Biomedical subjects

S Minami

Publications and source records attributed to S Minami.

At least 127 records · Page 7Linked to original sources

PubMed1997

Effects of chitin and chitosan particles on BALB/c mice by oral and parenteral administration.

Chitin and chitosan were administered orally and parenterally into mice and their toxicity was investigated. When 5 mg of chitin were injected intraperitoneally every 2 weeks over a 12-week period, the mice were apparently normal, but histologically, many macrophages with hyperplasia were observed in the mesenterium and foreign-body giant-cell-type polykaryocytes were observed in the spleen. The polykaryocytes were also observed in the spleen of the mice injected subcutaneously with 5 mg of chitin, but no other changes were observed. When 5 mg of chitosan were injected intraperitoneally, the body weights of the mice decreased significantly and inactivity was observed in the fifth week. Histologically, many macrophages with hyperplasia were observed in the mesenterium. Subcutaneous injection of 5 mg of chitosan did not evoke the general and cellular abnormalities. Oral administration of 5% chitosan via a casein diet caused mouse body weights to decrease and also decreased the number of Bifidobacterium and Lactobacillus in normal flora of the intestinal tract. These results indicate that special care should be taken in the clinical use of chitin and chitosan over a long time period.

Administration, Oral↗

PubMed1997

Effects of chitin and its derivatives on the proliferation and cytokine production of fibroblasts in vitro.

The effects of chitin and its derivatives on the proliferation of fibroblasts and on the production of cytokines were examined in vitro. Chitin and its derivatives showed almost no acceleratory effect on the proliferation of cultured fibroblasts. On the contrary, high-concentration 500 micrograms ml-1) D-glucosamine cultures supplemented with or without a 10% fetal calf serum (FCS) supplementation showed a significant (P < 0.05) reduction in the rate of proliferation of L929 fibroblast cells relative to control. High-concentration chitosan cultures supplemented with 10% FCS showed a significant (P < 0.05) reduction in the rate of L929 fibroblast proliferation. However, the inhibition of cell proliferation by high concentrations of chitosan did not show in cultures without FCS. Interleukin-8 (IL-8) was induced in the supernatants of rat primary cultured dermal fibroblasts stimulated with chitin and its derivatives. Chitin and its derivatives did not stimulate the production of IL-6 by mouse dermal primary cultured fibroblasts. IL-1 alpha, IL-1 beta and tumour necrosis factor-alpha were not detected in the fibroblast supernatants. These observations support the notion that cell proliferation is accelerated indirectly by chitin and its derivatives when these materials are used in vivo. In vivo findings of a angiogenesis and migration of neutrophils may be due to persistent release of IL-8 from fibroblasts.

Animals↗

PubMed1997

Unrelated bone marrow transplantation from the National Marrow Donor Program.

Between November 1992 and December 1996, we carried out bone marrow transplantation through the National Marrow Donor Program (NMDP) for 11 patients who lacked an appropriate donor among their family members and the Japan Marrow Donor Program (JMDP). They accounted for 11% of 101 patients who had registrated to the NMDP Transplant Center Office in Japan. The median time required from the initiation of preliminary search to transplant for these 11 patients was 198 days. The 11 donors included four Caucasians, one Native American and the others were Asian/Pacific islanders. A median of 17 h was required to transport bone marrow from harvest institutes to our hospital and their viability determined in our laboratory had a median of 96%. Engraftment was observed in all recipients and the incidence of grade III-IV acute graft-versus host disease was 27%. Of four patients three (75%) with chronic myelogenous leukemia in chronic phase (standard-risk) and two (29%) of seven patients in progressive state of the disease (high-risk), are alive at present. Cooperation between the JMDP and the NMDP, which began in April 1997, could shorten the time for donor search and allow transplantation to more patients with more appropriate timing.

Adolescent↗

PubMed1997

Prolonged selective neutropenia after allogeneic bone marrow transplantation: possible effect of presensitization by donor lymphocytes prior to transplant.

Selective neutropenia lasting over five months occurred in a 17-year-old adolescent male who received an allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling for severe aplastic anemia. Bone marrow specimens showed maturation arrest of myeloid precursor cells despite sustained engraftment. Cytogenetic analyses revealed complete donor-type chimerism in hematopoietic cells and mixed lymphoid chimerism. The patient received a second BMT from the same donor following more intensive conditioning, including total body irradiation. Neutrophil recovery was rapid and complete donor-type hematopoietic and lymphoid chimerism was observed within three weeks of the second transplant. The present case suggests that prolonged selective neutropenia following BMT is due to residual host-derived immunity which is resistant to the standard immunosuppressive conditioning used prior to BMT for aplastic anemia.

Adolescent↗

PubMed1997

Hepatic injury localized to the field of total lymphoid irradiation.

A 37-year-old woman with severe aplastic anemia underwent allogeneic bone marrow transplantation following cyclophosphamide (CY) and total lymphoid irradiation (TLI). On day +30, a CT scan was carried out because of a mild elevation in liver enzymes, and it revealed a low density area with a sharp border in the left lobe corresponding to the irradiated area. MRI showed a hypersignal intensity on both T1 and T2-weighted images and suggested that hepatic damage was mainly severe fatty change. These abnormalities resolved with no treatment. CY with TLI for adult patients with severe aplastic anemia may induce hepatic injury.

Adult↗

PubMed1997

Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia. Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho).

FLT3 is a member of receptor tyrosine kinases expressed in leukemia cells, as well as in hematopoietic stem cells. Recently, a somatic alteration of the FLT3 gene was found in acute myeloid leukemia, as an internal tandem duplication (FLT3/ITD) which caused elongation of the juxtamembrane (JM) domain of FLT3. Here we characterized the FLT3/ITD and investigated its clinical significance in acute promyelocytic leukemia (APL). Seventy-four newly diagnosed patients with APL, who were treated with the same protocol in a multi-institutional study, were studied for the FLT3/ITD. Genomic and message sequences of the FLT3 gene were amplified by means of polymerase chain reaction (PCR), and elongated PCR products were sequenced. Fifteen patients (20.3%) had FLT3/ITD, all of which were transcribed in frame. Location of the duplicated fragments (six to 30 amino acids) varied from patient to patient. However, they always contained either Y591 or Y599, but the tyrosine kinase domain was not significantly affected. This finding implied that signal transduction of FLT3 is amplified by the duplication. Clinically, the presence of FLT3/ITD was related to high peripheral white blood cell counts as well as peripheral leukemia cell counts (P < 0.0001), high LDH level (P = 0.04), and low fibrinogen concentration (P = 0.04). These data suggest that FLT3/ITD plays a significant role in progression of APL.

Adult↗

PubMed1997

Antibacterial activity of T-5575, a novel 2-carboxypenam, and its stability to beta-lactamase.

The in-vitro activity of T-5575, 2-carboxypenam, a new parenteral antibiotic and its stability to beta-lactamases were compared with those of ceftazidime and imipenem. The activity of T-5575 was equal or superior to that of ceftazidime or imipenem against Gram-negative bacteria that produced penicillinase with the exception of the enzyme OXA-1. Against strains that produced Cephalosporinase and zinc-dependent beta-lactamase, the activity of T-5575 was superior to that of ceftazidime or imipenem. T-5575 was a poor substrate and had low affinity for beta-lactamases produced by Citrobacter freundii, Enterobacter cloacae and Pseudomonas aeruginosa. The activity of T-5575 was less influenced by the derepressed production of chromosomal enzymes than that of ceftazidime. Overall, T-5575 had excellent activity against Gram-negative pathogens that produced various types of beta-lactamases.

Anti-Bacterial Agents↗

PubMed1997

Characteristics of quinolone-induced small colony variants in Staphylococcus aureus.

Exposure of Staphylococcus aureus to 1 x MIC of the quinolone antibiotic pazufloxacin for 24 h, followed by plating on drug-free media, led to the emergence of small colony variants (SCVs) in addition to large colony variants (LCVs). However, following incubation with 0.25 or 4 x MIC of pazufloxacin, only LCVs were obtained. The SCVs were half as susceptible to pazufloxacin or ciprofloxacin as wild-type S. aureus, while the susceptibilities of LCVs were essentially unchanged. The reduced susceptibilities of SCVs did not result from mutations in the quinolone-resistance-determining regions of DNA gyrase and topoisomerase IV, since the sequences of these genes were identical to those of the wild-type. However, the SCVs accumulated pazufloxacin and ciprofloxacin to a lesser degree than did wild-type. Furthermore, their susceptibility to quinolones was almost unaffected by reserpine or verapamil, suggesting that the reduced uptake resulted from decreased permeability, rather than from an active efflux pump. The ability of various quinolones to induce emergence of SCVs in S. aureus, correlated with the presence of carbon-bonded substituents at the C-7 position of a quinoline or naphthyridine nucleus, or with the presence of a benzoxazine nucleus. In conclusion, pazufloxacin-induced SCVs represent a mutant that one might expect to be rapidly eliminated in vivo and, hence, not to survive as a quinolone-resistant pathogen. This finding suggests a novel approach for development of future quinolones.

Animals↗

PubMed1997

Application of muscle microdialysis to evaluate the concentrations of the fluoroquinolones pazufloxacin and ofloxacin in the tissue interstitial fluids of rats.

Muscle microdialysis has been used to determine the unbound concentrations of the fluoroquinolones, pazufloxacin and ofloxacin, in tissue interstitial fluids (Cisf,u) of rats under steady state conditions. Cisf,u was estimated from the concentration in dialysate and the in-vitro permeability rate constant by the extrapolation method based on the clearance concept. Paper-disks were inserted under the abdominal skin of rats, and the drug concentrations in the fluids penetrating into the disks (Cdisk) were measured and compared with Cisf,u. The Cisf,u of pazufloxacin and ofloxacin in muscle were close to their unbound concentrations in the venous plasma; these were 75.3% and 77.1%, respectively, of the total concentrations in plasma at the steady state. The Cdisk of pazufloxacin and ofloxacin were also close to their Cisf,u. These results indicate that the unbound concentrations of the fluoroquinolones in the tissue interstitial fluids were the same as those in the venous plasma. The disk insertion technique seems to be useful for evaluating drug concentrations in tissue interstitial fluid.

Animals↗

PubMed1997

Quinolone susceptibility of norA-disrupted Staphylococcus aureus.

The MIC of norfloxacin for the norA-disrupted mutant termed RDN1, obtained from quinolone-susceptible Staphylococcus aureus RN4220, was eightfold lower than that for RN4220. The increase in susceptibility was related to an increase of drug accumulation by RDN1. These results indicate that NorA plays an important role in the susceptibility of quinolone-susceptible S. aureus to selected quinolones.

4-Quinolones↗

PubMed1997

Preantral ovarian follicles in serum-free culture: suppression of apoptosis after activation of the cyclic guanosine 3',5'-monophosphate pathway and stimulation of growth and differentiation by follicle-stimulating hormone.

Progression of preantral follicle development is essential to further follicle maturation and ovulation, but there are few models for studying the regulation of preantral follicle survival and growth. We have evaluated preantral follicle survival in vivo and in vitro, and have developed a serum-free rat follicle culture system that can be used to characterize the regulation of preantral follicle growth and differentiation. Analysis of ovarian cell DNA fragmentation during the first wave of follicle growth in the infantile rat indicated negligible apoptosis up to day 16 of age. However, a major increase in apoptosis was found by day 18, a time point associated with the appearance of large antral follicles. In situ analysis confirmed that apoptotic DNA fragments were limited to antral follicles. Culture of individual preantral follicles mechanically dissected from ovaries of 12- or 14-day-old rats in serum-free conditions led to major increases in follicle cell apoptosis, similar to that seen in cultures of antral and preovulatory follicles. In contrast to antral and preovulatory follicles, treatment of preantral follicles with gonadotropins or cAMP analogs did not prevent apoptosis. However, treatment with 8-bromo-cGMP or 10% serum suppressed apoptosis by 75% in cultured preantral follicles. In situ analysis identified granulosa cells as the cell type susceptible to apoptosis regulation. Taking advantage of the ability of the cGMP analog to suppress apoptosis, we evaluated the potential of FSH as a growth factor. In the absence of serum, FSH treatment for 48 h did not affect follicle size compared to controls; however, treatment with the cGMP analog together with FSH increased follicle diameter (13%; P < 0.01) and viable cells (2.4-fold; P < 0.01) compared to control values. Immunoblot analysis further indicated that the inhibin-alpha content of the cultured follicles was increased by treatment with the combination of FSH and 8-bromo-cGMP, demonstrating the induction of follicle cell differentiation during culture. Therefore, we demonstrated that activation of the cGMP pathway promotes the survival of cultured preantral follicles and that in the presence of alpha cGMP analog, FSH is a growth and differentiation factor for preantral follicles. The present serum-free follicle culture model system will be useful in further evaluation of the regulation of growth and differentiation of preantral follicles.

Aging↗

PubMed1997

A case of rest angina due to microvascular spasm.

A 66-year-old woman underwent elective cardiac catheterization for investigation of periodic attacks of chest pain at rest. During the examination, a chest pain attack occurred unexpectedly, resulting in ST elevation in the precordial leads on electrocardiography. Immediate coronary arteriography demonstrated no organic stenosis but markedly delayed contrast medium perfusion in the mild to distal portion of the left anterior descending artery. These phenomena spontaneously disappeared about 3 min later, and the patient was diagnosed as having angina pectoris due to microvascular spasm. The demonstration of angina pectoris due to microvascular spasm by coronary arteriography during a spontaneous attack is very rare.

Aged↗

PubMed1997

Successful laparoscopy assisted ovariohysterectomy in two dogs with pyometra.

Two dogs with pyometra were treated by laparoscopy assisted ovariohysterectomy. Hemostasis of the mesovarium was achieved with an ultrasonic scalpel and hemoclips. Both ovaries and the uterus were exposed via a 10-mm caudal port that was enlarged to 3 cm and the uterine cervix was excised after ligation of the uterine arteries. These cases were the first report on ovariohysterectomy for pyometra by laparoscopy assisted surgery in the veterinary field.

Animals↗

PubMed1997

Microinjection of rat GH but not human IGF-I into a defined area of the hypothalamus inhibits endogenous GH secretion in rats.

It has been surmised that GH exerts feedback action on the hypothalamus and thereby regulates its own secretion. Our previous studies suggested that GH acts on somatostatin neurons in the hypothalamic periventricular nucleus (PeV) and neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC). However, there remains uncertainty whether GH acts directly or indirectly through the generation of IGFs on the hypothalamus to regulate its own secretion. To examine this, rat GH (rGH) or human IGF-I was injected directly into a defined area of the hypothalamus, and the blood GH profile was observed in conscious male rats. In the rats given 0.5 microgram rGH into the ARC or PeV bilaterally, GH secretion was inhibited, and the inhibition lasted for 12 h. During the period of inhibition, the duration and amplitude of GH pulses were significantly decreased and the episodic secretion of GH appeared irregularly compared with the vehicle-injected control rats. In control rats given the vehicle or those given rGH into the lateral hypothalamus, the blood GH profile did not change and pulsatile GH secretion was produced every 3 h. When 0.1 microgram IGF-I was injected into the ARC or PeV bilaterally, the blood GH secretory pattern was not affected. Together with the results of our previous studies showing that c-fos gene expression was induced by systemic administration of GH and that GH receptor mRNA was contained in somatostatin neurons in the PeV and NPY neurons in the ARC, the data of the present study indicate that GH, but not IGF-I, acts on the cells in the ARC and the PeV or in their vicinity to inhibit its own secretion, presumably by activating the somatostatin and NPY neurons.

Animals↗

PubMed1997

Cushing's syndrome due to bilateral adrenocortical adenomas with different pathological features.

A 48-year-old woman with Cushing's syndrome due to bilateral adrenocortical adenomas is reported. The patient presented with a typical Cushingoid appearance. The serum cortisol level was elevated with loss of the diurnal rhythm and the plasma adrenocorticotropic hormone (ACTH) level was undetectable. Dynamic testing showed no suppression of urinary 17-OHCS by high-dose dexamethasone and no stimulation by metyrapone. An abdominal computed tomography (CT) scan showed bilateral adrenal tumors. Bilateral adrenalectomy was performed. The right adrenal gland contained a tumor that was encapsulated and consisted mainly of compact cells. The surrounding cortex was atrophic. The left adrenal gland contained an encapsulated tumor composed predominantly of clear cells. There were numerous small adrenocortical nodules in the surrounding cortex. Immunohistochemical analysis of steroidogenic enzymes (P450scc, 3beta-HSD, P450c21, P450c17 and P450c11) was performed. Immunoreactivity of all the enzymes was intense in the compact cells of the right adrenocortical adenoma, while the adjacent non-neoplastic cortex was negative for the enzymes. In the left adrenal tumor, the immunoreactivity of 3beta-HSD was intense, while that of P450c17 was weak. In the adrenocortical nodules, 3beta-HSD activity was sporadically observed. G protein genes encoding Gs alpha and Gi2 were examined for activating mutations at codons 201 and 227 (Gs alpha) and codons 179 and 205 (Gi2 alpha) in the bilateral adrenal tumors, but no mutations were found. The bilateral adenomas of this patient showed marked differences in microscopic and immunohistochemical studies, suggesting that the capacity of steroidogenesis differs between the right and left tumors.

Adrenal Cortex Neoplasms↗

PubMed1997

[Relationship between carotid atherosclerosis and plasma endothelin-1 concentration in senile patients with hypertension].

The relationship between carotid atherosclerosis and plasma endothelin-1 (ET-1) concentration was studied in senile patients with essential hypertension. A total of 212 patients (83 M, 129 F; mean age, 63 years) with essential hypertension (WHO stage I-II), and 109 age-matched control subjects (mean age, 61 years) were enrolled in the study. The maximum thicknesses of the intima-media complex (IMTmax) in the right common carotid artery (CCA) and the right internal carotid artery (ICA) was measured by B-mode ultrasonography, and ET-1 was measured by enzyme immunoassay. ET-1 levels were significantly higher in the hypertensive patients than in the control subjects. In middle-aged patients (35-64 years old), IMTmax values of the ICA in patients with high ET-1 concentrations (ET-1 > or = 1.71 pg/ml) were significantly higher than in patients with normal ET-1 concentrations (ET-1 < 1.71 pg/ml). However, the IMTmax of the CCA did not show a similar correlation. In senile patients (65-83 years old), both the CCA and ICA IMTmax values were significantly higher in patients with high ET-1 concentrations than in those with normal ET-1 concentrations. These results indicate that high ET-1 levels in middle-aged patients with essential hypertension may play a role in the progression of ICA atherosclerosis. High ET-1 levels in senile patients with essential hypertension may cause progression of atherosclerosis in both the ICA and CCA.

Adult↗

PubMed1997

[Effects of atherogenic risk factors on asymptomatic brain infarct].

This study was done to clarify the relationship between asymptomatic brain infarcts and risk factors for atherogenis. A total of 312 patients (151 men and 161 women) who had no neurologic deficits were enrolled. Their ages ranged from 41 to 83 years (mean age 63 years). The patients were divided into two groups: 158 patients without asymptomatic brain infarct and 154 patients with at least one asymptomatic brain infarct of at least 5 mm as diagnosed by magnetic resonance imaging. The patients with asymptomatic brain infarct were more likely than those without asymptomatic brain infarct to be 65 years old or older, and to have essential hypertension, diabetes mellitus, or atrial fibrillation. Among patients with hypertension the frequency of left ventricular hypertrophy or hypertensive ocular findings (Scheie's class H2) was significantly higher in those with asymptomatic brain infarct than in those without asymptomatic brain infarct. These results indicate that aging, essential hypertension (especially with left ventricular hypertrophy or hypertensive ocular findings), diabetes mellitus, and atrial fibrillation are associated with asymptomatic brain infarct.

Adult↗

PubMed1997

[The relationship between brain atrophy and asymptomatic cerebral lesions].

In order to clarify the relationship between brain atrophy and asymptomatic cerebral lesions, total of 235 subjects (130 males and 105 females), who had neither neurologic deficits nor organic lesions on cerebral computed tomography, were studied. The subjects' ages ranged from 40 to 86 years (mean 66). They were divided into two groups: 90 controls without hypertension or diabetes mallitus (Group C), and 145 patients with essential hypertension (Group H). Brain atrophy was diagnosed using the caudate head index (CHI). Asymptomatic cerebral lesions on magnetic resonance imaging were defined as asymptomatic lacunae and white matter lesions. Caudate head index was higher in Group H than it was in Group C, and CHI in both groups was significantly correlated with the number of asymptomatic lacunae and the severity of white matter lesions on magnetic resonance imaging. These results indicate that brain atrophy may progress along with asymptomatic cerebral lesions.

Adult↗