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Biomedical subjects

M Hosokawa

Publications and source records attributed to M Hosokawa.

At least 163 records · Page 9Linked to original sources
PubMed1997

Age-related changes in the brain transfer of blood-borne horseradish peroxidase in the hippocampus of senescence-accelerated mouse.

Age-related changes in the brain transfer of blood-borne horseradish peroxidase (HRP) were examined by light microscopy in senescence-accelerated prone mice (SAMP8) and senescence-accelerated resistant mice (SAMR1). The intracerebral HRP transferred from the blood stream was reacted with tetramethyl benzidine (TMB) and the area showing the presence of HRP-TMB reaction products was morphometrically evaluated. Areas containing HRP reaction products in the medial CA1 region and medial dentate gyrus of the hippocampus were observed in 3- and 13-month-old SAMP8 and SAMR1. The mean percentage of the positive area for the HRP to the area of interest was significantly higher in the rostral portion of the hippocampus in 13-month-old than in 3-month-old SAMP8. On the other hand, age-related changes in the area positive for HRP-TMB reaction products in the cortices and the caudal portion of the hippocampus in SAMP8 were not observed. In addition, positive staining reaction for HRP was also observed in the dorsal portion of the thalamus of 13-month-old SAMP8. There were no significant age-related changes in the area positive for HRP-TMB reaction products in rostral and caudal portions of the cortices and the hippocampus of SAMR1. These findings suggest that blood-borne macromolecules have access to the medial and rostral portion of the hippocampus, that this phenomenon becomes more pronounced during the process of senescence in the SAMP8 brain and, moreover, that intravascular macromolecules have access to the dorsal portion (periventricular area) of the thalamus of 13-month-old SAMP8.

Aging↗
PubMed1997

Learning in a problem-based medical curriculum: students' conceptions.

The purpose of this study was to examine students' conception of their learning in a problem-based learning medical curriculum. A multiple case study design was used with two units of analyses: two PBL lab groups; and 15 individual students within each lab group. Data collected included weekly journals by students, video-tapes of PBL sessions, focus group interviews with students, two open-ended questionnaires completed by students, and interviews with the PBL tutors. Three thematic categories of students' conceptions of their learning emerged: (1) awareness of PBL goals and expectations; (2) efficiency and expertise; and (3) the role of the tutor.

Attitude↗
PubMed1997

A new synthetic lipid A analog, ONO-4007, stimulates the production of tumor necrosis factor-alpha in tumor tissues, resulting in the rejection of transplanted rat hepatoma cells.

ONO-4007 is a new synthetic lipid A derivative with low endotoxic activities. We have examined the therapeutic effects of ONO-4007 on rat hepatocellular carcinoma KDH-8 cells, rat fibrosarcoma KMT-17 cells and rat mammary adenocarcinoma SST-2 cells in vivo. Multiple systemic i.v. administration of ONO-4007 was performed on days 7, 14 and 21 after tumor implantation of KDH-8 and SST-2 cells, and on days 5, 10 and 15 after tumor implantation of KMT-17 cells. ONO-4007 showed significant therapeutic effects on KDH-8 cells; by the administration of ONO-4007 (2.5 mg/kg) 70% of rats were cured and by the administration of ONO-4007 (5 mg/kg) 50% of rats were cured. Furthermore, the ONO-4007 treatment prolonged the mean survival time of KDH-8-bearing rats. However, ONO-4007 had no effect on KMT-17 and SST-2 cells, and it had no direct effect on the growth of KDH-8 cells in vivo. Albeit the stimulation with ONO-4007 induced mRNA expressions of interleukin (IL)-1alpha, IL-6 and tumor necrosis factor (TNF)-a, those of IL-2, IL-4, IL-10 and interferon (IFN)-gamma were not induced. Using a bioassay, we found that the production of TNF-alpha in the tumor tissues was induced by ONO-4007 in a dose-dependent manner. KDH-8 cells were sensitive to human natural TNF-alpha in vitro. However, KMT-17 and SST-2 cells were resistant against TNF-alpha in vitro. These results suggest that ONO-4007 is therapeutically useful for the treatment of TNF-alpha-sensitive tumors.

Adenocarcinoma↗
PubMed1997

The mechanism of locally enhanced production of tumor necrosis factor-alpha in tumor tissues by the administration of a new synthetic lipid A analog, ONO-4007, in hepatoma-bearing rats.

ONO-4007 is a new synthetic lipid A analog with low endotoxic activities. We previously found that ONO-4007 induced the production of tumor necrosis factor (TNF)-alpha in rat hepatoma KDH-8 tumor tissues and brought about the regression of transplanted KDH-8 cells. By contrast, ONO-4007 did not induce TNF-alpha production in spleens and sera 90 min after treatment. In the present study we attempted to elucidate how ONO-4007 induces TNF-alpha production in tumor tissues locally. We found that extracellular matrix including gelatin, fibronectin and Matrigel did not induce TNF-alpha production in splenocytes treated with ONO-4007 in vitro. However, splenocytes co-cultured with cKDH-8/11 tumor cells in the presence of ONO-4007 produced more TNF-alpha than splenocytes cultured by themselves in the presence of ONO-4007. The stimulation of cKDH-8/11 cells in the presence of ONO-4007 for splenocytes to produce TNF-alpha depended on the type of contact between the cells. The cKDH-8/11 cells fixed in formalin were not able to induce TNF-alpha production of splenocytes even in the presence of ONO-4007. However, syngeneic fibrosarcoma cell line KMT-17/A3, allogeneic hepatocellular carcinoma cell line LDH and rat lung endotherial cell line RLE induced TNF-alpha production in splenocytes, but their stimulation was weaker than that of cKDH-8/11. The soluble form of the cKDH-8/11 cell membrane did not stimulate splenocytes to produce TNF-alpha in the presence of ONO-4007. cKDH-8/11 cells did not stimulate the splenocytes devoid of macrophages to produce TNF-alpha in the presence of ONO-4007.

Animals↗
PubMed1997

Therapeutic effects of a new synthetic lipid A analog, ONO-4007, on rat hepatoma KDH-8 depend on tumor necrosis factor-sensitivity of the tumor cells.

ONO-4007 is a new synthetic lipid A derivative with low endotoxic activities. ONO-4007 was effective against KDH-8, a tumor necrosis factor (TNF)-sensitive rat hepatoma cell line, but neither effective against KMT-17, a TNF-resistant rat fibrosarcoma cell line, nor SST-2, a TNF-resistant rat mammary adenocarcinoma cell line. We have established two sublines from KDH-8 to further examine the therapeutic mechanisms of ONO-4007 in vivo: TNF-sensitive KDH-8/YK and TNF-resistant cKDH-8/11. The two sublines equally proliferated in vitro. Multiple systemic i.v. administration of ONO-4007 was performed on days 7, 14 and 21 after tumor implantation. Although treatment with ONO-4007 had no effect on the growth of cKDH-8/11 in WKAH rats in vivo, 60% of KDH-8/YK-bearing rats treated with ONO-4007 survived. The administration of ONO-4007 brought about significant therapeutic effects on KDH-8/YK-bearing rats but not on cKDH-8/11-bearing rats. These results suggest that ONO-4007 is therapeutically useful for the treatment of TNF-alpha-sensitive tumors.

Adenocarcinoma↗
PubMed1997

Enhancement of lymphokine-activated killer cell activity by fibronectin.

In this study, we demonstrated that immobilized fibronectin (FN) enhanced lymphokine-activated killer cell (LAK) activity, and that the enhanced LAK activity was completely abrogated by an anti-VLA-5 monoclonal antibody and RGD peptide. Fresh spleen cells expressed VLA-4, VLA-6, and vitronectin receptor, whereas VLA-5 was expressed only on the spleen cells activated with interleukin-2. LAK cells showed increased adhesion to immobilized FN compared with that to control bovine serum albumin, and the increased adhesion of LAK cells to immobilized FN was inhibited by anti-VLA-5 monoclonal antibody. Conjugate-formation assay showed that the LAK cells cultured on immobilized FN bound to target cells more efficiently than the control LAK cells, and that anti-LFA-1 monoclonal antibody inhibited the LAK-target cell binding. Immobilized type IV collagen and laminin, as well as FN, enhanced LAK activity. All of these results suggest that the interaction of integrins expressed on LAK cells with extracellular matrix proteins acts in a costimulatory manner for the enhancement of LAK activity, and that anchorage is necessary for full activation of LAK cells.

Animals↗
PubMed1997

Infrequent alterations of the p16 (MTS-1) gene in human gastric cancer.

p16 (MTS-1, multiple tumor suppressor gene 1), a putative tumor suppressor gene, is one of the cyclin-dependent kinase inhibitors (CDI) and it regulates the G1/S transition of the cell cycle. To clarify the role of p16 in primary gastric cancer, we have investigated somatic mutations of this gene by using the polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) method. In 23 surgical specimens of primary gastric cancer, none were detected in exon1 and exon 2. Among the 6 human gastric cancer cell lines examined, PCR products were not found in 2, MKN28 and MKN45, suggesting the presence of homozygous deletions. No mutation was found in the other 4 cell lines. Furthermore, decreased expression levels were not observed in 13 gastric cancer tissues by reverse transcription PCR (RT-PCR). Considering the above results of PCR-SSCP and RT-PCR, genetic alterations of the p16 gene are rarely implicated in human gastric cancer tumorigenesis.

Actins↗
PubMed1997

Endothelial dysfunction in the perfused kidney from the streptozotocin-induced diabetic rat.

The vasodilator effects of acetylcholine were examined in methoxamine-preconstricted perfused kidneys taken from rats with streptozotocin (STZ)-induced diabetes. Acetylcholine-dependent vasodilatation was significantly weaker in STZ-induced diabetic rats than in age-matched controls, and it was completely abolished by treatment with 60 mM K+ plus NG-nitro-L-arginine (L-NNA) plus methylene blue in the control rats and was significantly but not completely inhibited by these treatment in the diabetic rats. Although acetylcholine-induced vasodilation was not affected by indomethacin in control rats, it was attenuated by indomethacin in the diabetic rats. Arachidonic acid-induced vasoconstriction was slightly but significantly increased in the diabetic rats. Acetylcholine increased significantly the level of 6-keto-prostaglandin F1 alpha in the effluent from perfused kidneys from diabetic rats. These results suggest that the endothelium-dependent vasodilatation induced by acetylcholine in the renal vascular bed of age-matched control rats is due to the release of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), whereas the vasodilatation induced by acetylcholine in the STZ-diabetic kidney also involves prostaglandin I2 as well as NO and EDHF.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Characteristics of vasodilatation induced by cyclopiazonic acid in the rat perfused kidney.

We examined the possible existence of a novel endothelium-derived relaxing factor in the endothelium of the perfused rat kidney. Acetylcholine-induced vasodilatation was abolished by treatment with NG-nitro-L-arginine (L-NNA) and methylene blue in isotonic high K+ (60 mM) medium, whereas cyclopiazonic acid (CPA)-induced vasodilatation of the perfused kidney was slightly increased by this treatment. When the kidney was perfused with 0.47% CHAPS solution for 1 min, acetylcholine- or cyclopiazonic acid-induced vasodilatation was almost abolished. Acetylcholine- or cyclopiazonic acid-induced vasodilatation was not affected by indomethacin. These results suggest that CPA may release a novel endothelium-derived relaxing factor, which is not prostanoids, nitric oxide nor endothelium-derived hyperpolarizing factor in the endothelium of the renal vascular bed.

Acetylcholine↗
PubMed1997

[Strategy of lymph nodes dissection for the lower thoracic esophageal cancer without metastasis to the upper-mediastinal lymph nodes].

The incidence of metastasis to the lymph nodes in preoperative untreated patients with Ei, T2 or T3 esophageal cancer is 70.7% (41 of 58 cases) in our institute. Especially, a high incidence of metastasis to the abdominal lymph nodes has been noted. In contrast, metastasis to the cervical lymph nodes is not common. The majority of recurrence appear as a distant metastasis to the liver, lung or bone through the hematogenic route. However, recurrence in the peritoneum through the lymphatogenic route is not uncommon. Therefore, current strategy of lymph nodes dissection for esophageal carcinoma would be inadequate for the complete inhibition of recurrence, so that chemotherapy remains to be needed. Since the diagnostic procedure with ultrasonographic endoscopy and computerized tomography is highly accurate for the assessment of metastasis to the uppermediastinal lymph nodes, operative procedure suitable for each case should be determined on the basis of preoperative examination.

Endosonography↗
PubMed1996

Molecular cloning of guinea pig membrane cofactor protein: preferential expression in testis.

Human membrane cofactor protein (MCP) is a widely distributed cell-associated complement-regulatory protein, and recent findings suggest that MCP may be involved in sperm-egg interaction. We have isolated four cDNA clones and one reverse transcriptase-PCR product homologous to human MCP from guinea pig testis. These clones defined five isoform classes generated from a single copy gene by alternative splicing. Reverse transcriptase-PCR revealed that two classes for the clones termed GMP1 and GM2 were predominant. GMP1 consisted of four short consensus repeats (SCRs), regions corresponding to the human serine/threonine/proline-rich C (STP(C)) domain and a human region of unknown significance, a hydrophobic region presumed to be a transmembrane domain, and a cytoplasmic region. Identity with human MCP in the SCR region was 56% at the amino acid level and 71% at the nucleotide level. GM2 had the same structure as GMP1, except that it lacked the fourth SCR, which is presumed to be essential for C3b binding of human MCP. Northern blotting analysis of various tissues revealed a significant level of MCP transcripts in testis. Guinea pig MCP is likely to have only one STP domain that is homologous to human STP(C) and is similar in this respect to human spermatozoa MCP. Gene analysis revealed a single base deletion and a lack of consensus sequences for splicing in the guinea pig regions corresponding to human STP(A) and STP(B), respectively. These results suggest that guinea pig MCP plays a more restricted role in reproduction than does human MCP.

Amino Acid Sequence↗
PubMed1996

Defective calcium influx in rat myelomonocytic leukemia cells which are resistant to differentiation-inducing effects of lipid A.

We compared the calcium mobilization in parent lipid A-sensitive leukemia cells (P2) and lipid A-resistant cells (LR) after treating them with lipid A in order to clarify the signal transduction involved in the differentiation induced by lipid A. Lipid A induced differentiation in P2 cells; however, LR cells were completely resistant to it. A dramatic elevation of intracellular free calcium ion concentration ([Ca2+]i) occurred in P2 cells, but only a slight elevation of [Ca2+]i in LR cells. Calcium ionophore in combination with lipid A induced differentiation in LR cells. An elevation of [Ca2+]i observed in P2 cells was abrogated by an addition of EGTA, which partially inhibited the differentiation of P2 cells stimulated by lipid A. Altogether, these data indicate that calcium influx is essential for the differentiation of P2 cells stimulated by lipid A and that defective calcium influx is responsible for the resistance to lipid A in LR cells.

Animals↗
PubMed1996

The relationship between mastoid pneumatization and the position of the sigmoid sinus.

Using high-resolution computed tomography, we measured the cross-sectional area of mastoid air cells and the shortest distance between the external auditory canal and the anterior edge of the sigmoid sinus (DIST), and then compared the right-left difference in 70 patients with unilateral chronic otitis media and 23 cases without middle ear disease. DIST was significantly short where there was poor mastoid pneumatization (P < 0.0001), regardless of whether it was the right or left ear. Furthermore, on the well-pneumatized temporal bone, the increase in size of the cross-sectional area was closely correlated with the increase in DIST (r = 0.495). We suggest that the relative position of the external auditory canal and the sigmoid sinus is affected by middle ear inflammations in childhood.

Adolescent↗
PubMed1996

Experimental bilirubin pigmentation of rat dentine and its detection by a qualitative analytical method.

An animal model of bilirubinemia was used to determine whether bilirubin present in pigmented teeth can be extracted and qualitatively analysed. The bile ducts of 10 Long-Evans Agouti rats were ligated and bilirubin (14 mg/kg per day) was injected intraperitoneally for 4 days. When the animals were killed 2 weeks later, pigmented lower incisors were observed in three animals. These teeth were dried, powdered and bilirubin was extracted with chloroform/methanol/acetic acid, 30:10:0.5, v/v for 10 min under sonication. After centrifugation, the supernatant was collected and evaporated. The residue was dissolved in chloroform and its absorption spectrum measured before and after diazo reaction. This resulted in a shift of the absorption maximum from 450 to 540 nm and indicated the presence of bilirubin in pigmented teeth. No bilirubin was found in the lower incisors of untreated control rats. This technique may be useful in distinguishing bilirubin staning from other intrinsic discolorations of teeth.

Acetic Acid↗
PubMed1996

Transforming growth factor beta 1 (TGF-beta 1) produced in tumour tissue after chemotherapy acts as a lymphokine-activated killer attractant.

Using an under agarose migration (UAM) assay, we studied lymphokine-activated killer (LAK)-attractant activity in cultured conditioned medium of tumour tissues after chemotherapy as a possible mechanism of enhanced LAK cell accumulation into tumour tissues after chemotherapy. BMT-11 is a fibrosarcoma developed in C57BL/6 mice. The conditioned medium of BMT-11 tumour tissues obtained from mice treated with various anti-cancer drugs had chemotactic activity for LAK cells (LAK-attractant activity). mRNA expression of interleukin (IL)-1 alpha, IL-6, IL-8, interferon (IFN)-gamma, and tumour necrosis factor (TNF)-alpha was observed in untreated tumour tissues, which were not enhanced by cyclophosphamide treatment. mRNA expression of TGF-beta 1 was not detected in untreated tumour tissues by reverse transcription-polymerase chain reaction (RT-PCR), but was detected in tumour tissues treated with cyclophosphamide. Recombinant human TGF-beta 1 showed LAK-attractant activity at a concentration of 0.1 ng ml-1 and 1 ng ml-1, whereas fresh splenocytes were not attracted by TGF-beta 1. Anti-TGF-beta 1 antibody inhibited LAK-attractant activity in the conditioned medium of tumour tissues treated with cyclophosphamide to approximately 35% that of control at 100 micrograms ml-1. These findings indicate that TGF-beta 1 produced in the tumour tissues of mice treated with anti-cancer drugs could be a LAK attractant. By a 4 h 51Cr release assay of natural killer cell-resistant BMT-11 tumour cells, we observed that TGF-beta 1 at a concentration from 0.01 ng ml-1 to 10 ng ml-1 did not inhibit LAK activity in an effector phase. Taken together, we suggest that TGF-beta 1 produced in tumour tissues after chemotherapy participates in gathering transferred LAK cells and contributes to the therapeutic effects of transferred LAK cells.

Animals↗
PubMed1996

Accelerated senile amyloidosis induced by amyloidogenic Apoa-II gene shortens the life span of mice but does not accelerate the rate of senescence.

The SAMP1 strain is a mouse model for accelerated senescence and severe senile amyloidosis. We studied the effects of the amyloidogenic apolipoprotein A-II gene (Apoa2c) on senile amyloidosis and the life span and progress of senescence of congenic mice (R1.P1-Apoa2c) which have Apoa2c of the SAMPI strain on the genome of the normally aging SAMR1 strain. Age-associated and severe amyloid deposits were detected in R1.P1-Apoa2c, as well as a 20% shorter life span than that of SAMR1. The scores of senescence increased more rapidly with age in R1.P1-Apoa2c than that of SAMR1, and the Gompertz function showed a bigger Y intercept but the same slope of regression line. These results suggest that severe senile amyloidosis induced by the Apoa2c gene shortens the life span of mice but does not accelerate the rate of senescence.

Aging↗
PubMed1996

Evaluation of multi skin test in colorectal cancer patients and effects of serum immunosuppressive factor and cytokine production of peripheral mononuclear cells.

Decreased skin reactions using five kinds of recall antigens correlate d with the stage of colorectal cancer. Immunosuppressive factors in the serum (IS index) increased with the progression of the stage in cancer patients, but interleukin (IL)-I and IL-2 production in peripheral mononuclear cells (PBMC) did not correlate with the advance of the disease. In patients with low immunosuppressive factors, the score of skin reactions was significantly higher than that in patients with high immunosuppressive factors. Increased serum immunosuppressive factors seem to reduce skin reactions in the patients. Furthermore, significant difference in skin reaction score was observed between patients with high IL-1 production of PBMC and patients with low IL-1 production of PBMC. These results suggest that skin reaction might be controlled by serum immunosuppressive factors and IL-1 production of PBMC, and that the score of skin reaction using multirecall antigens is a useful parameter to learn the host immunity in colorectal cancer.

Adult↗