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Biomedical subjects

M Sawaki

Publications and source records attributed to M Sawaki.

At least 19 recordsLinked to original sources
PubMed1998

Apoptosis in the lens anlage of the heritable lens aplastic mouse (lap mouse).

Adult homozygous lap mice show various eye abnormalities, such as aphakia, retinal disorganization, and dysplasia of the cornea and anterior chamber. In the fetal eye of a homozygous lap mouse, the lens placode seems to develop normally. However, the lens vesicle progresses abnormally to form a mass of cells without a cavity, and the mass vanishes soon afterward. We examined cell death in the lens anlage of this mutant. The lens anlagen of homozygous lap and normal mice from days 10 to 12 of gestation were observed by light microscopy after DNA end-labeling by immunohistochemistry and by transmission electron microscopy. By light microscopy, a slight frequency of cell death was detected in the lens anlage encircling the surface ectoderm and in the anlage or in the anlage of both homozygous lap mice and normal mice at day 10 of gestation. Cell death was seen in the lens anlage encircling the surface ectoderm in the normal mouse and sporadically in the anlage of the homozygous lap mouse at day 10.5 of gestation. Cell death was visible at the area of the lens vesicle attached to the surface ectoderm and encircling the surrounding surface ectoderm in the normal mouse, and in the lens anlage encircling the surface ectoderm and the apex areas of the lens anlage in the homozygous lap mouse at day 11 of gestation. At day 12 of gestation, almost no cell death was observed in the lens anlage of the normal mouse. However, extensive areas of cell death were still seen in the lens anlage at its apex, at the inner region, and encircling the surface ectoderm in the homozygous lap mouse. Electron microscopic observation showed that the dead cells observed in the lens anlagen by light microscopy in normal and lap mice are the result of apoptosis. In lap mice, cells with cytoplasmic condensation were observed mainly at days 10 and 10.5 of gestation. Many apoptotic bodies which had been phagocytosed by adjacent cells were seen predominantly at day 11 of gestation. At day 12 of gestation, apoptotic bodies phagocytosed by adjacent cells, which were seen at day 11, were still predominant, but there were more apoptotic bodies per cell and more digested apoptotic bodies than at day 11. These results indicate that cell death, resulting from apoptosis is involved in the disappearance of the lens anlage of lap mice.

Animals↗
PubMed1998

Interleukin-6 spillover in the peripheral circulation increases with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure.

OBJECTIVES: We 1) evaluated whether interleukin-6 (IL-6) is produced in the peripheral circulation in patients with congestive heart failure (CHF), 2) estimated the factors for increased IL-6, and 3) clarified the prognostic role of high plasma levels of IL-6 in patients with CHF. BACKGROUND: Although plasma levels of IL-6 have been reported to increase in patients with CHF, and production of IL-6 in endothelial cells and vascular smooth muscle cells has been postulated from in vitro studies, the origin of the increase of IL-6 in CHF remains unknown. Moreover, the prognostic value of a high plasma level of IL-6, independent of classic neurohumoral factors, remains to be elucidated. METHODS: A comparison was made of the plasma levels of IL-6 between the femoral artery and the femoral vein in 13 normal subjects and in 80 patients with CHF. In another study, we measured plasma IL-6 in 100 patients with CHF and follow-up data. RESULTS: Plasma IL-6 levels increased significantly from the femoral artery to the femoral vein in normal subjects and in patients with CHF. Arteriovenous IL-6 spillover in the leg increased with the severity of CHF. Among the hemodynamic variables and the various neurohumoral factors, the plasma norepinephrine (NE) level showed an independent and significant positive relation with the plasma IL-6 level in patients with CHF. Moreover, treatment with beta-adrenergic blocking agents showed an independent and significant negative relation with plasma IL-6 levels. In 100 patients, plasma IL-6 (p < 0.0001), NE (p = 0.0004) and left ventricular ejection fraction (0.015) were significant independent prognostic predictors by Cox proportional hazards analysis. CONCLUSIONS: Our findings indicate that the IL-6 spillover in the peripheral circulation increases with the severity of CHF and that the increase in plasma IL-6 is mainly associated with the activation of the sympathetic nervous system. High plasma levels of IL-6 can provide prognostic information in patients with CHF, independent of left ventricular ejection fraction and plasma NE, suggesting an important role for IL-6 in the pathophysiology of CHF.

Adrenergic alpha-Agonists↗
PubMed1998

Chronic liver injury promotes hepatocarcinogenesis of the LEC rat.

The Long-Evans rat with a cinnamon-like color (LEC) is a mutant rat that spontaneously suffers from chronic liver injury and subsequent hepatocellular carcinoma (HCC) caused by abnormal copper accumulation in the liver. We attempted to elucidate the role of prolonged liver cell injury on LEC rat hepatocarcinogenesis using a copper-deficient diet (CuDD) to inhibit the occurrence of consequent liver injury. The animals were fed the CuDD from the age of 4 weeks until being killed at the age of 10 months. Diethylnitrosamine (DEN) was administered at the age of 8 weeks. Groups fed a basal diet (BD) with or without the administration of DEN were also assigned as control groups. The animals fed the BD manifested liver injury, while those fed the CuDD did not show liver dysfunction until death. The number and volume of glutathione S-transferase placental form (GST-P)-positive preneoplastic lesions in the liver, which were calculated from the data on two-dimensional planes, were examined to clarify the promotive effect of chronic liver injury on the development of HCC. Regarding the size of the lesions, which indicated the intensity of the promotive effect, the lesions in the livers of rats fed the BD with DEN were much larger than those of rats fed the CuDD with DEN. Feeding the LEC rats with CuDD completely suppressed the manifestation of liver injury, and it was clearly shown that prolonged liver injury had a promotive effect on the LEC rat hepatocarcinogenic process.

Alanine Transaminase↗
PubMed1998

Chronic effects of a novel, orally active endothelin receptor antagonist, T-0201, in dogs with congestive heart failure.

Endothelin (ET)-1 increases in plasma during congestive heart failure (CHF). Some ET antagonists improve hemodynamics, suggesting its potential benefits in the treatment of CHF. We examined the acute and chronic effects of a new ET receptor antagonist, T-0201 (Tanabe Seiyaku Co. Ltd., Japan), in CHF. To confirm the in vivo effects of T-0201, we observed the inhibitory effects of T-0201 (1-100 micrograms/kg) on the response of blood pressure to exogenously administered ET-1 (0.75 nmol/kg) in conscious normal dogs. Pretreatment with T-0201 significantly inhibited the ET-1-induced initial hypotension that is mediated by ETB receptors, and attenuated the subsequent hypertension, which is primarily mediated by ETA receptors. Thus, T-0201 at a dose of 100 micrograms/kg not only works as a potent ETA antagonist but also shows antagonist activity for ETB receptors in dogs. To evaluate the chronic therapeutic effects of T-0201, we administered T-0201 (0.3 mg/kg/day; n = 5) orally to dogs with CHF induced by rapid right ventricular pacing (22 days, 270 beats/min) for 15 days, beginning 8 days after pacing. T-0201 significantly prevented the deterioration of cardiorenal function during the development of CHF, expressed as a decrease in cardiac pressure and an increase in cardiac and urine output. These results suggest that chronic antagonism of both ET receptors prevents the progressive exacerbation of CHF.

Animals↗
PubMed1998

[A clinical study of respiratory infection isolating non-pathogenic Neisseria by transtracheal aspiration].

Neisseria species other than N. meningitidis and N. gonorrhoeae are generally regarded as commensal bacterial flora of the oropharynx, and little is known regarding cases of these non-pathogenic Neisseria species in the lower respiratory tract. We clinically examined respiratory tract infections from which non-pathogenic Neisseria species were isolated by transtracheal aspiration (TTA). The incidence of non-pathogenic Neisseria isolated was 54 (15.7%) out of 344 episodes of respiratory tract infections with isolated microorganisms from TTA, and was 17.6%, 15.8%, 14.3% for pneumonia, acute bronchitis, and chronic lower respiratory tract infection, respectively. All 54 episodes were isolated with other microorganisms such as alpha-Streptococcus spp. (75.9%), Haemophilus influenzae (25.9%) and anaerobics (22.2%). The isolation ratio according to the age group increased at 45 years of age or more, but did not increase with the advance of age. Predisposing factors were identified such as overt aspiration, iatrogenic procedure and heavy smoking. Cases without overt aspiration that had fevers of 38 degrees C or more or hypoxemia of less than PaO2 70 torr when detecting non-pathogenic Neisseria were observed more frequently in the aged than the non-aged. The findings suggest the detection of non-pathogenic Neisseria by TTA is influenced by the host state that the fall of microorganisms from the upper to lower respiratory tract cannot be defended or excluded by mucociliary transportation disorder due to underlying disease and smoking, or deterioration of physical status other than overt or silent aspiration.

Age Factors↗
PubMed1998

[Clinical evaluation of lung abscess diagnosed by transtracheal aspiration].

We have diagnosed lung abscess according to findings of infiltration with cavity formation on chest X-ray and/or CT-scan and pathogens isolated from transtracheal aspirates. We evaluated the clinical features of 20 patients with lung abscess (18 males and 2 females, mean age; 54.3 years). Diabetus mellitus and periodontal diseases were prominent underlying diseases in patients with lung abscess. Cough was complained in 13 patients, chest or back pain in 9, purulent sputum in 8 and hemosputum in 5 when the patients admitted to our hospital. A temperature higher than 38 degrees C was present in 12 patients but temperature les than 37 degrees C in 2. Multiple microorganisms were cultured from TTA in 15 patients. A mean of 2.7 bacterial species per patient was isolated, aerobes alone being isolated in 2 patients, anaerobes alone in 3, and mixed aerobic and anaerobic isolates in 10. Seventeen strains of aerobes and 35 of anaerobes were isolated. Major pathogens were Streptococcus pneumoniae, Streptococcus intermedius and other in aerobes, and Peptostreptococcus micros, Fusobacterium necrophorum, Prevotella melaninogenica and others in anaerobes. Abnormality of chest X-ray was located on the right upper lobe in 6 patients, the right lower lobe in 6, the left upper lobe in 6, the left lower lobe in 4 and the right middle lobe in 1. All patients were cured only by treatment of antimicrobial agents, but cavity formation on chest X-ray remained in 4 patients after the treatment.

Adult↗
PubMed1998

[Clinical analysis of patients with sepsis--comparison between underlying diseases].

We evaluated the clinical data in 83 patients with sepsis, which was diagnosed by both Bone's definition of sepsis and positive isolates from blood culture, according to their underlying diseases. This study enrolled a total of 117 septic episodes in 83 patients (57 males and 26 females, mean age: 52.0 years). We classified 3 groups, including hematological malignancies (46 patients, 72 episodes), solid malignant tumors (23 patients, 25 episodes) and non-malignancies (14 patients, 20 episodes), by the underlying diseases. Of the total number of isolates from blood culture, 53.0% were single gram-positive bacteria, 33.3% were single gram-negative bacteria, 7.7% were single fungus and 6.0% were polymicrobial organisms. In addition, coagulase negative staphylococci was isolated most often in patients with hematological malignancies. Sepsis was often caused by infectious focuses of hemorrhoid, stomatitis or intravenous catheter in patients with hematological malignancies, by pneumonia in patients with solid malignant tumors and by urinary tract infection in patients with non-malignancies. Mortality of sepsis in patients with solid malignant tumors (48%) was highest in 3 groups. Septic patients, who were complicated with shock and/or DIC, has poor prognosis in all groups. Serum albumin level was significantly lower in dead patients than patients who survived. These results suggest that clinical features may be different according to the underlying diseases of patients with sepsis.

Aged↗
PubMed1998

[An epidemiological investigation for MRSA and PRSP in Kinki area. Kinki Infection Working Group].

Recent trends in the development of resistance of the Staphylococcus aureus and Streptococcus pneumoniae to antibiotics were investigated, using a questionnaire delivered to participants at a meeting of the Kinki District Society of Infections. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 55.4% of all isolated S. aureus, and more than 80% of MRSA was detected within hospitals. In outpatients, MRSA was often detected in pus, while in hospitalized patients, MRSA was often detected in sputum. Further, MRSA was accompanied by some other organisms (most frequently Pseudomonas aeruginosa) in 64.7% of MRSA positive patients. The sensitivity of MRSA to vancomycin (VCM) was 100%, to sulfamethoxazole-trimethoprim (ST) 99.2%, and to arbekacin, 98.6%. In contrast, Penicillin-resistant Streptococcus pneumoniae (PRSP) accounted for 42.4% of all isolates of Streptococcus pneumoniae. About 50% of PRSP was detected in out-patients. For both hospitalized patients and outpatients, PRSP was most frequently detected in sputum. PRSP was accompanied by some other organisms (most frequently Haemophilus influenzae) in 49.3% of PRSP positive patients, PRSP had high sensitivity to cephems, carbapenems and VCM.

Aminoglycosides↗
PubMed1998

[Effect of clarithromycin treatment of natural killer cell activity in patients with advanced non-small cell lung cancer].

The treatment of a 14-membered ring macrolide, clarithromycin (CAM), prolongs the survival time of patients with unresectable nonsmall cell lung cancer, and improves the host factor. As we previously reported, one of the underlying mechanisms is that the treatment of CAM increases the bioactivity of interleukin-12 (IL-12). In the present study, we administered CAM to murine lung cancer treatment models with Lewis lung carcinoma and to 18 patients with unresectable non-small lung cancer whose anticancer treatment had been terminated. The timing of CAM administration was examined and the time course of NK activity was measured. In the murine lung cancer treatment models, administration of CAM 7 days after anticancer chemotherapy more strongly inhibited the tumor growth and more rapidly and significantly increased NK activity, compared to the concomitant use of CAM with an anticancer chemotherapy. In humans, the NK activity which had decreased after anticancer treatment, tended to be increased after one month of treatment with CAM (p = 0.06). One month of treatment with CAM significantly increased the NK activity (p < 0.05) of the following subjects: patients with stage III in the clinical stages, patients with squamous cell carcinoma, patients who had received radiotherapy alone as pretreatment therapy, and patients whose pretreatment therapy effect was partial response (PR). We conjectured that increasing NK activity was one of the underlying mechanisms of the macrobiotic effect of CAM. CAM was especially effective for patients in the early clinical stages and patients who responded well to pretreatment therapy. Murine lung cancer models showed that non-concomitant use of CAM with anticancer chemotherapy was more effective.

Aged↗
PubMed1997

[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↗
PubMed1997

[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↗
PubMed1997

[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↗
PubMed1997

[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↗
PubMed1997

[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↗