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Biomedical subjects

M Sakamoto

Publications and source records attributed to M Sakamoto.

At least 271 records · Page 15Linked to original sources

Hepatic stellate cells and intralobular innervation in human liver cirrhosis.

In normal and cirrhotic human liver tissues, we examined immunolocalization of alpha-smooth muscle actin (alpha-SMA), endothelin-1 receptor (ET-1R), and S-100 protein, with special emphasis on the intralobular spaces, using immunohistochemical methods. The ratio of the number of hepatic stellate cells (HSCs) with closely apposing nerve endings to the total number of HSCs in normal livers was compared with that in cirrhotic livers by electron microscopy. Immunolocalization of alpha-SMA and ET-1R was obviously recognized along the sinusoidal walls in cirrhotic liver and was significantly increased in cirrhotic liver compared with that in normal liver. Immunoreactive products for these substances were mainly localized in HSCs. However, immunolocalization of S-100 protein in intralobular spaces was markedly decreased in cirrhotic liver compared with that in normal liver. Nerve fibers were ultrastructurally hardly visible in intralobular spaces of cirrhotic livers. The ratio of the number of HSCs with closely apposing nerve endings to the total number of HSCs was significantly reduced in cirrhotic liver compared with that in normal liver. These results indicate that in liver cirrhosis, alpha-SMA-positive HSCs may play an important role in hepatic sinusoidal microcirculation through vasoactive agents such as ET-1 rather than through intralobular innervation.

Actins↗

Basic fibroblast growth factor regulates proliferation and motility of human hepatoma cells by an autocrine mechanism.

BACKGROUND/AIMS: Basic fibroblast growth factor has mitogenic and angiogenic properties. In this study, we aimed to evaluate the role of fibroblast growth factor in the development and progression of human hepatocellular carcinoma. METHODS: The expression of basic fibroblast growth factor, fibroblast growth factor receptor-1, and a receptor isoform was investigated by in situ hybridization, immunohistochemistry, reverse transcription-polymerase chain reaction, Western blot analysis and confocal laser-scanning microscopy. The influence of exogenous basic fibroblast growth factor on DNA synthesis and motility of human hepatoma cells were also evaluated. RESULTS: Basic fibroblast growth factor and fibroblast growth factor receptor-1 messenger RNAs were present mainly in tumor cells and less so in hepatocytes from noncancerous liver tissue. Immunoreactive products of basic fibroblast growth factor and fibroblast growth factor receptor-1 were observed in tumor cells. The isoform IIIc was expressed in hepatocellular carcinoma tissue and hepatoma cell lines. Exogenous basic fibroblast growth factor stimulated DNA synthesis and motility of hepatoma cells. The effect was more marked in poorly-differentiated hepatoma cells than in well-differentiated hepatoma cells. Fibroblast growth factor-1 expression on hepatoma cells was also more marked in poorly-differentiated hepatoma cells than in well-differentiated hepatoma cells. The stimulated motility on basic fibroblast growth factor was suppressed by an anti-fibroblast growth factor receptor-1 antibody. CONCLUSIONS: Basic fibroblast growth factor may play an important role in the development and progression of hepatocellular carcinoma via an autocrine mechanism involving fibroblast growth factor and its receptor.

Adult↗

Increased ubiquitin immunoreactivity in hepatocellular carcinomas and precancerous lesions of the liver.

BACKGROUND/AIMS: Ubiquitin covalently attaches to abnormal and short-lived proteins, thus marking them for ATP-dependent proteolysis in eukaryotic cells. Increased ubiquitin immunoreactivity was recently observed immunohistochemically in human malignant tumors. To clarify the change in protein metabolism during hepatocarcinogenesis, we studied ubiquitin immunoreactivity in hepatocellular carcinomas (HCCs) and precancerous lesions using immunohistochemistry and immunoblot analysis. METHODS: A total of 72 HCCs (37 advanced, 19 early, 16 early-advanced (advanced HCC component in early HCC nodule) type HCCs) and 18 precancerous lesions (8 atypical adenomatous hyperplasias (AAHs), 10 adenomatous hyperplasias (AHs)) were studied immunohistochemically. Immunoblot analysis was also performed in advanced HCC and early HCC cases. RESULTS: Non-tumorous hepatocytes were either immunonegative or weakly stained in their nuclei. Advanced HCCs showed strong immunoreactivity in most cases, while early HCCs showed relatively weaker immunoreactivity. In 14 of 16 early-advanced type tumors, the inner portion of the nodules, which corresponds to advanced HCC, showed stronger immunoreactivity than the outer low-grade portion. In 8 of 8 AAHs and 7 of 10 AHs, positive but weak staining was found. Immunoblot analysis showed an increase in 42 kDa ubiquitinated protein(s) in 8 of 16 advanced HCC cases (50%) and in 1 of 6 early HCC cases (16.7%), as well as an increase in several other bands in tumor tissues. CONCLUSIONS: The intensity of ubiquitin staining appeared to increase in a stepwise manner from AH to advanced HCC, and the results suggest a possible correlation between changes in the ubiquitinated proteins and multistep hepatocarcinogenesis.

Adenoma↗

Skin vasomotor reflex induced by laryngoscopy: comparison of the McCoy and Macintosh blades.

We studied 22 female patients (ASA I or II) to investigate if laryngoscopy and intubation induced the skin vasomotor reflex (SVmR), and to compare the effects of the McCoy and Macintosh blades on the SVmR. Anaesthesia was induced with fentanyl, midazolam, vecuronium and nitrous oxide. In 11 patients, the vocal cords were seen for 3 s with the McCoy blade. Two minutes later, laryngoscopy was performed with the Macintosh blade and the trachea was intubated. In the other 11 patients, the first and second laryngoscopies, respectively, were performed with the Macintosh and McCoy blades. Laryngoscopy alone and intubation with laryngoscopy significantly reduced skin blood flow in the ring finger of all patients (P < 0.01), indicating that both procedures provoked the SVmR. The magnitude of the SVmR and haemodynamic changes did not differ significantly between the two groups.

Adult↗

Intrahepatic cholangiocarcinoma presenting intrabile duct extension: clinicopathologic study of five resected cases.

Intrahepatic cholangiocarcinoma, which is ordinarily a very invasive tumor and often takes a rapid and fatal course, sometimes shows macroscopic intrabile duct extension. The purpose of this study is to illustrate the clinicopathologic features of this variant of intrahepatic cholangiocarcinoma, which has occasionally been reported. Five cases of the tumor with gross extension to the bile duct lumen were studied to determine their clinical and pathologic features. The tumor showed intrabile duct growth and superficial mucosal spread in two patients. In two other patients, an apparent mass lesion accompanied the intraluminal component. In the remaining patient, a polypoid tumor infiltrated the portal tract of the left lateral segment, where it had arisen. Microscopic examination did not reveal any vascular involvement or intrahepatic or lymph node metastasis. All of the patients are alive without recurrence, except for Patient 1 who died 7 years and 7 months after surgery from a rapidly growing tumor in the liver remnant. Intrabile duct growth of intrahepatic cholangiocarcinoma may reflect indolent biological behavior and thus warrants an aggressive surgical approach, which appears to give a good prognosis.

Adenocarcinoma↗

Retroperitoneal schwannoma mimicking hepatic tumor in the caudate lobe.

We report a 41-year-old woman with a retroperitoneal schwannoma mimicking hepatic tumor in the caudate lobe. Dynamic computed tomography in the early phase showed an enhanced tumor (2.7 cm in diameter) in the Spiegel lobe of the liver, which compressed the inferior vena cava (IVC). We also performed left hepatic angiographic computed tomography, and found that the tumor was less enhanced. The patient underwent laparotomy under a preoperative diagnosis of primary hepatic caudate tumor with faint neovascularity. At surgery, the tumor was found to be located between the left caudate lobe and the IVC, and was resected as being of a retroperitoneal origin. This case illustrates that tumor location must be determined with great care when the mass seems to exist at the dorsal edge of the liver, and especially when the tumor is hypovascular.

Adult↗

Pheochromocytoma growing exophytically from the right adrenal gland and invaginating into the liver.

A 5-cm pheochromocytoma located in segment 7 of the liver was found incidentally in a 45-year-old man with mild diabetes mellitus and hypertension, and resected. The tumor was demonstrated by computed tomography and magnetic resonance imaging to have completely invaginated itself into the liver and to be receiving blood from a dilated right hepatic artery alone. Surgery revealed the hepatic mass to be tightly adherent to the right adrenal gland. The histopathologic diagnosis was pheochromocytoma growing exophytically from the right adrenal gland. There was no association with multiple endocrine neoplasia type 1 and type 2. A postoperative 131I metaiodobenzylguanidine scan revealed no accumulation, and the patient is currently doing well without recurrence or hypertension one year after the operation. A pheochromocytoma deeply invaginating into the liver should be considered in the differential diagnosis of primary hypervascular hepatic tumors.

Adrenal Gland Neoplasms↗

Involvement of the anterior urethra in male patients with transitional cell-carcinoma of the bladder undergoing radical cystectomy with simultaneous urethrectomy.

Histological tumor extension into the prostate, urethra and ureters was examined in 52 specimens obtained by cystourethrectomy for transitional cell carcinoma of the bladder with one or more risk factors for urethral involvement. In four (21.1%) of 19 patients with diffuse carcinoma in situ in the bladder extending to the internal urethral orifice and prostatic urethra, the anterior urethra was affected by transitional cell carcinoma, including one specimen with invasion into the corpus spongiosum. However, none of 33 patients without these findings had synchronous anterior urethral transitional cell carcinoma involvement. It is recommended that patients with diffuse carcinoma in situ extending into the prostatic urethra undergo careful preoperative assessment of the anterior urethra before cystectomy. In other cases, the anterior urethra can be preserved and used for orthotopic neobladder replacement.

Adult↗

Measurement of plasma busulfan concentration by high-performance liquid chromatography with ultraviolet detection.

Busulfan is widely used in bone marrow transplantation. Increased area under the plasma concentration curve has been shown to correlate with venoocclusive disease, which occurs in approximately 20% of these patients. The authors developed a high performance liquid chromatography assay for the determination of plasma busulfan concentration using ultraviolet detection and a single-step derivatization and extraction. The absolute retention times of busulfan and the internal standard were 2.8 and 5.6 min, respectively. The assay possessed linearity up to 200 mumol/l, sensitivity to at least 0.2 mumol/l, average recovery of 101%, and run-to-run precision (n = 34) of < 7%. Furthermore, the assay proved to be free of interference from 59 medications and correlated highly with a validated method employing gas chromatography with electron capture detection (slope = 0.90, intercept = 0.17, r = 0.98, n = 31). The authors conclude that the method described here is ideally suited for the therapeutic monitoring of busulfan.

Busulfan↗

Measurement of plasma ketoprofen by a rapid high-performance liquid chromatography assay.

The authors developed a high performance liquid chromatography assay for the determination of plasma ketoprofen concentration using a single-step extraction, a short chromatographic separation of 3 min, and a sample volume of 50 microliters. The assay possessed linearity up to 500 mg/l, sensitivity down to at least 1 mg/l, average recovery of 100.1%, and run-to-run precision (n = 20) of 4.6% at a level of 10 mg/l and 2.2% at a level of 40 mg/l. Furthermore, the assay was free of interference from 51 prescription and over-the-counter medications. The authors conclude that the method described here is ideally suited for the determination of ketoprofen concentration in a clinical laboratory setting for the purpose of therapeutic monitoring and assessment of toxicity.

Chromatography, High Pressure Liquid↗

Increased DNA methyltransferase expression is associated with an early stage of human hepatocarcinogenesis.

The present study was designed to determine whether changes in DNA methyltransferase (DNA MTase) expression are involved in hepatocarcinogenesis. We examined DNA MTase expression in normal liver tissue (with no remarkable histological findings), liver tissue showing chronic hepatitis or cirrhosis, which are generally thought to be precancerous conditions, and hepatocellular carcinomas (HCCs) using the reverse-transcriptase polymerase chain reaction assay. DNA MTase mRNA levels were significantly higher in liver tissue showing chronic hepatitis and cirrhosis (DNA MTase mRNA/beta-actin mRNA ratio = 0.30 +/- 0.22, n = 24, P < 0.01) than in normal liver tissue either from patients with liver metastatic lesions of colonic cancer (0.14 +/- 0.05, n = 6) or from patients with HCCs (0.16 +/- 0.07, n = 3). DNA MTase mRNA levels were even higher in HCC tissue (0.34 +/- 0.18, n = 29). These results suggest that increased DNA MTase expression may be an early event during hepatocarcinogenesis. DNA MTase is a potential target for HCC preventive therapy.

Carcinoma, Hepatocellular↗

Prognostic factors of hemophagocytic syndrome in adults: analysis of 34 cases.

Hemophagocytic syndrome (HPS) presents with fever, pancytopenia, liver dysfunction and increase in hemophagocytic histiocytes in various organs. Although there are two major classifications of HPS in adults, malignant and reactive histiocytosis, it is often very difficult to distinguish between these disorders. We analyzed the laboratory data of patients with HPS to evaluate prognostic factors. Of 34 patients, 14 survived, and 20 died. The median age of survivors was 29.6+/-11.5 yr significantly younger than those who died (54.7+/-17.8 yr). Twenty patients had no obvious underlying disease, the other 13 had hematological malignancies or viral infections. Comparison of laboratory data revealed that nonsurvivors had significantly lower Hb and platelet values on admission. During treatment, worsening of anemia and thrombocytopenia, increase of transaminase and biliary enzymes were similarly more prominent. Risk factors associated with death were: age over 30 yr, presence of disseminated intravascular coagulation, increased ferritin and beta2-microglobulin, anemia accompanied by thrombocytopenia and jaundice. Our data suggests that patients with HPS and any of these risk factors should be treated aggressively with sufficient chemotherapy and supportive care.

Adolescent↗

[Campylobacter jejuni enteritis in three patients with HIV infection].

Gatrointestinal symptoms, which include diarrhea, are as common as respiratory symptoms in patients with HIV infection. Gastrointestinal symptoms may result from infections, neoplasma, HIV enteropathy or drug toxicity. Three HIV-infected patients admitted to our hospital complaining of diarrhea and fever. We confirmed their diagnosis as Campylobacter jejuni enteritis by bacteriological examination of their feces. All of them had eaten inadequately cooked meat in restaurants before the onset of their enteritis. Their symptoms immediately improved after the administration of antimicrobial agents. One strain of C. jejuni isolated in our cases, however, was resistant to ofloxacin. This case report suggests that we must counsel HIV-infected patients to avoid inadequately cooked food and observe resistant patterns of C. jejuni to antimicrobial agents in Japan in the future.

AIDS-Related Opportunistic Infections↗

[Analysis of prognosis of bronchopulmonary infectious disease with lung cancer].

Bronchopulmonary infection affects the prognosis of lung cancer patients. Thus, we investigated the relationship between the prognosis of bronchopulmonary infectious diseases and their causative bacteria isolated by transtracheal aspiration (TTA) in lung cancer patients. In the present study, we determined which factor is more predisposing for the outcome of bronchopulmonary infections, the type of causative bacteria or the host nutritional status. A total of 107 lung cancer patients, which consisted of 105 males and 5 females (mean age 67.3 +/- 8.0), were included in this study. The study was conducted from 1981 to 1994. They were classified into the survival group and the deceased group. Causative agents of infection were compared between these 2 groups. S. pneumoniae, alpha-Streptococcus sp., M. catarrhalis, and Neisseria sp. were predominant in organisms isolated from TTA-specimens of lung cancer patients with bronchopulmonary infections, regardless of prognosis. Nutritional status, as determined by serum levels of cholinesterase, albumin, and cholesterol, was poor in the deceased group than in the survival group. These results indicate that the outcome of bronchopulmonary infections in lung cancer patients are affected mainly by the nutritional status of the host.

Aged↗

[The evaluation of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) level in peripheral blood of patients with chronic lower respiratory tract infection].

In the present study, we assessed the serum level of IL-6 and TNF-alpha by ELISA in patients with chronic lower respiratory tract infection. The serum levels of IL-6 and TNF-alpha of patients in acute exacerbation phase are higher than that of in stable phase. We also classified patients in acute exacerbation phase into two groups according to the microorganism of persistent infection. The serum level of IL-6 and TNF-alpha in the patients with persistent infection with Pseudomonas aeruginosa were higher than that with Haemophilus influenzae. Moreover, the serum level of IL-6 and TNF-alpha were found to be related with malnutrition which assessed by clinical indices such as the serum level of albumin and cholinesterase. The present result suggests that IL-6 and TNF-alpha may have relationship with not only inflammation in airway but also indices of nutrition in patients with chronic lower respiratory tract infection.

Acute-Phase Reaction↗

[Prognostic analysis of sepsis in patients with lung cancer].

Sepsis is one of the most serious infections occurring in patients with lung cancer. Thus, we determined what is most predisposing factor in prognosis of sepsis in lung cancer patients; the type of causative bacteria, neutropenia or host nutritional status. A total of 27 lung cancer patients with sepsis, which consisted of 23 males and 4 females (mean age 70.7 +/- 6.6), were included in this study. The study was conducted from 1991 to 1995. All subjects were classified into the survival group and the dead group. Staphylococcus aureus or Esherichia coli most frequently isolated from the blood of the patients in the survival group, while either E. coli alone or multiple organisms were predominant in the dead group. Neutropenia did not affect the outcome of sepsis in lung cancer patients. In contrast nutritional status, as determined by serum albumin levels, was closely related to the mortality in septic lung cancer patients. These results predict that the prognosis of sepsis is dependent on nutritional status of lung cancer patients.

Aged↗

[Optimal antibacterial chemotherapy for infectious diseases associated with hematological malignancies].

The status quo of infectious diseases associated with hematological malignancies was examined for clinical consideration. In addition, in vitro antibacterial activities and combination effects were also examined by means of various isolated strains derived from sepsis. In clinical practice, 76% of the fevers in patients with hematological malignancies was attributed to infectious diseases mainly involving "fever with granulocytopenia", sepsis, and pneumonia. The detection rate of causal pathogen remained at a low level and more than half of the causes of death were infectious diseases. In the in vitro examination, a favorable antibacterial effect was noted with vancomycin (VCM) for methicillin resistant Staphylococcus aureus (MRSA) and Enterococcus spp., imipenem (IPM) for methicillin sensitive S. aureus (MSSA), and ciprofloxacin, amikacin (AMK), and IPM for Pseudomonas aeruginosa and intestinal flora. But its clinical effect is not enough. Synergic and/or additive effect can be expected by combining IPM with VCM for MRSA and Enterococcus spp., and IPM with AMK for P. aeruginosa. These combination therapies were considered to be optimal as antibacterial chemotherapy for infectious diseases associated with hematological malignancies.

Adult↗

[A case of multiple muscular abscesses of the lower limbs by Staphylococcus aureus after chemotherapy for lung cancer].

A 67-year-old male was admitted to our hospital because of lung cancer and interstitial pneumonia. Cisplatin, vindesie and mitomycin C were administered for treatment of lung cancer. The leucocyte-counts declined to 1700/microliter on the eighth day after the chemotherapy. Though granulocyte colony-stimulating factor was administered, pain in the right thigh and high grade fever developed. Because Staphylococcus aureus was isolated from the blood specimen, piperacillin was administered. But the high grade fever continued and the pain was expanded to the right hip, left hip, thigh and leg. Because a computed tomograph of the lower limbs showed low density areas in bilateral gluteus maximus muscle right adductor magnus muscle, left biceps femoris muscle and left soleus muscle and the culture of an aspirate from abscess of right leg detected S. aureus, multiple muscular abscesses of the lower limbs was confirmed. We changed the antibiotics from PIPC to imipenem/cilastatin and minocycline on nineteenth day after the chemotherapy. His symptoms improved after the change of antibacterial agents. But he died of acute exacerbation of interstitial pneumonia, after about two months of the chemotherapy. Muscular abscesses of the limbs are very rare in Japan. Only four cases with muscular abscess of the limbs were reported in Japan, since 1988. This case suggests that a muscular abscess must be considered in the differential diagnosis of fever in patients with neutropenia.

Abscess↗