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Biomedical subjects

J Sato

Publications and source records attributed to J Sato.

At least 253 records · Page 14Linked to original sources
PubMed1994

Regeneration of immunity and varicella-zoster virus infection after high-dose chemotherapy and peripheral blood stem cell autografts in children.

We assessed recovery of the immune system in 41 children who underwent high-dose chemotherapy (without total body irradiation) and autologous peripheral blood stem cell transplantation (PBSCT) for acute leukemias or non-Hodgkin's lymphoma. The analysis was in two parts. Firstly, we performed serial monitoring of regenerating subsets and blastogenesis of lymphocytes. We then reviewed the incidence of varicella-zoster virus (VZV) infection, based on the belief that this served as a clinical indication of immunological recovery. The CD4/CD8 ratio markedly decreased in all patients, with a nadir at 3 months, due to both abnormally low levels of CD4+ cells and sustained higher levels of CD8+ cells. These abnormalities were sustained for > 12 months post-graft. Within 6 months after PBSCT, all patients showed a decreased in vitro response to mitogens including PHA, Con A and PWM but these responses gradually recovered during the subsequent 6 months. All patients had a previous history of chicken pox. The actuarial incidence of VZV was 45% at 6 months and 67% at 12 months. All patients were treated with intravenous acyclovir with relief of pain and cutaneous healing within 10 days. No patient developed visceral dissemination. These findings suggest that at least in children, no major difference is apparent between immunological reconstitution in bone marrow transplantation and PBSCT. The development of minor and reversible VZV is a common event in this group of patients.

Adolescent↗
PubMed1994

[Clinical assessment of diffuse brain injury sequelae: with respect to so-called post-traumatic disorder].

Brain injury sequelae were observed in 24 patients who had sustained diffuse brain injury. According to their ability to lead social life, the severity was classified into 6 levels; vegetative, severe, moderate, mild, fair, and good. The severity levels statistically correlated with the length of the initial unconsciousness (Spearman's correlation coefficient r = 0.929, n = 24, p < 0.01), with posttraumatic amnesia (r = 0.827, n = 8, p < 0.05), with ventricular enlargement (r = 0.808, n = 24, p < 0.01) and with the presence of hemiplegia (r = 0.740, n = 24, p < 0.01). Children and young adults showed a tendency to improve to milder levels. Mild head injury patients who sustained concussion of less than 6 hours in duration also showed minimal sequelae such as mild ventricular dilatation and difficulty in recent memory. This memory impairment had often been ascribed to the so-called postconcussional syndrome. The threshold for occurrence of diffuse brain injury sequelae was estimated as concussion lasting 15-30 minutes or post-traumatic amnesia of a few days in duration in adults and about a week in children. Superficially localized brain contusion was frequently observed and was not correlated with the severity level, hemiplegia or post-concussional syndrome.

Adolescent↗
PubMed1994

Engraftment potential of peripheral and cord blood stem cells evaluated by a long-term culture system.

The experiment was performed in an attempt to seek a suitable indicator of allogeneic transplantation using cord blood cells. The number of colony-forming cells (CFC) recovered after 5 weeks of culture represents that of primitive progenitors present in the initiating cell population. In this study of nine children who underwent autologous peripheral blood stem cell transplantation (PBSCT), we measured the amount of colony-forming units-granulocyte/macrophage (CFU-GM) and total CFC output after 5 weeks in long-term culture (LTC-CFC) contained in the infused grafts and compared them to the speed of hematopoietic recovery after marrow ablation. In this patient population, we found a significant negative correlation between the number of infused CFU-GM/kg body weight and the time to achieve an absolute granulocyte count (AGC) of 0.5 x 10(9)/L (r = -0.867, p < 0.01), but not with the time to achieve a platelet count of 50 x 10(9)/L (r = -0.700, p = 0.05). Although the number of infused LTC-CFC/kg did not correlate with the early phase of granulocyte recovery, a significant correlation was observed with platelet recovery speed (r = -0.930, p < 0.01) and with the time to regain an absolute granulocyte count of 2 x 10(9)/L after the nadir of the transient decrease in the number of AGC, which occurred 3 to 7 weeks following PBSCT (r = 0.967, p < 0.01). On the other hand, CFU-GM/kg showed no significant correlation with this late engraftment speed. Thus, LTC assay may reflect the kinetics of immature progenitor cells which are capable of reconstituting stable hematopoiesis after marrow ablative therapy. The data were then used in a comparative analysis of the transplantation potential of peripheral vs. cord blood stem cells. The numbers of LTC-CFC and CFU-GM per mononuclear cell (MNC) from cord blood were 2.5-fold and two-fold greater than those from peripheral blood cells, respectively. These results suggest the advantage of cord blood as an additional stem cell source in transplantation.

Adolescent↗
PubMed1993

Adrenergic excitation of cutaneous nociceptors in chronically inflamed rats.

To probe the mechanisms underlying sympathetically maintained pain, the effects of lumbar sympathetic chain stimulation (SS) and close arterial injection of norepinephrine (NE) on cutaneous nociceptor activities were studied in adjuvant inflamed rats. Two to 28 weeks after adjuvant treatment, single nerve recordings of polymodal receptors from the saphenous nerve were performed. In treated rats but not in controls, SS and NE were excitatory in 35-40% of units. Yohimbine and CH-38083 blocked NE excitation, but prazosin did not. Our data show that chronic inflammation initiates circumstances in which alpha 2-adrenoceptor-mediated sympathetic activity excites some nociceptors.

Adjuvants, Immunologic↗
PubMed1993

Granulocyte colony-stimulating factor (CSF), macrophage-CSF, granulocyte-macrophage CSF, interleukin-3, and interleukin-6 levels in sera from children undergoing blood stem cell autografts.

Endogenous production of granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin-3 (IL-3), and interleukin-6 (IL-6) was investigated in 10 children who underwent a total of 12 courses of autologous peripheral blood stem cell transplant (PBSCT) by measuring their serum levels using immunoassay kits. The serum G-CSF level increased immediately following infusion of PBSC graft, peaked between days 3 and 7 posttransplant and then declined by the time the granulocyte count rose. No definitive association was found between the continuous high levels of G-CSF and infective episodes, the number of infused nucleated cells, monocytes, CFU-GM, or the number of days required to achieve greater than 0.5 x 10(9)/L granulocyte, greater than 1.0 x 10(9)/L leukocyte, or greater than 50 x 10(9)/L platelet counts. After PBSCT, IL-6 levels tended to be elevated. No detectable serum level of GM-CSF or IL-3 (< 50 pg/mL) was observed before PBSCT and 4 patients showed a transient increase in the GM-CSF level after PBSCT. No significant change was observed in the post-transplant serum levels of IL-3 or M-CSF. The role of endogenously secreted cytokines in early hematopoietic recovery after PBSCT needs further clarification, but, at present, routine use of exogenous G-CSF therapy is not recommended.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects.

The influence of usual multiple ingestions of dietary caffeine on oral single-dose pharmacokinetics of theophylline has been investigated in 6 healthy male subjects. The subjects consumed 2 to 7 cups of regular instant coffee during the 24 h study period. Their mean serum concentrations of caffeine varied from 1.2 to 3.1 mg/l. After their usual intake of dietary caffeine, the serum concentrations of theophylline from 3 to 24 h after administration were significantly higher than after deprivation of dietary caffeine. The apparent elimination of theophylline half-life was prolonged from 6.3 (0.61) h (mean with (SEM)) to 8.3 (0.47) h (32% increase, P < 0.01) and the total body clearance was reduced from 55.0 (1.31) ml.h-1.kg-1 to 42.5 (2.63) ml.h-1.kg-1 (23% decrease, P < 0.001). Saturation of theophylline metabolism and/or competition between theophylline and caffeine metabolism in addition to theophylline derived from caffeine may be the cause of the delayed elimination of theophylline. The present study has indicated that a significant reduction in theophylline metabolism may be caused by a conventional intake of dietary caffeine. In bronchodilator therapy with theophylline, therefore, the daily consumption of caffeine should be taken into consideration.

Administration, Oral↗
PubMed1993

Pontine gliomas causing locked-in syndrome.

The terminal phase of pontine glioma is reportedly characterized by disturbance of consciousness. The authors retrospectively reviewed 8 children who died of pontine gliomas in their hospitals. The hospital records were analyzed specifically in regard to neurological status and terminal case. All children became mute and quadriplegic with cranial nerve palsies. The oldest child, 17 years in age, unquestionably showed the classical locked-in syndrome for the last 4 months. Six of the remaining 7 (average 5 years of age), while labeled as semicomatose, responded to calling by blinking and/or vertical eyeball movement. The authors consider that they were indeed awake in the locked-in state until very near death. This would raise a serious ethical problem of whether or not they should be intubated and kept ventilator-dependent at the time of respiratory failure, which often occurs.

Adolescent↗
PubMed1993

Management problems in continuous care of male patients with mild hypertension with special reference to alcohol-intake.

Forty two male patients with borderline and mild hypertension were followed up for 3.9 years without medication. During this period, all subjects had nonpharmacological interventions including salt restriction, weight reduction, anti-smoking or anti-alcohol instruction, and physical exercise after the established protocol. Comparisons of biomedical data between pre- and post-observation revealed no significant improvements. Although the smoking habit decreased during this period, the drinking habit rarely changed and even significant increase of the total amount of alcohol ingestion was observed. These data indicate great limitation of nonpharmacological intervention in the care of these asymptomatic hypertensive patients for a lifelong base.

Adult↗
PubMed1993

Enhancement of anti-tumor activity of recombinant interleukin-2 (rIL-2) by immunocomplexing with a monoclonal antibody against rIL-2.

We have investigated biological properties of an immune complex of recombinant interleukin-2 (rIL-2) and a monoclonal antibody against rIL-2 in mice for induction of killer cells and for anti-tumor activity. We have also examined the clearance of subcutaneously-injected immune complex in mice and compared it with that of rIL-2 alone. Plasma rIL-2 levels were sustained longer in mice given the immune complex than in mice given rIL-2 alone at a dose of 10 micrograms/mouse, and they were detectable even at 24 hours after the administration of the immune complex, while they fell to undetectable levels by 6 hours after the administration of rIL-2 alone. A more significant portion of rIL-2 was detected in lymph nodes after subcutaneous injection of the immune complex than that of rIL-2 alone. Splenic lymphocytes from mice given the immune complex demonstrated a higher killer cell activity against YAC-1 cells than those from mice given rIL-2 alone. The immune complex also exerted more significant anti-tumor effect in a dose-dependent manner in Meth-A fibrosarcoma-bearing mice than rIL-2 alone. Our results indicate that immunocomplexing of rIL-2 with an antibody against rIL-2 provides a useful tool as the drug delivery system for cancer therapy using rIL-2.

Animals↗
PubMed1993

Metabolic changes associated with malnutrition in the patients with multiple organ failure.

To clarify the metabolic changes associated with malnutrition in the patients with multiple organ failure (MOF), we measured energy expenditure, nitrogen excretion, nonprotein respiratory quotient (NPRQ), caloric intake, and cumulative caloric balance (CCB) in 20 MOF patients (12 survivors and 8 non-survivors). The non-survivors exhibited significantly greater cumulative caloric deficit than the survivors. Metabolic activity tended to decline to normal in the survivors as organ failures were overcome. In the non-survivors, on the contrary, regardless of large caloric deficit hypermetabolism persisted and characteristically followed by the sudden decrease in metabolic activity at the time immediately prior to death. Compared to the survivors, the non-survivors generally exhibited poorer response in metabolic activity and greater NPRQ change to the altered amount of caloric intake. It seemed that protein sparing effect by increased caloric intake was preserved in both the survivors and the non-survivors only with CCB above -5 times basal energy expenditure. These results suggest that persistent hypermetabolism and poor metabolic response to nutritional support are partly responsible for existing organ failures and poor outcome in MOF patients.

Journal Article↗
PubMed1993

A simple method for affinity purification of radiolabeled monoclonal antibodies.

A simple method is described for affinity purification of radiolabeled antibodies using glutaraldehyde-fixed tumor target cells. The cell-bound antibody fraction is removed from the cells by an acid wash and then immediately subjected to buffer-exchange chromatography. The method was applied to the D3 murine monoclonal antibody which binds to a 290 kDa antigen on the surface of Line 10 guinea pig carcinoma cells. No alteration in the molecular size profile was detected after acid washing. Purification resulted in a significant increase in immunoreactivity by an average of 14 +/- 47% (SD; range 4-30%).

Animals↗
PubMed1993

Toxicities associated with cryopreserved and thawed peripheral blood stem cell autografts in children with active cancer.

To evaluate the safety of cryopreserved and thawed peripheral blood stem cell (PBSC) autografts in children with active cancer, a toxicity assessment was made of 54 PBSC transfusions to 52 children (aged 1-16 years; median, 9 years). Patients were conditioned with high-dose chemotherapy without total body irradiation. The volume of PBSCs transfused varied from 46 to 500 mL (219.6 +/- 118.4 mL, mean +/- SD), with a mean of 0.91 g per kg of dimethyl sulfoxide. Insignificant and transient toxicities included hemoglobinuria in 40 patients (74%), headache in 38 (70%), nausea in 37 (69%), and vomiting in 25 patients (46%). Significant shock developed in 8 patients (15%), but they recovered quickly, whether they had supportive therapy or not. Vomiting and hyperbilirubinemia were the only toxicities that showed a correlation with the amount of PBSCs transfused. The data suggest that transient toxicity associated with PBSC autografts is rather common in children, and close observation of patients for possible serious morbidity is required.

Adolescent↗
PubMed1993

Effect of methacholine on low-frequency mechanics of canine airways and lung tissue.

We measured tracheal flow, tracheal pressure, and alveolar capsule pressure in four anesthetized paralyzed tracheostomized open-chest dogs. Lung impedance between 0.12 and 4.88 Hz was measured with a forced volume oscillation technique before and after the intravenous administration of methacholine (MCh). Before MCh administration, lung impedance was well described by a model featuring a single airway leading to an alveolar region surrounded by tissue with a continuous distribution of viscoelastic time constants as used by Hantos et al. (J. Appl. Physiol. 68: 849-860, 1990). After MCh, however, this model gave a poor fit to the impedances. The impedances were well accounted for, however, when the model was enhanced to include an extra time constant term, which we suspect is required to account for the uneven ventilation distribution produced by MCh. Airway impedance before MCh administration was well described by a simple resistance-inertance model, but a model incorporating serial inhomogeneity of ventilation was again required after MCh. Our results support those of previous studies indicating that the impedance of the normal dog lung is well described by a homogeneously ventilated viscoelastic tissue model. In contrast, our results after MCh administration show strong evidence of marked regional ventilation inhomogeneity in addition to the rheological properties of the tissues.

Airway Resistance↗
PubMed1993

Mass screening for prostate cancer and the bias relating to survival rate.

Since 1981 we have been studying prostate cancer (Pca) by mass screening (MS) in the Gunma Prefecture, Japan. From 1981 to 1990, 9,067 subjects (total 15,451) were examined in connection with this project and 121 subjects were diagnosed as having Pca. The presence of Pca in 87 cases was confirmed at their initial MS (initial group); 34 cases were confirmed either the year after or several years after the first MS (repeat group). To evaluate the significance of MS for Pca, in this group of patients, the effects of 'lead time bias', 'self-selection bias' and 'length bias' on the survival rate were compared to Pca patients detected in the hospitals of the Gunma Prefecture during the same period. The survival curves of MS cases for each stage of the disease were better than those of the controls. Only in stage D was there a significant difference between the two groups. However, this MS curve decreased from the 4th year in the same manner as the control curve from the start. The clinical characteristics (age, pathological differentiation, prostatic acid phosphatase, gait disturbance, erythrocyte sedimentation rate, chronic disease, and pain in the patients with stage D disease) were compared between both groups. All characteristics studied, except age, in the MS group were clinically more favorable compared to those of the controls for each stage or in total. Moreover, the relative survival rate of subjects examined by MS was greater than 1.0. No significant difference was found in stage distribution between the initial group and the repeat group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗
PubMed1993

Structures of mefenamic acid metabolites from human urine.

Three major metabolites of mefenamic acid were isolated from the urine of a normal adult man receiving mefenamic acid orally. The structures of those metabolites were determined as glucuronides of mefenamic acid, its hydroxymethyl derivative, and its carboxylic acid derivative on the basis of spectral data.

Adult↗
PubMed1993

[Pharmaceutical characterization of silicone elastomer implant system containing chlormadinone acetate for prevention of estrus in bitches].

We developed a new subdermal silicone elastomer implants containing chlormadinone acetate (CMA), which was effective for prevention of estrus in bitches. The implants gave a continuous CMA release over a year. The CMA release from the implants was dependent on the CMA loading level and surface area of the implants. The CMA release patterns both in vitro and in vivo system fitted well with the Higuchi square root low. The dissolution test using organic solvents was found to be useful for the brief estimation of CMA release from the implants.

Animals↗