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Biomedical subjects

M Sakamoto

Publications and source records attributed to M Sakamoto.

At least 415 records · Page 23Linked to original sources

Chronic oral administration of methylcyclopentadienyl manganese tricarbonyl altered brain biogenic amines in the mouse: comparison with inorganic manganese.

This study was conducted to investigate the effects associated with high dose administration of organic manganese to mice and to compare these effects with those of inorganic manganese. The disposition and toxicity of methylcyclopentadienyl manganese tricarbonyl (MMT; a potential substitute for lead in gasoline) in the brains of ddY mice was studied after 12-months administration (at 0.5 g/kg of MMT) in food. Mice exposed to inorganic manganese received 2.0 g/kg of MnCl2 in food for the same period. There was no significant difference in food intake between the control mice and the MMT-exposed mice or MnCl2-exposed mice. Normetanephrine level in the cerebellum of the MMT-exposed group was significantly increased compared with the control, and correlated with the manganese concentration. The manganese concentration was significantly increased in the cerebellum of the MMT-exposed group compared with the control and MnCl2-exposed groups. On the whole, methoxylation from the 3-hydroxyl of catecholamine tended to be promoted by manganese.

Animals↗

Urethral involvement in female bladder cancer patients: mapping of 47 consecutive cysto-urethrectomy specimens.

We reviewed 47 consecutive step-sectioned cysto-urethrectomy specimens of bladder cancer in female patients to determine the incidence and characteristics of urethral involvement. Of the 47 cases 43 were transitional cell carcinoma: 10 (23%) papillary, 9 (21%) papillo-nodular and 18 (42%) nodular cancer, and 6 (14%) primary or secondary carcinoma in situ. There were 23 cases (54%) of invasive carcinoma of more than stage pT1 and 27 (63%) were grade 3 lesions. Urethral cancer was observed in only 3 cases: 1 stage pT4, grade 3 papillo-nodular cancer developed widely in the bladder and, overriding the bladder neck and proximal urethra, stage pTa, grade 2 papillary cancer was detected, while in 2 with nodular invasive lesions of the bladder (including the bladder neck) urethral cancer was detected either as a direct invasive extension via urethral carcinoma in situ or as an intralymphatic spread without urethral mucosal change. These findings indicate the necessity for prophylactic urethrectomy in cases of papillary or papillo-nodular cancer encroaching on the bladder neck, and nodular invasive cancer infiltrating the bladder neck and trigone. In other cases, preservation of the urethra seems possible for bladder reconstruction in female bladder cancer patients to ensure normal voiding after cystectomy.

Adenocarcinoma↗

Cultured rat hepatic sinusoidal endothelial cells express intercellular adhesion molecule-1 (ICAM-1) by tumor necrosis factor-alpha or interleukin-1 alpha stimulation.

This study investigated the expression of intercellular adhesion molecule-1, a leukocyte adhesion molecule, on cultured rat hepatic sinusoidal endothelial cells during stimulation with tumor necrosis factor-alpha or interleukin-1 alpha. Using immunoelectron microscopy and the immunogold technique against intercellular adhesion molecule-1, gold particles were shown to increase significantly on the surface of sinusoidal epithelial cells treated with tumor necrosis factor-alpha (100 U/ml) or interleukin-1 alpha (10 U/ml) for 8 h compared with unstimulated cells. In addition, semi-quantitative analysis of intercellular adhesion molecule-1 on the sinusoidal endothelial cells was performed by cytofluorometer. Even without stimulation, intercellular adhesion molecule-1 was weakly expressed. However, 8 h after tumor necrosis factor-alpha or interleukin-1 alpha treatment, the expression of intercellular adhesion molecule-1 on cells was increased in a dose-dependent manner. Kinetic analysis showed that the expression of intercellular adhesion molecule-1 on sinusoidal endothelial cells treated with these cytokines increased gradually from the beginning of stimulation to 24 h. These findings suggest that hepatic sinusoidal endothelial cells may mediate the direct interaction between leukocytes and sinusoidal endothelial cells by expressing leukocyte adhesion molecules such as intercellular adhesion molecule-1.

Animals↗

Centrally induced vasopressor and sympathetic responses to a novel endogenous peptide, adrenomedullin, in anesthetized rats.

Possible central actions of adrenomedullin were explored and compared with the peripheral effects by injecting it into the lateral ventricle, cisterna magna, and femoral vein in urethane-anesthetized rats. Adrenomedullin, 1.0 to 3.0 nmol/kg, injected intravenously (i.v.), caused a transient vasodepression of about 10 to 30 mm Hg, dose dependently, which lasted for < 15 min. On the other hand, intracerebroventricular (ICV) and intracisternal (IC) injections of adrenomedullin elicited sustained elevations of arterial pressure of gradual onset, dose dependently; the arterial pressure started to rise at about 3 min after the injection, and gained peak response after > 20 min. The pressor response lasted for > 2 h. Heart rate was not significantly influenced by these doses of adrenomedullin. The abdominal sympathetic outflow was markedly increased in relation to the blood pressure elevation. The time-course of the responses was quite similar with both ICV and IC injections. Hypotensive effects of i.v. injected adrenomedullin was partially attenuated, and the centrally induced vasopressor responses were abolished by the pretreatment with human calcitonin gene-related peptide (hCGRP)-receptor antagonist, hCGRP(8-37). These findings indicate that the receptors for adrenomedullin exist in the brain, and that the receptor site may be anatomically far from the surface of the brain and the ventricular system because the onset of the pressor response was delayed. Or, CGRP and adrenomedullin may share the same receptors, particularly in the brain.

Adrenomedullin↗

Effects of midazolam and flumazenil on carotid sinus baroreflex control of circulation in rabbits.

We have studied the effects of midazolam and flumazenil on the carotid sinus baroreflex, by examining mean arterial pressure (MAP) and heart rate (HR) responses to partial or complete bilateral carotid occlusion (BCO) in 12 conscious rabbits after aortic denervation. In eight rabbits, the responses to complete BCO were evaluated before and after cumulative doses of midazolam 0.5 and 1.0 mg kg-1, and after flumazenil 0.3 mg kg-1 following administration of midazolam. Midazolam and flumazenil had no effect on MAP or HR before complete BCO and neither affected the MAP response to complete BCO. Midazolam 0.5 and 1.0 mg kg-1 decreased the HR response to 60% and 58% of control, respectively. Flumazenil restored the midazolam-induced depression of the HR response to the control level. In the other four rabbits, we examined the MAP and HR responses to partial BCO (carotid artery pressure reduced by 5, 10 and 20 mm Hg) before and after midazolam 0.5 mg kg-1 and after flumazenil 0.3 mg kg-1 following administration of midazolam. The response to partial occlusion showed the same tendency as the response to complete BCO. These results indicate that midazolam attenuated the HR response of the carotid sinus baroreflex, flumazenil restored this midazolam-induced depression and neither drug affected the MAP response.

Animals↗

The entire nucleotide sequence and classification of a hepatitis C virus isolate of a novel genotype from an Indonesian patient with chronic liver disease.

Three hepatitis C virus (HCV) isolates were obtained from patients with chronic liver diseases in Indonesia which were not classifiable into any of the genotypes I/1a, II/1b, III/2a, IV/2b or V/3a reported previously. The entire nucleotide sequence was determined for one HCV isolate (HC-G9); the remaining two isolates were of the same genotype based on a > 95% similarity within their partial sequences spanning 2927 nucleotides (nt). The HC-G9 genome consisted of 9440 nt including the 5' untranslated region of 341 nt, an open reading frame of 9033 nt coding for a polyprotein of 3011 amino acids and the 3' untranslated region of 66 nt (U stretch of 17 to 47 nt at the extreme 3' terminus excluded). It differed by 20 to 33% in nucleotide sequence from any of 14 HCV genomes of genotypes I/1a to IV/2b whose full-length sequences are known. By the unweighted pair-group method with arithmetic mean, HC-G9 was on a major branch (group 1) of the phylogenetic tree of HCV to which genotypes I/1a and II/1b belong. It is proposed, therefore, that the novel genotype for HC-G9 should be called 1c. A method was developed to identify genotype 1c by PCR with a primer deduced from the core gene that was specific to it. Since genotype 1c was detected in seven (15%) of 48 HCV RNA samples from Indonesian patients with chronic liver disease, but not in any of 1097 from other districts of the world, it appears to have evolved and remained in Indonesia. In addition to its epidemiological importance, the association of genotype 1c HCV with the severity of liver disease and its response to interferons deserve to be evaluated.

Amino Acid Sequence↗

Hepatitis C virus variants from Nepal with novel genotypes and their classification into the third major group.

Five isolates of hepatitis C virus (HCV) RNA from patients with chronic liver disease in Nepal were not classifiable into the known genotypes I/1a, II/1b, III/2a, IV/2b or V/3a using PCR with type-specific primers deduced from the HCV core gene. Their nucleotide sequences were determined for the 5'-terminal 1.5 kilobases and 3'-terminal 1.2 kilobases, covering 30% of the entire genome, and compared with each other and with reported sequences of HCV isolates of various genotypes. They were more similar to a reported HCV isolate (NZL1) of genotype V/3a (in 81.6 to 84.1% of their nucleotides and 85.7 to 88.7% of the deduced amino acid sequence) compared with the genotypes I/1a to IV/2b (in 69.3 to 74.7% and 72.3 to 77.4%, respectively). Hence they were considered to be variants of the third major group (group 3). The five HCV isolates shared 81.3 to 85.2% of nucleotide sequence and 85.4 to 89.3% of deduced amino acid sequence. Thus they were substantially different from each other. One of them was classified as genotype VI/3b due to an 88.2% similarity in nucleotide sequence to that of the reported HCV isolates of this genotype, whereas the remaining four were classified into provisional genotypes 3c, 3d, 3e and 3f. These HCV variants have evolved and remained in Nepal, and have not been observed in the other areas of the world.

Amino Acid Sequence↗

Entire nucleotide sequence and characterization of a hepatitis C virus of genotype V/3a.

The entire nucleotide sequence of a hepatitis C virus (HCV) genome (NZL1) of genotype V/3a was determined from overlapping cDNA clones obtained from a human carrier in New Zealand. It comprised 9425 nucleotides (nt) including a 5'-untranslated region of 339 nt, a single large open reading frame encoding a polyprotein of 3021 amino acids, a 3'-untranslated region of 23 nt, and 3'-terminal poly(U) stretches of variable lengths. The NZL1 genome was compared with 15 HCV isolates of other genotypes for which the full-length sequence has been determined. It differed from them by 31.1 to 34.3% in nucleotide sequence identity and by 24.5 to 29.1% in amino acid sequence identity, confirming the distinction of genotype V/3a from the other isolates.

Amino Acid Sequence↗

Risk factors related to liver metastasis in colorectal carcinoma: a multivariate analysis of clinicopathologic and immunohistochemical variables.

Specimens from 48 consecutive patients undergoing surgery for colorectal carcinoma and having synchronous or metachronous liver metastases (Group 1) and those from 52 consecutive patients who had no evidence of hepatic metastases within at least 5 year after colorectal resection (Group 2) were selected and compared using a multiple logistic regression analysis. A multivariate analysis using a stepwise logistic regression revealed six independent risk factors significantly related to hepatic metastases. In addition, the following logistic regression model was obtained from this analysis. P = exp a/(1 + exp a): a = 3.524(SM-V) + 2.731(Ex-V) + 2.718(E/M) + 2.562(Lo) + 1.858(p53) + 1.941(HIR) - 4.397, where P is the probability of hepatic metastasis given six independent risk factors (E/M, Ex/M ratio; Lo, location; HIR, host inflammatory cell reaction). When the estimated probability "P" in the above logistic regression model is more than 0.55 after an examination of surgical specimens, we must consider adjuvant chemotherapy and closely monitor the patient to ensure early detection of hepatic metastases.

Adenocarcinoma↗

Anti-obesity and anti-diabetic effects of carteolol in non-insulin-dependent diabetic mice.

1. When carteolol, a beta-adrenergic blocker, was administered to KK-Ay/Ta Jc1 mice that are obese and develop spontaneously non-insulin dependent diabetes, their increase in bodyweight was arrested from the age of 16 weeks. Since their intake of food and water was not influenced by carteolol treatment, compared with the control KK-Ay/Ta Jc1 mice, abolition of the weight gain might be attributed to increased energy metabolism. 2. Non-fasting serum glucose levels in carteolol-treated mice at the age of 17 weeks were within normal range (118 +/- 4 vs 186 +/- 12 mg/dL). An intraperitoneal glucose-tolerance test revealed that the carteolol treatment markedly restored glucose metabolism; fasting plasma glucose (88 +/- 6 mg/dL) was within normal range, and immunoreactive insulin (IRI; 5.8 +/- 0.8 vs 33.3 +/- 10.5 ng/mL) and plasma glucose levels at 60 min post glucose (361 +/- 44 vs 541 +/- 32 mg/dL) were significantly lower in carteolol-treated mice than those in the control group at the age of 20 weeks. 3. From these findings, carteolol is considered to have little effect on the growth of mice but to correct the obesity that develops after age 16 weeks, when their growth terminates. In addition, the normalization of blood glucose and marked decrease in IRI levels suggests that carteolol improves glucose tolerance by increasing the insulin sensitivity. 4. Since brown adipose tissue (BAT) is closely associated with thermogenesis and energy consumption, we tested whether carteolol may affect BAT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗

Arthritis and ankylosis in twy mice with hereditary multiple osteochondral lesions: with special reference to calcium deposition.

A murine autosomal recessive mutant named twy (tiptoe walking-Yoshimura) mouse showing multiple osteochondral lesions including ankylosis of the vertebral column and limb joints underwent sequential histopathological analysis of posterior limb joint lesions and intervertebral disc lesions. In the articular cartilage, a decrease in alcian blue-positive extracellular matrix and the presence of degenerated collagen fibers were found at the age of around 4-8 weeks. Calcium deposits in the articular cartilage were found at that time and later in the articular space and synovial tissue. Calcium deposits were also found in the intervertebral discs at 4 weeks. Using electron microscopy, some of the crystals were seen inside small vesicles. In both joints, degeneration of, and calcium deposition in, the articular cartilage progressed with age, finally producing bony ankylosis. These histological observations suggest that calcification and degeneration of the articular cartilage are the major factors in the pathogenesis of joint disorders in the twy mouse, and this mutant mouse provides a good model for studying the process and mechanism of osteoarthritic lesions, destructive arthritis and ankylosis.

Aging↗

[Suppression of the Pseudomonas aeruginosa-induced biofilm formation on human epithelial cells by erythromycin].

In the present study, were examined the inhibitory effect of erythromycin on the biofilm formation by a temperature-sensitive mutant (Ts25) of Pseudomonas aeruginosa N-42 on the surface of Ishikawa cells which can produce a mucin-like glycoprotein physicochemically similar to mucoproteins produced in the human airway. Usually, 38-45 microcolonies (biofilms) were formed after 10 days of incubation in cultures of Ishikawa cells and P. aeruginosa Ts25. Erythromcin suppressed the adhesion to Ishikawsa cells of P. aeruginosa and its subsequent biofilm formation at doses as low as 0.2 microgram/ml. Erythromycin also exhibited the suppressive effect on the production of glycoproteins by Ishikawa cells at doses higher than 1 microgram/ml and the production of elastase and exoenxyme A from P. aeruginosa at doses higher than 2 micrograms/ml. These results suggest that erythromycin can inhibit the biofilm formation in culture of human epithelial cells and P. aeruginosa and the in-vivo bacterial biofilm formation may be attributed to host cell-derived factors rather than bacterial products.

Biofilms↗

[An evaluation of pathogens in patients with bronchopulmonary infection by transtracheal aspiration: December 1978-March 1993].

We performed transtracheal aspiration (TTA) in 1165 patients, who were suspected to have bronchopulmonary infection, from December 1978 to March 1993. We isolated pathogens from TTA in 806 patients (69.2%). We isolated H. influenzae (62 cases), S. pneumoniae (39 cases) and M. catarrhalis (24 cases) in patients with acute bronchitis, S. pneumoniae (65 cases), alpha-Streptococcus sp. (52 cases), H. influenzae (32 cases) and S. aureus (29 cases) in patients with pneumonia or lung abscess and H. influenzae (174 cases), S. pneumoniae (84 cases), P. aeruginosa (81 cases) and M. catarrhalis (42 cases) in patients with chronic lower respiratory tract infection. Anaerobic bacteria isolated from TTA included Peptostreptococcus sp. (19 cases), Bacteroides sp. (19 cases) and others. Mycoplasma pneumoniae was isolated from TTA in 8 patients with pneumonia without other organisms. Virus isolated from TTA included Rhinovirus (6 cases) and others. These results suggest that various pathogens affect the pathogenesis of bronchopulmonary infection. Therefore, we must diagnose the bronchopulmonary infection by the correct methods such as TTA.

Adult↗

[A clinical study of respiratory infections due to mucoid Pseudomonas aeruginosa diagnosed by transtracheal aspiration].

We performed a clinical study of 20 cases (33 episodes) of respiratory infections due to mucoid Pseudomonas aeruginosa by transtracheal aspiration (TTA) in the recent 10 years. There was only one pneumonia without underlying chronic lower respiratory infection (CLRTI) case positive for mucoid P. aeruginosa and others were all CLRTI among 33 TTA trials. In contrast, nonmucoid P. aeruginosa was recovered from 9 cases of respiratory infections without underlying CLRTI among 46 TTA trials. Monomicrobial infection of mucoid P. aeruginosa was 69.7%, and polymicrobial infection containing mucoid P. aeruginosa was 30.3%, and Haemophilus influenzae was the most frequent microorganism recovered with mucoid P. aeruginosa. The recovery rate of mucoid P. aeruginosa among P. aeruginosa-colonized cases was 56.3% in diffuse panbronchiolitis, and that was 42.9% and 40.0% in bronchiectasis and chronic bronchitis, respectively. Mortality due to pneumonia with nonmucoid P. aeruginosa was 46.1%, but there was no fatal pneumonia case with mucoid P. aeruginosa. In CLRTI, laboratory data were not remarkably different between mucoid and non-mocoid P. aeruginosa-colonized cases. Thus, these results suggest that mucoid P. aeruginosa is a more important organism in persistent infections in the lower respiratory tract compared with nonmucoid P. aeruginosa, and further investigations is required on the mechanism and clinical role of this infection.

Adult↗

[The role of viral infection in adults with bronchopulmonary infections].

We isolated the virus from the respiratory specimens of 16 patients (7.9%) when we investigated the bronchopulmonary infections of 203 adult patients by the viral isolation method for the diagnosis of the viral infection and transtracheal aspiration (TTA) for taking directly the specimen from the lower respiratory tract. The bronchopulmonary infections, isolated the virus, consisted of acute bronchitis (3 cases), pneumonia (8 cases) and the acute exacerbation of chronic lower respiratory infection (5 cases). The positive viral isolation consisted of Rhinovirus (11 strains), Herpes simplex virus I (3 strains), Parainfluenza virus III (1 strain) and Respiratory syncytial virus (1 stain). There were 9 transtracheal aspirates, 8 pharyngeal swabs and 5 nasal washings in the positive viral specimens. We experienced 5 cases who had the same virus isolated from both the upper respiratory tract and the lower respiratory tract. H. influenzae, P. aeruginosa and other bacteria were found in 14 of the 16 TTA cultures. These results suggest that the role of the viral infection is important either independently or relating the bacterial infection in the adult bronchopulmonary infections.

Adult↗

[A clinical study of Pseudomonas pneumonia diagnosed by transtracheal aspiration].

We performed a clinical study of 16 cases (18 episodes) of Pseudomonas pneumonia by transtracheal aspiration (TTA) from April 1983 to March 1993. The isolation rate of Pseudomonas aeruginosa (P. aeruginosa) among 235 episodes of pneumonias with positive microorganism by TTA was 7.7%. All patients had one or more underlying disease. The most frequent underlying disease was chronic lower respiratory tract infection, followed by lung epidermoid cell carcinoma. More than half of the cases had been given antibiotics prior to the occurrence of pneumonia, and administration of adrenal corticosteroid, heavy smoking habit, and aspiration were seen as other predisposing factors concerning the onset of pneumonias. Monomicrobial infection of P. aeruginosa was 61.1%, and polymicrobial infection containing P. aeruginosa was 38.9%. Community-acquired pneumonia was 61.1% and hospital-acquired pneumonia was 38.9%; the rates of polymicrobial infections and prior administration of antibiotics were higher in the latter group. Mortality due to Pseudomonas pneumonia was 27.8% and the levels of serum albumin and total protein at the onset of pneumonia were significantly lower in the fatal cases than in the recovered cases. It was considered that not only general underlying disease which weaken the immunological resistance of the host, but local bronchial lesion was also important to the onset of the Pseudomonas pneumonia. Also, nutrition is an important prognostic factor on the host's side.

Adult↗

[Determination of neutrophil function in respiratory infection by chemiluminescence (CL). II: Changes in neutrophil's CL by chemotherapy against chronic lower tract infection].

Neutrophil's CL (CL-index) in were assayed in 18 patients with chronic lower tract infection (13 cases in the exacerbated phase and five cases in the stable phase) three times per case: before, during and after chemotherapy. Before the initiation of chemotherapy, the CL-index.N (neutrophil numbers x CL-index) in patients with exacerbation remained higher than in those without exacerbation. At the exacerbated phase, the CL-index of nine patients and the CL-index.N of 10 patients fell lower than those obtained before treatment. AT the stable phase, the CL-index and the CL-index.N did not change remarkably during and after chemotherapy.

Adult↗

[Clinical study of pneumonia in elderly patients using transtracheal aspiration (TTA)].

A clinical study was conducted to clarify the clinical state of pneumonia in elderly patients using transtracheal aspiration (TTA). Without prior administration of antibiotics, S. pneumoniae was the most clinically significant in both elderly and non-elderly groups whether the onset of pneumonia was hospital acquired pneumonia or community acquired pneumonia. Compared to the non-elderly group, multiple pathogens were isolated more frequently in the elderly group. Analysis about host factors showed that the number of underlying diseases per patient was more along those with poorer general conditions in the elderly group. The Brinkmann Index was also significantly higher in the elderly group. Clinical examinations before onset of pneumonia indicated that serum total protein, albumin and DNCB skin reaction were significantly lowered in the elderly group. Over the clinical course, the prognosis was poorer and the incidence of adverse reactions of antibiotics tended to be more in the elderly group. These results suggest that a complex clinical background exists for pneumonia of elderly people, related to poorer prognosis. Therefore, more cautious and meticulous care should be provided to elderly patients with pneumonia.

Adolescent↗