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Biomedical subjects

M Oka

Publications and source records attributed to M Oka.

At least 199 records · Page 11Linked to original sources

Involvement of dendritic cell response to resistance of stomach carcinogenesis caused by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

The involvement of immune response in the resistance of chemically induced stomach cancer was studied in a resistant rat strain (Buffalo) and a sensitive rat strain (ACI). Groups of 10 male Buffalo and ACI rats, 6 weeks of age, were given drinking water with or without N-methyl-N'-nitro-N-nitrosoguanidine (MNNG; 100 mg/l) for 14 days. Total RNA was isolated from the stomach pyloric mucosa from five rats, and cDNA was prepared with reverse transcriptase. Tissue sections of the stomach pyloric mucosa from five rats were stained with antibodies recognizing molecules expressed by various immune cells. Reverse transcription-PCR (RT-PCR), competitive RT-PCR, and Northern blot demonstrated that the expression of MHC class II group genes [MHC class II, MHC class II-associated invariant chain (Ii), CD4 and IgM (B cell marker)], MHC class I group genes (MHC class I and CD8), B7-1 (costimulator on dendritic cells), and CD28 (receptor to B7 on T cells) in the pyloric mucosa was elevated by MNNG in both rat strains but was elevated to a 4-7-fold greater extent in Buffalo rats than in ACI rats. These genes were scarcely expressed in control rats. Histochemical antibody staining after MNNG exposure showed a greater number of cells stained with monoclonal antibody to Ii, OX-62 (dendritic cell marker), and ED-1 (dendritic cell and macrophage common marker) in the interstitial tissue of the pyloric mucosa of Buffalo rats compared with ACI rats. Cell proliferation, as measured by 5-bromo-2-deoxyuridine (BrdUrd)-labeling indices, revealed the presence of BrdUrd-labeled cells only among epithelial cells in the proliferative zone; cells in the interstitial tissue were not labeled with BrdUrd. The results suggest the involvement of dendritic cell response in the resistance to the MNNG induction of stomach carcinogenesis in rats.

Animals↗

A novel Na+/Ca2+ channel blocker NS-7 inhibits evoked but not spontaneous dopamine release from rat striatum, as measured by intracerebral microdialysis.

The spontaneous dopamine release from rat striatum, measured by intracerebral microdialysis, was markedly reduced by local perfusion of tetrodotoxin (1 microM) through the dialysis probe. In addition, striatal microinjection of omega-conotoxin GVIA (10 pmol) or omega-agatoxin i.v.A (1 pmol), but not local perfusion of nimodipine, suppressed the spontaneous dopamine release. Therefore, the spontaneous dopamine release may depend on the activity of both Na+ channel as well as N-type and P/Q-type Ca2+ channels. In contrast, local perfusion of a novel Na+- and Ca2+-channel blocker NS-7 (10 microM) did not affect spontaneous dopamine release, whereas it markedly blocked KCl- and veratridine-evoked dopamine release. Therefore, NS-7 may block Na+- and Ca2+-channels only when the ion channels are highly activated.

Animals↗

Breast cancer associated with Recklinghausen's disease: report of a case.

A 49-year-old woman with Recklinghausen's disease presented to our department for investigation of a left breast lump, measuring 60 mm x 50 mm, which she had first noticed 6 months earlier, but had disregarded, believing it to be another manifestation of her Recklinghausen's disease. The lump was suspected to be malignant based on physical examination and ultrasonography. Biopsy and frozen sections subsequently confirmed a diagnosis of scirrhous carcinoma. A standard radical mastectomy was performed, followed by postoperative chemoendocrine therapy. However, lungs, liver, and bone metastasis, as well as a contralateral breast tumor, developed and she died 4 months after surgery.

Adenocarcinoma, Scirrhous↗

Positive and negative controls by protein kinases of sodium-dependent Ca2+ efflux from cultured bovine adrenal chromaffin cells stimulated by lysophosphatidic acid.

We previously found that lysophosphatidic acid (LPA), a bioactive phospholipid, induced Na+-dependent Ca2+ efflux from cultured bovine adrenal chromaffin cells, possibly by activating a Na+/Ca2+ exchanger. The present study on the structure-activity relationship of its action revealed that 1-acyl type LPAs were stronger stimulants than the corresponding 1-O-alkyl type LPAs having a long alkyl moiety with the same chain length. Lysophosphatidylglycerol, suramin and N-palmitoyl-tyrosine phosphoric acid have all been reported to inhibit the action of LPA in some animal cells and platelets, but only lysophosphatidylglycerol was found to inhibit selectively LPA-induced Ca2+ efflux from chromaffin cells. LPA-induced Ca2+ extrusion was suggested to be involved in both acceleration of return of intracellular Ca2+ in Fura 2-loaded bovine chromaffin cells after addition of carbachol, and inhibition of carbachol-induced catecholamine release when the cells were co-incubated with LPA. The Ca2+ efflux from chromaffin cells stimulated by LPA was augmented by their pretreatment with staurosporine or calphostin C, inhibitors of protein kinase C, but reduced by their preincubation with phorbol 12-myristate 13-acetate. Furthermore, the response to LPA was potentiated by sodium vanadate, a protein tyrosine phosphatase inhibitor, but inhibited by genistein, an inhibitor of protein tyrosine kinase. These results suggest that protein kinase C and protein tyrosine kinase are involved negatively and positively, respectively, in the signal transduction triggered by LPA, leading to activation of the Na+/Ca2+ exchanger.

Adrenal Glands↗

Bone bonding in bioactive glass ceramics combined with bone matrix gelatin.

To determine how to encourage inductive osteogenesis on bioactive ceramics and accelerate the bonding of implants to the surrounding bone, we studied the role of autolyzed antigen-extracted allogeneic bone gelatin (AAAG) in bone bonding to bioactive ceramic implants in rabbit tibiae. Smooth-surfaced plates (15 x 10 x 2 mm) of apatite and wollastonite containing glass-ceramic were implanted into the proximal metaphyses of tibiae, with AAAG packed into the medullary cavity in one limb but not in the contralateral limb, which served as a paired control. After 2, 4, 8, 16, and 25 weeks, bone bonding and bone formation at the bone/implant interfaces were evaluated by a detaching test and undecalcified histological examination. The tensile failure load increased from 2 to 25 weeks for both groups. The failure load of the AAAG-treated group was significantly greater than that of the control group at every stage. Histologically, the AAAG-treated specimens showed active new bone formation in the medullary cavity and extensive bonding between the implant and bone at early periods. The percentage of bony covering in the AAAG-treated group was significantly higher than that of the controls at all intervals except at 25 weeks. The results of this study suggest that the addition of osteoinductive AAAG to a bioactive implant may significantly accelerate bone apposition to the implant and improve the bonding process at the interface, which would help to establish an earlier and stronger bonding between the implants and the surrounding bone.

Animals↗

Osteoclastic resorption of bone-like apatite formed on a plastic disk as an in vitro assay system.

We have investigated the applicability of a simple and inexpensive osteoclastic assay system using bone-like apatite-coated polyethyleneterephthalate (PET) disks. A 1 microm thick apatite layer, uniform and homogeneous bone-mineral-like with no organic components, was made on PET disks using a biomimetic process. As substrates for an osteoclastic assay, these coated disks were compared with dentine as well as with bone-like or heat-treated apatite of various thicknesses on apatite- and wollastonite-containing glass ceramic (A-W GC) disks. The unfractionated bone cells, including osteoclasts, of a neonatal rabbit were seeded onto these substrates. By scanning electron microscopic examination, the resorption lacunae of the thick bone-like apatite clearly showed track-like shapes at various depths, similar to those of dentine although the border between the A-W GC and the apatite was unclear. In contrast, those of heat-treated apatite showed small and shallow shapes with irregular margins, quite different from those of dentine. By reducing the thickness of bone-like apatite to 1 microm as well as using PET as its substrate, the margins of the resorption lacunae became quite clear, and with the use of phase-contrast microscopy during culture, osteoclasts and resorption pits could be precisely observed. The resorbed area, easily measured with the aid of bright-field microscopy and an image analyzer, was found to have increased in a time-dependent manner and at the end of 4 days of culture was not statistically different from that of dentine.

Animals↗

Immunological competence and nutritional status in patients with lung cancer.

The rate of infection in patients with malignant disease is significantly higher than in patients with benign disease. To investigate whether immunological competence is impaired in patients with lung cancer, we assessed neutrophil function (chemotaxis, phagocytosis, bacterial killing activity, and superoxide production), monocyte function (phagocytosis and killing activity), lymphocyte subsets using flow cytometry, and proliferation of lymphocytes stimulated by phytohemagglutinin, concanavalin A, and pokeweed mitogen. Studies were performed on 22 untreated patients with lung cancer and 21 age-matched healthy volunteers. Nutritional status was assessed by Niederman's nutritional index. In patients with lung cancer neutrophil chemotaxis, monocyte phagocytosis and killing, proliferation of lymphocytes stimulated by phytohemagglutinin and concanavalin A, but not pokeweed mitogen, and the number of natural killer cells were significantly lower than in healthy volunteers, whereas gammadelta T cells were increased (p < 0.05). The mean score on Niederman's nutritional index was worse in patients than in healthy volunteers (p < 0.001). Our results suggest that the impaired immunological competence and undernutrition may be among the mechanisms causing increased susceptibility to infection in patients with lung cancer.

Adenocarcinoma↗

A decrease in cerebral cortex intensity on T2-weighted with ageing images of normal subjects.

To determine the change in intensity in the cerebral cortex on T2-weighted MRI with ageing, we reviewed the T2-weighted images of 83 normal subjects and measured the signal intensity in the cerebral cortex in 30 subjects randomly selected from them. Low-intensity areas were more common in the cerebral cortex of the aged. The intensity of different cortical regions varied, and the intensity in the temporal and parietal to be decreased with ageing. Presumably, this change of the intensity reflects senile changes, although low intensity is not evident in the temporal cortex because of its high basal intensity level.

Aging↗

Linoleic acid and alpha-linolenic acid lightens ultraviolet-induced hyperpigmentation of the skin.

This study was conducted to evaluate the effects of unsaturated fatty acids on ultraviolet-induced hyperpigmentation of the skin. An efficient lightening effect was observed following topical application of linoleic acid or alpha-linolenic acid to UV-stimulated hyperpigmented dorsal skin of brownish guinea pigs. The number of melanocytes in the treated skin was similar to the number in the skin of the pigmented control, indicating that the pigment-lightening effect was not due to depletion of melanocytes. In vitro experiments using cultured murine melanoma cells showed that melanin production was inhibited most effectively by alpha-linolenic acid, followed by linoleic acid and then by oleic acid. Furthermore, the turnover of the stratum corneum, which plays an important role in the removal of melanin pigment from the epidermis, was accelerated by linoleic acid and by alpha-linolenic acid. Taken together, the results suggest that the pigment-lightening effects of linoleic acid and alpha-linolenic acid are, at least in part, due to suppression of melanin production by active melanocytes, and to enhanced desquamation of melanin pigment from the epidermis.

Administration, Topical↗

Influence of various structure treatments on histological fixation of titanium implants.

In this study, three types of titanium test pieces were manufactured with different surfaces and implanted into dog femoral condyles, and tissue response was assessed histologically and radiographically for 24 weeks thereafter. The study confirmed that thickening of lamellar bone could be observed around titanium plasma spray-coated titanium alloy implants 24 weeks after implantation, whereas thick fibrous tissue surrounded by corticalized bone formed around those made of smooth-sided titanium alloy. With an implant made of an artificial osteochondral composite material, thickening of ingrown trabeculae could be observed as early as 4 weeks, and abundant bone growth into the titanium fiber mesh continued to increased with time. This bone ingrowth resulted in the complete integration of this composite device implant and the host bone. Our findings suggest that cell response to the various implants is quite different, even though the implants were made of the same kind of material. The implants with the open-pore structure has great significance in the ideal fixation between the implants and the viable bone.

Alloys↗

Oral absorption tests: absorption site of each substrate.

Three oral absorption tests have been used in patients with short bowel syndrome (SBS) to evaluate the absorption site of each substrate. In this study, three absorption tests were applied: the oral pancreatic function test using N-benzoyl-L-tyrosyl-p-aminobenzoic acid (NBT-PABA), the D-xylose tolerance test, and the oral fat tolerance test. Examinations were performed in eight patients with either a duodenostomy or a jejunostomy located less than 60 cm from the ligament of Treitz, and in a patient with an end ileostomy. Forty-six healthy volunteers participated as controls for the oral fat tolerance test. PABA and D-xylose concentrations were measured in urine. The serum triacylglycerol concentration was determined at 0, 1, 2, and 3 h after ingestion. All eight patients with SBS demonstrated pathologic absorption on each test. We conclude that small bowel integrity is critical for evaluation of the NBT-PABA test. We also determined that the duodenum and proximal jejunum do not play an important role in the absorption of D-xylose and triacylglycerol. We could also evaluate limitations and advantages of the other kinds of oral absorption tests and nutrients through patients with SBS.

4-Aminobenzoic Acid↗

Unresponsiveness of CD4-8+/- thymocytes to lectin stimulation in LEC mutant rats.

A mutant strain of rat, LEC, shows a novel arrest of T-cell maturation from CD4+8+ to CD4+8-, but not to CD4-8+ cells in the thymus. The responsible mutant locus is designated the thid, which was acted upon in a recessive manner of inheritance. We found that LEC rat thymocytes failed to respond to interleukin (IL)-1, IL-6 and IL-7 in the presence of the mitogenic lectins, Allo A or concanavalin A (Con A). The unresponsiveness appeared to be due to unresponsiveness to the lectin stimulation rather than because of cytokine stimulation. Normal rat CD4-8+/- (consisting of CD4-8+ and CD4-8- thymocytes), CD4+/-8- (consisting of CD4+8- and CD4-8- thymocytes), and CD4-8- thymocyte subsets normally responded to mitogenic stimulation, while CD4+8+ thymocytes did not. In contrast, all LEC rat CD4-8+/-, CD4+/-8-, CD4-8- and CD4-8+ thymocytes did not respond to the mitogenic stimulation, suggesting that the unresponsiveness of the CD4-8+/- thymocytes seems to be responsible for the unresponsiveness of whole thymocytes in LEC rats. LEC rat CD4-8+/- thymocytes normally expressed Con A receptor (R), lymphocyte function-associated antigen-1 (LFA-1), and CD45, which are thought to be important molecules for lectin stimulation. When backcross rats from (F344xLEC)F1xLEC were examined, the phenotype for the thid mutation correlated with the [3H]thymidine deoxyribose (TdR) incorporation level in response to Con A stimulation; thymocytes from backcross rats showing +/thid phenotype responded to Con A stimulation normally, whereas thymocytes from backcross rats showing thid/thid phenotype showed significantly lower responsiveness compared with +/thid rats. However, in WKAH.C-thid congenic rat thymocytes that carry the thid mutation, the responsiveness to mitogenic stimulation was comparable to that of normal rat thymocytes. These results suggest that a defect in responsiveness to mitogenic stimulation in LEC rat thymocytes is controlled by multiple genetic loci and the thid locus is one of the important loci for the development of this abnormal phenotype.

Animals↗

MPO-ANCA-positive crescentic necrotizing glomerulonephritis and tubulointerstitial nephritis with renal eosinophilic infiltration and peripheral blood eosinophilia.

We present the case of a 67-year-old woman with myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-positive pauci-immune crescentic necrotizing glomerulonephritis and tubulointerstitial nephritis with renal eosinophilic infiltration and peripheral blood eosinophilia. Staining for eosinophil cationic protein indicated that activated eosinophils were involved in the tubulitis, as well as in the glomerular injury. Marked peripheral blood eosinophilia is uncommon in ANCA-positive crescentic necrotizing glomerulonephritis associated with tubulointerstitial nephritis, except in Churg-Strauss syndrome. However, our patient had no clinical history or signs of asthma, no other signs suggestive of allergic diseases, and no histologic findings of granulomas in the kidney, thus failing to fulfill the criteria for Churg-Strauss syndrome.

Aged↗

Argyrophilic structures stimulate glial reactions in neurofibrillary tangles and senile plaques.

Neurofibrillary tangles (NFT) and senile plaques (SP) contain various pathological structures, and the majority of these pathological structures are argyrophilic. To investigate the glial reactions of the argyrophilic substance, we performed immunohistochemistry for microglia or for astroglia after Gallyas-Braak staining, which is one of the most sensitive silver impregnation techniques detecting argyrophilic structures in NFT and SP. We found that extracellular argyrophilic structures in NFT and SP showed glial reactions, and we observed reactive microglia in the center of NFT and SP in contrast to astroglia, which were situated in the periphery. These findings suggest that the exposed argyrophilic components in the extracellular space stimulate both glial reactions, but that there is a striking difference in localization between microglia and astroglia.

Alzheimer Disease↗

Structure and property of model peptides of proline/arginine-rich region in bactenecin 5.

Bactenecin 5 (Bac 5), a cationic antibacterial peptide, contains a repeating region of Arg-Pro-Pro-X (X = hydrophobic residue). To investigate the structure and property of a Pro/Arg-rich region, we synthesized a series of repeating peptides, Ac-(Arg-Pro-Pro-Phe)n-NHCH3 (n = 2, 4, 6, 8 and 10) (PR2, PR4, PR6, PR8 and PR10) as models. The circular dichroism (CD) study suggested that the peptides with longer repeats, PR6, PR8 and PR10, formed a conformation similar to poly(proline)-II in aqueous solution. The CD spectra did not change in the presence of dipalmitoyl-DL-alpha-phosphatidylcholine (DPPC), but they changed in the presence of DPPC/ dipalmitoyl-DL-3-phosphatidylglycerol (DPPG). The gamma-helix, which is very similar in conformation to the poly(proline)-II helix, had the lowest energy conformation for the peptides by energy calculations. Peptides PR6, PR8 and PR10 caused slight leakage of fluorescent dye entrapped in DPPC vesicles, and in the presence of DPPC/DPPG, these peptides showed a considerable level of dye-leakage activity. In contrast, the shorter peptides PR2 and PR4 showed no activity. The same tendency was found in measurements of membrane-fusion activity. Judging from these results, the repeating region of Bac 5 may make a framework to hold a conformation resembling the poly(proline)-II structure in aqueous solution. In addition, this region may interact with acidic lipids, resulting in a change in conformation of the peptide.

Amino Acid Sequence↗