Biomedical subjects

M Hosokawa

Publications and source records attributed to M Hosokawa.

At least 109 records · Page 6Linked to original sources

PubMed1999

Aminoguanidine has both an anti-inflammatory effect on experimental colitis and a proliferative effect on colonic mucosal cells.

BACKGROUND: The aim of this study was to assess the effect of aminoguanidine (AG) on developed colitis and cell proliferation. METHODS: Colitis was induced by means of trinitrobenzene sulphonic acid (TNB) in male Wistar rats weighing about 250 g. Seven days after induction of TNB colitis the rats were divided into two groups at random, and one group was orally treated with 1.5 micromol/kg AG each day. We assessed the effect of AG by measuring the mucosal damage, the ulcer area, myeloperoxidase (MPO) activity, inducible nitric oxide synthase (iNOs) activity, and nitrogen oxide in serum 7 days after the beginning of treatment. RESULTS: AG significantly ameliorated the macroscopic damage score (AG versus control, 5.25 +/- 0.80 versus 7.50 +/- 0.50), the microscopic damage score (5.88 +/- 1.13 versus 9.25 +/- 0.31), ulcer area (0.57 +/- 0.14 versus 1.24 +/- 0.17 cm2), decreased MPO activity (51.5 +/- 9.4 versus 192.2 +/- 60 units/g tissue), and nitrogen oxide in serum (27.2 +/- 1.4 versus 32.3 +/- 1.8 microM) but did not decrease iNOs activity (8732 +/- 435 versus 8672 +/- 357 cpm/g tissue). Moreover, AG accelerated T84 cell proliferation in a dose-dependent manner. CONCLUSIONS: These results suggest that AG ameliorates TNB colitis not only by its anti-inflammatory effect but also by accelerating the proliferation of colonic mucosal cells. AG, accordingly, might well be a useful new medicine to ameliorate inflammatory bowel disease.

Analysis of Variance↗

PubMed1999

Aminoguanidine supplementation delays the onset of senescence in vitro in dermal fibroblast-like cells from senescence-accelerated mice.

The effects of aminoguanidine supplementation on senescence acceleration in vitro were examined in fibroblasts from the dorsal dermis of newborn SAMP11 (accelerated senescence-prone mice), and were compared to the effects in cell lines from SAMR1 (accelerated senescence-resistant) mice. Four millimolar aminoguanidine supplementation significantly delayed the senescence/crisis in cell lines from SAMP11 mice, but did not affect the senescence/crisis in cell lines from SAMR1 mice. Flow cytometric analysis of the DNA content of confluent cells revealed that aminoguanidine supplementation significantly decelerated the increase in the number of tetraploid cells until senescence/crisis. Although mean concentrations of lipid peroxides in the primary cultures did not differ significantly, considerably higher lipid peroxidation was observed in some SAMP11 cultures, and aminoguanidine supplementation reduced them to the levels in SAMRI cultures. These results strongly suggest that oxidative stress derived from polyamine catabolism may contribute to the senescence acceleration in vitro in cell lines from SAMP11 mice.

Animals↗

PubMed1999

High-linoleate and high-alpha-linolenate diets affect learning ability and natural behavior in SAMR1 mice.

Semipurified diets incorporating either perilla oil [high in alpha-linolenate, 18:3(n-3)] or safflower oil [high in linoleate, 18:2(n-6)] were fed to senescence-resistant SAMR1 mouse dams and their pups. Male offspring at 15 mo were examined using behavioral tests. In the open field test, locomotor activity during a 5-min period was significantly higher in the safflower oil group than in the perilla oil group. Observations of the circadian rhythm (48 h) of spontaneous motor activity indicated that the safflower oil group was more active than the perilla oil group during the first and second dark periods. The total number of responses to positive and negative stimuli was higher in the safflower oil group than in the perilla oil group in the light and dark discrimination learning test, but the correct response ratio was lower in the safflower oil group. The difference in the (n-6)/(n-3) ratios of the diets reflected the proportions of (n-6) polyunsaturated fatty acids, rather than those of (n-3) polyunsaturated fatty acids in the brain total fatty acids, and in the proportions of (n-6) and (n-3) polyunsaturated fatty acids in the total polyunsaturated fatty acids of the brain phospholipids. These results suggest that in SAMR1 mice, the dietary alpha-linolenate/linoleate balance affects the (n-6)/(n-3) ratio of brain phospholipids, and this may modify emotional reactivity and learning ability.

Aging↗

PubMed1999

Inhibitory effect of ND2001 on spontaneous multiple metastasis of NC 65 tumors derived from human renal cancer cells intradermally transplanted into nude mice.

The NC 65 tumor cell line derived from human renal cell carcinoma was selected from among nine human cell lines by determining the inhibition of invasion by ND2001 (sodium D-glucaro-delta-lactam) in vitro. The efficacy of this agent against these tumor cells was investigated in an experimental metastatic model of human tumors in vivo. Although ND2001 did not inhibit growth of NC 65 cells intradermally transplanted into male KSN mice (nu/nu), this agent inhibited multiple spontaneous metastasis.

Animals↗

PubMed1999

Single treatment with cisplatin or UFT, but not their combination treatment enhances the metastatic capacity of mouse fibrosarcoma cells.

To elucidate the roles of chemotherapeutic agents in tumor progression, we examined whether cis-diamminedichloroplatinum (II) (cisplatin) and UFT would promote malignant progression of a weakly tumorigenic and poorly metastatic fibrosarcoma cell line OR-32SK in vivo. C57BL/6 mice, transplanted with QR32SK, were treated with either cisplatin or UFT alone and in combination. After treatment with or without cisplatin and/or UFT, we established in vitro culture cell lines from the tumors arising in the mice on day 21 and then i.v. injected the established cell lines into syngeneic mice. As a result, the cell lines established from cisplatin-treated mice and UFT-treated mice had significantly higher metastatic capacity in lung compared to the ones from control untreated mice (64 and 65%, respectively, versus 26.7%). The cell lines established from the mice with the combination therapy showed lower lung metastasis (11%) than the ones from control untreated mice. Furthermore, we found the incidences of these experimental metastases were closely related with in vitro chemotactic activities and the production of MMP-9 of the cultured cell lines. These results indicate that cisplatin and UFT as a single agent promote the chemotactic activities and the production of MMP-9 in non-metastatic fibrosarcoma cells, resulting in the conversion to highly metastatic ones, and that cisplatin and UFT in combination failed to promote the chemotactic activities and the conversion. These results suggest that the combination therapy with cisplatin and UFT is useful in preventing the emergence of more malignant tumor cells after chemotherapy.

Animals↗

PubMed1999

Clinicopathologic study of esophageal squamous cell carcinoma confined to the mucosa.

The authors studied patients with esophageal squamous cell carcinoma confined to the mucosa (ESCM) with respect to various clinicopathologic factors to investigate the course of invasion of very early-stage esophageal cancers. A total of 74 patients with ESCM were studied. Fifty of these patients had tumor invasion of the basement membrane confined to the lamina propria mucosae (m2 cancer), and 24 patients had tumor invasion of the muscularis mucosa (m3 cancer). All lesions were investigated with regard to clinicopathologic factors such as tumor differentiation, pattern of invasion, endoscopic morphology, and inflammatory response. The patients were divided into groups of 8 patients with positive lymphatic invasion, lymph node involvement, or both (Inv[+] group), and a group of 66 patients with no lymphatic invasion or lymph node involvement (Inv[-] group). The inflammatory response was evaluated on the basis of lymphocyte infiltration at the tumor invasion front and lymphocytic follicles beneath the tumor invasion front. Mean lesion size was significantly greater in the Inv(+) group than in the Inv(-) group (p < 0.05). However, there was no significant difference in the mean area of invasion of the lamina propria mucosae or deeper between the Inv(+) group and Inv(-) group. Patients with m2 cancer had a significantly higher rate of high-degree lymphocytic follicles than those with m3 cancer (p < 0.01). In patients with m2 cancer, the mean area of invasion of the lamina propria mucosae in patients with high-degree lymphocytic follicles was significantly greater than that in patients with low-degree lymphocytic follicles (p < 0.05), whereas there was no significant difference in mean lesion size between patients with high-degree and low-degree lymphocytic follicles. In patients with ESCM, lesion size was an important risk factor for lymphatic invasion and nodal involvement, lymphocytic follicles were prominent beneath the front of relatively broad cancer invasion, and lymphocytic follicles were less common with deeper cancer invasion.

Carcinoma, Squamous Cell↗

PubMed1999

Preliminary report on usefulness of magnetic resonance imaging for outcome prediction in early-stage Legg-Calvé-Perthes disease.

The usefulness of magnetic resonance imaging (MRI) for predicting prognosis was evaluated in 11 patients with unilateral early-stage Legg-Calvé-Perthes disease who were treated with a non-weight-bearing abduction brace. Six to 10 months after disease onset, severity of cartilage hypertrophy and physeal curvature of the femoral head were scored on MRI. Femoral head deformity was radiographically evaluated. Among five patients whose MRI score was 8 or greater, radiographic evaluation after the treatment was "poor" or "fair," whereas evaluation for the other six patients whose MRI score was 7 or less was "good." The MRI scores indicated possible occurrence of femoral head deformation. Treatment method should be considered carefully when the MRI score is high.

Braces↗

PubMed1999

Effects of ginseng radix on sugar absorption in the small intestine.

Ginseng radix (GR) is often used in traditional Japanese kampo medicine. We studied the effect of GR on glucose and maltose transport in rat and human duodenal mucosa by Ussing's method, and on smooth muscle movement in rat duodenal muscle by Magnus' method. GR inhibited absorption of glucose or maltose in rat and human duodenal mucosa, but increased duodenal muscle movement. It suggests that the inhibition of sugar absorption by GR is more dominant than enhancement of duodenal muscle movement by GR.

Adult↗

PubMed1999

[Effects of mouth wash on the removing beclomethasone dipropionate delivered by pressurized aerosol metered-dose inhaler in the mouth].

Effects of mouth wash (mouth rinsing and gargling) on the removal of drug residues in both mouth and pharynx after the use of pressurized aerosol metered-dose inhaler (MDI) were studied. The concentration of beclomethasone dipropionate (BM) in mouth wash after a splay of Becotide inhaler was measured by the method using HPLC. The total amount of the removed BM was measured by a sum of the concentrations of BM in 4 or 5 times of mouth washes in the following 4 kinds of methods. In method 1, mouth wash was done with 5 times of water change after a splay of MDI on wetted mouth. In method 2, mouth wash was done with 5 times of change water on dried mouth. In method 3, mouth wash was done with 4 times of change saliva on wetted mouth. In these methods, the actual inhalation of BM was not done. In method 4, mouth wash was done with 5 times of change water after a splay and a inhalation on wetted mouth. The mouth wash procedures removed totally 47.9%, 51.1%, 31.3%, and 33.3% of a splayed amount of BM in each method, respectively. It was required for the removal of 90% of the totally recovered BM to do one time of mouth wash in method 1, two times in method 2, three times in method 3, and two times in method 4, respectively. These data suggest that the mouth wash procedure is shown to have prophylactic benefit for candidiasis induced by steroid delivered by MDI.

Administration, Inhalation↗

PubMed1999

The suppression of metastases and the change in host immune response after low-dose total-body irradiation in tumor-bearing rats.

We have shown that metastasis is suppressed by low-dose total-body irradiation (TBI) in tumor-bearing rats. We have evaluated the immunological effects of low-dose TBI. Total-body irradiation with 0.2 Gy was given 14 days after the implantation of 5 x 10(5) allogenic hepatoma cells (KDH-8) which produce transforming growth factor beta (TGF-beta). On day 21, the splenocytes and tumor-tissue infiltrating lymphocytes were analyzed by FACScan and RT-PCR for the mRNA of the genes that encode tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), TGF-beta, interleukin (IL)-4, IL-10 and IL-6. The same procedure was conducted with untreated rats and with rats that underwent local irradiation with 0.2 Gy. The low-dose TBI significantly decreased the incidence of lung and lymph node metastasis (P < 0.01), whereas the same dose of local irradiation had no effect on the incidence of metastasis. The proportion of CD8+ cells in splenocytes increased in the low-dose TBI group (P < 0.01) compared to the locally irradiated and the untreated groups. The tumor-tissue infiltrating lymphocytes were also significantly increased after low-dose TBI (P < 0.01). The FACScan analysis revealed that 72% of the tumor-tissue infiltrating lymphocytes were CD8+. In both spleen and tumor tissue after low-dose TBI, mRNA expression of the genes that encode IFN-gamma and TNF-alpha increased, while that of the Tgfb gene decreased. There was no expression of the mRNAs of the Il4, Il6 and Il10 genes. CD8+ cells and the cytokine network may play an important role in the antitumor effect of low-dose TBI.

Animals↗

PubMed1999

[Histologic occurrence of Barrett's carcinoma].

It is generally agreed that the diagnosis of Barrett's esophagus is justified when the columnar epithelium 3 cm or more from the E-C junction is involved. Microscopically, the epithelium has three distinct appearances: (1) gastric fundic type; (2) junctional type: and (3) specialized columnar type. In mucin histochemistry in 6 cases of Barrett's carcinoma, 5 cases of Barrett's esophagus were positive for HID-AB. Four cases of Barrett's carcinoma were also positive. These results suggest that Barrett's carcinoma developed from the specialized columnar type of Barrett's esophagus.

Barrett Esophagus↗

PubMed1999

[Use of the multifocal electroretinogram to evaluate retinal function after pars plana vitrectomy for diabetic macular edema].

PURPOSE: Multifocal electroretinograms (multifocal ERGs) were performed to evaluate retinal function in patients with diabetic macular edema. MATERIALS & METHODS: Eight eyes of 5 patients underwent pars plana vitrectomy for diabetic macular edema. Multifocal ERGs, fundus examinations, and fluorescent angiographies were done both before and after the operation. RESULTS: Post-operative visual acuity was improved by two or more lines in 3 eyes. In multifocal ERGs, the amplitude of the positive wave (P1) from the macular area decreased transiently after surgery (p < 0.05), but it improved with the passage of time. The P1 amplitude from the peripheral area was decreased throughout the observation period of six months (p < 0.05). For both areas, the P1 latency was increased significantly (p < 0.05) at one month post-operatively, and then decreased. CONCLUSION: These findings are consistent with the possibility that the surgical method, especially removal of the posterior cortical vitreous, can cause retinal damage.

Diabetic Retinopathy↗

PubMed1999

Troglitazone inhibits bicarbonate secretion in rat and human duodenum.

Troglitazone is a new, orally effective antidiabetic agent that decreases plasma glucose in obese patients with non-insulin-dependent diabetes mellitus. Unfortunately, troglitazone also has a propensity to cause edema. This study was designed to determine how troglitazone affects intestinal ion transport and water absorption. Short circuit current (I(sc)) was measured in rat and human duodenal mucosa in Ussing chambers. Five minutes later, the serosal addition of troglitazone caused I(sc) to decrease gradually, and after 50 min, I(sc) reached the peak of decrease. EC(50) values and maximum response to I(sc) in rat and human mucosa were 8.4 and 8.7 microM and 8.56 +/- 1.0 and 8.00 +/- 2.0 microA/cm(2), respectively. In an HCO(3)(-)/CO(2)-free system, the decrease in I(sc) caused by troglitazone was 1.31 +/- 0.83 microA/cm(2). When 10 mM acetazolamide was preadministered, the small decrease in I(sc) evoked by troglitazone (20 microM) was 4.56 +/- 0.22 microA/cm(2), whereas the preadministration of 100 microM amiloride and 100 nM tetrodotoxin did not influence the decrease in I(sc) evoked by troglitazone. The serosal preadministration of 100 nM vasoactive intestinal peptide potently enhanced the decrease in I(sc) evoked by 20 microM troglitazone (21.1 +/- 1.63 microA/cm(2)). The cyclic AMP contents of rat duodenal mucosa incubated with and without troglitazone (20 microM) for 50 min were 3.2 +/- 0.25 and 5. 8 +/- 0.46 pmol/mg protein, respectively (P <.01). These results indicate that the ionic basis for the decrease in I(sc) that is induced by troglitazone may be inhibition of electrogenic bicarbonate secretion. The alteration of intestinal ion transport by troglitazone could cause edema.

Animals↗

PubMed1999

[TRAM flap breast reconstruction using a fascia-sparing technique].

Although the TRAM flap has been accepted as one of the most common methods for breast reconstruction utilizing the autologous tissue, its disadvantage is that scarring of the abdominal sheath and muscle may result in postoperative abdominal bulge or hernia. To solve this problem, the authors developed the fascia-sparing technique in TRAM flap breast reconstruction. The technique, in which most of the anterior rectus sheath is preserved, has been applied in 3 patients after radical mastectomy and 7 patients after modified radical mastectomy. With an average follow-up period of 1 year and 2 months, no abdominal bulge or hernia was noted in any patient without the use of prosthetic mesh for the abdominal closure. This fascia sparing technique is particularly effective for TRAM flap reconstruction requiring bilateral rectus abdominis muscle portions and containing only a few minor perforators, for which a DIEP flap is not suitable.

Adult↗

PubMed1998

Oxidative damage in the senescence-accelerated mouse.

The senescence-accelerated mouse (SAM) exhibited a shortened life span (about 18 months) and early manifestation of various signs of senescence, including changes in physical activity, skin, and spinal curvature. The mechanism of senescence acceleration in SAM is thought to be related to free radical damage. Oxidative phosphorylation was estimated in liver mitochondria from SAMPS and the senescence-resistant subtrain, SAMR1. The respiratory control ratio decreased during aging, and the ATP/O, an index of ATP synthesis, was depressed at 18 months of age in SAMPS. DNP-dependent uncoupled respiration in liver mitochondria was markedly decreased, and active uptake of calcium was markedly dysfunctional with aging. These findings suggest that the functional disorders in mitochondria may be closely related to the shorter life span of SAMPS. White-footed (WF) mice can live at least to 5.5 years, when some animals are still capable of reproducing and their external body condition remains healthy. The mitochondrial functions were examined in the same way as in the SAM experiments. However, no particular finding responsible for their longevity was observed in WF mice at 3 and 12 months old. More comprehensive examinations on more aged WF mice are needed for explanation of their greater longevity.

Aging↗

PubMed1998

Age-related changes in the brains of senescence-accelerated mice (SAM): association with glial and endothelial reactions.

Twelve substrains of inbred senescence-accelerated mice (SAM) have been developed, among which the SAMP8 and SAMP10 strains show a significant age-related deterioration in learning and memory for passive and active avoidance tasks. These strains have, respectively, a low and high incidence of systemic senile amyloidosis. Although we found no amyloid deposits in their brain parenchyma, a variety of age-related alterations were identified, involving neurons, glia, and vessels in the brain tissues. Here we review the degenerative changes in aged SAMP8 and SAMP10 brains. These changes are generally similar to the pathology of aging human brain and may be characterized by their association with some specific glial reactions.

Aging↗

PubMed1998

An early stage mechanism of the age-associated mitochondrial dysfunction in the brain of SAMP8 mice; an age-associated neurodegeneration animal model.

In order to characterize the early stage of mitochondrial dysfunction, we investigated the redox state and oxidative phosphorylation of the brain mitochondria from 2-month-old Senescence-accelerated mouse (SAM)P8 and SAMR1 mice; SAMP8 mice exhibit various signs of age-associated neurodegeneration and rapid mitochondrial dysfunction, although SAMR1 mice do not. The redox state was estimated as the reduction rate of Cu-pyruvaldehyde-bis (N4-methylthiosemicarbazone) (Cu-PTSM), the reduction of which is closely related to the electron leakage from the mitochondrial electron transport system in the brain, using electron spin resonance spectrometry (ESRS). The oxidative phosphorylation was measured polarographically. The SAMP8 mouse brain mitochondria demonstrated higher redox state and a higher activity of mitochondrial respiration with lower respiration control ratio than the mitochondria of SAMR1 mouse brains. This indicates that an inefficient hyperactive state can exist in the mitochondrial electron transport system before the age-associated mitochondrial dysfunction develops.

Aging↗

PubMed1998

Familial essential thrombocythemia associated with one-base deletion in the 5'-untranslated region of the thrombopoietin gene.

Familial essential thrombocythemia (ET) is inherited in an autosomal-dominant manner. This finding implies that familial ET may arise as a consequence of a mutation(s) that activates platelet production. In 1994, the thrombopoietin (TPO) gene was isolated and cloned. The TPO-TPO receptor, encoded for by the c-mpl gene, are essential regulators of thrombopoiesis. Alterations of TPO or c-Mpl thus may constitute a pathogenic event leading to familial ET. In a case of familial ET presented in our institute, serum TPO levels were significantly elevated in affected members of the family as compared with nonaffected members. Moreover, we identified a one-base deletion in the 5'-untranslated region of the TPO gene in affected but not in nonaffected family members. In vitro experiments showed that the identified mutation increased TPO production. Based on our findings, we propose that this region of the TPO gene may play a crucial role in regulating TPO expression. Our results strongly suggest that the identified mutation leads to familial ET.

DNA Mutational Analysis↗