jugular vein distension were noted. Acute cardiac failure was diagnosed following a chest X-ray and cardiac echo showing an enlarged heart, CTR of 80%, left ventricular dilation, and contractile failure. Tympanic membrane tubing only was performed. Sevoflurane was discontinued and the patient was treated for the cardiac failure under an ICU oxygen tent. The patient was discharged when his general condition improved. He showed elevated levels of viral antibodies, suggesting myocarditis. Later he was treated for dilating cardiomyopathy before undergoing a heart transplant.

Anesthesia, Inhalation↗
PubMed2006

[An autopsy case of Aspergillus pneumonia after inhalation of a great deal of dust in a mushroom factory].

A man in his forties with alcoholic liver injury was referred to our hospital because of progressive dyspnea and diffuse infiltrative shadows in both lung fields. Two weeks before admission he had carried a lot of rotten Enoki mushrooms in his factory, and then inhaled a great deal of airborne dust. Serological examination showed extremely elevated beta-D-glucan and positive Aspergillus antigen. Culture of dust collected from the floor of the factory proved to be positive for Aspergillus fumigatus. Aspergillus pneumonia was diagnosed and treatment with anti-fungal drugs was started. In spite of intensive treatment he died of respiratory failure. The autopsy disclosed multiple abscess formation containing hyphae of Aspergillus fumigatus and granulomatous reaction with multinuclear giant cells. However, there was no Aspergillus invasion in other organs. This was a rare case of invasive pulmonary aspergillosis that developed after inhalation of organic dust in a non-immunocompromised host.

Adult↗
PubMed2005

Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis: a randomized, controlled pilot trial with long-term follow-up.

OBJECTIVE: It is proposed that Fusobacterium varium might be one of the elusive pathogenic factors in ulcerative colitis (UC). Our goal was to assess whether an antibiotic combination therapy against F. varium is effective for induction and maintenance of remission of UC. MATERIAL AND METHODS: Twenty chronic, active UC patients with F. varium infection were enrolled consecutively and were randomly assigned to receive amoxicillin, tetracycline or metronidazole per os for 2 weeks (treatment group; n=10), or no antibiotics (control group; n=10). F. varium was sensitive to the antibiotics. Symptom assessment, endoscopic and histological evaluations were performed blind before enrollment at 3-5 months and 12-14 months after the treatment. Serum immunoglobulins to F. varium were measured using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemical detection of F. varium in biopsy specimens was carried out using the avidin-biotin complex method. RESULTS: The clinical activity, endoscopic and histological scores in the treatment group decreased significantly at 3-5 and 12-14 months after the end of treatment compared with those in the control group (p=0.001-0.036). The remission rate in the treatment group was higher than that in the control group (p=0.037). In addition, the titers of antibody to F. varium and the F. varium density in the mucosa decreased at both the short- and long-term follow-ups in the treatment group (p=0.0002-0.049). No serious drug-related toxicity was observed during the trial. CONCLUSIONS: The 2-week antibiotic combination therapy against F. varium was effective and safe in patients with chronic, active ulcerative colitis in this long-term follow-up study.

Adolescent↗
PubMed2005

[Which anesthetic technique is more suitable for hip fracture surgery in patients above the age of 85, spinal or epidural?].

BACKGROUND: Anesthesia for hip fracture in elderly patients is a challenge because of their reduced functional reserve. We compared spinal and epidural anesthesia retrospectively in the operations of hip fracture in patients above the age of 85. METHODS: Two hundred and eighteen operations from April 1995 to September 2003 in our hospital were examined. Epidural anesthesia was scheduled in 94 operations, and bupivacaine spinal anesthesia in 86 operations. Successful anesthetic cases of each group were compared. Blood pressure, heart rate, doses of vasopressors used were recorded before anesthesia and first and second 30-minute periods after anesthesia. RESULTS: Failed anesthetic cases in epidural anesthesia were significantly more than those in spinal anesthesia. Blood pressure in the first 30-minute period after epidural anesthesia was significantly lower than that after spinal anesthesia. CONCLUSIONS: Spinal anesthesia is preferable for the operation for hip fracture compared with epidural anesthesia, because of fewer failed cases and smaller decreases of blood pressure.

Aged↗
PubMed2005

[Treatment strategy for primary gastric cancer with peritoneal dissemination].

Curative resection is considered to be a standard therapy for gastric cancer with localized peritoneal metastases. For tumors with diffuse dissemination, chemotherapy may play a major role, however, the benefits of reduction surgery and standard chemotherapy have not yet been clarified. Median survival time after reduction surgery was reported to be 4-13 months for patients diagnosed by surgery and/or CT and 5-6 months for chemotherapy for those diagnosed by CT alone. Reduction surgery has a high risk, with a morbidity of 12-44% and a mortality of 3-14%. Palliative surgery should be indicated for stenosis or bleeding due to primary tumors. 5-FU, MTX-5-FU, TS-1, paclitaxel, and their combination are candidates for practice and clinical trials. It is important to evaluate the severity of peritoneal dissemination by diagnostic laparoscopy or laparotomy for decision making.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Spindle checkpoint function is required for mitotic catastrophe induced by DNA-damaging agents.

Mitotic catastrophe is an important mechanism for the induction of cell death in cancer cells by antineoplastic agents that damage DNA. This process is facilitated by defects in the G1 and G2 checkpoints of the cell cycle that are apparent in most cancer cells and which allow the cells to enter mitosis with DNA damage. We have now characterized the dynamics of mitotic catastrophe induced by DNA-damaging agents in p53-deficient cancer cells. Cells that entered mitosis with DNA damage transiently arrested at metaphase for more than 10 h without segregation of chromosomes and subsequently died directly from metaphase. In those metaphase arrested precatastrophic cells, anaphase-promoting complex appeared to be inactivated and BubR1 was persistently localized at kinetochores, suggesting that spindle checkpoint is activated after the DNA damage. Furthermore, suppression of spindle checkpoint function by BubR1 or Mad2 RNA interference in the DNA damaged cells led to escape from catastrophic death and to subsequent abnormal mitosis. Dysfunction of the spindle checkpoint in p53-deficient cancer cells is thus likely a critical factor in resistance to DNA-damaging therapeutic agents.

Base Sequence↗
PubMed2004

Clinical diagnosis of metastatic gastric tumors: clinicopathologic findings and prognosis of nine patients in a single cancer center.

The clinical features of metastatic gastric tumors (MGTs) have not been well documented. We present a clinical series of nine patients with MGTs. Among 2579 patients with gastric tumors seen between 1992 and 2001, we studied 9 (0.3%) patients with MGT according to a prospective database. The MGTs were diagnosed based on findings in the surgical or endoscopic specimen, and patients with malignant lymphoma or direct invasion from adjacent organs were excluded from the study. MGTs were detected simultaneously with the primary tumors in three and afterward in six patients at 14 to 74 months. The primary tumors included one each of squamous cell carcinoma of the esophagus, signet-ring cell carcinoma of the breast, large-cell or small-cell carcinoma of the lung, renal cell carcinoma, hepatocellular carcinoma, squamous cell or epidermoid carcinoma of the uterus, and melanoma. Multiple organ metastases were present simultaneously in six patients. Although six patients underwent gastrectomy, macroscopic eradication of gastric metastatic disease was accomplished in only four, in whom a UICC R0 resection was possible in only two. Five patients were treated by chemotherapy with no apparent survival benefit. A median survival after MGT diagnosis was 170 days (range 16-892 days) for all cases, 384 days for those who underwent gastrectomy (n = 6), and 27 days for those without active treatment (n = 3) (p = 0.002). The cause of death was multiple organ metastases in most cases. Because multiple metastases are common, the prognosis of MGT is poor even after curative resection. MGT is likely to be a preterminal event, and surgical resection may be useful only for palliation.

Aged↗
PubMed2004

Route from the paraaortic lymphatic system to the tracheobronchial lymph nodes evidenced on lymphangiogram in a patient with gastric cancer.

Lung metastasis from gastric or colonic cancer, without liver metastasis, is seldom seen. However, its metastatic pathway has not been delineated on imaging. We present and discuss such a lymphatic route in a patient with gastric cancer. The appearance of the mediastinum on a lymphangiogram is discussed. To the best of our knowledge, the lymphangiographic demonstration of the route from the paraaortic lymphatics to the tracheobronchial lymph nodes has been not reported. Lymphatics running from the paraaortic to the tracheobronchial lymph nodes through the diaphragm may play an important part in direct metastasizing to lung or tracheobronchial lymph nodes in certain patients.

Aorta↗
PubMed2004

Combination electro-gene therapy using herpes virus thymidine kinase and interleukin-12 expression plasmids is highly efficient against murine carcinomas in vivo.

We report the use of plasmid DNA-mediated combination gene therapy for tumor-bearing mice using in vivo electroporation, also called electro-gene therapy (EGT), that resulted in uncomplicated and complete cures in more than 90% of the mice. Subcutaneously inoculated CT26 tumors in syngeneic BALB/c mice were subjected to repeated EGT treatments consisting of intratumoral co-injection of naked plasmids encoding the cytokine interleukin-12 (IL-12) (p35 and p40 subunits) and the suicide gene herpes simplex virus thymidine kinase (HSV-tk), followed by in vivo electroporation. The early anti-tumor effect was always stronger, and the rate of cure, as seen in the long-term follow-up, was always greater in the groups treated with combination EGT than in those treated with IL-12 or HSV-tk EGT alone. Systemic levels of IL-12 and IFN-gamma increased in both combination and IL-12-alone EGT-treated groups. Moreover, combination EGT for established subcutaneous tumors strongly reduced hematogenous lung metastases and increased survival time when live CT26 tumor cells were injected through the tail vein. Limited experiments on C57/B16 mice with murine melanoma also showed very similar trends. These results suggest that this simple and safe method of plasmid-mediated combination EGT may provide a potentially effective gene therapy for cancer.

Animals↗
PubMed2004

Tracheo-bronchitis associated with Crohn's disease improved on inhaled corticotherapy.

We report a case of tracheo-bronchitis in Crohn's disease. A 23-year-old Japanese woman who had been diagnosed with Crohn's disease three years previously was hospitalized. She had been suffering from dry cough for one month. Computed tomography of the chest revealed marked thickening of the tracheal wall. Bronchoscopy showed erythematous and edematous mucosa with diffuse whitish granular lesions in the trachea and bronchi. The bronchial biopsy specimens showed non-specific inflammatory infiltrates consisting of lymphocytes and plasma cells, and hyperplasia of bronchial glands. Inhaled corticotherapy, fluticasone propionate 800 microg/day, was effective for both the inflammatory mucosa and thickened tracheal wall.

Administration, Inhalation↗