Biomedical subjects

Y Inoue

Publications and source records attributed to Y Inoue.

At least 865 records · Page 48Linked to original sources

PubMed1996

Size effect on the antibody production induced by biodegradable microspheres containing antigen.

Poly(L-lactic acid) (PLLA) microspheres containing a model antigen, ovalbumin (OVA), were prepared by the evaporation method using double emulsion, and fractionated into different sizes by counterflow elutriation. Following the intraperitoneal (i.p.) and subcutaneous (s.c.) injection of the microspheres to mice, the titer of anti-OVA antibody in the serum was measured to assess the size effect on the profile of antibody production. OVA was released from the microspheres for 80 days, irrespective of the microsphere size. In both the s.c. and i.p. immunization, the serum level of anti-OVA IgG antibody in the mice induced by the microspheres containing OVA was higher than that of free OVA when compared at the same dose. The serum level of antibody in the mice i.p. injected with the microspheres tended to increase with the decreasing size. On the other hand, in the s.c. immunization, the microsphere size had little influence on the antibody production. It is possible that the injected microspheres tend to aggregate in the s.c. tissue, disappearing the size effect on the antibody production. Since the amount of microspheres injected increases with the decreasing size when their OVA loading is fixed, the increase in the amount will promote the interaction with immune cells, resulting in an enhanced antibody production. The cell interaction with the microspheres in the peritoneal cavity seems to be influenced by their size to a greater extent than in the s.c. tissue, probably because of their more frequent interaction with immune cells.

Animals↗

PubMed1996

Size effect on systemic and mucosal immune responses induced by oral administration of biodegradable microspheres.

Induction of systemic and mucosal immune responses following oral administration of biodegradable poly(D,L-lactic acid) (PDLLA) microspheres containing a model antigen, ovalbunin (OVA) was studied using microspheres with different average diameters of 0.6, 1.0, 4.0, 7.0, 11.0, 15.0, 21.0, and 26.0 microns. They were prepared from double emulsion with the solvent evaporation method, followed by size fractionation on counterflow elutriation. OVA was released from the microspheres in vitro over 80 days, irrespective of their size. Production of the serum anti-OVA IgG antibody and secretory OVA-specific IgA antibody in the mice gut was assessed following the oral administration of PDLLA microspheres containing OVA. Microspheres with a diameter of 4.0 microns enhanced the serum antibody in contrast with that of free OVA, but were not effective in inducing the gut secretion of IgA antibody. On the other hand, OVA-containing microspheres with a diameter of 7.0 microns enhanced IgA secretion to a significant extent compared with free OVA, whereas those with 26.0 microns in diameter were ineffective. Body distribution study revealed that the amount of microspheres taken up into Peyer's patches (PP) increased with the increasing size up to 11.0 microns, thereafter decreased, and finally became zero when their diameters were 21.0 microns or larger. The microspheres taken up into PP were translocated to the spleen, but no microspheres were noticed in the spleen when the size was larger than 5 microns. After being taken up inot PP, microspheres < 5 microns in diameter seemed to be transported to the spleen, a systemic lymphoid tissue, where the released antigen stimulated a serum antibody response, but larger microspheres probably remained at PP without being translocated to the spleen over the course of their antigen release, leading to induction of IgA secretion. It was concluded that the body distribution pattern of microspheres following the PP uptake was a key factor to regulate the induction of systemic and mucosal immune responses.

Administration, Oral↗

PubMed1996

No interaction between desipramine and bromperidol.

1. The authors studied the effects of coadministration of desipramine, which is a substrate of CYP2D6, on plasma concentrations of bromperidol and its reduced metabolite (reduced bromperidol). Clinical changes were also evaluated by the CGI and UKU. 2. The subjects were 13 schizophrenic inpatients receiving bromperidol 12.24 mg/day for 1.20 weeks. Desipramine 50 mg/day was coadministered for 1 week, and blood samplings and clinical ratings were performed before and after the coadministration. 3. Plasma concentrations of bromperidol and reduced bromperidol were measured by a HPLC method. 4. Desipramine coadministration did not affect plasma concentration of bromperidol (9.6 +/- 4.5 vs. 9.6 +/- 2.8 ng/ml) nor that of reduced bromperidol (2.8 +/- 2.5 vs. 2.8 +/- 2.1 ng/ml). 5. There was no significant change in the CGI scores nor UKU scores after desipramine coadministration. 6. The present study thus suggests that there is no interaction between desipramine and bromperidol.

Adult↗

PubMed1996

Impairment of suckling response, trigeminal neuronal pattern formation, and hippocampal LTD in NMDA receptor epsilon 2 subunit mutant mice.

Multiple epsilon subunits are major determinants of the NMDA receptor channel diversity. Based on their functional properties in vitro and distributions, we have proposed that the epsilon 1 and epsilon 2 subunits play a role in synaptic plasticity. To investigate the physiological significance of the NMDA receptor channel diversity, we generated mutant mice defective in the epsilon 2 subunit. These mice showed no suckling response and died shortly after birth but could survive by hand feeding. The mutation hindered the formation of the whisker-related neuronal barrelette structure and the clustering of primary sensory afferent terminals in the brainstem trigeminal nucleus. In the hippocampus of the mutant mice, synaptic NMDA responses and longterm depression were abolished. These results suggest that the epsilon 2 subunit plays an essential role in both neuronal pattern formation and synaptic plasticity.

Animals↗

PubMed1996

Primary culture of chicken hepatocytes in serum-free medium (pH 7.8) secreted albumin and transferrin for a long period in free gas exchange with atmosphere.

To study liver functions of chicken, we examined the primary culture of chicken hepatocytes, and found an easy method of long-term culture with free atmosphere exchange. Chicken hepatocytes were obtained by collagenase perfusion and cultured at 37 degrees C as a monolayer without substratum in serum-free L-15 medium (pH 7.8) with free atmosphere exchange. The amounts of albumin and transferrin in medium were assayed by ELISA. The culture of chicken hepatocytes was maintained in the serum-free L15-medium )pH 7.) and 37 degrees C with free atmosphere exchange for 20 days. The amount of albumin secreted in the medium decreased to low levels early in culture; however, this was followed by marked increase from day 9 to day 17 of culture. The amount of transferrin was constant until day 6, then it too increased with further culture. We reported an easy method for the simple monolayer culture of chicken hepatocytes in serum-free L12 medium (pH 7.8) with free atmosphere exchange over an extended period. Expression of liver-specific functions, viz. albumin and transferrin synthesis, was observed after 1 week of culture.

Air↗

PubMed1996

Schedule-dependent interaction between paclitaxel and 5-fluorouracil in human carcinoma cell lines in vitro.

We assessed the cytotoxic interaction between paclitaxel and 5-fluorouracil administered at various schedules against four human carcinoma cell lines, A549, MCF7, PA1 and WiDr. The cells were exposed simultaneously to paclitaxel and to 5-fluorouracil for 24 h or sequentially to one drug for 24 h followed by the other for 24 h, after which they were incubated in drug-free medium for 4 and 3 days respectively. In another experiment, the cells were exposed simultaneously to both agents for 5 days. Cell growth inhibition was determined by MTT reduction assay. The effects of drug combinations at IC80 were analysed by the isobologram. The cytotoxic interaction of paclitaxel and 5-fluorouracil was definitely schedule dependent. Simultaneous exposure to paclitaxel and 5-fluorouracil for 24 h showed mainly subadditive effects in A549, MCF7 and WiDr cell lines, whereas it showed additive effects in PA1 cells. Sequential exposure to paclitaxel followed by 5-fluorouracil showed additive effects in all cell lines. Sequential exposure to 5-fluorouracil followed by paclitaxel showed subadditive effects in A549, MCF7 and PA1 cells. Whereas it showed additive effects in WiDr cells. These findings suggest that maximum cytotoxic effects can be obtained when paclitaxel precedes 5-fluorouracil. Interestingly, the continuous (5-day) exposure to paclitaxel and 5-fluorouracil had additive effects in A549, PA1 and WiDr cells, indicating that the prolonged simultaneous administration of these agents may circumvent the antagonistic interaction produced by short-term simultaneous administration. These findings may be useful in clinical trials of combination chemotherapy with paclitaxel and 5-fluorouracil.

Antimetabolites, Antineoplastic↗

PubMed1996

Acellular human dermal matrix as a small vessel substitute.

In both vascular and microvascular surgery, there is a need for a non-thrombogenic, small-caliber, arterial substitute. Clinically, most vessel substitutes with diameters under 4 mm have low patency rates. An arterial conduit made from a biocompatible human acellular dermis may be useful as a small vessel conduit. The purpose of this study was to evaluate and compare the patency rates of a vascular conduit made from rolled human acellular dermal (ACD) matrix and a similar-sized polytetrafluoroethylene (PTFE) tube, using the rat femoral artery interposition model. Twenty-eight days after implantation, 9 or 10 (90 percent) ACD grafts and 5 of 8 (62.5 percent) PTFE grafts were patent. False aneurysms formed in 6 ACD conduits along the longitudinal suture line. The three patent non-aneurysmal ACD conduits developed an endothelial luminal lining. While further studies are needed, acellular dermis appears to be a promising material for use as a vessel substitute.

Aneurysm, False↗

PubMed1996

Diverse effects of tumor necrosis factor-alpha on three subclones from human myelomonocytic leukemia cell line ME-1 exhibiting different differentiation stages.

The effects of tumor necrosis factor-alpha (TNF-alpha) were examined in three subclone cells from human myelomonocytic leukemia cell line ME-1. These three subclone cells exhibit different differentiation stages of the myelomonocytic lineage. TNF-alpha exerted a growth-suppressive effect on the least mature subclone cells, ME-F2 cells. On the other hand, TNF-alpha induced the most mature ME-F1 cells and intermediate ME-F3 cells to differentiate along the monocytic pathway. TNF-alpha also enhanced interferon-gamma (IFN-gamma)-induced complement C2 production by ME-F1 and ME-F3 cells but did not affect production by differentiated ME-F1 and ME-F3 cells. These results suggest that the diversity of the effects of TNF on subclone cells from ME-1 depends on the stage of cell differentiation.

Cell Differentiation↗

PubMed1996

Studies of retroorbital tissue xenografts from patients with Graves' ophthalmopathy in severe combined immunodeficient (SCID) mice: detection of thyroid-stimulating antibody.

The pathogenesis of Graves' ophthalmopathy (GO) is still unclear and the possible role of TSH receptor antibody in the development of GO is controversial. However, the recent availability of severe combined immunodeficient (SCID) mice has provided a means to study of human autoimmune thyroid disease in an in vivo environment. In the present study, we xenografted human retroorbital (RO) tissues from 9 patients with GO into 9 SCID mice and the autologous peripheral blood mononuclear cells (PBMC) from 5 of 9 GO patients were engrafted into 5 separate SCID mice to reconstitute the immunological environment of human GO. Mice blood samples were taken every 2 weeks for the measurements of human IgG, thyroglobulin antibody (Tg-Ab), thyroperoxidase (TPO)-Ab, thyroid-stimulating antibody (TSAb), and interferon-gamma (IFN-gamma). Eight weeks after xenografting, mice were killed; RO tissues were analyzed histologically, SCID mice with RO tissues from 2 of 9 GO patients produced human IgG peaking at 6-8 weeks after xenografting. TPO-Abs and TG-Abs were detectable in low titer in mice with RO tissue xenografts from 3/9 and 4/9 GO patients, respectively. The mean level of IFN-gamma in SCID mice with GO RO xenografts was higher than that of a control subject (RO tissue from a non-GO patient). TSAbs were actually produced from 7 of 9 mice xenografted with GO RO tissues, and reached their peaks at 2-8 weeks after xenografting; autologous PBMC (alone, without RO tissues)-engrafted SCID mice did not produce any detectable level of TSAb. The control mouse did not produce any detectable levels of human IgG, TPO-Ab, Tg-Ab, or TSAb. Immunohistochemical analysis of orbital mononuclear cell infiltrates revealed a predominance of T lymphocytes, with a small percentage of B lymphocytes in GO RO tissue graft. In conclusion, we have successfully reconstituted the SCID mice with human lymphocytes of RO tissues from patients with GO. Autoreactive B cell clones responsible for secreting TSAb exist in GO RO tissue and may be a key factor in the initiation and/or the progression of GO.

Adult↗

PubMed1996

Sympathetic overactivity of intraocular muscles evaluated by accommodation in patients with hyperthyroidism.

Sympathetic overactivity occurs in Graves' disease, but little is known about autonomic nervous function in the eyes of subjects with this disease. We examined this function of the intraocular muscles in 12 patients with hyperthyroid Graves' disease and 12 healthy controls. Pupil size, pupillary unrest, and accommodation were measured with a computer-assisted infrared optometer and pupillometer. The mean and the coefficient of variation of the areas of the pupils were used to express pupil size and the degree of pupillary unrest, respectively. Accommodation was measured with the target light beam moving slowly and steadily, or instantaneously, and the results are expressed as the change in the eye's refractive power in response to these movements. The mean pupil size of the patients was not different from that of the controls. Pupillary unrest in the patients was smaller than in the controls. Accommodation in the patients was lower than that of the controls. Five patients were examined again 3 months later when they became euthyroid; pupillary unrest and accommodation had improved in all five patients. There were no significant differences in the activity of sympathetic nerves governing intraocular muscles in patients with or without eyelid retraction. These results indicate that intraocular muscles are sympathetically overactive in patients with hyperthyroidism, and suggest that eyelid retraction is not caused by sympathetic overactivity alone, but by another factor or factors, in addition.

Accommodation, Ocular↗

PubMed1996

Localization and clinical significance of thyrotropin receptor mRNA expression in orbital fat and eye muscle tissues from patients with thyroid-associated ophthalmopathy.

We have studied the cellular localization of thyrotropin receptor (TSH-R) mRNA in orbital fat and extraocular muscle tissues from patients with thyroid-associated ophthalmopathy (TAO) using Northern blot, reverse transcriptase polymerase chain reaction (RT-PCR), and in situ hybridization, and we correlated the findings with clinical estimates of ophthalmopathy. Although we failed to detect TSH-R mRNA in orbital tissues by Northern blot, TSH-R cDNA was amplified in orbital fat tissue from 13 of 25 patients with TAO and from 2 of 4 control subjects, in eye muscle tissue from 2 out of 7 patients with TAO, and in cultured orbital fibroblasts and subcutaneous fibroblasts from TAO patients. In situ hybridization showed that TSH-R mRNA was detected in cultured orbital fibroblasts as well as skin fibroblasts obtained from the patient. Furthermore, the expression of TSH-R mRNA in orbital fat tissue from patients with TAO significantly correlated with the orbital fat volume and the severity of ophthalmopathy, especially the extent of eye muscle dysfunction. These results suggest that the expression of TSH-R in the orbit, especially fibroblasts, may play a role in the pathogenesis and clinical manifestations of the ophthalmopathy in patients with TAO, although a secondary effect, involving fibroblasts in TAO is also possible.

Adipose Tissue↗

PubMed1996

Use of whole-body imaging using Tc-99m RBC in patients with soft-tissue vascular lesions.

We investigated the usefulness of whole-body imaging as an adjunct to spot imaging in soft-tissue vascular lesions, such as hemangiomas and vascular malformations. Spot imaging of the known lesion and whole-body imaging were performed 1-3 hours after the injection of Tc-99m RBC in 42 patients with soft-tissue vascular lesions. Whole-body imaging was considered to be useful in only two patients, who had multiple distant occult lesions in addition to large known lesions. It was suggested that the routine addition of whole-body imaging is not cost effective in patients with soft-tissue vascular lesions, although it may be beneficial for detecting occult lesions in patients with hemangiomas.

Adolescent↗

PubMed1996

A numerical model for the analysis and evaluation of global 137Cs fallout.

Fallout 137Cs from atmospheric nuclear detonation tests has been monitored worldwide since the late 1950's. The deviation and the correlation among these monitoring data were analyzed, and their surface deposition characteristics were estimated by the compartment model developed in this research. In the analysis, the scale of space (i.e., size of each compartment) and the degree of detail (i.e., number of compartments) were statistically determined using the global distribution data of 137Cs. The mathematical model was evaluated by comparing the numerically stimulated results with the fallout monitoring data including the 137Cs concentration in sea water. The major findings obtained in this research include that the deposition pattern of 137Cs is dependent on the latitude zone but not on the longitude, the mathematical model is promising for evaluating the dynamic performance of 137Cs in global atmospheric environment and its surface deposition, 137Cs is accumulated more in both the surface and deep ocean water of the North Pacific Ocean and the North Atlantic Ocean than that of other oceans, the 137Cs inventory is decreasing after the peak time in 1965, and the 137Cs inventory in the deep ocean water is decreasing more slowly than that in the surface ocean water.

Cesium Radioisotopes↗

PubMed1996

The angiosomes of the forearm: anatomic study and clinical implications.

The angiosome concept was introduced in 1987 by Taylor and Palmer. Their anatomic study correlated the blood supply to the skin from the named segmental or distributing "source" arteries with their supply to the underlying muscles, tendons, nerves, and bones. Although this investigation encompassed the body, there were areas where the supply to individual tissues was not examined in detail. The present study, therefore, examines one of these regions where certain voids in our knowledge still exist--the forearm. Ten upper limbs from fresh cadavers were studied over an 18-month period after perfusing each with a radiopaque lead oxide mixture. The arterial supply to the skin and the bones of the forearm, together with that of a total of 200 muscles, was examined. The contribution to each was defined by dissection, by metal clip tagging of vessels, by radiography, and by mapping the branches with colored pins coded to match the respective source arteries. In the case of the muscles, a subtraction technique was used whereby the bones of the extremity were replaced with radiolucent balloons to obtain an unobscured picture of the forearm vasculature. Then the muscles were removed one by one from the muscle mass and x-rayed again. In this way, the angiosomes in the forearm, provided by the brachial, radial, ulnar, and interosseous arteries, were defined. Similarly, the contribution from each angiosome to the skin, to each muscle, and to the radius and the ulna was identified and the territories were color-coded to match these source arteries. Results showed that in most cases the connections between adjacent angiosomes occurred within tissues, not between them. The skin, the bones, and most muscles received branches from the source arteries of at least two angiosomes, thus revealing one of the important anastomotic pathways by which the circulation is reconstituted in those cases where a source artery is interrupted by disease or trauma. Several muscles, however, were supplied within one angiosome. This helps explain the variable clinical pictures seen in cases where the circulation is interrupted, such as that which occurs in a Volkmann's ischemic contracture. Finally, this anatomic study provides further information to help design various flaps from the forearm for local or free transfer. In the case of muscles, the supply to most from multiple angiosomes allows for refinements whereby a portion only of a muscle can be used. Similarly, this anatomic information reveals the pathway by which the supply to remaining muscle groups is reconstituted when one of the source arteries is harvested with a skin flap, a muscle, or part thereof.

Brachial Artery↗

PubMed1996

Human herpesvirus 7 infection of CD4+(+) T cells does not require expression of the OKT4 epitope.

To evaluate the role of the OKT4 epitope in human herpesvirus 7 (HHV-7) infection, we studied the susceptibility to HHV-7 infection of CD4+ T cells isolated from two individuals with OKT4 epitope deficiency. HHV-7-infected OKT4-Leu3a+ T cells exhibited the characteristic cytopathic effect, reactivity with HHV-7-seropositive serum by immunofluorescence and down-modulation of surface CD4 in a manner similar to HHV-7-infected OKT4+Leu3a+ T cells. A semiquantitative PCR revealed that the amounts of HHV-7 replicated in OKT4+Leu3a+ T cells and OKT4-Leu3a+ T cells were not significantly different. Although it has been reported that OKT4 monoclonal antibody efficiently inhibits HHV-7 infection, the present study demonstrated that the interaction of HHV-7 with CD4+ T cells does not require participation of the epitope defined by OKT4 monoclonal antibody.

Antibodies, Monoclonal↗

PubMed1996

Gas chromatographic-mass spectrometric metabolic profiling of patients with fatal infantile mitochondrial myopathy with de Toni-Fanconi-Debré syndrome.

The metabolic profiles of three patients with fatal infantile mitochondrial myopathy with de Toni-Fanconi-Debré syndrome were studied by simultaneous analysis, after urease treatment of urinary organic acids, carbohydrates, polyols and amino acids using gas chromatography/mass spectrometry (GC/MS). All three patients persistently showed lactic aciduria, phosphaturia, glucosuria and generalized amino aciduria. This abnormal urinary metabolic profile was observed before the onset of any clinical symptoms, indicating that chemical diagnosis may be done presymptomatically. In one patient, the concentration of lactate increased in parallel with the severity of the clinical condition, whereas the urinary levels of 3-hydroxybutyrate, amino acids and glucose fluctuated and showed only a general tendency to increase with the clinical course. The above results suggest that simultaneous GC/MS analyses, without fractionation, of urinary metabolites facilitate not only the early chemical diagnosis either before or after the first onset, but also follow-up studies, providing an important index for the evaluation of the severity and clinical course in patients with this disorder.

Fanconi Syndrome↗

PubMed1996

Altered gene expression of the N-methyl-D-aspartate receptor channel subunits in Purkinje cells of the staggerer mutant mouse.

The gene expression of five NMDA receptor channel subunits, the epsilon(1), epsilon(2), epsilon(3), epsilon(4) and zeta(1) subunits, was examined in cerebellar Purkinje cells of the staggerer mouse at postnatal day 21. In the midline region of the staggerer cerebellum, signals for the epsilon(1), epsilon(4) and zeta(1) subunit mRNAs were distributed in Purkinje cells, which have a large cell body aligned in a monolayer between the granular and molecular layers. In addition to the midline region, labelled neurons in the intermediate cerebellar region were, though at lower levels, aligned almost in a monolayer between the granular and molecular layers. In the hemisphere, most labelled neurons occurred in various locations in the granular layer and the cerebellar medulla. These regions, populated with Purkinje cells expressing the epsilon(1), epsilon(4) and zeta(1) subunit mRNAs, were separated from each other by narrow gap regions that contained neurons without any detectable NMDA receptor channel subunit mRNAs. These results suggest that there is discrete mediolateral heterogeneity in staggerer Purkinje cell populations, in terms of expression properties of the NMDA receptor channel subunits. When compared with wild-type Purkinje cells that express the zeta(1) subunit alone, additional expression of the epsilon subunits presumably explains the persistence of NMDA responses in adult staggerer Purkinje cells (Dupont et al., Neuroscience, 12, 613-619, 1984).

Animals↗

PubMed1996

Regional variation in expression of calbindin and inositol 1,4,5-trisphosphate receptor type 1 mRNAs in the cerebellum of the staggerer mutant mouse.

The Purkinje cells in the staggerer mutant mouse have various cellular abnormalities, including reduced cell number, ectopia, smaller size and absence of dendritic spines. It is also know that some of these abnormalities exhibit regional variations in the cerebellum. In this paper we have investigated expression in the staggerer Purkinje cells of the calbindin and inositol 1,4, 5-trisphosphate receptor type 1 mRNAs by in situ hybridization. Although the transcription levels of both mRNAs were significantly reduced compared with the wild-type cells, the reduction among the Purkinje cell populations was not even, varying greatly from region to region. Purkinje cells with different transcription levels were distributed in discrete regions and arranged alternately in the mediolateral direction. Moreover, the cell bodies with higher transcription levels were larger in size and aligned in a monolayer between the granular and molecular layers, whereas those with lower levels were smaller in size, fewer in number and dispersed throughout the granular layer. These findings suggest that there is a distinct mediolateral heterogeneity in the staggerer cerebellum with respect to transcription levels of these Purkinje cell-specific molecules, which might correlate with some cytological phenotypes.

Animals↗