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Biomedical subjects

H Kawaguchi

Publications and source records attributed to H Kawaguchi.

At least 109 records · Page 6Linked to original sources
PubMed1999

Mechanisms of glomerular macrophage infiltration in lipid-induced renal injury.

BACKGROUND: A number of studies have demonstrated an important role for macrophages (M phi) in lipid-induced glomerular injury; however, little is known of the mechanisms that facilitate M phi infiltration in this disease. This study examined the expression of M phi chemotactic molecules M phi migration inhibitory factor (MIF) and leukocyte adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) during the induction of glomerular M phi infiltration in ExHC rats, a strain that is susceptible to lipid-induced glomerular injury. METHODS: Groups of five ExHC rats were fed a high-cholesterol diet (HCD) containing 3% cholesterol, 0.6% sodium cholate, and 15% olive oil and were killed after three days or one, two, or six weeks. Control animals were killed on day 0 or after six weeks on a normal diet. RESULTS: ExHC rats fed an HCD showed marked hypercholesterolemia in the absence of any increase in plasma triglyceride levels from day 3 and developed mild proteinuria and segmental glomerular lesions at week 6. Immunoperoxidase staining identified a significant increase in glomerular ED1+ M phi at week 1, which was further increased at week 6, when M phi-derived foam cells were seen in almost all glomeruli. Many of the infiltrating glomerular M phi expressed lymphocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4), which are ligands for ICAM-1 and VCAM-1, respectively. Coincident with the induction of hypercholesterolemia on day 3 and prior to significant M phi infiltration, combined in situ hybridization and immunohistochemistry staining demonstrated a marked up-regulation of M-CSF and MIF mRNA expression by glomerular mesangial cells and podocytes. There was also a significant increase in ICAM-1 and VCAM-1 mRNA expression by intrinsic glomerular cells, including endothelial cells, on day 3 of the HCD. CONCLUSION: These results suggest that hypercholesterolemia can induce a classic proinflammatory response within the kidney glomerulus, involving production of well-described M phi chemotactic and adhesion molecules, which results in M phi recruitment and the development of glomerular injury.

Animals↗
PubMed1999

Involvement of fibroblast growth factor-2 in joint destruction of rheumatoid arthritis patients.

OBJECTIVE: To investigate the effect of the synovial fluid from knee joints of rheumatoid arthritis (RA) patients with different severities of joint destruction on osteoclastogenesis and bone resorption. METHODS: Synovial fluid was harvested from the knee joints of 59 RA patients and 37 ostcoarthritis (OA) patients. RA patients with Larsen's knee grade 1-3 were classified as mild RA (n = 30) and those with grade 4 or 5 as severe RA (n = 29). Cytokine concentrations in synovial fluid were measured by ELISA. Osteoclastogenesis was measured by tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell (MNC) formation in a co-culture of mouse osteoblastic cells and bone marrow cells, and bone resorption by 45Ca release from pre-labelled cultured neonatal mouse calvariae. RESULTS: The synovial fluid of severe RA patients significantly stimulated TRAP-positive MNC formation and 45Ca release compared to those of mild RA and OA patients. Among the bone-resorptive cytokines fibroblast growth factor-2 (FGF-2), tumour necrosis factor alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), IL-6 and soluble IL-6 receptor (sIL-6R), only FGF-2 concentration in the synovial fluid was positively correlated to Larsen's grade, and severe RA patients showed significantly higher FGF-2 concentrations than mild RA patients. Osteoclastogenesis in a co-culture system which was stimulated by the synovial fluid of severe RA patients was significantly inhibited by a neutralizing antibody against FGF-2 and this inhibition was stronger than antibodies against other cytokines. CONCLUSION: The increase in endogenous FGF-2 levels in the synovial fluid of RA patients may play a role in the joint destruction by inducing osteoclastogenesis.

Animals↗
PubMed1999

Adult onset of inflammatory linear verrucous epidermal nevus.

Adult onset of inflammatory linear verrucous epidermal nevus (ILVEN) is reported in a 44-year-old Japanese man. A mild pruritic eruption appeared one year earlier and extended from the left dorsal foot to the gluteal region. Histologically, acanthosis and papillomatous thickening of epidermis as well as spongiotic edema and exocytosis with lymphocytes and neutrophils were observed. Topical tacalcitol was not effective, but the pruritus as well as the eruption slightly improved with topical corticosteroid and vaseline containing salicylic acid. This adult onset of ILVEN is considered to be a rare case.

Administration, Topical↗
PubMed1999

Vitamin D receptor gene polymorphism in patients with sarcoidosis.

The active form of vitamin D, 1,25-dihydroxyvitamin D(3), is known to be produced at sites of granulomatous reactions in sarcoidosis. 1, 25-dihydroxyvitamin D(3) has multiple immunomodulatory effects, and acts as a promoter of multinucleated giant cell formation. Polymorphism of the vitamin D receptor (VDR) gene has recently been shown to be related to bone mineral density, and also associated with hyperparathyroidism and risk of prostatic carcinoma. Considering that this might affect sarcoidosis, we investigated polymorphism of the VDR gene in 101 patients with sarcoidosis and 105 healthy control subjects. Their genotypes were determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism. In the patients with sarcoidosis, the BB, Bb, and bb genotypes accounted for 1.0%, 37.6%, and 61.4%, whereas in healthy control subjects the figures were 1.0%, 20.0%, and 79.0%, respectively. The difference in the genotype distribution between healthy control subjects and sarcoidosis patients was significant (p < 0.05) with the frequency of the B allele being elevated (p < 0.05). From the result, we suggest that in VDR gene polymorphism the B allele might be a genetic risk factor for sarcoidosis.

Alleles↗
PubMed1999

Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopenia.

We recently identified a new gene, klotho, which is involved in the suppression of multiple aging phenotypes. The mouse homozygous for a disruption of the klotho locus (kl/kl) exhibited multiple pathological conditions resembling human aging. Histomorphometric analysis revealed low-turnover osteopenia in kl/kl mice. The decrease in bone formation exceeded that of bone resorption, resulting in a net bone loss. The number of osteoblast progenitors determined by ex vivo bone marrow cultures was reduced in kl/kl mice. In addition, cultured osteoblastic cells derived from kl/kl mice showed lower alkaline phosphatase activity and matrix nodule formation than those from wild-type mice. Osteoclastogenesis in the coculture of marrow cells and osteoblastic cells was decreased only when marrow cells originated from kl/kl mice independently of the origin of osteoblastic cells. We also found that the expression of osteoprotegerin, an osteoclastogenesis inhibitor, was significantly upregulated in kl/kl mice. We conclude that a defect in the klotho gene expression causes the independent impairment of both osteoblast and osteoclast differentiation, leading to low-turnover osteopenia. Because this state represents a characteristic feature of senile osteoporosis in humans, kl/kl mice can be regarded as a useful model for investigating cellular and molecular mechanisms of age-related bone loss.

Aging↗
PubMed1999

A novel A-kinase anchoring protein in the heart interacts with G alpha 13.

A cDNA of a tentative A-kinase anchoring protein, presumably coupled with heterotrimeric GTP binding protein alpha 13 subunit (G alpha 13), was cloned from a human heart cDNA library. It was approximately 650 bases and its mRNA was expressed in the heart. Homology search of DNA sequences revealed that it was a novel cDNA with 84% homology with the partial sequence of rabbit cDNA of AKAP 120 without a stop codon. 3'-Rapid Amplification of cDNA Ends (3'-RACE) and yeast functional assay were performed to determine the 3'-end of the cDNA and ribosomal frameshifting was suggested as a translational mechanism. Here we report that a protein encoded by the cDNA may be involved in intracellular signal transduction via the G alpha 13 and PKA in hearts.

A Kinase Anchor Proteins↗
PubMed1999

Transcatheter arterial embolization for impending rupture of an isolated internal iliac artery aneurysm complicated with disseminated intravascular coagulation.

A 90-year-old male, with impending rupture of an isolated internal iliac artery aneurysm (IIAA) complicated with disseminated intravascular coagulation (DIC) was successfully treated with transcatheter arterial embolization (TAE). After TAE, enlargement of the aneurysm was arrested and coagulation-fibrinolytic abnormalities induced by DIC improved without severe complications. Although IIAA is relatively rare, the post-operative mortality of patients with ruptures is reportedly high. We assessed the usefulness of this procedure for impending rupture of IIAA, especially for patients in high risk groups.

Aged↗
PubMed1999

[Treatment strategy for and clinical results in patients with recurrent esophageal cancer].

In the current study, we evaluate the frequency and pattern of recurrence in patients with esophageal cancer. Among 116 patients who had undergone curative resection for esophageal cancer, recurrence was found in 33 (28.4%). The most frequent pattern of recurrence was lymphatic (54.5%), followed by the mixed type (18.2%), hematogenic (12.1%), locoregional (12.1%), and anastomotic (3.0%) patterns. Recurrence was found within 1 year after surgery in 18 (54.5%), within 2 years in 12 (36.4%), and within 3 years in 3 (9.1%). In patients with recurrence, lymph node metastasis and advanced stage were seen more frequently than in those without recurrence. The prognosis for patients with recurrent disease is poor. However, in some cases surgical resection, systemic chemotherapy, hepatic arterial infusion chemotherapy, and local radiation therapy have proven to be effective. The most appropriate therapy should be selected based on the region of extension and patient performance status to provide optimum treatment of recurrent disease.

Aged↗
PubMed1999

[Atopic dermatitis on infant physical examination].

The prevalence rate of atopic dermatitis was investigated in 4-month-old infants, who were examined by dermatologists at regular health checks at a health center. Among 739 infants examined, 150 were diagnosed as having atopic dermatitis, giving a prevalence rate of 20.3%. Most of the cases were mild, and no severe cases were observed. The prevalence rate in spring and autumn was significantly higher than that in summer and winter. The eruptions were seen mainly on the head, face, and trunk. A familial history of atopic dermatitis was positively correlated with infant atopic dermatitis in this series, whereas a familial history of bronchial asthma and allergic rhinitis showed no such correlation. It is important to make a correct diagnosis of mild atopic dermatitis by differentiation from other diseases by dermatologists, and it will be of interest to observe the condition of the infants when they attend for their next physical examination at the age of 18 months.

Dermatitis, Atopic↗
PubMed1998

Proliferative activity of cancer cells in front and center areas of carcinoma in situ and invasive sites of esophageal squamous-cell carcinoma.

Intraepithelial carcinoma contiguous with invasive squamous-cell carcinoma is a conspicuous feature of esophageal cancer. However, whether the mechanism of intraepithelial spreading is due to cell proliferation or field carcinogenesis has yet to be clarified. This study investigated the mechanism of intraepithelial spreading by measuring the cell proliferative activity using argyrophilic nucleolar organizer region (AgNOR) and proliferating cell nuclear antigen (PCNA)-positive cell counting. We examined the AgNOR number and PCNA-positive ratio (PCNA ratio) in the center and outer edge of intraepithelial carcinoma and in the center and deep margin of invasive squamous-cell carcinoma of the esophagus in 50 specimens from 18 cases of esophageal squamous-cell carcinoma concomitant with contiguous intraepithelial carcinoma. The proliferative activity was thus found to differ between the normal epithelium and cancerous lesions (p < 0.001), between intraepithelial carcinoma and invasive cancer (p < 0.001) and between deep margin and center areas of invasive cancer (p < 0.005). On the other hand, such activity was observed to be similar in the center and outer edge of the intraepithelial spread. These findings suggest that cell proliferation is the main mechanism of tumor progression at the invasive site of cancer, whereas in intraepithelial carcinomatous areas, "field carcinogenesis" or a paracrine mechanism, and not cell proliferation, is thought to be the cause of intraepithelial spread of esophageal cancer. These results therefore support the concept of field carcinogenesis.

Carcinoma in Situ↗
PubMed1998

Structure of 3-isopropylmalate dehydrogenase in complex with 3-isopropylmalate at 2.0 A resolution: the role of Glu88 in the unique substrate-recognition mechanism.

BACKGROUND: 3-Isopropylmalate dehydrogenase (IPMDH) and isocitrate dehydrogenase (ICDH) belong to a unique family of bifunctional decarboxylating dehydrogenases. Although the ICDH dimer catalyzes its reaction under a closed conformation, known structures of the IPMDH dimer (without substrate) adopt a fully open or a partially closed form. Considering the similarity in the catalytic mechanism, the IPMDH dimer must be in a fully closed conformation during the reaction. A large conformational change should therefore occur upon substrate binding. RESULTS: We have determined the crystal structure of IPMDH from Thiobacillus ferrooxidans (Tf) complexed with 3-isopropylmalate (IPM) at 2.0 A resolution by the molecular replacement method. The structure shows a fully closed conformation and the substrate-binding site is quite similar to that of ICDH except for a region around the gamma-isopropyl group. The gamma group is recognized by a unique hydrophobic pocket, which includes Glu88, Leu91 and Leu92 from subunit 1 and Val193' from subunit 2. CONCLUSIONS: A large movement of domain 1 is induced by substrate binding, which results in the formation of the hydrophobic pocket for the gamma-isopropyl moiety of IPM. A glutamic acid in domain 1, Glu88, participates in the formation of the hydrophobic pocket. The C beta and C gamma atoms of Glu88 interact with the gamma-isopropyl moiety of IPM and are central to the recognition of substrate. The acidic tip of Glu88 is likely to interact with the nicotinamide mononucleotide (NMN) ribose of NAD+ in the ternary complex. This structure clearly explains the substrate specificity of IPMDH.

3-Isopropylmalate Dehydrogenase↗
PubMed1998

Family aggregation of carcinoma of the hypopharynx and cervical esophagus: special reference to multiplicity of cancer in upper aerodigestive tract.

The role of family history in the multiple occurrence of cancer in the upper aerodigestive tract (UADT) remains unclear. The family histories of close relatives were examined in 167 patients with either hypopharyngeal or cervical esophageal cancer (PhCe cancer) and in 167 control subjects with benign diseases. The odds ratio for PhCe cancer was 2.6 in relation to family history of UADT cancers. Based on the family histories of close relatives, 167 cases with PhCe cancer were divided into 3 groups (Group I, 18 cases with a family history of UADT cancer; Group II, 37 cases with a family history of other cancers; Group III, 112 cases with no family history of any cancers). The mean age of the cases in group I was 59.4, which was younger than in group III (64.2). Second primary squamous-cell carcinomas in the UADT were more frequently recognized in group I (39%) than in group III (11%). However, no differences were observed in the smoking and drinking habits of male patients between each group. These results thus suggest that a family history of UADT cancers appears to be associated with the multiple occurrence of UADT cancers as well as the development of PhCe cancer.

Aged↗
PubMed1998

Long-term results of ABO-incompatible living kidney transplantation: a single-center experience.

BACKGROUND: Despite great efforts to promote the donation of cadaveric organs, the number of organ transplantations in Japan is not increasing and a serious shortage of cadaveric organs exists. These circumstances have forced a widening of indications for kidney transplantation. For this purpose, ABO-incompatible living kidney transplantations (LKTs) have been performed. Although we have already reported the short-term results of ABO-incompatible LKT, there is no report of long-term results in such cases; anti-A and anti-B antibodies could cause antibody-induced chronic rejection and result in poor long-term graft survival. In this study, we have reviewed the long-term results of ABO-incompatible LKT and tried to identify the most important factors for long-term renal function in ABO-incompatible LKT. METHODS: Sixty-seven patients with end-stage renal failure underwent ABO-incompatible living kidney transplantation at our institute between January, 1989, and December, 1995. The mean age was 34.9 years (range, 8-58 years), with 38 males and 29 females. Incompatibility in ABO blood group antigens was as follows: A1-->O, 23 patients; B-->O, 19 patients; A1B-->A1, 7 patients; B-->A1, 8 patients; A1-->B; 4 patients; A1B-->B, 4 patients; A1B-->O, 2 patients. The number of HLA-AB, and -DR mismatches were 1.6+/-1.1 and 0.76+/-0.6, respectively. Plasmapheresis and immunoadsorption were carried out to remove the anti-AB antibodies before the kidney transplantation. In the induction phase, methylprednisolone, cyclosporine, azathioprine, antilymphocyte globulin, and deoxyspergualin were used for immunosuppression. Local irradiation of the graft was performed at a dose of 150 rad, on the first, third, and fifth days after transplantation. Splenectomy was done at the time of kidney transplantation in all cases. RESULTS: Patient survival was 93% at 1 year and 91% at 8 years. Graft survival was 79% at 1, 2, 3, and 4 years, 75% at 5 and 6 years, and 73% at 7 and 8 years. Patient survival was not significantly different from that of ABO-compatible patients. However, graft survival was significantly different between ABO-incompatible grafts and ABO-compatible grafts. Specifically, ABO-incompatible transplant recipients experienced a significantly higher rate of early graft loss up to 3 years but showed an equivalent graft loss by year 4. Among 67 patients, 16 grafts were lost during the observation period. Loss was due to acute rejection in 5 patients, followed by chronic rejection in 5 patients and death with function in 3 patients, whereas immunosuppression was withdrawn in 3 patients due to nonimmunological reasons. Of 16 grafts lost, 15 were lost within 1 year after transplantation. Of the 67 patients, 5 died during observation. Three patients with functioning grafts died of uncontrolled bleeding due to duodenal ulcer, malignant lymphoma, and cerebral hemorrhage (one patient each). One patient died of ischemic colitis due to secondary amyloidosis and one patient of cerebral hemorrhage after graft loss due to humoral rejection. There was no fatal infectious complication, whereas 10 patients had non-tissue-invasive cytomegalovirus infection. The stepwise logistic regression model was employed to identify the most important factors for long-term renal function. Patients were subdivided into those with serum creatinine of less than 2.0 mg/dl (group 1, n=39) versus those with serum creatinine of more than 2.0 mg/dl (group 2, n=22) at one year after renal transplantation. Six patients were excluded because of death with functioning graft (three patients) and withdrawal of immunosuppression (three patients). Rejection episodes within 6 months were significantly frequent in group 2 compared with group 1 (P=0.0008). Odds ratio was 112-fold in the rejection episodes. Obviously, the high incidence of early humoral rejection is caused by ABO incompatibility, because ABO-incompatible grafts experience a higher rate of early rejection and graft loss compa

ABO Blood-Group System↗
PubMed1998

Recent advances in preoperative hyperthermochemoradiotherapy for patients with esophageal cancer.

BACKGROUND AND OBJECTIVES: Hyperthermochemoradiotherapy (HCR) has been performed on numerous patients with esophageal cancer. The purpose of this study is to demonstrate the recent advances in HCR. METHODS: From 1965 to 1997, 294 patients given preoperative chemoradiotherapy (CR) or HCR were classified according to the anticancer agent that was administered (CR; group A given bleomycin (BLM); group B given cis-diamminedichloroplatinum (II) (CDDP), HCR; group C given BLM; and Group D given CDDP). The local response and the long-term results were investigated. RESULTS: The cases in which CR or HCR was evaluated to be effective numbered 44 (48.4%) in group A, 22 (73.3%) in group B, 79 (63.7%) in group C, and 36 (73.5%) in group D. A significant difference was observed between groups A and B (P < 0.05). The highest incidence of markedly effective cases was observed in group D. The 5-year survival rates for the group A and B patients were 17.2% and 43.9%, respectively (P < 0.01), while the same rates for those of groups C and D were 25.6% and 57.8%, respectively (P < 0.05). Our results thus showed CDDP to have a greater effect than BLM, while HCR had a greater effect than CR. CONCLUSIONS: Preoperative HCR has improved thanks to recent advances in anticancer agents.

Aged↗
PubMed1998

Single local injection of recombinant fibroblast growth factor-2 stimulates healing of segmental bone defects in rabbits.

The effects of a single local injection of recombinant human fibroblast growth factor-2 on the healing of segmental bone defects were evaluated in rabbits. One month after the external fixator originally designed for this experiment was installed in the tibia of the rabbit, a 3-mm bone defect was created by an osteotomy in the middle of the tibia and 0, 50, 100, 200, or 400 microg of fibroblast growth factor-2 in 100 microl of saline solution was injected into the defect. Injection of the growth factor increased the volume and mineral content of newly made bone at the defect in a dose-dependent manner with significant effects at concentrations of 100 microg or greater. These significant effects were observed at 5 weeks and later. One hundred micrograms of the growth factor increased the volume and mineral content of newly made bone by 95 and 36%, respectively, at 5 weeks. These results indicate that a single local injection of fibroblast growth factor-2 stimulates the healing of segmental defects. We speculate that such an injection could be clinically useful for the healing of fractures even when the fracture gap is rather large.

Animals↗