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Biomedical subjects

K Kajiwara

Publications and source records attributed to K Kajiwara.

At least 91 records · Page 5Linked to original sources

Functional significance of IL-4 receptor on B cells in IL-4-induced human IgE production.

IL-4 with the IgE-inducing activity is shown to upregulate the expression of IL-4 receptor (IL-4R) on lymphocytes. Antisense strategy was used that aimed at investigating the significance of IL-4-induced upregulation of IL-4R on B cells in human IgE production. When an antisense phosphorothioate oligodeoxynucleotide to IL-4R (S-oligo 1) was added to B cells together with IL-4, the agent selectively abrogated the upregulation of IL-4R without affecting its constitutive level expression. Moreover, S-oligo 1 had a suppressive effect on the T-cell-independent synthesis of IgE by B cells costimulated with IL-4 and anti-CD40 antibody. This suppression was accompanied by inhibition of mature but not germline C epsilon transcription. These findings indicate that constitutively expressed IL-4R provides a signal or signals responsible for the induction of germline C epsilon transcription and suggest that IL-4R upregulation may be required for the subsequent class switch recombination that leads to mature C epsilon transcription and IgE synthesis. The IL-4R signal transduction mechanism underlying germline C epsilon transcription was also analyzed in a human Burkitt lymphoma B-cell line, DND39. Induction of germline C epsilon transcripts in DND39 cells by IL-4 required at least two distinct signaling cascades. One was mediated by enhancement of tyrosine phosphorylation of a 57 kd protein associated with phospholipase C-gamma 1 (PLC-gamma 1) that resulted in PLC-gamma 1 activation, inositol lipid hydrolysis, and protein kinase C delta translocation. The other was dependent on phosphatidylinositol 3-kinase, whose activation induced protein kinase C zeta translocation. In fact, kinase inhibitors such as herbimycin A, K-252a, and wortmannin were effective in inhibiting IL-4-induced germline C epsilon transcription. Therefore, in addition to activation of protein tyrosine kinases, coordinated actions of PLC-gamma 1 and phosphatidylinositol 3-kinase may be involved in IL-4-driven germline C epsilon transcription in DND39 cells.

Antigens, CD↗

Inhibition of IL-4 receptor up-regulation on B cells by antisense oligodeoxynucleotide suppresses IL-4-induced human IgE production.

IL-4 is shown to up-regulate its own receptor (IL-4R) on human lymphocytes, but the functional significance of up-regulated IL-4R is not clear regarding IgE production. This study investigated the possible role of IL-4-induced up-regulation of IL-4R on B cells in the induction of human IgE synthesis by means of antisense strategy. Among three antisense oligodeoxynucleotides designed against the downstream of translation initiation site of IL-4R cDNA, S-oligo 1, complementary to nucleotide 1-24, showed the strongest inhibition of the constitutive expression of IL-4R on Daudi cells. Addition of S-oligo 1 together with IL-4 also decreased the up-regulated but not constitutive levels of IL-4R on peripheral blood B cells without affecting the concomitant enhancement of CD23, CD40, HLA-DR and surface IgM expression, indicating that its effect is specific for IL-4R up-regulation. When S-oligo 1 was added to B cells costimulated with IL-4 and anti-CD40 MoAb, it induced a dose-dependent inhibition of IgE production. This inhibition was accompanied by a decrease in the expression of mature C epsilon transcripts, whereas the accumulation of germ-line C epsilon transcripts was not affected by S-oligo 1. These data suggest that the signal transduction mediated by the up-regulated IL-4R on B cells may be intimately associated with the induction of isotype switching to IgE that leads to mature C epsilon transcription and IgE production.

Antigens, CD↗

Development of a ferrocene-mediated needle-type glucose sensor covered with newly designed biocompatible membrane, 2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate.

To prepare the long-life and stable glucose sensor, we developed the ferrocene-mediated needle-type glucose sensor covered with newly designed biocompatible membrane, 2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate (MPC-co-BMA) membrane. In this membrane, the hydrophilic phosphorylcholine chains were grafted on the hydrophobic polymer surface. 1. The poly(MPC-co-BMA) membrane inhibited platelet activation and protein adhesion on the surface, showing excellent biocompatibility. These results suggested that the hydrophilic phospholipids chains might have the potential for suppressing activation and adsorption of biochemical molecules. 2. The ferrocene-mediated needle-type glucose sensor covered with poly(MPC-co-BMA) membrane achieved excellent results in vitro. Subcutaneous tissue glucose concentrations were measured in a wide range from 1.7 to more than 16.7 mmol/l. The correlation between subcutaneous tissue (Y) and blood (X) glucose concentrations was Y = 1.04X + 0.12 (r = 0.98). The subcutaneous tissue glucose concentrations could be monitored precisely for 7 days without any in vivo calibrations, and for 14 days by introducing in vivo calibrations. We therefore conclude that this sensor is stable and reliable, as compared to any other glucose sensors we developed.

Adult↗

[The effects of stellate ganglion block on conjunctival oxygen tension and intraocular pressure in patients with retinal vein occlusion].

We evaluated the effects of stellate ganglion block (SGB) on conjunctival oxygen tension, ocular surface temperature (n = 7) and intraocular pressure (n = 18) in patients with retinal vein occlusion and other retinopathy. The conjunctival oxygen tension (PcjO2) increased from 45.6 +/- 5.0 mmHg to 76.3 +/- 19.9 mmHg in 45 minutes by SGB and then gradually returned to the control level. PcjO2 120 minutes following SGB remained still at a higher level compared with the control value. Ocular surface temperature increased from 35.1 +/- 0.3 degrees C to 35.9 +/- 0.3 degrees C 25 minutes following SGB. Intraocular pressure decreased below the control level from 15 minutes to 120 minutes by SGB following an initial temporary increase. In conclusion, we have found that SGB does increase oxygen tension in ocular tissue and decrease IOP.

Adult↗

Brain temperature before and after brain death.

Although there has been renewed interest in human brain temperature, very little information is available on the association between brain temperature and cerebral perfusion pressure. In this study, we measured brain, tympanic, and rectal temperatures, arterial blood pressure and intracranial pressure in a case of massive hemorrhage deteriorating to brain death, and showed for the first time that when cerebral perfusion pressure began to decrease markedly brain temperature fell rapidly. Rectal and tympanic temperatures were higher than brain temperatures during the period of very low cerebral perfusion pressure. Circadian change in temperature (high at day, low at night) was preserved during the period of brain death.

Body Temperature Regulation↗

[A case of infantile ganglioglioma].

Gangliogliomas are common in childhood, but rare in infancy. The authors report a rare case of ganglioglioma who had an initial episode of complex partial seizure in infancy. A two-year-old girl was admitted for the surgical treatment of intractable seizures. She presented with an annual episode of seizure at two months old. The CT scan at 2 months old showed a light high-density tumor in the left medial temporal lobe. However, she had no treatment because she had no seizure since then and her psychomotor development was normal. She was treated with anticonvulsants from 1 year and 10 months old since seizures recurred. She was admitted to our ward at 2 years old because the frequency of seizures increased. Plain CT on admission showed an enlarged high density mass in left medial temporal lobe. The T1 weighted images of MRI demonstrated the mass to be isointense compared with the cortex, with homogeneously contrast enhancement. Total removal of the tumor was performed and histological diagnosis was ganglioglioma. She is seizure-free after surgery and synaptophysin was useful for the histological diagnosis. This case may indicate that gangliogliomas can be a congenital brain tumor which slowly enlarges.

Age of Onset↗

Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci.

In spite of recent advances in identifying genes causing monogenic human disease, very little is known about the genes involved in polygenic disease. Three families were identified with mutations in the unlinked photoreceptor-specific genes ROM1 and peripherin/RDS, in which only double heterozygotes develop retinitis pigmentosa (RP). These findings indicate that the allelic and nonallelic heterogeneity known to be a feature of monogenic RP is complicated further by interactions between unlinked mutations causing digenic RP. Recognition of the inheritance pattern exemplified by these three families might facilitate the identification of other examples of digenic inheritance in human disease.

Alleles↗

Possible role of tyrosine kinase activity in interleukin 4-induced expression of germ-line C epsilon transcripts in a human Burkitt lymphoma B-cell line, DND39.

Despite the recent advances in knowledge of the molecular mechanism by which interleukin-4 (IL-4) induces IgE production, little is known about the signal transduction pathway that leads to this event. This study investigated the signal transduction mechanism responsible for IL-4-induced expression of germ-line C epsilon transcripts with use of a human Burkitt lymphoma B-cell line, DND39, which is known to express germ-line C epsilon transcripts in response to IL-4. On stimulation with IL-4, the generation of inositol triphosphate was observed in the cells. In addition, this generation was associated with activation of phospholipase C-gamma 1 (PLC-gamma 1). Although herbimycin A, a potent inhibitor of tryosine kinase, inhibited IL-4-induced activation of PLC-gamma 1 and generation of inositol triphosphate, direct phosphorylation of PCL-gamma 1 was not determined. Nevertheless, IL-4 stimulation could induce activation of FYN but not LYN kinase, suggesting that additional molecule(s) might link FYN kinase to PLC-gamma 1. Interestingly, herbimycin A almost completely inhibited IL-4-induced expression of germ-line C epsilon transcripts when present during the entire culture period. These results indicate that the induction of germ-line C epsilon transcripts in IL-4-stimulated DND39 cells is essentially dependent on the activation of tyrosine kinase, possibly FYN kinase.

B-Lymphocytes↗

Conformation of (2-->1)-beta-D-fructan in aqueous solution.

The conformation and dilute solution properties of (2-->1)-beta-D-fructan in aqueous solution were studied by gel permeation chromatography, low-angle laser light-scattering photometry, viscometry, small-angle X-ray scattering and electron microscopy. Fractions covering a broad range of weight-average molecular weights (Mw) from 1.49 x 10(4) to 5.29 x 10(6) were obtained from a native sample by ultrasonic degradation and fractional precipitation. For Mw < 4 x 10(4), the intrinsic viscosity [eta] varies with Mw0.71, indicating that the fructan chain behaves as a random coil expanded by an excluded-volume effect in this molecular weight region. For Mw > 10(5), [eta] exhibits an unusually weak dependence on Mw and finally becomes almost independent of molecular weight. This behaviour is interpreted in terms of a globular conformation of the high-molecular-weight fructan molecules. Small-angle X-ray-scattering measurements and electron microscopic observations support this interpretation of the values of [eta] observed.

Aspergillus↗

Artificial endocrine pancreas and optimal blood glucose regulation in diabetic patients--from bedside-type to wearable-type.

The artificial endocrine pancreas is a feedback control system regulating insulin delivery on a minute-by-minute basis according to the measured blood glucose levels. The bedside-type artificial endocrine pancreas has been proven to be useful not only as a therapeutic tool for diabetes mellitus but also as an elegant research tool for investigating the pathophysiology of the disease. With significant advances in the development of a subcutaneous tissue glucose monitoring system, the wearable-type artificial endocrine pancreas has been applied to diabetic patients. With this system, perfect glycemic control can be obtained for longer periods in ambulatory diabetic patients. The trend in the development of the artificial endocrine pancreas is now directed to implantable devices. Much efforts have been conducted to realize these devices.

Blood Glucose↗

Pyramidal tract Wallerian degeneration and correlated symptoms in stroke.

In order to reveal the precise degree of injury in the pyramidal tract after stroke, we studied 35 patients with motor deficit associated with cerebrovascular disease of the internal capsule using the T2-weighted coronal image along the 'pyramidal line'. According to the severity of the motor deficit, the patients were divided into three groups. The Wallerian index was calculated as: (area of Wallerian degeneration in the pons divided by area of the ipsilateral half of the pons) x 100. There were significant differences between the three groups. It is concluded that the area of Wallerian degeneration is related to the severity of motor deficit.

Adult↗

Self-assembling process of cylindrical virus coat proteins as observed by synchrotron small-angle X-ray scattering.

The self-assembly process of cucumber green mottle mosaic virus (CGMMV) protein and tobacco mosaic virus (TMV) protein was examined by the thermodynamic analysis of small-angle X-ray scattering (SAXS) data. Each polymerization step of the coat proteins was assumed to be specified by a single equilibrium constant, and the equilibrium constant was evaluated by fitting the size and shape of the constituents observed by SAXS to those calculated from an assumed polymerization scheme. The logarithmic plots of the equilibrium constant against the inverse of temperature were fitted with a straight line at each buffer concentration and the thermodynamic quantities were evaluated from its intercept (yielding entropy) and slope (yielding enthalpy). The enthalpy and entropy values of TMV protein were found to be independent of buffer concentration, whereas those of CGMMV protein depended strongly on buffer concentration. In the limit, as ionic strength tends to infinity, both the enthalpy and entropy values of CGMMV protein approach those of TMV protein. The higher negative surface charge of CGMMV protein is considered to be responsible for the formation of stable single-layered disks, and for the slow polymerization process even at higher temperature and higher buffer concentrations.

Biopolymers↗

Allergen-specific human IgE helper T cell lines derived from patients allergic to Japanese cedar pollen.

To study the regulatory mechanism of allergen-dependent human IgE synthesis, Cry j I-specific and interleukin 4 (IL-4)-producing CD4+ T cell lines (SN-4 and SS-12) were established from 2 patients allergic to Japanese cedar pollen who highly expressed IL-4 mRNA in T cells in response to Cry j I stimulation. Upon stimulation of SN-4 and SS-12 cells with Cry j I, IL-4 production, which was observed at the protein and the mRNA levels, was induced in an HLA-DR-restricted manner, using autologous and allogeneic antigen-presenting cells. In addition to IL-4, not only considerable amounts of IL-5 and IL-6 but also very small amounts of IL-2 and interferon-gamma (IFN-gamma) were secreted by SN-4 and SS-12 cells, indicating that they fit into the Th2-like phenotype. The culture supernatant from Cry j I-activated SN-4 cells had the ability to induce IL-4-dependent IgE synthesis, CD23 expression and soluble CD23 release. Moreover, Cry j I-dependent IgE synthesis medated by SN-4 cells derived from 1 patient expressing HLA-DRw8, w9 could be specifically induced in both autologous and HLA-DRw9-matched allogeneic B cell cultures. This IgE induction was inhibited by neutralizing antibodies to IL-4, IL-5 and IL-6, but was not enhanced by anti-IFN-gamma antibody. On the other hand, neither IL-4 production nor IgE synthesis was induced when SN-4 cells were cocultured in the presence of Cry j I with HLA-DRw8-matched or histoincompatible allogeneic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Recombinant soluble form of the human high-affinity immunoglobulin E (IgE) receptor inhibits IgE production through its specific binding to IgE-bearing B cells.

A recombinant soluble form of the alpha subunit of the human high-affinity receptor for IgE (rsFc epsilon RI alpha), one of the potent IgE-binding molecules, was tested for its ability to regulate IL-4-induced IgE synthesis by human lymphocytes. Addition of rsFc epsilon RI alpha to cultures induced a dose-dependent inhibition of the T cell-dependent and independent synthesis of IgE. The suppression of IgE synthesis was observed at the protein and the mRNA levels, and it was IgE class specific. By flow cytometry, specific binding of rsFc epsilon RI alpha was detected on surface IgE-bearing B cells as well as on U266 cells, and it was completely blocked by preincubation with IgE. rsFc epsilon RI alpha bound to the cell surface IgE could be effectively dissociated not only by a large excess of IgE, but also by an anti-rsFc epsilon RI alpha mAb that competes with IgE for the binding to rsFc epsilon RI alpha. This mAb abolished the rsFc epsilon RI alpha-mediated suppression of IgE synthesis. These data suggest that rsFc epsilon RI alpha may have a function in selectively suppressing IgE synthesis through its interaction with the membrane-bound form of IgE.

Adult↗

Distal posterior cerebral artery aneurysms--three case reports.

One case of an aneurysm in the P3 segment and two cases of aneurysms in the P4 segment of the posterior cerebral artery are described. The P3 aneurysm in a 60-year-old female and a P4 aneurysm in a 63-year-old male were clipped or coated via the occipital interhemispheric approach. The other P4 aneurysm in a 73-year-old female was clipped via a hematoma cavity. The occipital interhemispheric approach should be selected for small or large P3 aneurysms and for P4 aneurysms associated with slack brain, as brain retraction is minimal and the approach to the aneurysm is straightforward.

Aged↗

Development of a miniaturized glucose monitoring system by combining a needle-type glucose sensor with microdialysis sampling method. Long-term subcutaneous tissue glucose monitoring in ambulatory diabetic patients.

OBJECTIVE: To develop a reliable and practical glucose monitoring system by combining a needle-type glucose sensor with a microdialysis sampling technique for long-term subcutaneous tissue glucose measurements. RESEARCH DESIGN AND METHODS: A microdialysis Cuprophan hollow-fiber probe (inner diameter, 0.20 mm; length, 15 mm) was perfused with isotonic saline solution (120 microliters/h) and glucose concentrations in the dialysate were measured by a needle-type glucose sensor extracorporeally. This system was tested both in vitro and in vivo. Subcutaneous tissue glucose concentrations were then monitored continuously in 5 healthy and 8 diabetic volunteers for 7 to 8 days. A hollow-fiber probe was inserted into the abdominal subcutaneous tissue. RESULTS: This monitoring system achieved excellent results in vitro. Subcutaneous tissue glucose concentrations were measured in a wide range from 1.7 to > 27.8 mM glucose, with a time delay of 6.9 +/- 1.2 min associated with a rise in glucose and 8.8 +/- 1.6 min with a fall in the glucose level (means +/- SE). The overall correlation between subcutaneous tissue (Y) and blood (X) glucose concentration was Y = 1.08X + 0.19 (r = 0.99). The subcutaneous tissue glucose concentration could be monitored precisely for 4 days without any in vivo calibrations and for 7 days by introducing in vivo calibrations. CONCLUSIONS: Glycemic excursions could be monitored precisely in the subcutaneous tissue by this microdialysis sampling method with a needle-type glucose sensor in ambulatory diabetic patients.

Adult↗

[Shunting operation with the medos programmable valve shunt system].

We reviewed 13 patients with hydrocephalus of varied etiology and two patients with arachnoid cyst who underwent shunting operations using Medos programmable valve shunt system. This shunt system allows 18 pressure settings, ranging from 30 to 200mmH2O in 10mmH2O differentials, percutaneously. Following the shunting operation, the size of the ventricle or arachnoid cyst was reduced in all cases and the clinical symptoms improved in 14 cases. The valve pressure was reset during the postoperative course in all cases. In five cases, resetting was performed because of management of complications. In the others, it was performed to find the most appropriate valve pressure for each patient. Complications were subdural effusion (2 cases), chronic subdural hematoma (2 cases) and slit ventricle syndrome (1 case). Subdural effusion and slit ventricle syndrome were improved easily by resetting the valve pressure, but both cases of chronic subdural hematoma finally required surgical treatment. Artifacts in MR imaging and movement of the valve pressure by MR imaging were small and created no clinical problem. In cases 1 and 2, clinical symptoms and CT finding were improved by a change of 30mmH2O. In case 2, hydrocephalus with slight subdural effusion followed a good course with frequent change of the valve pressure. Accordingly, we consider the Medos system to be useful for a more thorough treatment of hydrocephalus and arachnoid cyst after shunting operations.

Adolescent↗