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Biomedical subjects

T Kosaka

Publications and source records attributed to T Kosaka.

At least 145 records · Page 8Linked to original sources
PubMed1995

[A study of chemotherapy for patients with severely advanced gastric cancer--comparison of chemotherapy and route].

We analyzed the clinical response, toxicities, ambulatory and overall survival time among 51 patients with inoperable gastric cancer, to evaluate chemotherapies and drug delivery routes. Twenty-nine patients were treated by Methotrexate/5-FU (FMTX) therapy and 22 by 5-FU/CDDP (FP) therapy. Twenty-five patients were treated by intra-arterial (IA) route and 26 by intra-venous (IV). The response rate of IA therapy was higher than that of IV therapy (p < 0.05), 48% and 19%, respectively. Median survival times of FMTX and FP were 361 and 289 days, respectively, and the 1-year survival rates of FMTX and FP were 44% and 33%, respectively, with no significant differences. Duration of home chemotherapy with FMTX was longer than that with FP, at 130 and 85 days, respectively. There was no difference between duration of home chemotherapy of IA and that of IV. IA chemotherapy showed a higher response rate than IV, but there were no differences in the incidence of side effects and ambulatory and overall survival time.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Effect of low dose CDDP/5-fluorouracil therapy on PCNA labeling index and TS inhibition rate of gastric cancer].

The response of gastric cancer to intravenous application of low-dose CDDP plus 5-fluorouracil (FP) was assessed by changes in DNA indices (DIs) and PCNA labeling indices (LIs) by flow cytometry, and by the thymidylate synthetase inhibition rate (TSIR). Pretherapy samples were compared to specimens resected at operation. FP therapy was performed in 10 of 26 specimens and not in the others (C). There was no difference between change in DIs of FP group and that of C group. In FP group, PCNA LI of resected specimen was higher than that of biopsy, although they showed almost the same values in C group. Change in PCNA LIs correlated to TSIR in FP group. These results suggest that FP therapy affects gastric cancer cells in PCNA LIs and TSIR, and that PCNA LIs could be an indicator of the effect of FP therapy as TSIR.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[The effects of prostaglandins on the blood-retinal barrier].

The effects of prostaglandin (PG), a novel PG-related compound, and epinephrine on the blood-retinal barrier (BRB) in the rabbit eye were examined by ophthalmoscopy, fundus photography, fluorescein angiography (FAG), vitreous fluorophotometry (VFPM), light and electron microscopy, and the horseradish peroxidase tracer. Intravitreal injection of PGE2 produced retinal vasodilation and large increase in a vitreous fluorescein leakage in VFPM. Intravitreal injection of PGF2 alpha produced a small increase in vitreous fluorescein leakage in VFPM, but no retinal vasodilation. Intravitreal injection of epinephrine produced retinal vasodilation and a small increase in vitreous fluorescein leakage in VFPM. But intravitreal injection of latanoprost (PhXA41) produced no retinal vasodilation and no increase in vitreous fluorescein leakage in VFPM. After intravitreal injection of PGE2, morphological changes in the retina were found, but intravitreal injection of PhXA41 did not induce morphological changes in the BRB or the retina. PhXA41 was less destructive to the BRB and the retina than PGE2, PGF2 alpha, and epinephrine.

Animals↗
PubMed1995

Leukocytapheresis therapy with leukocyte removal filter for inflammatory bowel disease.

Leukocytapheresis (LCAP) with a leukocyte removal filter was administered to 44 patients with inflammatory bowel disease (IBD), diagnosed as ulcerative colitis (UC) in 25 and Crohn's disease (CD) in 19. Clinical and blood examinations showed no side effects in any of the patients. During intensive therapy, clinical improvement was recognized in 21 of the 25 UC patients (84%), 8 of whom had an excellent response, and in 16 of the 19 CD patients (84.2%), 4 of whom had an excellent response. The clinical improvement continued throughout the maintenance therapy in 19 of the UC patients (76%) and in 12 of the CD patients (63.2%). In both the UC and the CD patients, flow cytometry study showed that those who had improved generally had high values for the percentages of HLADR+, HLADR+CD3+, HLADR+CD8+, and CD11a+CD8+ cells before the first LCAP, and that these values decreased to near the normal range after both intensive and maintenance therapy. In the patients who showed poor response, in contrast, the values had been at or near normal before the initial LCAP administration. The clinical improvement and the findings on flow cytometry suggest that LCAP exerts an immuno-modulatory effect and is an effective therapy for patients with IBD in whom conventional drug treatments have failed.

Case-Control Studies↗
PubMed1995

Efficacy of nutritional therapy for active Crohn's disease.

We investigated the effect of nutritional therapy with an elemental diet (ED) for active Crohn's disease. One hundred and thirty-nine patients with Crohn's disease were enrolled in this study. Remission was judged to be present when the International Organization of Inflammatory Bowel Disease score was < or = 1 and the CRP and ESR values were within the respective normal ranges. An amount of 30kcal per 1kg of ideal body weight (IBW) per day was administered enterally, and the effect on the induction of remission in relation to various patient background factors, such as disease type, history of bowel resection, and the presence/absence of complications, was determined. An excellent remission rate was achieved in those patients to whom an adequate amount of ED could be administered. Remission rates were lower in the patient groups with any of the following complications: stenotic bowel lesions, abdominal masses, fistulas, and anal lesions. Even in those groups in which stenotic lesions or abdominal masses were present, when adequate amounts of ED could be administered, the remission rate did not differ from that in the groups without these complications. The remission rates in the groups with and without fistulas at any site, including fistulas in the anal region, were 40.0% and 82.5%, respectively, with remission being considerably easier to achieve in the patients without fistulas. Similarly, remission was difficult to achieve when anal lesions were present. These results suggest that, for active Crohn's disease, nutritional therapy with ED ( > or = 35kcal/kg IBW) should be enthusiastically administered, and in patients in whom the presence of complications necessitates therapy for 3 months or more, this point be considered to indicate a possible surgical approach.

Adult↗
PubMed1995

The effects of prostaglandins on the blood-ocular barrier.

The effects of prostaglandins (PGs) and PG-related compounds on the blood-ocular barriers were examined using pigmented rabbits. Latanoprost (PhXA41), PGF2(alpha)-isopropyl ester (PGF2(alpha)-IE) or PGE2 was topically applied once only or once daily for 8 weeks. Aqueous flare was measured with a laser flare-cell meter, and morphological changes in the ciliary processes after repeated applications of a test drug were investigated by means of light or electron microscopy using horseradish peroxidase (HRP) as a tracer. PGF2(alpha)-IE and PGE2, but not PhXA41, caused an initial rise in the aqueous flare after application. On the other hand, no morphological changes were found in the ciliary processes after 8-week PhXA41 application. After 8-week application of PGF2(alpha)-IE or PGE2 dilation of ciliary channels in the ciliary processes were found. Leakage of intravenously injected fluorescein was measured by a vitreous fluorophotometer after an intravitreal injection of PGE2, PGF2(alpha), or PhXA41. Vitreous fluorescence was significantly higher in treated eyes than in controls after intravitreal injection of PGE2 or PGF2(alpha), while it showed no significant change after intravitreal injection of PhXA41. Only PGE2 caused morphological changes in the retina. These results suggest that PhXA41 does not compromise the integrity of the blood-ocular barriers, and has a potential as a future anti-glaucoma eyedrop.

Administration, Topical↗
PubMed1994

Three-dimensional organization of neuronal and glial processes: high voltage electron microscopy.

Neurons and glia cells in the mammalian central nervous system have many complicated processes. They are too fine for light microscopic study and too complicated and widely spread for thin section electron microscopy. High-voltage electron microscopic (HVEM) stereo observation of thick Golgi preparation provides detailed 3-D images of their processes. Three-dimensional fine structures of astocytic processes in the neuropile and on the surface of neuronal somata, and those of the ruffed cell axon initial segment and thorny excrescences of CA3 pyramidal cell dendrites, are elucidated with the aid of HVEM stereoscopy of thick Golgi preparations. In addition, some results obtained by 3-D morphometrical analysis of dendritic spines using HVEM stereo images are shown. The examples presented here clearly show the usefulness of high-voltage electron microscope stereo observation of thick specimens for detailed morphological and morphometric study of the central nervous system.

Animals↗
PubMed1994

Synaptic contacts between mitral/tufted cells and GABAergic neurons containing calcium-binding protein parvalbumin in the rat olfactory bulb, with special reference to reciprocal synapses between them.

It has been believed so far that in the mammalian olfactory bulb, only granule cells form reciprocal synapses with mitral/tufted cells in the external plexiform layer (EPL). However, the present electron microscopic study demonstrated for the first time that another group of immunocytochemically defined interneurons different from granule cells, viz., neurons containing a specific calcium-binding protein parvalbumin, also made reciprocal synapses with mitral/tufted cells in the EPL.

Animals↗
PubMed1994

Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2.

The human gene (PTGS2) encoding an inducible isozyme of prostaglandin-endoperoxide synthase (prostaglandin-endoperoxide synthase 2) that is distinct from the well-characterized and constitutive isozyme (prostaglandin-endoperoxide synthase 1), was isolated using a polymerase-chain reaction-generated cDNA fragment probe for human prostaglandin-endoperoxide synthase 2. Nucleotide sequence analysis of the entire human prostaglandin-endoperoxide-synthase-2 gene demonstrated that it is more than 8.3 kb in size and consists of ten exons; this gene is very similar to the murine and chicken prostaglandin-endoperoxide-synthase-2 genes. The structures of exons in the human prostaglandin-endoperoxide-synthase-2 gene were also similar to those of the human prostaglandin-endoperoxide-synthase-1 gene (PTGS1). However, the sizes of introns in the human prostaglandin-endoperoxide-synthase-2 gene were generally smaller than those of the human prostaglandin-endoperoxide-synthase-1 gene. Primer-extension analysis indicated that the transcriptional-start site is 134 bases upstream of the translational-initiation site. The sequence of the 1.69-kb region of nucleotides preceding the transcriptional-start site and the first 0.8-kb intron contained a canonical TATA box and various transcriptional-regulatory elements (CArG box, NF-IL6, PEA-1, myb, GATA-1, xenobiotic-response element, cAMP-response element, NF-kappa B, PEA-3, Sp-1 and 12-O-tetradecanoyl-phorbol-13-acetate-response element). The nucleotide sequence of the 5'-flanking region (275 bp) of the human prostaglandin-endoperoxide-synthase-2 gene showed 63% similarity to the sequence of murine prostaglandin-endoperoxide-synthase-2/TIS10 gene, but essentially no homology to the chicken prostaglandin-endoperoxide-synthase-2 gene, and human and murine prostaglandin-endoperoxide-synthase-1 genes. A fluorescence in situ hybridization study showed that the human genes coding for prostaglandin-endoperoxide synthase 1 (PTGS1) and prostaglandin-endoperoxidase synthase 2 (PTGS2) were mapped to distinct chromosomes 9q32-q33.3 and 1q25.2-q25.3, respectively, indicating that these genes are not genetically linked.

Amino Acid Sequence↗
PubMed1994

Regional difference in the distribution of parvalbumin-containing neurons immunoreactive for monoclonal antibody HNK-1 in the mouse cerebral cortex.

Using preembedding immunocytochemistry at light microscopic level, we found that, although monoclonal antibody HNK-1 selectively outlined a subpopulation of GABAergic neurons containing a specific calcium-binding protein parvalbumin (PV) in the adult mouse cerebral cortex, the proportion of HNK-1-positive cells to PV-containing cells showed prominent regional difference. In the parietal cortex, approximately 50% of PV-positive cells were HNK-1-positive whereas only approximately 10% of PV-positive cells were HNK-1-immunoreactive in the occipital and temporal cortices. There were also prominent differences in this proportion among allocortical areas. These observations indicate that the cellular composition of chemically defined subpopulations of GABAergic neurons are different from area to area in mouse cerebral cortex.

Animals↗
PubMed1994

Calcium-binding protein parvalbumin-immunoreactive neurons in the rat olfactory bulb. 1. Distribution and structural features in adult rat.

The laminar distribution and morphological features of parvalbumin-immunoreactive [PV(+)] neurons, one of the subpopulations of GABAergic neurons, were studied in the rat olfactory bulb at a light microscopic level. In the main olfactory bulb of adult rats, PV(+) neurons were mainly located in the external plexiform layer (EPL), and a few were scattered in the glomerular layer (GL), mitral cell layer (ML), and granule cell layer (GRL); whereas PV(+) neurons were rarely seen in the accessory olfactory bulb. The inner and outer sublayers of the EPL (ISL and OSL) appeared to be somewhat different in the distribution of PV(+) somata and features of PV(+) processes. PV(+) somata were located throughout the OSL, and PV(+) processes intermingled with one another, making a dense meshwork in the OSL; whereas, in the ISL, PV(+) somata were mainly located near the inner border of the EPL, and PV(+) processes made a sparser meshwork than that in the OSL. PV(+) neurons in the EPL were apparently heterogeneous in their structural features and appeared to be classifiable into several groups. Among them there appeared five distinctive types of PV(+) neurons. The most prominent group of PV(+) neurons in the OSL were superficial short-axon cells, located in the superficial portion of this sublayer and giving rise to relatively thick processes, in horizontal or oblique directions, which usually bore spines and varicosities. Another prominent group of PV(+) neurons extended several short, branched dendrites with spines and varicosities, which appeared to intermingle with one another, making a relatively small, spherical or ovoid dendritic field around the cell bodies; most of them resembled Van Gehuchten cells reported in previous Golgi studies. A third distinctive and most numerous group of PV(+) neurons were of the multipolar type; their somata and processes were located throughout the EPL. Their relatively smooth processes with frequent varicosities and a few spines were extended horizontally or diagonally throughout the EPL. A fourth group, which could be a subtype of the multipolar type, were located in or just above th ML and extended several thin, smooth dendrites in the EPL, some of which appeared to reach the border between the GL and EPL. Occasionally, axon-like processes arose from their cell bodies and extended into the ML. This fourth type of PV(+) neuron was named inner short-axon cells. A fifth group of neuron was located in the ML; processes of these neurons were extended horizontally, so they were named inner horizontal cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Calcium-binding protein parvalbumin-immunoreactive neurons in the rat olfactory bulb. 2. Postnatal development.

The laminar development of the external plexiform layer (EPL) in the rat main olfactory bulb and the postnatal development of parvalbumin-immunoreactive [PV(+)] neurons mainly located in this layer were studied in animals at postnatal week 1-4 at a light microscopic level. The EPL in the adult olfactory bulb consists of two sublayers, the inner sublayer (ISL) and the outer sublayer (OSL). The ISL was already developed well even at postnatal day 7 (P7), whereas the OSL was first recognized at P10 as a thin zone consisting of more or less loosely packed large-sized and small-to-medium-sized somata subjacent to the glomerular layer (GL). The OSL increased in thickness and came to occupy nearly one-third to -half of the EPL at P14. PV(+) neurons first appeared at P10 mainly in the inner border of EPL. Only a few PV(+) neurons were scattered in the EPL at P10, but they increased remarkably in number during P14-21. Some of these PV(+) neurons at P10 had an intensely immunoreactive soma, extending relatively long processes with varicosities and/or spines. At P14, PV(+) neurons were located not only in the ISL but also at the border between the ISL and OSL, but in the OSL proper they were rarely observed. These PV(+) neurons showed branched and complicated processes with numerous varicosities and spines, displaying more mature features than those in previous stages. Even at P14 many of these PV(+) neurons appeared to exhibit some characteristic structural features of those in the adult stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Quantitative analysis of GABA-like-immunoreactive and parvalbumin-containing neurons in the CA1 region of the rat hippocampus using a stereological method, the disector.

The numerical density of neurons in the CA1 region of the rat dorsal hippocampus has been estimated by a stereological method, the disector, using pairs of video images of toluidine blue-stained, plastic-embedded, 0.5-microns-thick sections, 3 microns distant from each other. The chemical properties of those disector-counted cells were further analyzed by postembedding immunocytochemical methods on adjacent, semithin sections using antibodies against gamma-aminobutyric acid (GABA) and a specific calcium-binding protein, parvalbumin (PV). The density of neurons in the CA1 region was 35.2 x 10(3)/mm3; numerical densities in the stratum oriens (SO), stratum pyramidale (SP), and strata radiatum-lacunosum-moleculare (SRLM) were 11.3 x 10(3)/mm3, 272.4 x 10(3)/mm3, and 1.9 x 10(3)/mm3, respectively. The numerical densities of GABA-like immunoreactive (GABA-LIR) and PV-immunoreactive (PV-IR) neurons were 2.1 x 10(3)/mm3 and 1.1 x 10(3)/mm3, respectively, which were 5.8% and 3.2% of all neurons, respectively. In the CA1 region only about 60% of PV-positive neurons were GABA-LIR. However, taking the previous observation into consideration that almost all hippocampal PV-positive neurons were immunoreactive for the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD), neurons that were immunoreactive to either GABA or PV or both (GABA+ and/or PV+ neurons) were regarded as a better representative of GABAergic neurons in this region; thus, the numerical density of these GABA+ and/or PV+ neurons was 2.5 x 10(3)/mm3 and they were 7.0% of all neurons in the CA1 region. Lamellar analysis showed that the numerical densities of GABA+ and/or PV+, GABA-LIR, and PV-IR neurons were highest in the SP, where they were 8.2 x 10(3)/mm3, 6.2 x 10(3)/mm3, and 5.4 x 10(3)/mm3, respectively. The results of the present study indicate that the proportions of GABAergic neurons and a subpopulation of them, PV-containing GABAergic neurons, to other presumable non-GABAergic neurons are far smaller in the CA1 region of the hippocampus than in several neocortical regions previously reported.

Animals↗
PubMed1994

Protective effects of serum thymic factor to Leptospira interrogans serovar Copenhageni infection in Mongolian gerbils.

The susceptibility to Leptospira interrogans serovar copenhageni in Mongolian gerbils treated with 10 micrograms of serum thymic factor (FTS) 1 day before infection was examined. Susceptibility of gerbils treated 5 times with 10 micrograms of FTS was also investigated. Mortality of FTS-treated gerbils was significantly lower than that of controls when small challenge doses were used. To analyse the FTS-induced resistance to leptospiral infection, natural killer (NK) cell activity and macrophage activity were studied. Macrophage activity was unaltered but NK cell activity was enhanced in FTS-treated gerbils, with or without leptospiral infection. Since no side-effects of FTS were observed, this compound should be considered for the treatment of leptospirosis.

Animals↗
PubMed1994

Distribution of Ia antigen-expressing nonlymphoid cells in various stages of induced periapical lesions in rat molars.

Periapical lesions were experimentally produced in rat lower first molars by exposing the pulp to the oral environment for 1 to 56 days. Temporal changes in the number and distribution of la antigen-expressing nonlymphoid cells in the periapical tissue were examined immunohistochemically on decalcified cryostat sections using OX6, a monoclonal antibody against rat la antigen. Influx of la-positive exudative cells into the periapical tissue was observed from 1 day postoperatively. Between 14 and 28 days when expansion of the periapical lesion was most evident, numerous la-positive macrophage-like and dendritic cell-like cells of diverse morphologies were found in the periapical tissue. The number of these cells showed further increase at 56 days postoperatively, when the lesion expansion had ceased. These results suggest the involvement of la antigen-expressing nonlymphoid cells in the development and perpetuation of periapical pathosis. They may act primarily as antigen-presenting cells, which are essential for the initiation of antigen-specific immune defense.

Animals↗
PubMed1994

Biosynthesis of human endothelins in transformants expressing cDNAs for human prepro-endothelins.

To understand the biosynthesis of the human ET family, three kinds of cloned cDNA for human prepro-endothelin-1 (prepro-ET-1), prepro-ET-2, and prepro-ET-3 were stably expressed in Chinese hamster ovary cells (CHO-K1). Immunoreactive (ir-) ET polypeptides in the culture media of the transformants were purified by reverse-phase high-performance liquid chromatography (HPLC) coupled with sandwich-type enzyme immunoassay (EIA). Amino acid sequencing and FAB mass spectrometry of the purified ir-ET polypeptides revealed the presence of human big ET-1 (1-38), big ET-2 (1-38), and big ET-3 (1-41)NH2 as intermediate forms. These results directly revealed the biosynthetic pathways of three human ETs at the peptide level.

Amino Acid Sequence↗
PubMed1994

Differential inhibition of platelet aggregation and calcium mobilization by nitroglycerin and stabilized nitric oxide.

We compared the mechanisms of the antiplatelet effects of nitroglycerin (NTG) and stabilized nitric oxide (NO). Stabilized NO was in the form of S-nitrosothiols [S-nitroso-albumin (S-NO-Alb) and S-nitrosocaptopril (S-NO-Cap)] or heme-NO [sodium nitro-prusside (SNP)]. The molecular structure of S-NO-Cap was confirmed by mass spectrometry. NTG, SNP, S-NO-Alb, and S-NO-Cap inhibited ADP-induced platelet aggregation dose dependently. The inhibitory IC50 value was 109 microM for NTG, 0.98 microM for SNP, 2.99 microM for S-NO-Alb, and 2.5 microM for S-NO-Cap. NTG (200 microM) released 15.4 microM nitrite anion into platelet-rich plasma (PRP) after 60-min incubation, to which platelets contributed 5.4 microM. On the other hand, SNP and S-NO-Cap released undetectable amounts of NO2- when incubated in either PRP or platelet-poor plasma (PPP). The platelet cytosolic calcium ion (Ca2+) concentration was measured fluorometrically in Fura-2-loaded gel-filtered platelets. Thrombin-induced Ca2+ mobilization was significantly inhibited by 10 microM NTG, SNP, S-NO-Alb, and S-NO-Cap, whereas resting Ca2+ was unaltered. Ca2+ mobilization was inhibited 28.6% by NTG, 91.9% by SNP, 90.0% by S-NO-Alb, and 92.7% by S-NO-Cap. These results demonstrate that NTG is an exogenous donor of NO, but releases it only slowly. On the other hand, SNP and S-nitrosothiols inhibited platelet aggregation by the action of stabilized NO incorporated in their structure and did not release NO. NTG and stabilized NO shared a common mechanism of antiplatelet activity, which involved inhibition of calcium mobilization.

Adult↗