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Biomedical subjects

J Sato

Publications and source records attributed to J Sato.

At least 127 records · Page 7Linked to original sources
PubMed1999

[Recurrent pulmonary infarction associated with familial protein S deficiency type III].

A 38-year-old woman was admitted to our hospital because of recurrent chest pain and fever. Chest X-ray films and computed tomograms showed subpleural consolidation containing small cavity-like opacities. Open lung biopsy revealed non-infectious abscess and vessels with organizing thrombus. The patient was given a diagnosis of pulmonary infarction due to the existence of deep venous thrombosis. Coagulation studies demonstrated that she had decreased plasma protein S activity, whereas her free and total protein S antigen levels were normal. Because her mother and maternal uncle and aunt also demonstrated decreased protein S activity with normal plasma protein S antigen levels, the patient was considered to be affected by familial protein S deficiency type III.

Adult↗
PubMed1999

Host immune profiles and genotyping analysis of HIV-1 among Japanese hemophiliac patients.

We studied the immune profiles of 21 Japanese hemophiliac patients who had been infected with human immunodeficiency virus type 1 (HIV-1) by the blood preparations during the 1982-84 period, and carried out the genotyping of HIV-1 V3 region for uncultivated peripheral blood mononuclear cells (PBMC) from 8 patients. Ten years after infection, asymptomatic carrier (AC, 14 cases) yet outnumbered those in AIDS related complex (ARC, 4 cases) and AIDS (3 cases), and the CD4+ and CD8+ T-cell numbers were not correlated with clinical stages. Macrophage tropic sequences, as identified according to the known tropism determinants, appeared to be more frequent as the CD4+ T-cell numbers were higher. There was no correlation of the cell tropism with the disease stages, however. It might be due to HIV-1 of CD4+ T-cells being more productive. The mutation in the V3 region appears to differentially influence the escape from antibody attack and clinical stages, and the cell tropism may not be related to the cell immunity of the host.

Adolescent↗
PubMed1998

Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart.

This study investigated whether conditions known to alter the activity and phosphorylation state of the pyruvate dehydrogenase complex have specific effects on the levels of isoenzymes of pyruvate dehydrogenase kinase (PDK) in rat heart. Immunoblot analysis revealed a remarkable increase in the amount of PDK4 in the hearts of rats that had been starved or rendered diabetic with streptozotocin. Re-feeding of starved rats and insulin treatment of diabetic rats very effectively reversed the increase in PDK4 protein and restored PDK enzyme activity to levels of chow-fed control rats. Starvation and diabetes also markedly increased the abundance of PDK4 mRNA, and re-feeding and insulin treatment reduced levels of the message to that of controls. In contrast with the findings for PDK4, little or no changes in the amounts of PDK1 and PDK2 protein and the abundance of their messages occurred in response to starvation and diabetes. The observed shift in the relative abundance of PDK isoenzymes probably explains previous studies of the effects of starvation and diabetes on heart PDK activity. The results indicate that control of the amount of PDK4 is important in long-term regulation of the activity of the pyruvate dehydrogenase complex in rat heart.

Animals↗
PubMed1998

Nitric oxide relaxes bovine ciliary muscle contracted by carbachol through elevation of cyclic GMP.

It is generally accepted that nitric oxide relaxes vascular smooth muscles by activating guanylyl cyclase, which in turn increases cyclic 3':5' guanosine monophosphate level. Despite the physiological significance of nitric oxide, very few studies have attempted to characterize the mode of action of this mediator in ciliary muscles. Therefore, the present experiments were designed to investigate whether or not the relaxation induced by sodium nitroprusside as a donor of nitric oxide is accompanied by the increase in cyclic 3':5' guanosine monophosphate level in the bovine ciliary muscle, and these responses are affected by methylene blue as an inhibitor of guanylyl cyclase and 3-isobutyl-1-methylxanthine as an inhibitor of phosphodiesterases. The relaxation activity of exogenous 8-bromo-cyclic 3':5' guanosine monophosphate was also determined. Sodium nitroprusside produced a concentration-dependent relaxation in the bovine ciliary muscle strips which had been contracted by carbachol as a cholinergic agonist. Relaxation in response to sodium nitroprusside was accompanied by a significant (P<0.05 and P<0.005) increase in cyclic 3':5' guanosine monophosphate level. The relaxation response and the increase in cyclic 3':5' guanosine monophosphate caused by sodium nitroprusside were significantly (P<0.01 and P<0.05) augmented by the pretreatment with 3-isobutyl-1-methylxanthine, and were significantly (P<0.005 and P<0.05) attenuated in the presence of methylene blue. The exogenously applied 8-bromo-cyclic 3':5' guanosine monophosphate relaxed the ciliary muscle strips in a concentration-dependent manner. These results suggest that nitric oxide causes relaxation of the bovine ciliary muscle through the activation of guanylyl cyclase and an increase in cyclic 3':5' guanosine monophosphate level.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Loss of water from the stratum corneum induces epidermal DNA synthesis in hairless mice.

Many clinical studies have shown that low humidity has a deleterious effect on skin, but the mechanisms involved are poorly understood. To clarify the changes that occur in skin, we examined epidermal cell proliferation in mice kept in a dry (relative humidity < 10%) or a moist (relative humidity > 90%) environment. In animals exposed to low humidity, epidermal DNA synthesis started to increase within 12 h, reaching twice the original level, and the increased level was maintained for up to 5 days. The transepidermal water loss (TEWL) of mice kept for 12 h in the dry environment was the same as that of mice kept in the moist environment, but the skin conductance was lower. The increase in epidermal DNA synthesis following exposure to the dry environment was inhibited by topical application of petrolatum. It is concluded that loss of water from the stratum corneum induces epidermal cell proliferation within 12 h, and this change occurs in the absence of apparent cutaneous barrier dysfunction.

Animals↗
PubMed1998

Solitary fibrous tumor of the parotid gland extending to the parapharyngeal space.

Solitary fibrous tumors (SFT) arise in the pleura and less commonly in extrapleural sites. Head and neck regions have included the nose and paranasal sinuses, soft palate, epiglottis, thyroid, parotid and submandibular glands, as well as the infratemporal fossa and parapharyngeal space. We report a case of SFT arising from the parotid gland and extending to the parapharyngeal space. To our knowledge, this is the fourth case of SFT originating from the parotid gland and is the largest of its kind among the extrapleural lesions described. The characteristics revealed by computed tomography and magnetic resonance imaging are presented.

Fibroma↗
PubMed1998

Dry condition affects desquamation of stratum corneum in vivo.

We examined whether a dry condition actually induces scaly skin in vivo. Hairless mice were kept in a high humidity condition or a low humidity condition and skin changes were examined. Scales appeared on the backs of mice kept for 3 days under the dry condition. The weight of stratum corneum (SC) was increased at this point, and these alterations were not accompanied with hyperproliferation of the nucleated cell layer of the epidermis. A decrease of desmosomal degradation was observed, though, desquamation-related enzyme activity was not altered. The regulation mechanism of desquamation is not yet clear, however, in vitro experiments suggest that the water content in SC is an important factor. The water content of SC was decreased in the dry condition. These results indicate that a dry environment perturbs desmosome degradation in intact SC by decreasing the water content of SC, and the consequent impairment of desquamation in normal skin in vivo may lead to the induction of a scaly skin surface.

Animals↗
PubMed1998

Endogenous asymmetrical dimethylarginine and hypertension associated with puromycin nephrosis in the rat.

1. The present experiments were designed to investigate the role of asymmetrical NG,NG-dimethyl-L-arginine (ADMA) in causing hypertension associated with the focal and segmental glomerulosclerosis (FSGS) produced by a single bolus of puromycin aminonucleoside (PAN) and successive injection of protamine for 7 days in rats which had undergone unilateral nephrectomy. 2. After the unilateral nephrectomy, and administering PAN and protamine, histological examinations of the kidney revealed a typical FSGS, that is, evident abnormalities including segmental mesangial proliferation, obliteration of glomerular capillary lumens and adhesions between the glomerulus and Bowman's capsule could be observed. Changes in the glomerular epithelial cells consisted of the swelling with bleb formation. 3. In the FSGS rats, urine volume and urinary protein were significantly (P<0.05 and P<0.005) increased throughout 4-week experimental period, while the creatinine clearance was significantly (P<0.005) and transiently decreased, and recovered 4 weeks later. These changes were associated with the sustained elevation of the systolic blood pressure. 4. ADMA levels in aortic endothelial cells, plasma and urine were significantly (P<0.05 and P<0.005) increased in the FSGS rats, but the level in the kidney remained unchanged. 5. The basal level and net production of cyclic GMP in the aortic vessel wall with endothelium when stimulated by norepinephrine and acetylcholine were significantly (P<0.05 and P<0.01) attenuated in the FSGS rats. 6. There were significant and positive correlations between systolic blood pressure (y) and ADMA levels (x) in endothelial cells (y=4.43x+122.2, r=0.979, P<0.0001), plasma (y=0.10x+71.9, r=0.921, P<0.001) and urine (y=0.48x+126.9, r =0.699, P<0.005), but not significant in the kidney (y=0.06x+102.7, r=0.252, NS). 7. These findings suggest that ADMA as an endogenous inhibitor of NO synthesis may play an important role for the pathogenesis in the hypertension associated with the experimental FSGS in the rat.

Animals↗
PubMed1998

New consecutive high-dose chemotherapy modality with fractionated blood stem cell support in the treatment of high-risk pediatric solid tumors: a feasibility study.

For the treatment of childhood solid tumors, we performed a pilot feasibility study of consecutive high-dose therapies, in which each course was followed by transplantation with granulocyte colony-stimulating factor-mobilized peripheral blood cells which had been separated into CD34-positive and -negative fractions by an Isolex system (Baxter). Positive selection of CD34+ cells has been associated with inevitable cell loss. To overcome this loss, CD34+ cells that had migrated into the negative fraction were saved and used for the first transplant, which was followed by a second transplant after a 3- to 5-month interval. In this phase I feasibility study, the results in six children were evaluated for safety and engraftment. Multi-drug cytoreductive regimens using ranimustine (MCNU), melphalan, thiotepa, carboplatin, cyclophosphamide or VP-16 were comparable between the two transplant procedures in terms of their intensity. The number of CD34+ cells in the 'CD34(+) fraction' was 3.31 x 10(6)/kg (0.63-4.3 x 10(6)/kg), while this number in the 'CD34(-) fraction' could not be evaluated correctly due their scarcity (<0.1%). The median numbers of infused MNC and CFU-GM were, respectively, 4.2 x 10(6)/kg and 1.75 x 10(5)/kg in the CD34(+) fraction, and 4.8 x 10(8)/kg and 3.35 x 10(5)/kg in the CD34(-) fraction. The number of days required to achieve an ANC >0.5 x 10(9)/l and a platelet count >20 x 10(9)/l and >50 x 10(9)/l were, respectively, 14.5, 15.0 and 19.5 in the first transplant with CD34- cells, and 13.5, 18.0 and 25.0 in the second transplant with CD34+ cells, with no essential difference between the two treatments. Although the small number of patients, the variation in clinical status and treatment, and the short follow-up invalidate any evaluation of the therapeutic benefit of this strategy, the encouraging results support the feasibility of this strategy, which enables an escalation of dose intensity with an improved cost/benefit ratio.

Adolescent↗
PubMed1998

Clinically applicable bulk isolation of blood CD34+ cells for autografting in children.

CD34+ cells were purified in bulk from apheresis-collected cells of children with cancer using monoclonal antibody (MoAb) and magnetic beads (Baxter ISOLEX system). To improve the purity of the final product for possibly better tumor cell purging and to make the manufacturer's original procedure more cost-effective, we incubated the cells for 30 min with l-phenylalanine methylester hydrochloride (PME) to reduce the cell number by removing contaminating granulocytes and monocytes in the initial step before incubation with MoAb. Our modification prevented nonspecific interactions between MoAb and magnetic beads, and thereby saved expensive materials for purification. A total of 40 purifications were performed with samples containing a mean of 3.1 x 10(9) blood cells mobilized from 15 children by chemotherapy plus granulocyte colony-stimulating factor (G-CSF). The entire purification procedure, from the end of apheresis to storage, was completed within 5h. After incubation with PME and double-layered (40/60%) Percoll separation, the number of CD34+ cells was reduced to 48+/-29%, which suggests the possibility that half of the CD34+ cells in the inoculum were nonclonogenic in the hematopoietic progenitor assay. PME/Percoll-treated cells were then subjected to a final isolation procedure with MoAb according to the manufacturer's suggestions, and 52+/-42% and 32+/-22%, respectively, of the CFU-GM and CD34+ cells present in the initial bag inoculums were recovered. The recovery rates were, respectively, 54% and 67%, when the calculation was limited to the isolation procedure with MNoAb. The purity of isolated CD34+ cells and the plating efficiency in methylcellulose culture were, respectively, 77+/-24% and 33+/-13%. Fourteen children were subsequently autografted with purified CD34+ cells after marrow ablative chemotherapy. The median number of days to achieve an ANC of 0.5 x 10(9)/l was 12 and that to achieve a platelet count of 50 x 10(9)/l was 22.5, which were comparable to those in our historical group of 55 patients who underwent transplant with unmanipulated blood cells (13 and 16 days). These results suggest that our modified purification procedure with PME is useful for the initial reduction of cell numbers to save costly materials, and that cells isolated by this procedure can be directly used in clinical transplantation procedures.

Adolescent↗
PubMed1998

Evidence of idiotypic modulation in the immune response to gp43, the major antigenic component of Paracoccidioides brasiliensis in both mice and humans.

Paracoccidioidomycosis (PCM) is a systemic mycosis endemic in Latin America, with a high prevalence in Brazil, Argentina, Colombia and Venezuela. The aetiologic agent of disease is a thermal dimorphic fungus, Paracoccidioides brasiliensis. A glycoprotein of 43,000 D (gp43) is the major antigen of P. brasiliensis. Antibodies directed to this antigen are detected in the sera of all patients with PCM. Gp43 binds to laminin, thus participating in adhesion, invasion and pathogenesis of the fungus. As the role of antibodies in PCM is not fully understood, we decided to investigate the outcome of mice immunization with three distinct anti-gp43 MoAbs (17c, 8a and 24a) coupled with keyhole limpet haemocyanin (KLH). Results show not only the expected presence of anti-Id (AB2) antibodies in the sera of these animals but also a spontaneous and increasing amount of anti-anti-Id (AB3) antibodies after the third course of immunization. Hybridomas producing both AB2 and AB3 MoAbs were obtained using spleen cells from mice immunized with MoAb 17c. AB3 MoAbs were also obtained with spleen cells of mice immunized with MoAbs 8a and 24a. It was also shown that human PCM patients' sera with high titres of anti-gp43 antibodies generate anti-Id antibodies. These data suggest that the immune response to P. brasiliensis can be spontaneously modulated by the idiotypic network.

Animals↗
PubMed1998

Cholesterol sulfate inhibits proteases that are involved in desquamation of stratum corneum.

We previously reported that desmosomes play a key role in the adhesion of corneocytes, and their digestion by two types of serine proteases leads to desquamation. Patients with recessive X-linked ichthyosis show hyperkeratosis attributable to desmosomes, associated with an increased content of cholesterol sulfate (CS) and an increased thickness of stratum corneum. In this study, therefore, we examined the possibility that CS provokes the abnormal desquamation, acting as a protease inhibitor. Scaling was induced on mice after topical application of chymostatin and leupeptin. Visible scale was also observed on mice after topical application of CS. We found that the stratum corneum thickness of CS-treated mice was increased in comparison with that of vehicle-treated mice. The thickness of the epidermis and the labeling index with proliferating cell nuclear antigen from CS-treated mice was almost the same as that from vehicle-treated mice. Moreover, in the stratum corneum of CS-treated mice, the content of desmosomes was higher than that in vehicle-treated mice. CS also inhibited the protease-induced cell dissociation of human stratum corneum sheets. In vitro, CS competitively inhibited both types of serine protease: the Ki for trypsin was 5.5 x 10(-6) M and that for chymotrypsin was 2.1 x 10(-6) M. These results indicate that CS retards desquamation by acting as a protease inhibitor. Thus, accumulation of stratum corneum in recessive X-linked ichthyosis may be a result of the inhibition by excessive CS of proteases involved in the dissolution of desmosomes, required for desquamation of the stratum corneum.

Animals↗
PubMed1998

Exposure to a dry environment enhances epidermal permeability barrier function.

Previous studies have suggested that transepidermal water movement may play an important role in epidermal homeostasis and barrier repair. Here we analyzed cutaneous barrier function, epidermal morphology, and lipid content of the stratum corneum in hairless mice maintained in a high relative humidity (RH > 80%) versus low humidity (RH < 10%) environment for 2 wk. Basal transepidermal water loss was reduced by 31% in animals maintained in a dry versus humid environment. Moreover, the number of lamellar bodies in stratum granulosum cells, the extent of lamellar body exocytosis, and the number of layers of stratum corneum increased in animals kept in a dry environment. Furthermore, the dry weight of the stratum corneum and the thickness of the epidermis also increased in a dry environment. In addition, total stratum corneum lipids increased but lipid analysis revealed no significant differences in lipid distribution. Lastly, barrier recovery following either acetone treatment or tape stripping was accelerated after prolonged prior exposure to a dry environment, while conversely, it was delayed by prior exposure to a humid environment. These studies demonstrate that environmental conditions markedly influence epidermal structure and function, and suggest mechanisms by which the environment could induce or exacerbate various cutaneous disorders.

Animals↗
PubMed1998

Low humidity stimulates epidermal DNA synthesis and amplifies the hyperproliferative response to barrier disruption: implication for seasonal exacerbations of inflammatory dermatoses.

Although seasonal changes in humidity are thought to exacerbate various skin diseases, whether these flares can be attributed to prolonged exposure to extremes in environmental humidities has not been studied systematically. We recently showed that prolonged exposure to high versus low humidities induced profound changes in epidermal structure and permeability barrier homeostasis. Therefore, we asked here whether comparable extremes in humidity could initiate not only homeostatic, but also potentially pathophysiologic alterations. We showed first that exposure to low humidity increases epidermal DNA synthesis in normal murine epidermis. Moreover, exposure to a low humidity for 48 h further amplifies the DNA synthetic response to barrier disruption, resulting in marked epidermal hyperplasia. Additionally, exposure to a dry environment for 48 h prior to barrier disruption results in dermal mast cell hypertrophy, degranulation, as well as histologic evidence of inflammation. To demonstrate the role of changes in external moisture on these phenomena, we applied either an occlusive, water-impermeable plastic membrane, Petrolatum, or a nonocclusive humectant, both to nonperturbated and to perturbed skin. All three forms of treatment prevented the epidermal hyperplasia and dermal mast cell hypertrophy and degranulation induced by exposure to low humidity. These studies indicate that (i) exposure to changes in environmental humidity alone induces increased keratinocyte proliferation and markers of inflammation, and (ii) that these changes are attributable to changes in stratum corneum moisture content. Finally, these studies provide evidence that changes in environmental humidity contribute to the seasonal exacerbations/amelioration of cutaneous disorders, such as atopic dermatitis and psoriasis, diseases which are characterized by a defective barrier, epidermal hyperplasia, and inflammation.

Acetone↗
PubMed1998

Recessive x-linked ichthyosis: role of cholesterol-sulfate accumulation in the barrier abnormality.

Cholesterol sulfate is a multifunctional sterol metabolite, produced in large amounts in squamous keratinizing epithelia. Because patients with recessive x-linked ichthyosis display not only a 10-fold increase in cholesterol sulfate, but also a 50% reduction in cholesterol, we assessed here whether cholesterol sulfate accumulation and/or cholesterol deficiency produce abnormal barrier function in recessive x-linked ichthyosis. Patients with recessive x-linked ichthyosis display both an abnormal barrier under basal conditions, and a delay in barrier recovery after acute perturbation, which correlate with minor abnormalities in membrane structure and extensive lamellar-phase separation. Moreover, both the functional and the structural abnormalities were corrected by topical cholesterol. Yet, topical cholesterol sulfate produced both a barrier abnormality in intact skin and extracellular abnormalities in isolated stratum corneum, effects largely reversed by coapplications of cholesterol. Together, these results suggest that cholesterol sulfate accumulation rather than cholesterol deficiency is responsible for the barrier abnormality. Despite the apparent importance of cholesterol sulfate-to-cholesterol processing for normal barrier homeostasis, neither steroid sulfatase activity nor mRNA levels are upregulated following acute perturbations. These results demonstrate both a potential role for cholesterol sulfate-to-cholesterol processing in normal permeability barrier homeostasis, and that basal levels of steroid sulfatase are sufficient to accommodate acute insults to the permeability barrier.

Administration, Topical↗
PubMed1998

Genetic instability and chromosomal aberrations in colorectal cancer: a review of the current models.

Our understanding of the pathogenesis of cancer has undergone a revolution over the past decade. Tumors develop by the accumulation of damage to genes that regulate cell growth. Many of the genes responsible for disregulation of cell growth have been identified, as have the processes that lead to the genetic damage. One of the most important concepts that has facilitated our understanding of carcinogenesis is that of genetic or "genomic" instability, which is required to permit a sufficient amount of genetic damage to accumulate to permit the neoplastic phenotype to emerge and evolve. Two mechanisms that lead to genomic instability--one of which involves the loss of chromosomal fragments from the nucleus, and a second which is characterized by microsatellite instability--are discussed.

Chromosome Aberrations↗
PubMed1998

Intra-apheresis recruitment of blood progenitor cells in children.

BACKGROUND: Determination of the optimal duration of apheresis requires a careful examination of blood progenitor cell (BPC) kinetics during apheresis. Intra-apheresis recruitment of BPCs should be evaluated. STUDY DESIGN AND METHODS: Twenty-six apheresis procedures were performed in 13 children with various malignant disorders (ages, 10 months to 17 years; median, 7 years) to collect BPCs for autologous transplant, using a blood cell separator with 2 to 5.2 blood volumes processed. The subjects were divided into three groups according to age: below 1 year (n = 4), 2 to 10 years (n = 5), and 11 to 20 years (n = 4). BPCs were mobilized by a combination of chemotherapy and granulocyte-colony-stimulating factor (G-CSF; 2-7.5 micrograms/kg/day intravenous drip). The levels of circulating CD34+ cells and colony-forming units-granulocyte-macrophage (CFU-GM) were monitored to examine intra-apheresis recruitment. For every 50 mL per kg or 2 L of processed blood, 5-mL blood samples were collected via a central line. RESULTS: In the first apheresis procedure, more CD34+ cells were mobilized by the procedure itself in the infant group than in the older groups, and the number of cells decreased with the subject's age. When the same analysis was made during the second apheresis procedure, performed 1 day later, the levels of both CD34+ cells and CFU-GM had decreased to below the preapheresis values in all of the populations. Cell yields in the second apheresis procedure were significantly lower than those in the first. CONCLUSION: Although several factors prevent a reliable analysis, the data suggest that the intra-apheresis recruitment of BPCs may be age-specific; the continuous and prolonged supply of cells from the bone marrow to peripheral blood that occurs during apheresis is more predominant in infants, which leads to the collection of proportionately more BPCs in younger children than in their older counterparts.

Adolescent↗