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Biomedical subjects

M Sakamoto

Publications and source records attributed to M Sakamoto.

At least 325 records · Page 18Linked to original sources

Numerical chromosome aberrations in hepatocellular carcinoma detected by fluorescence in situ hybridization.

AIMS/METHODS: Numerical aberrations of chromosomes 7,8,9,10,12,17,18, X and Y were examined in 38 hepatocellular carcinoma specimens using centromere-specific DNA probes by the fluorescence in situ hybridization method. RESULTS: Numerical aberrations in more than one of the chromosomes examined were found in 27 of 38 (71%) specimens; 6 of 15 (40%) well-differentiated hepatocellular carcinomas; 15 of 17 (88%) moderately differentiated hepatocellular carcinomas; and all of 6 (100%) poorly differentiated hepatocellular carcinomas. Of 6 early hepatocellular carcinomas, numerical chromosome aberrations were detected in 2. The incidence of numerical chromosome aberrations was 93.8% in patients with portal vein thromboses and/or intrahepatic metastases, 52.4% without portal vein thromboses and/or intrahepatic metastases (p < 0.05), while 89.5% of patients with a tumor more than 3 cm in diameter and 50.0% with a tumor less than 3 cm in diameter had chromosome aberrations (p < 0.05). CONCLUSIONS: These results suggest that numerical chromosome aberrations start to occur in the early stage of hepatocellular carcinoma and to accumulate during tumor progression.

Carcinoma, Hepatocellular↗

Bone uptake of vanadium in mice: simultaneous tracing of V, Se, Sr, Y, Zr, Ru and Rh using a radioactive multitracer.

The radioactive multitracer technique, which enables simultaneous tracing of a number of elements in a variety of bio-systems and an accurate comparison of their biobehavior, was employed in a study on uptake behavior of trace elements in various mice tissues, focusing on uptake of V by bone. We found that the bone uptake behavior of trace V closely resembles that of trace Sr and Y. It is suggested that V is a bone-seeking element which probably plays an important role in bone formation. The multitracer technique was thus shown to be useful for comparative studies of behavior of trace elements in living organisms.

Animals↗

E-cadherin is involved in the intrahepatic metastasis of hepatocellular carcinoma.

In human hepatocellular carcinoma (HCC), the liver is the major target organ of metastasis, which is known as intrahepatic metastasis. To analyze the mechanism of this metastasis, we established two sublines from the human HCC cell line Li7. Subline Li7HM produced multiple liver metastasis, whereas subline Li7NM never did so after intrasplenic injection into nude mice. Two-dimensional gel electrophoresis and immunoblot analysis showed that only Li7NM expressed vimentin and lacked E-cadherin expression, indicating that this clone had undergone epithelial-mesenchymal transition. We then transfected mouse E-cadherin complementary DNA into Li7NM cells and found that the transfectant cells (EM16.21B.3) formed liver metastasis (8/16 mice) after intrasplenic injection and liver tumors (11/13 mice) after intrahepatic injection, whereas the control cell line formed no tumors. These results suggest that E-cadherin plays an important role in the process of intrahepatic metastasis of HCC.

Animals↗

Hypoxia inhibits gastric emptying and gastric acid secretion in conscious rats.

This study examines the effects of hypoxia in the gastric function in conscious rats which adapted to a meal-feeding schedule, that allowed free access to a high protein (HP) diet (550 g casein/kg diet, Exp.1,2 and 4), a normal protein (NP) diet (200 g casein/kg diet, Exp.3) or a nonpurified rat (NPR) diet (Exp. 5 and 6) for 4 h every day for 2 wk. In Exp. 1, after 4 h of consuming the HP diet, rats were exposed to 7.6 or 10.5% O2 normobaric hypoxia. Hypoxia delayed the excretion of urinary urea for 12 h. In Exp.2 and 3, when rats were exposed to 7.6%O2 after 4 h of consuming the HP diet and exposed to 10.5% O2 after 4 h of consuming the NP diet, respectively, a significant delay in gastric emptying was found in the hypoxic rats. In Exp. 4, when rats were exposed to 7.6 O2 hypoxia after 4 hr of eating the HP diet, the plasma gastrin concentration in the 7.6% O2 hypoxic rats was 2.3-fold that of the normoxic rats after 6 h of hypoxia. Furthermore, when rats that did not consume any HP diet on the day of the experiment were exposed to 7.6 or 10.5% O2 hypoxia, the plasma gastrin concentration was higher in both hypoxic groups than in the normoxic group after 3 and 6 of hypoxia. In Exp. 5, rats that were not fed the NPR diet on the day of study were exposed to 7.6 or 10.5% O2 hypoxia for 3 h after pylorus ligation. Hypoxia inhibited the secretion of gastric acid and elevated the plasma gastrin concentration. In Exp. 6, unfed rats that had been consuming the NPR diet were exposed to 7.6% O2 hypoxia for 3 h after pylorus ligation and were orally administered HCl. The rise of the gastrin concentration due to hypoxia was completely inhibited by oral HCl. These results demonstrate that hypoxia inhibits gastric emptying and gastric acid secretion and that the inhibitory effect of hypoxia on gastric acid secretion stimulates gastrin release through positive feedback regulation.

Analysis of Variance↗

Treatment of rupture of a liver metastasis from esophageal leiomyosarcoma.

We describe a case of rupture of a liver metastasis from esophageal leiomyosarcoma which was treated successfully by hepatic arterial embolization, thus facilitating hepatectomy. A 59-year-old woman who had previously undergone esophagectomy for leiomyosarcoma was admitted in a state of hypovolemic shock. Ultrasonography revealed multiple tumors in the left lobe of the liver and massive intraperitoneal hemorrhage, confirmed by paracentesis, possibly due to spontaneous rupture. Subsequent hepatic angiography showed extravasation from the tumor, and embolization of the feeding left hepatic artery was performed. After achieving hemostasis, a left hepatic lobectomy was carried out just beneath the reconstructed stomach tube. The patient made an uneventful recovery and remains well after one year. Emergency arterial embolization followed by hepatectomy is an appropriate treatment for patients with spontaneous rupture of liver metastases.

Combined Modality Therapy↗

Successful radical surgery for an undifferentiated gallbladder carcinoma with lymph node metastases to the mesocolon.

We report successful radical systematic surgery for an undifferentiated gallbladder carcinoma with metastasis to the mesocolonic lymph nodes. The patient, a 70-year-old woman, was admitted with abdominal fullness and appetite loss. Imaging modalities revealed a 10-cm tumor originating from the gallbladder and infiltrating both the liver and transverse colon. As multiple mesocolonic lymph node metastasis was confirmed on laparotomy, right hemicolectomy with systematic lymph node dissection (D3 resection) was performed, in addition to extended cholecystectomy with partial resection of segments 4, 5 and 6 of the liver and distal gastrectomy. Histologically, the tumor was diagnosed as an undifferentiated carcinoma, and metastases were indentified in the mesocolonic lymph nodes (17/50 nodes) but not in the peri-gallbladder lymph nodes (0/16 nodes). The patient has been recurrence-free for 4 years after the operation. This case illustrates that even if gallbladder cancer infiltrates into adjacent organs with regional lymph node metastasis, it is of value to perform radical surgery with systematic lymph node dissection for the involved organs.

Aged↗

Effect of heavy alcohol intake on long-term results after curative resection of hepatitis C virus-related hepatocellular carcinoma.

We studied the effect of heavy alcohol intake (ethanol intake > or = 80 g/day for > or = 5 yr) on long-term results in 53 patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) who had undergone curative hepatic resection. Cell proliferative activity in the tumor and non-tumorous liver was also assessed by counting argyrophilic nucleolar organizer region-associated proteins (Ag-NOR) in the resected specimens. Twenty patients (20 males, 0 females) were positive for heavy alcohol intake [AI(+)] and 33 (28 males, 5 females) were not [AI(-)]. All patients were positive for HCV antibody and negative for hepatitis B surface antigen. Carcinoma recurred within 3 to 51 postoperative months in 42 (79.2%) of the 53 patients. The median disease-free survival time was 12.6 mo in the AI(+) group and 25.4 mo in the AI(-) group (P < 0.01). The AI(+) group also had significantly poorer survival than the AI(-) group (P < 0.05, 3-year survival rate: 66.7% vs. 93.5%). HCC tumor in the AI(+) group showed significantly increased proliferative activity compared with that in the AI(-) group (P < 0.05, Ag-NOR number: 2.3 +/- 0.8 vs. 1.9 +/- 0.4). However, there was no significant difference between the numbers of Ag-NORs in non-tumorous liver from these two groups (1.5 +/- 0.2 vs. 1.5 +/- 0.2). Patients with heavy alcohol intake should be followed particularly closely, even if they have received curative surgery, since heavy alcohol intake is closely related to a poor postoperative prognosis.

Carcinoma, Hepatocellular↗

Aberrant DNA methylation on chromosome 16 is an early event in hepatocarcinogenesis.

In order to clarify the significance of DNA methylation in both earlier and later stages of hepatocarcinogenesis, the DNA methylation state on chromosome 16, on which loss of heterozygosity (LOH) has frequently been detected in human hepatocellular carcinomas (HCCs), was examined. DNA from primary HCCs and tissues showing chronic hepatitis and liver cirrhosis, which are considered to be precancerous conditions, was analyzed by digestion with methylation-sensitive and non-sensitive restriction enzymes. DNA hypermethylation at the D16S32, tyrosine aminotransferase (TAT) and D16S7 loci and hypomethylation at the D16S4 locus were detected in 18%, 58%, 20% and 48% of examined HCCs, respectively. Aberrant DNA methylation occurred more frequently in advanced HCCs than in early HCCs. Moreover, DNA hypermethylation at the D16S32, TAT and D16S7 loci was frequently observed in chronic hepatitis and liver cirrhosis. The incidence of DNA hypermethylation was higher than that of LOH (42% at the TAT locus). These data suggest that DNA hypermethylation might predispose the locus to allelic loss. Aberrant DNA methylation is a significant change which may participate in the early developmental stages of HCCs.

Carcinoma, Hepatocellular↗

Protective effects of Ca2+ channel blockers against methyl mercury toxicity.

The protective effects of Ca2+ channel blockers against the toxicity of methyl mercury were examined by both in vivo and in vitro experiments. In the in vivo study we first examined the effects of the Ca2+ channel blockers (20 mg/kg/day), flunarizine, nifedipine, nicardipine, and verapamil against the toxic level of methyl mercury treatment (5 mg/kg/day of methyl mercuric chloride for 12 consecutive days). However, there was a difference in potency of the effects among the reagents. All the Ca2+ channel blockers prevented a decrease in body weight and/or the appearance of the symptoms of neurological disorders in the rats treated with methyl mercury. In the next experiment, we examined flunarizine at different levels of supplementation (1, 25 and 50 mg/kg/day). Flunarizine in a dose-dependent manner prevented a decrease in body weight, appearance of the symptoms of neurological disorder and mortality in the rats treated with methyl mercury. Flunarizine treatment (25 mg/kg/day) for the first 5 days did not affect mercury distribution among the tissues, suggesting that the mechanism of protection against methyl mercury-induced toxicity may be attributed to its own pharmacological effect. In the in vitro study we examined the effect of flunarizine (0, 0.5, 5 and 50 microM) using primary cultures of cerebellar granular cells in 96-well culture plates. Viable cell numbers were estimated 1 and 3 days after treatment with methyl mercury. The estimated 50% lethal concentration (LC50) of methyl mercury was higher in plates treated with 5 and 50 microM of flunarizine both on days 1 and 3, indicating that flunarizine protected the primary cultured cerebellar granular cells against the toxicity of methyl mercury. As such, Ca2+ channel blockers protected against the toxicity of methyl mercury both in vivo and in vitro, suggesting that Ca2+ plays an important role in the mechanisms of methyl mercury toxicity.

Animals↗

Sepsis associated with hematological malignancies: prophylaxis of Pseudomonas aeruginosa sepsis.

Underlying diseases, pathogenic bacteria, clinical background and outcome were studied during 91 febrile episodes complicated by sepsis in 55 patients with hematological malignancies, who had been admitted to our hospital (Jikei University Kashiwa Hospital) between January 1990 and December 1994. Particularly in patients with P. aeruginosa sepsis, we compared the prophylactic effect of ciprofloxacin (CPFX) alone with that of the combination of polymyxin B (PL-B) plus kanamycin (KM). The major underlying diseases were acute myelocytic leukemia and malignant lymphoma, followed by myelodysplastic syndrome, acute lymphocytic leukemia and chronic myelocytic leukemia. Nearly two-thirds of the pathogenic microorganisms isolated were gram-positive bacteria (including coagulase-negative staphylococci and Staphylococcus aureus); approximately one-quarter were gram-negative bacteria (such as Pseudomonas aeruginosa), and the remainder were fungi. These microorganisms usually induced sepsis when granulocyte counts were decreased. Sepsis was a direct cause of death in about 60% of the patients and P. aeruginosa sepsis had the worst outcome. Oral administration of CPFX was more effective than PL-B plus KM in preventing P. aeruginosa sepsis. The difference in effectiveness might depend on the absorption profile of the drugs.

Adolescent↗

[Two cases of gram-positive sepsis successfully treated with vancomycin in combination with imipenem or cilastatin].

Against gram-positive sepsis, vancomycin (VCM) was administered in combination with imipenem or cilastatin (IPM/CS). Its excellent efficacy was confirmed in 2 cases, one affected with methicillin resistant Staphylococcus aureus and another with Gemella morbillorum. By calculating the FIC index according to a checkerboard technique, the in vitro synergistic effect was also demonstrated. At the present state multi-drug resistant gram-positive infections prevailed, the combination of VCM with IPM/CS can be expected as an effective measure for treating these diseases.

Adolescent↗

[A clinical features of acute respiratory infection with Haemophilus influenzae by transtracheal aspiration].

We performed a clinical study of 26 cases (27 episodes) of acute respiratory infection with H. influenzae by trans tracheal aspiration (TTA) from May 1987 to April 1995. 15 episodes (14 cases) were bronchitis and 12 episodes (12 cases) were pneumonia. 8 episodes were monomicrobial infection and 19 episodes were polymicrobial infection. Compared to the group of patients of monomicrobial infection, the number of elderly patients and the levels of WBC and CRP were higher in the group of patients of monomicroibal infection. In bronchitis cases, monomicrobial infections of H. influenzae were 7 episodes and polymicrobial infection containing H. influenzae were 8 episodes. In the latter group, PaO2 level was lower and CRP was higher on average. All patients recovered, but the period for treatment was longer in the latter group. In the pneumonia group, only one episode was monomicrobal infection and 11 episodes were polymicrobial infection. Inspite of treatment, one patient died. It was considered that polymicrobial infection was an important factor of acute respiratory infection with H. influenzae.

Acute Disease↗

[A clinical study of chronic lower respiratory infection with Haemophilus influenza by transtracheal aspiration].

We have performed a clinical study on chronic lower respiratory tract infection (CLRTI) with Haemophilus influenzae (H. influenzae) by transtracheal aspiration (TTA) and analyzed clinical factors of the acute exacerbation. In 40 episodes (38 cases) of H. influenzae isolated from CLRTI, monobacterial infection with H. influenzae were 21 episodes and polymicrobial infection were 19 episodes. We classified the disease into acute exacerbated (27 episodes) and stable (13 episodes) phase and the former episodes were divided into bronchitis type (7 episodes) and pneumonia type (20 episodes). Polymicrobial infections were seen more in the pneumonia type (13 episodes) than in the bronchitis type (2 episodes). The principal organism detected with H. influenzae were alpha-Streptococcus and Neisseria sp. in the bronchitis type and S. pneumoniae in the pneumonia type. The acute exacerbated cases were divided into the following 4 patterns; 1. polymicrobial infection with continuous infection of P. aeruginosa, 2. monomicrobial infection after acute upper respiratory tract infection, 3. polymicrobial infection with S. pneumoniae after continuous infection of H. influenzae, 4. bacterial replacement by P. aeruginosa after acute exacerbation. The results of the study suggests that polymicrobial infection is an important chronic lower respiratory tract infection when caused H. influenzae.

Acute Disease↗

Aggressive non-Hodgkin's lymphoma with massive involvement of the right ventricle.

A 69-year-old women with malignant lymphoma (diffuse large:Working formulation) had associated with intracavital involvement of the right ventricle. The patient was referred to us for further examination with a diagnosis of heart failure. A tumor mass was detected by magnetic resonance imaging in the right ventricular outflow tract. While in the hospital the patient experienced cardiogenic shock due to neoplastic pulmonary embolism. The tumor was surgically resected and the patient was then treated with systemic chemotherapy. She went into complete remission and has continued in this state for six months. This case demonstrates that early diagnosis and intensive chemotherapy contribute to a good prognosis of patients with malignant lymphoma associated with massive involvement of a cardiac chamber. A review of the Japanese literature is presented.

Aged↗

Cardiorespiratory changes when balancing one's whole body on one leg with eyes closed.

Postural control system has been extensively studied in terms of somatic motor function, but little is known about its connection with human autonomic function. The purpose of this study was to determine the cardiorespiratory changes in response to the 3-min load that was performed by balancing one's whole body on one leg with eyes closed (SOLEC load) or eyes open (SOLEO load) in 11 healthy young subjects (5 males and 6 females, mean age 20.8 +/- 1.9 year). Blood pressure (BP), heart rate (HR), respiratory rate (RR), inspiratory and expiratory duration (Ti and Te), tidal volume (VT), and oxygen uptake (VO2) were measured before, during, and after the load. The SOLEC load produced significant increases in HR and systolic BP within 1 min. There were further increases in systolic and diastolic BP during the late period of the load. Metabolic rate (VO2) showed a gradual increase during the SOLEC load, indicating that the late responses would be partly due to metabolic alteration. The early responses are considered to be mediated neurally through the postural control system which receives the afferent inputs arising from vestibular system and from muscle proprioceptors of the leg. In contrast, SOLEO load caused small insignificant changes in BP, HR, VT, and VO2, suggesting that a visual input is essential for balancing a postural change. The balance test with eyes closed may have value in a clinical neurological rehabilitation setting.

Adult↗

[Photodynamic therapy (PDT) for early cervical cancer].

The incidence of carcinoma in situ (CIS) and dysplasia of the uterine cervix has been increasing among young women in recent years. Most of these patients want to preserve their fertility. Also, to accommodate high-risk patients with complications, elderly patients, and those who refuse surgery, we perform PDT as a method to preserve fertility. The technique required for PDT is relatively simple, and can be performed without anesthesia, since it causes no pain or bleeding. PDT, with the use of Excimer Dye Laser (EDL), a type of low pulse laser, has a considerably higher degree of tissue penetration, even compared to PDT using Argon Dye Laser (ADL). Also, PDT using EDL can manage glandular involvement of CIN, and its special feature of selective destruction of malignant cells with almost no effect on normal tissues is noteworthy. Beginning in 1995, PDT using YAG-OPO Laser with a variable laser wavelength has been performed. PDT is performed 48 hours after intravenous injection of 1.5 mg/kg to 2 mg/kg photosensitizer Porfimer sodium (PHE) when the difference in density of PHE becomes greatest between malignant cells and normal tissue. The most advanced features of our method compared to conventional radiation which uses cut fiber are: First, by using colposcope with an optical path for the laser, it is possible to show a 10 mm circular spot at the focus of observation. With this method, cervical lesions can be observed and checked while receiving stable and precise photoradiation by using colposcope through direct observation. Second, for cervical canal treatment, by using a cervical probe to administer photoradiation in the forward direction in the cervical canal and to the side walls, 70% of the laser light is scattered to the side walls, so that all of the cervical canal can be radiated. Also, the cervical canal probe used to administer photoradiation, by inserting 2 cm to 3 cm depending on the conditions of the cervical canal and withdrawing the probe 1 mm, can be performed precisely and promptly by using the cervical probe manipulator feature of the colposcope. At the present time, studies using the PDT method have been conducted on 56 patients (39 CIS and 17 dysplasia patients). Out of these 56 patients, there were 54 CR (96.4%), only one NC, and one PR with very limited remnants but most of the lesions had disappeared. The NC was highly suspected to be invasive carcinoma and the PR was CIS. In the CIS case, some remnant was evident at the end of the cervical canal, and PDT was administered again. After this treatment, it became CR. This was 10 months ago, and no abnormal condition has been reported since. The first CR case was reported 6 years ago among the 56 cases studied, and no recurrence has been observed to date. Five patients became pregnant after the treatment. Four had normal deliveries and one had a cesarean section. PDT's side effect is similar to symptoms of sunburn such as minor skin irritation due to sensitive reaction to sunlight. Normally, it can be relieved by applying carmine lotion, and even cases that required treatment were cured completely within a few days after applying steroid ointment. Before hospitalization, if the patient gets a sunburn from being outside, the sensitive reaction to laser light is almost nonexistent. Thus, we advise patients to get some exposure to the sun before being hospitalized. Also, in cases where strict shading time is observed, side effects are not apparent at all, and no abnormal findings are recognized in the blood and urine due to using PHE. With almost no side effects, bleeding or pain, and with certain improvements in administration methods, a better choice of photosensitizer which would shorten the shading time, PDT is considered to be the best therapy for treating CIS and dysplasia while preserving fertility.

Adult↗