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Biomedical subjects

M Sakamoto

Publications and source records attributed to M Sakamoto.

At least 577 records · Page 32Linked to original sources

Growth and spread of hepatocellular carcinoma. A review of 240 consecutive autopsy cases.

All 240 consecutive cases of hepatocellular carcinoma (HCC) that underwent autopsy at the National Cancer Center Hospital (Tokyo, Japan) between September 1962 and August 1986 were reviewed. Among these cases, 162, for which photographs of cut surfaces of the primary tumors were available, were grossly classified using a combination of both Eggel's classification and our own into three major types, i.e., nodular, massive, and diffuse as described by Eggel (Eggel H, Beitr Pathol Anat 1901; 30:506-604), and three subgroups of nodular type, i.e., single nodular type (type 1), single nodular type with extranodular growth (type 2), and contiguous multinodular type (type 3) by our classification (Kanai T et al., Cancer 1987; 60:810-819). Seventy-eight cases were classified as nodular type, comprising seven cases of type 1, 61 cases of type 2, and ten cases of type 3. Sixty-seven and 17 cases were classified as massive and diffuse type, respectively. Of the 78 nodular-type tumors, 59 measured less than 10 cm, whereas 64 of 67 massive-type tumors were 10 cm or more in size. The incidence of intrahepatic and extrahepatic tumor spread of HCC was significantly higher for tumors measuring more than 5 cm. As to the relationship between macroscopic type and tumor spread, the frequency of spread was lowest for type 1 tumors, and high for the other types. Intrahepatic metastasis was detected in 28.6% of type 1, 93.4% of type 2, 100% of type 3, and 98.5% of massive-type tumors. Lymph node metastasis was detected in 14.3% of type 1, 24.6% of type 2, 70% of type 3, 38.8% of massive-type and 52.9% of diffuse-type tumors. Hematogenous extrahepatic metastasis was detected in 14.3% of type 1, 47.5% of type 2, 70% of type 3, 74.6% of massive-type and 82.4% of diffuse-type tumors. It appears that not only primary tumor size but also its macroscopic type has an important influence on the growth and spread of HCC.

Adolescent↗

Malignant transformation of adenomatous hyperplasia to hepatocellular carcinoma.

To clarify the course of adenomatous hyperplasia (AH) of the liver, 17 patients with 20 biopsy-proven AH nodules were followed clinically for 1-5 years. At the initial biopsy the mean nodular diameter was 10 (SD 4) mm and the relative cellularity [( mean cellularity of AH divided by mean parenchymal cellularity] x 100) 141 (27). The criteria for diagnosis of malignant transformation of AH were both a doubling of nodular volume and changes on imaging. Between 6 and 50 months after biopsy, 9 of the 18 nodules which could still be accurately identified met the criteria for transformation; histological proof of hepatocellular carcinoma (HCC) was obtained later for 7 of these 9 nodules. The product of diameter and cellularity (transformation index) was the strongest predictor of the time to transformation. 9 AH nodules did not undergo transformation--7 did not meet one or both criteria and 2 became undetectable by imaging. Because of the high risk of malignant transformation, it can be concluded that AH is an absolute precursor of HCC. It should therefore be treated as a potential malignant disorder.

Adenocarcinoma↗

Bone resorption by isolated osteoclasts in living versus devitalized bone: differences in mode and extent and the effects of human recombinant tissue inhibitor of metalloproteinases.

The incubation of isolated osteoclasts with devitalized bone has become a widely used method for the recent study of bone resorption. Although the studies employing this method have definitively demonstrated that isolated osteoclasts have an avid capacity to resorb devitalized bone, the resorption in this model appears to be different from that of living bone as observed in vivo and in organ culture studies. To evaluate how the resorption of living bone is different from that of devitalized bone, we have extended this bone resorption model using isolated osteoclasts by including both devitalized and living bone substrates. Living bone substrates were freshly prepared from calvaria of 8- to 12-month-old mice. Periosteum, cellular components, and osteoid were completely scraped off to leave a rigid, smooth, mineral-exposed surface for the isolated osteoclasts to act upon. Some of the bone pieces were devitalized by repeated freezing and thawing. Living and devitalized bones were cultured with isolated rabbit osteoclasts for 60 h with or without recombinant human tissue inhibitor of metalloproteinases (100 micrograms/ml). The extent of bone resorption was assessed by measuring both the area and the depth of resorption pits. Comparing the areas of the resorption pits showed significantly more resorption in living bone than in devitalized bone (27% of that of living bone). Recombinant human TIMP reduced the resorption of living bone by 73% but did not, however, inhibit the resorption of devitalized bone. Similarly, resorption pits formed on the living bones were significantly deeper (on the average, 12.4 microns) than those formed on the devitalized bones (on the average, 4.3 microns). The average depth of the resorption pits on living bone was significantly reduced by the presence of the inhibitor, whereas there was no difference between the control and inhibitor-treated devitalized bones. These results suggest that the mechanisms underlying the resorption of living bone and that of devitalized bone are not the same and that the resorption of living bone is aided by osteocytes.

Animals↗

Structure and expression of tomato mitochondrial genes coding for tRNA(Cys) (GCA), tRNA(Asn) (GUU) and tRNA(Tyr) (GUA): a native tRNA(Cys) gene is present in dicot plants but absent in monocot plants.

The nucleotide sequences of tRNA(Asn) (GUU) and tRNA(Tyr) (GUA) genes from tomato mitochondria and their flanking regions have been determined. The tomato mitochondrial tRNA(Asn) gene is located 2.1 kb downstream from the tRNA(Cys) gene reported previously (Izuchi and Sugita 1989) and shows a nearly complete identity with the corresponding chloroplast gene. The tRNA(Tyr) gene, which shows only 73% homology with the corresponding chloroplast gene, has to be considered a "native" mitochondrial tRNA gene and is 535 bp from the "chloroplast-like" tRNA(Asn) gene on the same strand. Northern hybridization analysis revealed that the three tRNA genes are transcribed in tomato mitochondria. Southern hybridization analysis of tomato, sugar beet. rice and wheat mitochondrial DNAs, with oligonucleotide probes for mitochondrial or chloroplast tRNA genes, demonstrated that the mitochondrial tRNA(Cys) gene found in tomato is present in dicot plants but not in monocots. On the other hand, a chloroplast-like tRNA(Cys) gene exists in monocot plants.

Base Sequence↗

Primary lung cancer in an 18-year-old boy: case report.

An autopsy case of an 18-year-old boy with adenocarcinoma of the lung is reported. He experienced dyspnea and hemosputum in July 1988. Chest radiographs showed a diffuse bilateral streaky shadow, bilateral pleural effusion and cardiac enlargement. The diagnosis of adenocarcinoma was made by transbronchial biopsy at another hospital. He visited the National Cancer Center Hospital on October 7, 1988. The diagnosis of lung cancer was strongly suggested by positive immunohistochemical staining for pulmonary surfactant apoprotein in biopsy specimens from supraclavicular lymph nodes. Intensive systemic survey demonstrated no other primary site than the lung. The patient was treated with cisplatin, adriamycin and etoposide and his subjective symptoms such as cough and dyspnea significantly improved over the next three months. Tumor shadows in the lung increased steadily, however after February, 1989. A significant lymphangitic spread of the carcinoma and marked obsteoblastic bone metastases were revealed at autopsy.

Adenocarcinoma↗

Heterogeneity of proliferative activity in nodule-in-nodule lesions of small hepatocellular carcinoma.

Surgically resected small hepatocellular carcinomas showing "nodule-in-nodule" formation were analyzed in terms of cell proliferative activity. The analysis was achieved by successful immunohistochemical demonstration of proliferating cell nuclear antigen in formalin-fixed paraffin-embedded tissue sections. Eight nodules (up to 3 cm in diameter) examined were either atypical adenomatous hyperplasia or hepatocellular carcinoma of low histologic grade, containing a discrete inner nodular area composed of obvious hepatocellular carcinoma of higher histologic grade. In all cases, the proliferating cell nuclear antigen labeling index of the latter area was much higher than that of the former, which in turn was slightly higher than that of the non-cancerous liver of the patient in 6 cases. The data presented here provide supporting evidence that the successive emergence and expansion of a more rapidly proliferating subclone within a nodule result in the stepwise progression of malignancy of human hepatocellular carcinoma.

Antigens, Neoplasm↗

Cloning and nucleotide sequence of cDNA for Ki antigen, a highly conserved nuclear protein detected with sera from patients with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) produce autoantibodies against a variety of nuclear antigens including Ki antigen. Although anti-Ki autoantibodies were found in a significant number of SLE patients, the nature of Ki antigen is poorly characterized. By using anti-Ki serum as a probe we have cloned a bovine cDNA directing the synthesis in Escherichia coli of a polypeptide immunologically indistinguishable from the authentic Ki antigen. A homologous human cDNA was also cloned and its nucleotide sequence predicted the entire primary structure of a novel nuclear protein with a molecular weight of 29 508 and with highly hydrophilic and weakly acidic character. The gene is highly conserved not only in the coding region but also in the 3'-untranslated region. The bacterially produced Ki antigen would be valuable for diagnosis of SLE.

Amino Acid Sequence↗

Effects of diazepam on the carotid sinus baroreflex control of circulation in rabbits.

To examine the effects of diazepam on the carotid sinus baroreflex control of circulation, bilateral carotid occlusion was performed on 14 conscious rabbits with aortic denervation. The responses of mean arterial pressure, heart rate, cardiac output and total peripheral resistance were obtained. The haemodynamic responses to carotid occlusion were evaluated at cumulative doses of 0.5 and 1.0 mg kg-1 of diazepam. The administration of diazepam decreased cardiac output and increased total peripheral resistance significantly, but did not affect the arterial pressure and heart rate. The response of total peripheral resistance to carotid occlusion was significantly increased from 0.118 +/- 0.018 (mean +/- SE) to 0.154 +/- 0.026 mmHg min ml-1 at 1.0 mg kg-1 of diazepam. The heart rate response was attenuated significantly from 41 +/- 5 to 24 +/- 4 beats min-1 at 1.0 mg kg-1 of diazepam. Diazepam did not alter the response of arterial pressure to carotid occlusion. We suggest that the dissociated effects of diazepam on the reflex control of circulation reflect the dissociated influences of diazepam on the central sympathetic and vagal-mediated pathways.

Animals↗

The mechanism of protective effect of diltiazem on reperfusion-induced arrhythmias in isolated rat heart.

This investigation was undertaken to define the mechanism by which diltiazem protects against life-threatening, reperfusion-induced arrhythmias. Using an isolated retrogressively perfused rat heart preparation with transient coronary artery occlusion, we compared the effects of diltiazem in its active form (d-cis) to its stereo-isomer (1-cis). Pre-ischemic administration of d-diltiazem (5 x 10(-8), 5 x 10(-7), 5 x 10(-6) M) caused a dose-dependent reduction in ventricular arrhythmias upon reperfusion following 10 min of regional ischemia. The incidence of reperfusion-induced ventricular fibrillation (RVF) was 50%, 0% (p less than 0.05) and 0% (p less than 0.05) with 5 x 10(-8), 5 x 10(-7), 5 x 10(-6) M diltiazem, respectively, compared with 60% in the control group. Preischemic administration of the 1-isomer caused different dose-dependent reduction in RVF. With 5 x 10(-6) M, the 1-isomer also reduced the incidence of RVF to 0% (p less than 0.05). However below this concentration it was ineffective (67%). D-diltiazem (5 x 10(-7) and 5 x 10(-6) M) increased coronary flow from 11.5 +/- 1.9 ml/min to 15.3 +/- 1.6 ml/min (p less than 0.05) and 15.2 +/- 1.0 ml/min (p less than 0.05) respectively, prior to ischemia. In contrast, the same dose of the 1-isomer did not alter coronary flow. The highest dose (5 x 10(-6) M) of d-diltiazem decreased heart rate by approximately 30% during the reperfusion phase, but all other concentrations had no significant effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Antibacterial activity and chemical modifications of PS-5 at the C-3 side chain.

Using PS-5 as starting material, the effects of chemical modification at the C-3 side chain were studied on the antibacterial activity against Gram-positive and Gram-negative bacteria including beta-lactamase-producers. Among 35 side chains tested, 4-pyridylthio showed the highest antibacterial activity against the Gram-positive bacteria, and D-cysteinyl against the Gram-negative microbes. In general, compared with acetamidoethylthio in PS-5, basic side chains showed improved antibacterial activity against the staphylococci and pseudomonads, whereas the antibiotic activity against the Gram-negative bacteria decreased with bulky side chains. The introduction of 6-aminopenicillanate and 7-aminocephalosporanate to the C-3 side chain of carbapenem significantly reduced the antibacterial activity against the beta-lactamase-producing microbes.

Gram-Negative Bacteria↗

[Urinary excretion rate of methylguanidine as a new maker of active oxygen in vivo: demonstration in hyperbaric oxygen therapy].

Methylguanidine (MG) which is known as a uremic toxin, is synthesized from creatinine (Cre). We have clarified that active oxygen plays an important role on MG synthesis in vitro and in rat hepatocytes. On the other hand, hyperoxia is very injurious in various tissues, and it has been reported that active oxygen produced in hyperoxia plays an important role on the tissue injury. This study was performed to investigate the effect of hyperoxia on MG synthesis in vivo. The subjects in this study were patients who were treated by hyperbaric oxygen therapy (HBO). Serum Cre, MG, and urinary Cre, MG before and after HBO were measured in these subjects. The subjects were classified into four groups. Group I-III were undergone HBO with condition of 100% O2, 2 atmosphere absolute (ATA), 1 hour, (I: Ccr less than 10 ml/min, II: 10 less than or equal to Ccr less than 50 ml/min, III: Ccr greater than or equal to 50 ml/min) and group IV (Ccr greater than or equal to 50 ml/min) with 100%O2, 3ATA, 1 hour. Urinary excretion rate of MG (urine MG/urine Cre) significantly increased after HBO therapy in every group. Urine MG/urine Cre/serum Cre ratio which was used as a index of MG synthesis rate also increased. In this study, it is clarified that MG excretion rate increases in hyperoxic condition. These results suggest that active oxygen plays an important role on MG synthesis in vivo, and that the urine MG/urine Cre/serum Cre ratio can be a useful maker of the active oxygen products in vivo.

Adult↗

Prevalences of malocclusions and dental caries in molars in female adolescents.

Prevalences of malocclusions and dental caries in molars were investigated on a database of high school students collected between 1977 and 1986. A total of 6,665 schoolgirls were evaluated. The proportions of 54.1% in the seventh grade and 56.6% in the tenth grade students were judged as having malocclusions. The prevalences of dental caries for the lower first and the second molars were significantly higher (p less than 0.001) than those for the upper opponents during the observation period. The prevalence of dental caries increased linearly for all kinds of molars in accordance with age, but they were lower than those reported by the Ministry of Health and Welfare in Japan determined for the entire nation. The percent of dental caries for the second molars revealed abrupt increases from 10% at the seventh grade to 50% at the 12th grade. These changes were particularly noticeable between the eighth and the tenth grades. These results suggest the significance of oral health care education during the adolescent period based on a long-term cooperation made by dentists, school nurses, teachers through the participation of students into the oral health care programme.

Adolescent↗

[An operated case of multiple well-differentiated hepatocellular carcinomas and adenomatous hyperplasia].

A 66-year-old male with non-A, non-B liver cirrhosis underwent an operation for a partial resection of the S8 area. Intraoperative ultrasound (US) examination of the entire liver revealed 10 space-occupying lesions (SOLs), and a biopsy of 5 out of the 10 SOLs showed 3 hepatocellular carcinomas (HCCs), adenomatous hyperplasia (AH), and an atypical AH (AAH). In a resected specimen that including 4 SOLs that had been detected by operative US, 6 early HCCs, an HCC of the Edmondson grade I + II, and 2 AAHs were found. All tumors were less than 2 cm and were not encapsulated.

Aged↗

[Rupture of an infected vein graft in the course of mediastinitis following coronary artery bypass grafting: report of a case].

A 51-year-old man developed a Staphylococcal mediastinitis and septicemia 23 days after coronary artery bypass grafting. He was initially treated with surgical debridement and closed irrigation with 0.5% povidone iodine solution. However, since the infection could not be eradicated by this method, an open packing method was subsequently required. Nineteen days after the diagnosis of mediastinitis, massive bleeding occurred due to rupture of an infected vein graft to the LAD. Although he went into profound hemorrhagic shock, suture ligation of the vein graft was successfully performed. The sternum was reapproximated 34 days after the initial debridement. Postoperative coronary angiograms revealed the patent vein grafts to the RCA and LCX, and PTCA was performed to the native stenosis of the LAD. The patient was discharged 5 months after the bypass operation and is now doing well 3 years postoperatively. Rupture of the heart or vessels in the course of postoperative mediastinitis is a very rare but highly lethal complication. We think that it is important to eradicate the infection as soon as possible to prevent the bleeding complication and that the decision as to which method, closed or open, should be employed, is crucial.

Blood Vessel Prosthesis↗