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Biomedical subjects

N Okimoto

Publications and source records attributed to N Okimoto.

At least 19 recordsLinked to original sources

Effect of monoclonal anti-human gp130 antibody (GPX7) on bone turnover in normal and ovariectomized rats.

We examined the effects of a monoclonal antihuman gp130 antibody (GPX7), which is known to inhibit interleukin-6 (IL-6) and leukemia inhibitory factor-mediated responses in human cells on the bone metabolism in normal and ovariectomized (OVX), 7-month-old, Wistar rats for 8 weeks. After confirming the cross-reactivity of the antibody in suppressing the IL-6-mediated proliferation of rat liver cells, GPX7 was injected once a week at doses of 1 (low dose) or 4 (high dose) mg/kg body weight (BW). In the lumbar body, bone mineral density values and the trabecular bone volume (BV/TV) were maintained in the GPX7 groups. The values of the trabecular osteoclast surface and number in the GPX7 high-dose group were significantly smaller than those in the OVX controls. The double-labeled surface and bone formation rates in the GPX7 high-dose group were significantly increased. In the proximal tibia, however, the bone mineral content and BV/ TV values in the GPX7 groups were smaller, but the trabecular thickness value in the GPX7 high-dose group was larger than in the OVX control. The single-labeled surface in the GPX7 high-dose group was significantly larger than that in the OVX control rats. Though the parameter values of trabecular osteoclasts were apparently smaller, the differences were not significant. 17-beta estradiol (0.125 mg/kg BW a week) administration prevented the bone loss by reducing the parameters of bone formation and resorption in both the lumbar and the proximal tibia. The antibody administration to the normal rats did not cause any significant changes in the parameters of bone mass and turnover. These data demonstrate that while GPX7 modulates the bone turnover after ovariectomy in rats, it does not compensate for the action of estrogen after ovariectomy in rats.

Alkaline Phosphatase

Effects of a weekly injection of human parathyroid hormone (1-34) and withdrawal on bone mass, strength, and turnover in mature ovariectomized rats.

One hundred fifteen Wistar rats, 7 months of age, were ovariectomized (ovx) or sham-operated to evaluate the effects of a weekly injection of human parathyroid hormone (hPTH) and withdrawal on the bone mass, strength, and turnover in mature ovariectomized rats. At 3 months, ovx rats were given a weekly injection of hPTH(1-34) at the respective doses of 0 (vehicle), 10, and 90 microg/kg body weight (BW) for 3 months. Then, hPTH-treated rats were divided into two groups each: continuously treated groups, and the groups treated with vehicle only for another 3 months. Weekly hPTH injections at doses of 10 or 90 microg/kg BW maintained the lumbar BMD values and increased the values of the femoral cortical bone, increasing the bone formation rates in the trabecular, endocortical, and periosteal envelopes. Trabecular osteoclasts were increased in the 90 microg/kg dose group. Trabecular bone surface relative to the volume was decreased by hPTH. The compressive load of the lumbar bone and the bending moment of the midfemur were increased. The lumbar compressive load values, corrected for BMD and volume, and the moment of inertia of the midfemur were also increased. The intracortical porosity values were not increased by the treatment. After withdrawal of hPTH treatment, the BMD values in both the lumbar and the midfemur were reduced to ovx control levels. The bone mass stimulated by the 90 microg/kg dose was reduced faster than that by the 10 microg/kg dose. However, the parameters of bone strength were still larger than those of the ovx controls after cessation of the hPTH treatment. Thus, a weekly hPTH injection effectively stimulated the bone formation in both the trabecular and cortical bone, leading to positive effects on mass and structure of the bone. These data suggest the possibility of benefits of both a lower frequency of hPTH injections as well as high-frequency injections for human osteoporotics.

Absorptiometry, Photon

Prednisolone prevents decreases in trabecular bone mass and strength by reducing bone resorption and bone formation defect in adjuvant-induced arthritic rats.

We examined the effects of prednisolone (PSL) administration in normal female Sprague Dawley rats and adjuvant-induced arthritic rats at the age of 6 weeks. Rats were intramuscularly injected with PSL twice a week at doses of 0 (control), 10, 30, 90, or 270 mg/kg body weight (b.w.). In the normal rats, serum osteocalcin level at 14 days and serum carboxyterminal pyridinoline cross-linked telopeptide of type 1 collagen (1CTP) level at 28 days in the 270 mg/kg dose group was lower than the respective value in control animals. The BMC and the trabecular bone formation rate (BFR/BS) of the lumbar body (L-4) in the 270 mg/kg dose group at 14 and 28 days were significantly lower than the values in the control rats. In the arthritic rats, however, serum osteocalcin levels in the PSL-treated groups did not differ compared with arthritic controls. The serum 1CTP levels in all of the PSL-treated groups were significantly reduced at 28 days. The age-dependent increases in the L4 BMC, BMD, and L-3 ultimate compressive load values were maintained. The BFR/BS values in the 90 mg/kg and 270 mg/kg dose groups were significantly higher than those in the arthritic control rats. The trabecular osteoclast number and surface values in all of the PSL-treated groups were significantly lower than the values in arthritic controls. These data demonstrate that PSL administration prevented reduction in bone mass and strength of the lumbar trabecular bone in adjuvant-induced arthritic rats by reducing the increase in bone resorption and the decrease in bone formation at both the local and systemic levels.

Animals

Bone marrow cell development and trabecular bone dynamics after ovariectomy in ddy mice.

To clarify the relationship between the sequential changes of trabecular bone turnover and bone marrow cell development in ovariectomized (ovx) mice, bilateral tibiae of 8-week-old ddy mice were obtained. Histomorphometric analyses of the trabecular bone of the proximal tibia of ovx mice revealed increases in the bone formation rate and the osteoclast surface for the first 28 days postovariectomy. The trabecular bone volume showed a rapid decrease for the first 28 days and a steady state for the subsequent 14 days. In bone marrow cell culture experiments, the numbers of total and nonadherent bone marrow cells per tibia obtained from the ovx mice increased. The formation of osteogenic nodules and osteoclast-like multinucleated cells in the marrow cultures obtained from ovx limbs showed a significant increase on days 14 and 28 and returned to the sham-operated level by day 42. The numbers of colony forming units (fibroblastic) and colony forming units (granulocytes and macrophages) that developed from the marrow cells did not differ between the ovx and sham limbs at any time during the study period. Fluorescence-activated cell-sorter analysis revealed no population changes in the cell development of macrophages. These results demonstrate that there are two stages in the development of osteopenia after ovx. During the first 28 days after ovx, the ovariectomy enhances the developmental process from bone marrow stromal cells to osteoblasts and the terminal differentiation from osteoclast precursors to mature osteoclasts. The trabecular bone turnover also increases. In the subsequent 14 days, the changes in the osteogenic and osteoclastogenic potentials of the bone marrow cells are alleviated and the trabecular bone dynamics are in a steady state. The changes in bone marrow cell development are closely associated with those at the trabecular bone surface.

Animals

[Nosocomial pneumonia experienced in a community hospital].

To clarify the characteristic features of nosocomial pneumonia in a community hospital, we performed a clinical analysis of 147 patients (155 episodes) with nosocomial pneumonia. The following results were obtained. 1, Regarding the risk factors for nosocomial pneumonia, factors such as the patient whose age was over 65 years, a duration of admission of over one month, performance status 4 and underlying respiratory diseases associated with the appearance of nosocomial pneumonia. 2, The causative microorganism isolated from the sputum of the patient with nosocomial pneumonia was frequently a multi-drug resistant microorganism such as Methicillin-resistant Staphylococcus aureus (MRSA). 3, regarding treatment, although several antibiotics were administered for a long time, mechanical ventilation was used on 31% of the patients, and steroid pulse therapy was carried out on 24%. The clinical efficacy was poor with a 50% mortality rate. The reason why treatment of nosocomial pneumonia was difficult is thought to be been related to the general condition of these inpatients and to the appearance of a multi-drug resistant, polymicrobial microorganisms.

Adult

[A case with chronic active EB virus infection accompanied with pulmonary candidiasis].

A 44-year-old woman with a history of intermittent fever for several years was admitted because of burn on her leg. On admission, she had hepatosplenomegaly and fever. Antibiotic therapy was started for bacterial infection of the burn. She lost her appetite and IVH was started. During the treatment, high fever appeared and chest X-ray films showed multiple nodular infiltrates throughout both lung fields. Candida albicans was isolated from IVH catheter culture and pulmonary candidiasis was suspected. Her fever and lung involvements were successfully treated with fluconazole. During the course, serum anti-EB-VCA-IgG antibody persisted at a high titer and anti-EBNA antibody remained negative. EB virus DNA was detected in the peripheral blood and bone marrow. Thus, she was diagnosed as chronic active EB virus infection.

Adult

[A case of Listeria monocytogenes sepsis in an elderly who survived].

A 81-year-old man who complained of fever and disturbance of consciousness was admitted to our hospital. Listeria monocytogenes type 1/2aA was cultured from only the blood. He was treated with gamma-globrine and sensitive antibiotics (PAPM/BP, EM) immediately after admission, and recovered in spite of multiple organ failure due to septic shock. He was not an immunocompromised host and did not have complication of meningitis, but had rhabdomyolysis and liver dysfunction.

Aged

[Human parvovirus B19-induced aplastic crisis in a case with spherocytosis].

A 43-year-old female with spherocytosis was admitted to the hospital because of fever, headache, and rapidly progressive anemia. On admission, she had severe anemia (Hb 3.9 g/dl) with marked decrease in reticulocytes (0.3%). Some premature leukocytes, such as promyerocyte, were observed in the peripheral blood. Bone marrow smear revealed normocellular marrow with normal presence of erythroid cells. Anti-human parvovirus B19 IgM and IgG antibody was positive in the serum on admission. The DNA of the virus was also detected in the peripheral blood by PCR assay. Thus, this case was diagnosed as acute aplastic crisis caused by human parvovirus B19 infection. Blood transfusion was performed on day 1 and day 2. The symptoms gradually disappeared and increase in reticulocyte (11.5%) was observed on day 5. Premature leukocytes in the peripheral blood disappeared on day 2. She recovered from anemia and was discharged on day 7.

Adult

[Clinical analysis of patients with severe pneumonia requiring mechanical ventilation].

To clarify the clinical features and select the appropriate antibiotic therapy for patients with severe pneumonia requiring mechanical ventilation, we performed a clinical analysis of 65 patients with this condition. The following results were obtained. The majority of the patients were elderly males, whose performance status was poor (PS 2.2) and who had an underying disease. Abnormal physical signs included tachypnea, tachycardia and consciousness disturbance. Abnormal laboratory findings included hypoalbuminemia, and liver and renal dysfunction. The causative microorganisms were isolated from half of these patients. A number of antibiotics were administered and steroid pulse therapy was also performed for half of these patients. Nevertheless the prognosis was poor because the percentage of deaths was high (50.8%).

Adult

[Clinical analysis of patients with nosocomial pneumonia during mechanical ventilation (so-called ventilator-associated pneumonia)].

To clarify the clinical features of nosocomial pneumonia during mechanical ventilation (ventilator-associated pneumonia) and to select the appropriate antibiotic therapy for patients, we performed a clinical analysis of 19 patients (26 episodes) with this condition. The following results were obtained. 1, The average age of the patients was 68 years old (male 16, female 3). 2, VAP occurred three times in 2 cases, twice in 3 cases, and once in 14 cases. 3, The duration of mechanical ventilation was from 7 days to 11 years and 5 months (the average was 2.1 years). 4, The microorganism isolated from the aspiration sputum of the VAP patients was Pseudomonas aeruginosa frequently, but it was difficult to determine whether this microorganism was the causative microorganism. Ten strains of Staphylococcus aureus (MRSA seven strains and MSSA three strains) were newly isolated at the same time as VAP and especially in the cases in which these were thought to be causative microrganisms, all the patients died within a short time. 5, Antibiotics were clinically effective for 53.8% of all the VAP patients and carbapenem antibiotics (for example, IPM/CS) were also used for the effective group. 6, Regarding the risk factors for VAP, factors such as the duration of mechanical ventilation, the existence of chronic obstructive pulmonary disease, a hyponutritional state, prior antibiotics, aspiration of gastric contents, histamine-type-2 receptor antagonist, and multiple organ failure showed significant differences and were suspected to be associated with the appearance of VAP.

Adult

Responses of trabecular and cortical bone turnover and bone mass and strength to bisphosphonate YH529 in ovariohysterectomized beagles with calcium restriction.

Thirty-six beagles, 18 months of age, underwent ovariohysterectomy (OHX) or a sham operation. Sham-operated animals were given a diet with standard calcium (1.4%) (group 1, n = 6) or a restricted calcium diet (0.14%) (group 2, n = 6). The OHX animals were given the restricted calcium diet and YH529 orally with respective daily doses of 0, 0.02, 0.1, and 0.5 mg/kg of body weight (groups 3-6, n = 6 each) for 12 months. At the end of this period, the lumbar bone mineral densities (BMDs) in groups 2 and 3 and the load values for group 3 were significantly smaller than those for group 1. The midfemur BMD did not differ among the groups. The urinary deoxypyridinoline (U-Dpy) and bone formation rates (BFR/BS, BFR/BV) in groups 2 and 3 and the osteonal BFR/BS and trabecular osteoclast number (Oc.N/BS) in group 3 were significantly larger than the respective values for group 1. However, these parameters did not significantly differ between groups 2 and 3. The serum osteocalcin (OC) level, wall thickness (W.Th), and mineral apposition rate values for group 3 were significantly larger than those for group 2. In group 2, the trabecular activation frequency (Ac.F) increased by 3.11 times, and the percent values of the number of labeled osteons (L-Ot.N/T-Ot.N, %) in the tibia by 3.28 times over those for group 1. In group 3, the Ac.F increased by 3.20 times and the number of labeled osteons by 3.77 times over those for group 1. In groups 4-6, the U-Dpy and Oc.N/BS values were smaller, but their OC levels did not significantly differ from the level for group 3. The lumbar BMD, the load, and W.Th were dose-dependently significantly larger than those for group 3. The Ac.F values were significantly smaller, and the respective value in groups 4-6 was 67.9, 25.5, and 10.2% of that in group 3. The BMDs of the midfemur in groups 4-6 were significantly larger than those in group 3, but the ultimate load values did not significantly differ. The L-Ot.N/T-Ot.N values were also significantly smaller, and the respective value in groups 4-6 was 82.0, 48.5, and 55.2% of that in group 3. The tibial endocortical and periosteal BFR/BSs did not differ significantly. These data demonstrate that the effects of OHX on bone mass and turnover were small in the beagles fed a restricted calcium diet. YH529 maintained the mass and strength of the lumbar bone by reducing the bone resorption. The cortical bone appeared to be less sensitive to the agent than the trabecular bone in this animal model.

Administration, Oral

[Home oxygen therapy in the elderly].

Between 1984 and September 1995, we prescribed home oxygen therapy for 155 patients (96 men and 59 women), mean age 68.6 years) with chronic respiratory failure. Here we describe the underlying diseases, laboratory findings (arterial blood gas analysis and pulmonary-function tests), and outcomes. We also report differences between those who were of least 70 years old (n = 82) and those less than 70 years old (n = 73). The underlying diseases were chronic obstructive pulmonary disease in 55 patients, lung cancer in 33, old pulmonary tuberculosis in 29, and pulmonary fibrosis in 27. Chronic obstructive pulmonary disease, especially pulmonary emphysema, was the most frequently encountered underlying disease in the older patients, whereas pulmonary fibrosis and lung cancer were most common in the younger patients. The duration of observation ranged from less than 1 month to 10 years. At the time of this study 82 patients had died, 31 were still being treated as outpatients at our hospital, 32 had transferred to other hospitals, and the status of 10 patients was unknown. The older and younger patients did not differ with regard to arterial blood gases, pulmonary function at the time home oxygen therapy began, or outcome: We believe that home oxygen therapy was very beneficial in these patients with chronic respiratory failure, because their quality of life improved after the start of this therapy.

Aged

[Clinical and laboratory findings associated with the severity of community-acquired pneumonia].

To clarify the clinical features of severe community-acquired pneumonia, we retrospectively studied 121 patients treated at our hospital. We divided the patients into three groups, based on the severity, of their disease. Patients were put in the "mild" group (n = 56) if they recovered after treatment with antimicrobial agents only, they were put in the "moderate" group (n = 34) if the required oxygen therapy and recovered, and they were put in the "severe" group (n = 31) if they required mechanical ventilation. Age and underlying disease were recorded, as well as signs, symptoms, and laboratory data obtained during the first 24 hours after admission. The data indicated that the following nine findings were associated with the severity of disease: age of at least 65 years, an underlying disease of (31) the respiratory or central nervous system, dyspnea, a pulse rate of at least 90 beats per minute, a respiratory rate of at least 25 breaths per minute, an albumin concentration no greater than 3.5 g/dl, a blood urea nitrogen level of at least 20 mg/dl, a PaO2 no greater than 60 mmHg or an SaO2 no greater than 90%, and a high score on a scale of the extent of roentgenographic evidence of pulmonary infiltrates. Patients in whom these are found be managed carefully.

Adult

[A case of Plasmodium ovale malaria with thrombocytopenia and an abnormality grade in FDP concentration despite the use of chloroquine as a malaria prophylaxis].

A 45-year-old Japanese male, who had been to the Central African Republic, was admitted to our hospital because of high fever with chills on July 29, 1994. He used chloroquine as a malaria prophylaxis during his stay and for 6 weeks after his return to Japan. On admission, Plasmodium ovale was detected in his blood smears and in the DNA analysis. He was treated successfully with chloroquine (1500 mg over 3 day period) and primaquine (15 mg/day for 14 days beginning day 4). Disappearance of malarial parasites in the peripheral blood smear occurred on the third day and his temperature returned to normal on the 4th day. Interestingly, he had thrombocytopenia and an abnormal grade in fibrin degradation products (FDP) concentration. This led to the suspicion of disseminated intravascular coagulation (DIC). This report indicates the importance of thrombocytopenia which may develop into DIC even though P. ovale malaria infection rarely becomes severe. This is the second report of a P. ovale malaria case in the Central African Republic.

Animals

[A case of Aspergillus niger pneumonia cured with an early diagnosis].

We have experienced a case with A. niger aspergilloma who developed Aspergillus pneumonia after bacterial pulmonary infection. Examinations of sputum cytology and detection of serum Aspergillus antigen were useful for an early diagnosis of his condition. Early and intensive antifungal chemotherapy mainly with intravenous amphotericin B brought about his complete remission.

Amphotericin B