Biomedical subjects

E Kondo

Publications and source records attributed to E Kondo.

At least 37 records · Page 2Linked to original sources

PubMed2001

Numerical, morphological and phenotypic changes in Langerhans cells in the course of murine graft-versus-host disease.

BACKGROUND: In the course of graft-versus-host disease (GVHD) or diseases that histologically mimic GVHD (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome), it is known that epidermal Langerhans cells (LCs) are depleted from the epidermis. However, the mechanism and significance of LC depletion is not well known. OBJECTIVES: To investigate the numerical, morphological and phenotypic changes in LCs and apoptosis of LCs in the course of GVHD using a non-irradiated mouse GVHD model. METHODS: BALB/c nu/nu mice and C57BL/6 mice were used as recipients and donors, respectively. Recipient mice were injected with T-cell-enriched donor spleen cells. Skin samples were harvested at various times after the inoculation. The numerical and morphological changes were examined by an immunofluorescence study of epidermal sheets. Apoptosis was studied by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling method and flow cytometric analysis using annexin V. Phenotypic change was studied by flow cytometric analysis of epidermal cell suspensions. The mixed epidermal cell lymphocyte reaction (MELR) was performed to examine functional changes in the epidermal cells. RESULTS: Five days after inoculation, a graft-versus-host reaction occurred. Epidermal LCs began to decrease from the sixth day. On the fifth day, the LCs became larger and had prominent dendrites. Immediately before the LCs began to decrease, many LCs became round in shape, with scanty dendrites. LC apoptosis was not observed in the epidermis either on the fifth or seventh day. Phenotypically, the expression of CD40, CD80, CD86 and major histocompatibility complex class II antigen on the LCs was upregulated on the fifth and seventh day. Epidermal cells from GVHD mice showed an increased allostimulatory capacity in the secondary MELR. CONCLUSIONS: These results suggest that at early GVHD onset, most LCs may not undergo apoptosis in the epidermis but are phenotypically activated, resulting in further activation of alloreactive T cells and aggravation of the disease.

Animals↗

PubMed2001

Destruction of acetabular bone caused by early failure of a constrained acetabular component.

Use of a constrained acetabular component is 1 option for the treatment of dislocation after total hip arthroplasty. We report a case of a constrained acetabular component that resulted in postoperative early fixation loss and required revision 12 days after primary surgery. The superoposterior wall of the acetabulum was destroyed by the migrated acetabular component. Sharp ends of screws with a metal shell may have plowed up acetabular bone gradually after fixation loss of the component. This failure illustrates the potential risk of using a constrained acetabular component for total hip arthroplasty.

Acetabulum↗

PubMed2001

The effect of electroacupuncture on pain behaviors and noxious stimulus-evoked Fos expression in a rat model of neuropathic pain.

Chronic-constriction injury (CCI) of the sciatic nerve causes mechanical and heat hyperalgesia and mechanical allodynia in the plantar surface of the hindpaw. The underlying mechanism thought to account for these phenomena include central sensitization induced by peripheral nerve injury, ie, the increase in neuronal activity of spinal dorsal horn neurons. As a marker of neuronal activation of the central nervous system, Fos expression has been used widely to monitor the change in neuronal activity evoked by peripheral input. In this study, we examined the antinociceptive effect of electroacupuncture (EA) on pain behavior and noxious stimulus-evoked Fos expression in dorsal horn neurons of the spinal cord in CCI rats 14 days after injury. Male Sprague-Dawley rats (180 to 200 g) received loose ligation of the left sciatic nerve. Heat and mechanical hyperalgesia and mechanical allodynia were examined by the plantar foot test, the pin-prick test, and the von Frey test before and after the EA treatment (100 Hz, 0.3 millisecond, 3 or 1 mA, 20 minutes) into the Zusanli point (S36). When EA stimulation to the Zusanli point was applied, the mechanical and heat hyperalgesia were significantly suppressed; however, mechanical allodynia was not affected. The EA stimulation to nonacupuncture point did not show any significant effect. Next, pinch stimulation was applied to the plantar surface of the operated hindpaw of the CCI rats for 10 minutes, and the stimulus-evoked Fos expression in dorsal horn neurons in L4-L6 spinal cord levels was then examined by using immunohistochemistry. The number of noxious stimulus-evoked Fos-labeled neurons in both the superficial and deep laminae of the dorsal horn in the CCI rats was increased significantly compared with those in sham-operated rats, suggesting an increased excitability of dorsal horn neurons to noxious stimuli. Concurrent EA treatment to the Zusanli point with the pinch stimulus suppressed the increase in the number of Fos-labeled cells in the spinal dorsal horn in the CCI rats. The present results show that EA treatment has antinociceptive effects on both pain behavior and neuronal activation of the spinal dorsal horn neurons in CCI rats.

Journal Article↗

PubMed2000

Nerve growth factor applied onto the olfactory epithelium alleviates degenerative changes of the olfactory receptor neurons following axotomy.

The olfactory neuroepithelium of the mammalian nervous system manifests continuous neurogenesis throughout life. Recent studies suggest that neurotrophic factors and their receptors may play a role in the regulation of development and regeneration in the olfactory system. However, there have been very few in vivo studies investigating the effect of exogenous neurotrophic factors in the olfactory system. In the present study, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were administered into the rat olfactory mucosa for 5 days just after the transection of the olfactory nerve. We then examined the effect of exogenous neurotrophic factors on the degenerative changes in axotomized olfactory receptor neurons (ORNs). Further, we examined the location of their receptors, Trk A and Trk B. We found that both mature and immature ORNs expressed more intense signals for olfactory marker protein and beta-tubulin mRNAs, respectively, when NGF was applied to the axotomized olfactory neuroepithelium for 5 days, compared to the ORNs of saline-treated controls. BDNF at a 10 microg total dose did not show this effect. The effect of NGF applied onto the olfactory epithelium is consistent with the immunohistochemical finding that Trk A was present in the dendrites and axon bundles in normal and axotomized ORNs. These results suggest that NGF may protect the degenerative changes in mature and immature ORNs following axotomy through the binding to the Trk A receptor located on the surface of the olfactory epithelium.

Animals↗

PubMed2000

A novel nuclear phosphoprotein, GANP, is up-regulated in centrocytes of the germinal center and associated with MCM3, a protein essential for DNA replication.

Antigen (Ag) immunization induces formation of the germinal center (GC), with large, rapidly proliferating centroblasts in the dark zone, and small, nondividing centrocytes in the light zone. We identified a novel nuclear protein, GANP, that is up-regulated in centrocytes. We found that GANP was up-regulated in GC B cells of Peyer's patches in normal mice and in spleens from Ag-immunized mice. GANP-positive cells appeared in the light zone of the GC, with coexpression of the peanut agglutinin (PNA) (PNA)-positive B220-positive phenotype. The expression of GANP was strikingly correlated with GC formation because Bcl6-deficient mice did not show the up-regulation of GANP. GANP-positive cells were mostly surrounded by follicular dendritic cells. Stimulation with anti-micro and anti-CD40 induced up-regulation of ganp messenger RNA as well as GANP protein in B220-positive B cells in vitro. GANP is a 210-kd protein localized in both the cytoplasm and nuclei, with a homologous region to Map80 that is associated with MCM3, a protein essential for DNA replication. Remarkably, GANP is associated with MCM3 in B cells and MCM3 is also up-regulated in the GC area. These results suggest that the up-regulation of GANP might participate in the development of Ag-driven B cells in GCs through its interaction with MCM3.

Acetyltransferases↗

PubMed2000

Involvement of decidual Valpha14 NKT cells in abortion.

The immunological mechanisms that regulate abortion are largely unknown. Here, we found that a distinct subset of lymphocytes, Valpha14 NKT cells expressing an invariant antigen receptor encoded by Valpha14/Jalpha281 and Vbeta7 segments, accumulated in the decidua during pregnancy and provoked abortion upon stimulation with alpha-galactosylceramide (alpha-GalCer), a specific ligand for Valpha14 NKT cells. The alpha-GalCer-mediated abortion was not observed in Valpha14 NKT-, IFN-gamma-, tumor necrosis factor alpha-, or perforin-knock-out mice and appeared to be due to the degeneration of embryonic trophoblasts mediated by the activated Valpha14 NKT cells whose perforin-dependent killing and production of IFN-gamma and tumor necrosis factor alpha were essential. The possible role of the decidual Valpha14 NKT cells in the pathogenesis of abortion is discussed.

Abortion, Induced↗

PubMed2000

Differential effect of brain-derived neurotrophic factor on high-threshold mechanosensitivity in a rat neuropathic pain model.

We investigated the effect of the systemic infusion of brain derived neurotrophic factor (BDNF) on the behavioral response in a rat neuropathic pain model. One microgram per hour infusion of BDNF significantly attenuated mechanical hyperalgesia tested by the pin-prick test, however, 20 microg/h-BDNF infusion, on the contrary, enhanced the response. Neither 0.5 nor 10 microg/h-BDNF infusion influenced the mechanical hyperalgesia. Mechanical allodynia and thermal hyperalgesia, tested using a von Frey filament (23.0 mN) and the plantar test, were not influenced by BDNF treatment. These data suggest that systemic BDNF treatment can specifically alter high-threshold mechanosensitivity.

Animals↗

PubMed2000

Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: A novel neuronal marker of nerve injury.

Activating transcription factor 3 (ATF3), a member of ATF/CREB family of transcription factors, is induced in a variety of stressed tissue. ATF3 regulates transcription by binding to DNA sites as a homodimer or heterodimer with Jun proteins. The purpose of this study was to examine the expression and regulation of ATF3 after axonal injury in neurons in dorsal root ganglia (DRG) and spinal cord. In naive rats, ATF3 was not expressed in the DRG and spinal cord. Following the cut of peripheral nerve, ATF3 was immediately induced in virtually all DRG neurons and motoneurons that were axotomized, and the time course of induction was dependent on the distance between the injury site and the cell body. Double labeling using immunohistochemistry revealed that the population of DRG neurons expressing ATF3 included those expressing c-jun, and in motoneurons ATF3 and c-jun were concurrently expressed after axotomy. In contrast to c-jun, ATF3 was not induced transsynaptically in spinal dorsal horn neurons. We conclude that ATF3 is specifically induced in sensory and motoneurons in the spinal cord following nerve injury and should be regarded as an unique neuronal marker of nerve injury in the nervous system.

Activating Transcription Factor 3↗

PubMed2000

Recurrent idiopathic iridocyclitis after autologous peripheral blood stem-cell transplantation followed by G-CSF administration for acute lymphoblastic leukemia.

We describe a patient who experienced a recurrence of idiopathic iridocyclitis on day 12 after autologous peripheral blood stem-cell transplantation (auto-PBSCT) followed by G-CSF administration for acute lymphoblastic leukemia (ALL). Autologous SCT has been reported to be effective and safe in achieving dose intensification of chemotherapeutic drugs for the treatment of hematopoietic malignancies, but its therapeutic effect on autoimmune diseases is not definite. The findings from the present case suggest that auto-PBSCT followed by G-CSF administration for patients with a history of some kind of autoimmune disorders may induce exacerbation or recurrence of its symptoms after hematopoietic recovery.

Combined Modality Therapy↗

PubMed2000

Biomechanical comparisons of anterior cruciate ligament: reconstruction procedures with flexor tendon graft.

An experimental study was conducted to compare the biomechanical characteristics of six currently available anterior cruciate ligament (ACL) reconstruction procedures with flexor digitorum profundus tendons. Forty porcine knees were divided into eight groups, of 5 knees each. In groups A, B, C, and D, the flexor tendon graft was fixed with sutures and an Endobutton, with 20-mm-wide polyester tapes and staples, with 10-mm-wide polyester tapes and an Endobutton, and with bone plugs and interference screws, respectively. In group E, the graft was fixed using a combined procedure of those in groups B and D. In group F, the graft was directly fixed with interference screws. In groups G and H, the bone-patellar tendon-bone graft was fixed with interference screws, and sutures, respectively. Each femur-graft-tibia complex specimen was tested with a tensile tester by anteriorly translating the tibia until failure. This study demonstrated that the biomechanical properties of the femur-graft-tibia complex reconstructed with the flexor tendon graft were significantly affected by synthetic fixation devices. Regarding the average maximal load of the groups with the flexor tendon graft, group B had the highest (893 N) and group C had the second highest (770 N). Groups E and A were in the third rank. Group F had the second lowest (312 N), and Group D had the lowest (230 N). The maximal load of group B was significantly greater (P < 0.01) than that of group G (656 N) with the bone-patellar tendon-bone grafts. As to clinical relevance, this study indicated that the flexor tendon graft can be an alternative substitute for the bone-patellar tendon-bone graft for ACL reconstruction, if we understand the biomechanical characteristics of each reconstruction procedure.

Animals↗

PubMed2000

Suppression of neuropeptides' mRNA expression by herbal medicines in a rat model of peripheral inflammation.

The traditional Chinese medicines have been used clinically for a long time in some Asian countries, however, very few studies have been done to demonstrate the working mechanisms of these medicines using recently developed biochemical methodologies. In this study, we examined the anti-inflammatory effect of Huang-Lian-Jie-Du-Tang (HLJDT), a combination of herbs used in traditional Chinese medicine, on paw edema, thermal hyperalgesia and the mRNA increase of neuropeptides in spinal dorsal horn and hypothalamic neurons using a rat model of peripheral inflammation and hyperalgesia. The rats that received HLJDT from 3 days before the injection of complete Freund's adjuvant (CFA) into the plantar had significantly less edema and reduced thermal hyperalgesia compared to control rats that received CFA injection. The up-regulation of preprodynorphin mRNA in L4-5 dorsal horn neurons 8 hours after CFA injection that was observed in control rats, was also decreased in the HLJDT-treated rats. Moreover, there was a significant decrease in mRNA level of corticotropin-releasing factor in the paraventricular hypothalamic nucleus in the HLJDT-treated rats. These data demonstrate that HLJDT is anti-inflammatory, and produces changes in mRNA expression in dorsal horn and hypothalamic neurons. This is the first demonstrated that a traditional Chinese medicine can affect the excitability of neurons through an anti-inflammatory action.

Animals↗

PubMed2000

Dorsal column-thalamic pathway is involved in thalamic hyperexcitability following peripheral nerve injury: a lesion study in rats with experimental mononeuropathy.

A total of 68 neurons were recorded from the ventro-postero-lateral nucleus of thalamus (VPL) in rats with a unilateral chronic constriction injury (CCI) of the sciatic nerve (n=20), sham operation (n=24) and naive rats (n=24), and effects of the lesion of dorsal column (DC) pathway [DC lesion or DC+gracile nucleus lesions] on VPL nucleus neuronal activities were studied. In the VPL nucleus contralateral to the CCI (receiving input from the injured nerve), response latencies of low threshold mechanoreceptive (LTM) and wide dynamic range (WDR) neurons to electrical stimulation of the sciatic nerve were significantly longer than that in the contralateral VPL nucleus receiving input from the sham-operated side (P<0.05). In contrast, response latencies of LTM and WDR neurons to DC stimulation were not different between the sham operated and CCI sides (0.05). Background activity of WDR neurons was significantly higher in the VPL nucleus contralateral to the CCI side when compared to neurons in the VPL nucleus contralateral to the sham operated side and in naive animals. Responses of LTM and WDR neurons to innocuous mechanical stimulation of the receptive fields were significantly decreased after DC and DC+gracile nucleus lesions in all animals. However, the responses of WDR neurons to noxious stimuli were selectively reduced only in rats with CCI by DC and DC+gracile nucleus lesions (P<0.05). The decrease in noxious stimulus-evoked responses of WDR neurons in the VPL nucleus contralateral to the CCI side after DC and DC+gracile nucleus lesions was greater than that in the VPL nucleus contralateral to the sham operated side and naive animals. These results indicated that DC and DC+gracile nucleus lesions produced selective and stronger effect on noxious responses of VPL nucleus WDR neurons receiving input from the site of nerve injury. The findings suggest that the gracile nucleus-thalamic pathway conveys, or modulates, nociceptive information to the VPL nucleus following peripheral nerve injury, resulting in an increase in VPL nucleus response to noxious stimuli that contributes to the development of mechanical hyperalgesia.

Animals↗

PubMed2000

Nonsurgical and nonextraction treatment of skeletal Class III open bite: its long-term stability.

Two female patients, aged 14 years 5 months and 17 years 3 months with skeletal Class III open bite and temporomandibular dysfunction are presented. They had previously been classified as orthognathic surgical cases, involving first premolar removal. The primary treatment objective was to eliminate those skeletal and neuromuscular factors that were dominant in establishing their malocclusions. These included abnormal behavior of the tongue with short labial and lingual frenula, bilateral imbalance of chewing muscles, a partially blocked nasopharyngeal airway causing extrusion of the molars, with rotation of the mandible and narrowing of the maxillary arch. Resultant occlusal interference caused the mandible to shift to one side, which in turn produced the abnormal occlusal plane and curve of Spee. As a result, the form and function of the joints were adversely affected by the structural and functional asymmetry. These cases were treated by expanding the maxillary arch, which brought the maxilla downward and forward. The mandible moved downward and backward, with a slight increase in anterior facial height. Intruding and uprighting the posterior teeth, combined with a maxillary protraction, reconstructed the occlusal plane. A favorable perioral environment was created with widened tongue space in order to produce an adequate airway. Myofunctional therapy after lingual and labial frenectomy was assisted by vigorous gum chewing during and after treatment, together with a tooth positioner. Normal nasal breathing was achieved.

Adolescent↗

PubMed2000

Genetic heterogeneity in three Chinese children with Fukuyama congenital muscular dystrophy.

Three Chinese patients, two boys and one girl, were afflicted with the typical clinical, myopathological and neuroradiological findings of Fukuyama congenital muscular dystrophy (FCMD). Polymorphism analysis of our patients did not reveal the founder haplotype (138-192-147-183 in D9S2105-D9S2170-D9S2171-D9S2107) of Japanese FCMD, even though one patient was descended from Japanese ancestry. Full mutational analysis of the fukutin gene revealed that there is neither 3 kb insertion nor point mutation. These findings suggest genetic heterogeneity between Chinese and Japanese FCMD patients.

Child↗

PubMed2000

Experimental lupus nephritis in severe combined immunodeficient (SCID) mice: remodelling of the glomerular lesions by bystander IgM antibodies.

MRL/Mp-lpr/lpr (MRL/lpr) mice develop glomerular lesions with regular variations in their histopathological manifestations, similar to those in lupus nephritis. These lesions are mainly either cell-proliferative or wire loop-like and are associated with glomerular deposits of immunoglobulins, most frequently IgG and IgM. We previously established a nephritogenic IgG3-producing hybridoma clone, B1, from an MRL/lpr mouse, which induces only a 'wire loop-like' type of glomerular lesion when injected into SCID mice. Injection of SCID mice with an anti-trinitrophenyl IgM antibody-producing hybridoma clone, Sp6, following injection of the B1 clone, however, resulted in the development of a 'cell-proliferative' type of glomerular lesion, associated with an accumulation of both antibodies in glomeruli. This accumulation occurred even though Sp6 IgM antibodies did not react with B1 IgG3 antibodies and vice versa. A mutant clone of Sp6, T/13microE/3.1, which produces antibodies deficient in C1q binding, produced a similar effect as that of the Sp6 clone, i.e. 'cell-proliferative' lesions. Again the B1 antibodies did not react with T/13microE/3. 1-IgM antibodies and vice versa. We therefore conclude that bystander IgM antibodies contribute to the remodelling of glomerular lesions in situ, following glomerular injury by the nephritogenic antibodies.

Animals↗

PubMed2000

Association of insulin receptor substrate proteins with Bcl-2 and their effects on its phosphorylation and antiapoptotic function.

Insulin receptor substrate (IRS) proteins are docking proteins that couple growth factor receptors to various effector molecules, including phosphoinositide-3 kinase, Grb-2, Syp, and Nck. Here we show that IRS-1 associates with the loop domain of Bcl-2 and synergistically up-regulates antiapoptotic function of Bcl-2. IRS-2 but not IRS-3 binds to Bcl-2, and IRS-1 associates with Bcl-XL but not with Bax or Bik. Overexpression of IRS-1 suppresses phosphorylation of Bcl-2 induced by stimulation with insulin, and the hypophosphorylation may lead to its enhanced antiapoptotic activity. The binding site for Bcl-2 is located on the carboxyl half-domain of IRS-1. IRS-3, which lacks the corresponding region, dominant-negatively abrogates the survival effects of IRS-1 and Bcl-2. For the antiapoptotic activity of IRS-1, binding to Bcl-2 is more critical than activating phosphoinositide-3 kinase. Our results indicate that IRS proteins transmit signals from the insulin receptor to Bcl-2, thus regulating cell survival probably through regulating phosphorylation of Bcl-2.

Animals↗

PubMed2000

Clinicopathological features of gastric mucosa associated lymphoid tissue (MALT) lymphomas: high grade transformation and comparison with diffuse large B cell lymphomas without MALT lymphoma features.

AIMS: To investigate the clinicopathological differences among gastric low grade MALT lymphomas (low MALT), large B cell lymphomas with low grade components (secondary high grade MALT lymphomas, high MALT), and diffuse large B cell lymphomas without low grade features (primary high grade MALT lymphomas, DLL). METHODS: Clinicopathological and morphological characters of 126 gastric lymphoma cases were studied: 82 cases of low MALT lymphoma including 40 that were surgically resected, 17 cases of high MALT lymphoma including 13 surgically resected, and 27 cases of DLL including 12 surgically resected. RESULTS: Age ranges were as follows: low MALT lymphoma, 34 to 85 years (mean 59.9); high MALT lymphoma, 53 to 88 years (mean 68.5); DLL, 29 to 83 years (mean 62.3). The average age for low and high MALT lymphomas was significantly different (p < 0.05), but there were no differences in other comparisons. There was a female predominance of low MALT lymphoma patients (female to male ratio, 47/35), while for high MALT patients the ratio was almost even (8/9), and for DLL patients there was a male predominance (11/16). Examination of surgically resected material showed that MALT lymphomas had a wider distribution in the gastric wall than DLL. CONCLUSIONS: The findings suggest that at least some of the high grade gastric lymphomas, especially in patients younger than the fifth decade, do not originate from high grade transformation of low MALT lymphomas. It seems to take about one decade at least for high grade transformation of low MALT lymphomas.

Adult↗

PubMed2000

Not hMSH2 but hMLH1 is frequently silenced by hypermethylation in endometrial cancer but rarely silenced in pancreatic cancer with microsatellite instability.

Disruption of the DNA mismatch repair (MMR) system has been found to play an important role in sporadic human cancers of several organs such as colorectum, stomach, endometrium, and pancreas. In cancers of the former three organs, disruption of the MMR system is mainly caused by hypermethylation of the hMLH1 gene. We investigated the expression of the hMLH1 and hMSH2 proteins immunohistochemically in pancreatic and endometrial cancers with high frequency microsatellite instability (MSI-H). Loss of expression of hMLH1 was found in none of seven pancreatic cancer, whereas eight (57%) of 14 endometrial cancer showed loss of expression of hMLH1. On the other hand, one (14%) of seven pancreatic cancers and two (14%) of 14 endometrial cancers showed loss of hMSH2 expression. We further analyzed the methylation status at the promoter region of the hMLH1 and hMSH2 genes and found hypermethylation of hMLH1 at the promoter region in the great majority of endometrial cancers with loss of expression. However, no pancreatic cancer showed hypermethylation. We then further analyzed 22 pancreatic cancer cell lines and obtained similar results. These results suggested that MSI-H in pancreatic cancer is probably caused by different mechanisms from those of other sporadic cancers with MSI-H.

Adaptor Proteins, Signal Transducing↗