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Shigeo Hara

Publications and source records attributed to Shigeo Hara.

17 recordsLinked to original sources
PubMed2006

Outcome and treatment of bucillamine-induced nephropathy.

BACKGROUND: Bucillamine (BCL), a treatment for rheumatoid arthritis, occasionally causes proteinuria. Renal specimens are reported to show segmental granular deposition of immunoglobulin G, associated with membranous nephropathy. Long-term course and optimal treatment have remained unknown, and were investigated here. METHODS: We examined clinical records of 400 patients treated with BCL for rheumatoid arthritis, at our hospital from 1998 to 2003, finding 17 with proteinuria and biopsy-proven BCL-induced nephropathy. RESULTS: In all 17 patients, proteinuria resolved without loss of renal function between 3 and 85 months after discontinuing BCL (14.1 +/- 3.4). The only factor influencing time to remission was pathologic stage of membranous nephropathy (stage I vs. stage II or III: 11.5 +/- 4.8 vs. 21.6 +/- 3.3 months; p = 0.02). Maximal proteinuria, total amount of BCL, BCL exposure time, and use of prednisolone or other immunosuppressant agents did not significantly influence time until remission. CONCLUSION: The most important therapeutic step in treating BCL-induced nephropathy is to discontinue BCL. Prednisolone or other immunosuppressant agents might not be effective.

Adult↗
PubMed2006

Genital beta2-microglobulin amyloidoma in a long-term dialysis patient.

We present the case of a 58-year-old Japanese woman with a huge amyloid tumor in the genital region. Hemodialysis therapy was started for renal failure secondary to polycystic kidney disease in 1974. From 1989 to 1991, carpal tunnel decompression was performed surgically, and beta(2)-microglobulin (beta2MG)-amyloid deposition was found in the wrists. She was hospitalized at our institute for evaluation of lower-abdominal fullness and lower-extremity edema in March 2003. Magnetic resonance imaging showed a huge mass measuring 9.0 x 6.0 x 5.0 cm sandwiched between the vagina and rectum. The mass was hypointense compared with adjacent muscle on T2-weighted images. Computed tomography showed soft-tissue density accompanied by diffuse calcification. A biopsy specimen of the mass obtained by using a transvaginal approach showed material that was positive for beta2MG-amyloid immunohistologically. When patients on long-term dialysis therapy develop a genital mass with low-signal intensity on T2-weighted images by magnetic resonance imaging and diffuse calcification by computed tomography, beta2MG-amyloidoma should be considered as a differential diagnosis.

Amyloidosis↗
PubMed2006

Fluorescence (Förster) resonance energy transfer imaging of oncogene activity in living cells.

A hallmark of cancer cells is their uncontrolled activation of growth signal transduction cascades comprised of oncogene products. Overexpression and activating mutations of the growth factor receptors Ras and Raf are frequently observed in human cancer cells. Several research groups, including our own, have been developing probes based on the principle of fluorescence (Förster) resonance energy transfer (FRET) to visualize how signaling molecules, including oncogene products, are regulated in normal and cancerous cells in the living state. In this review, we will briefly introduce the principle of FRET-based probes, present an overview of the probes reported to date, and discuss the perspectives of these probes and fluorescent imaging systems in cancer biology.

Animals↗
PubMed2006

Use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors is associated with risk of lymphoid malignancies.

It has been speculated that the use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors (statins) is associated with the risk of malignant diseases. Considering their immunosuppressive activities, malignant diseases that are associated with an immunosuppressive status seem feasible to examine the association. We therefore examined the association between statin use and development of lymphoid malignancies in a case-control study. Cases were 221 consecutive incident cases with histopathologically proven lymphoid malignancies (lymphoma and myeloma), hospitalized in the Department of Hematology of Toranomon Hospital (Tokyo, Japan) between 1995 and 2001. Two independent control groups, comprising 442 and 437 inpatients without malignancies from the Departments of Orthopedics and Otorhinolaryngology of the same hospital, were selected to test for consistency of association. Controls were matched individually with cases for age, sex and year of admission. Subject information, including statin use, was abstracted from medical records at the time of hospitalization. Strength of association was evaluated as an adjusted odds ratios (aOR) using a conditional logistic regression model. A higher frequency of statin use was found among patients with lymphoid malignancies in comparison with both orthopedic (aOR 2.11, 95% CI 1.20-3.69, P = 0.009) and otorhinolaryngology patients (aOR 2.59, 95% CI 1.45-4.65, P = 0.001), the significance being maintained when the two control groups were combined (aOR 2.24, 95% CI 1.37-3.66, P = 0.001). In conclusion, we observed an elevated risk of lymphoid malignancy with statin use among Japanese patients. Further evaluations in different populations are required to draw conclusions as to the carcinogenicity of lymphoid malignancies with statin use.

Aged↗
PubMed2006

Safety of reduced-dosage ketoprofen for long-term oral administration in healthy dogs.

OBJECTIVE: To evaluate the safety of reduced-dosage ketoprofen (RDKET) for long-term oral administration in healthy dogs. ANIMALS: 14 healthy Beagles. PROCEDURES: Racemic ketoprofen (0.25 mg/kg, PO) and gelatin capsules, as a drug-free placebo, were each administered to 7 dogs for 30 days. Dogs were periodically monitored via physical examination, blood analyses, endoscopic examinations, fecal occult blood tests (tetramethylbenzidine and guaiac methods), renal function tests (effective renal plasma flow and glomerular filtration rate), urinalyses, urinary enzyme indices (N-acetyl-beta-D-glucosaminidase and gamma-glutamyl-transferase), and hemostatic function tests (buccal mucosa bleeding time, cuticle bleeding time, prothrombin time, activated partial thromboplastin time, and fibrinogen concentration). RESULTS: Pyloric antrum lesion grade was significantly higher in the RDKET group on day 28, compared with the pretreatment and control group grades. Fecal occult blood grade measured by use of the tetramethylbenzidine method was significantly higher in the RDKET group on day 30, compared with the pretreatment grade. No other significant differences were detected between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: RDKET induced mild to moderate gastric mucosal injuries especially in the pyloric antrum in healthy Beagles, whereas no adverse effects were observed in renal function or hemostasis. Fecal occult blood tests may be useful as screening tests for adverse gastrointestinal effects induced by RDKET in dogs.

Administration, Oral↗
PubMed2005

Early immune reaction after reduced-intensity cord-blood transplantation for adult patients.

BACKGROUND: To investigate immune reactions after reduced-intensity cord-blood transplantation (RI-CBT). MATERIALS AND METHODS: We reviewed medical records of 57 adult RI-CBT recipients. Preparative regimen comprised fludarabine, total-body irradiation, and either melphalan (n=51) or busulfan (n=6). Graft-versus-host disease (GvHD) prophylaxis was cyclosporine. PostRI-CBT immune reactions were classified according to time course: pre-engraftment immune reactions (PIR), engraftment syndrome (ES), and GvHD. RESULTS: Forty-five patients achieved engraftment at a median of day 19. PIR was characterized by high-grade fever and weight gain and developed on a median of day 9 in 35 of the 45 evaluable patients, including 3 who did not achieve engraftment. PIR subsided spontaneously in 12 patients, whereas corticosteroids were required in the other 23. ES and grade I to IV acute GvHD developed in 36 and 29 patients, respectively. GvHD could not be distinguished from preceding PIR or ES in 10 patients. Causes of the 32 nonrelapse mortalities included GvHD (n=5) and PIR (n=1). There were no significant differences in relapse and nonrelapse deaths between patients with PIR and those without it (18% vs. 5%, and 60% vs. 65%, respectively). CONCLUSIONS: Immune reactions after RI-CBT can be categorized into three distinct subtypes.

Adult↗
PubMed2005

A patient with symptomatic osteomalacia associated with Fanconi syndrome.

We report a patient with renal tubulointerstitial fibrosis and symptomatic osteomalacia associated with Fanconi syndrome. A 55-year-old woman was hospitalized because of an inability to walk. Beginning approximately 2 years previously, she had experienced gradually worsening pain in the hips, shoulders, and trunk, culminating in a bedridden state. Serum urea nitrogen was 38 mg/dl; creatinine, 2.6 mg/dl; uric acid. 3.6 mg/dl; phosphate, 2.3 mg/dl; and alkaline phosphatase, 2111 IU/l. Urinary beta2 microglobulin was 72 331 microg/day. Aminoaciduria, renal glucosuria, and proximal renal tubular acidosis with a normal anion gap were also noted. The patient was diagnosed with Fanconi syndrome. Radiography demonstrated typical Looser zones in the proximal portion of the left and especially the right femoral shaft, and at several other sites. A renal biopsy specimen disclosed severe tubulointerstitial fibrosis with little cellular infiltration. Glomeruli were largely intact. A bone biopsy specimen indicated osteomalacia; no tetracycline labeling could be seen along most trabecular bone surfaces, and the ratio of total osteoid volume to bone volume was increased (71.8%). Bicarbonate administration (9 g/day) gradually lessened most symptoms, permitting ambulation. Calcitriol administration decreased excessive intact-parathyroid hormone emerging after 2 months of acidosis correction. Thus, severe acidosis associated with Fanconi syndrome can induce osteomalacia showing serious skeletal complications, but also responsiveness to bicarbonate therapy.

Journal Article↗
PubMed2005

Distribution of IgG subclasses in a biopsy specimen showing membranous nephropathy with anti-glomerular basement membrane glomerulonephritis: an uncharacteristically good outcome with corticosteroid therapy.

Few occurrences of anti-glomerular basement membrane glomerulonephritis superimposed on membranous nephropathy have been reported; most reported cases began as membranous nephropathy. Little is known about the etiology, pathogenesis, or immunoglobulin G subclasses in glomerular basement membrane deposits in these combined cases. The authors report the case of an elderly patient with apparently simultaneous onset of both membranous nephropathy and anti-glomerular basement membrane glomerulonephritis who had an excellent outcome with only pulse corticosteroid therapy. Successive renal biopsy specimens showed occurrence and disappearance of immunoglobulin G4 deposits in the glomerular basement membrane. Immunoglobulin G subclass analysis was important in recognizing membranous nephropathy underlying the anti-glomerular basement membrane disease.

Aged↗
PubMed2005

Long-term course of post-transplant mesangial IgA deposition: clinicopathologic study of nine cases.

We conducted the present study to elucidate the fate of post-transplant mesangial IgA deposit under the long-term observation. Out of a total of 45 cases with post-transplant mesangial IgA deposition, nine cases with more than 4 yr of follow-up term were enrolled in this study, and clinicopathologic characteristics were described. The study included three men and six women with a mean age of 34.2 yr. The average observation time from the detection of mesangial IgA deposition was 6.1 yr. Three cases were categorized as recurrent IgA nephropathy, while six cases were classified into latent mesangial IgA deposition. One case with hypertension developed end-stage renal disease. The significant improvement in microscopic hematuria was observed in one recurrent IgA nephropathy case. Microscopic findings included mild mesangial stalk thickening in all but one case. IgA deposition demonstrated a significant decrease in three latent mesangial IgA deposition cases. No apparent reduction in dense deposit quantity was observed on electron microscopy. There was no association between clinicopathologic findings and the regimen of anti-immunosuppressive agents. This study showed the improvement of the disease activity did occur in both recurrent IgA nephropathy and latent mesangial IgA deposition. Further investigation of latent mesangial IgA deposition may present the important clue to the pathogenesis of IgA nephropathy.

Adult↗
PubMed2005

Effects of long-term oral administration of ketoprofen in clinically healthy beagle dogs.

To investigate the adverse effects of long-term administration of ketoprofen in dogs, ketoprofen (1 mg/kg) was administered to five clinically healthy beagle dogs (ketoprofen group) and gelatin capsules (control group) were administered to four clinically healthy beagle dogs for 30 days. We monitored the dogs through periodic physical examination, blood analyses, endoscopic examinations, fecal occult blood tests, renal function tests, urinalysis, urinary enzyme indices and cuticle bleeding time analysis. The lesions in the stomach, especially in the pyloric antrum, and fecal occult blood progressively worsened in the ketoprofen group. However, the differences between the ketoprofen group and the control group were not statistically significant. One dog in the ketoprofen group temporarily exhibited a decrease in renal plasma flow and two dogs exhibited enzymuria. However, these changes did not persist and the other examinations showed no significant difference between premedication and postmedication in the ketoprofen group. Therefore, the adverse effects of long-term administration of ketoprofen observed in this study were not clinically important in healthy dogs. Nevertheless, further investigation of adverse renal effects from long-term administration of ketoprofen is necessary in the dogs with subclinical renal disease.

Animals↗
PubMed2005

Membranous glomerulopathy induced by myeloperoxidase-anti-neutrophil cytoplasmic antibody-related crescentic glomerulonephritis.

A 68-year-old woman was referred for evaluation of nephrotic-range proteinuria and a course suggesting rapidly progressive glomerulonephritis. Serum anti-neutrophil cytoplasmic antibody against myeloperoxidase (MPO) was 204 U/ml. A renal biopsy specimen revealed necrotizing glomerulonephritis with crescent formation. However, immunofluorescence showed staining with IgG and C3 along capillary walls. IgG positivity included both IgG1 and IgG4. Electron microscopic examination disclosed both paramesangial and subepithelial deposits. This case suggests that rarely, MPO-ANCA-related crescentic glomerulonephritis may present nephrotic-range proteinuria and show immune deposits along capillary walls.

Aged↗
PubMed2004

Morphological variations in brachial plexus of beagle dogs: evaluation of utility as sources of allogeneic nerve grafts.

Basic studies were carried out to apply frozen allogeneic nerve grafts in dogs after wide-ranging defects of the brachial plexus due to surgical resection of tumor. In this study, morphological variations in branching patterns of the brachial plexus were examined in ten beagle dogs, to evaluate whether the brachial plexus might represent a useful source of allogeneic nerve grafts. Spatial relationships between the axillary lymph node, which had the possibility of carcinomatous metastasis, and the musculocutaneous (MC) nerve, which was important for the function of the forelimbs, were also investigated. In all ten cases examined, the brachial plexus received ventral roots from the fifth cervical nerve to the first thoracic nerve. No significant variation in the branching pattern was found in any nerve except the phrenic, MC and dorsal thoracic nerves. Four communicating branches were observed and had some morphological variations which might be negligible for nerve grafting. Considering previous physiological and anatomical reports, the most important nerve to be reunited in graft operations for functional recovery is the radial nerve. The MC nerve and median or ulnar nerve should also be considered as possibilities for reuniting. Distances between the axillary lymph nodes and the MC nerve ranged from 11.2 mm to 21 mm (mean +/- SD: 16.1 +/- 2.3 mm). In conclusion, it was suggested that morphological variations in the brachial plexus were technically acceptable to apply allogeneic nerve grafts at least in beagle dogs.

Animals↗
PubMed2003

Origin of plasma insulin-like growth factor-I (IGF-I) during estrus in goats.

The objective of this study was to clarify the origin of the increase in plasma insulin-like growth factor-I (IGF-I) during estrus in goats. Focusing on the uterus, the effect of estradiol-17 beta (E2) on the secretion of IGF-I was examined using ovariectomized and hysterectomized animals. A single 5 microg/kg BW of E2 was injected intramuscularly into ovariectomized and hysterectomized goats for 3 consecutive days, and plasma IGF-I concentrations in the two groups were compared. The concentrations of IGF-I rose after the treatments in both groups. The concentrations were significantly higher from 3 to 8 days after the treatment than before the treatment in ovariectomized goats (P<0.05), and from 1 to 3 days after the treatment than before in hysterectomized goats (P<0.05). Thus higher concentrations of plasma IGF-I tended to last longer in ovariectomized than hysterectomized goats. The area under the IGF-I response curve for the 8-day period after the first injection of E2 tended to be greater in ovariectomized than in hysterectomized goats. The results show that E2 increases plasma IGF-I concentrations in goats, and suggest that E2-stimulated IGF-I in plasma may originate mainly from the uterus.

Animals↗
PubMed2003

Chinese herbs and bone disease.

We treated a patient with an unusual bone disease at least partly associated with Chinese herbs. Seven years after 65-year-old man had begun to consume Chinese herbs, multifocal osteoarthralgias were noted, and the patient was hospitalized for renal dysfunction (serum creatinine, 2.8 mg/dl; urea nitrogen, 19 mg/dl). Fanconi syndrome also was apparent. A renal biopsy specimen showed tubulo-interstitial fibrosis. Chinese herbs were discontinued and prednisolone was started, but bone and joint pain as well as renal function gradually worsened. Four years later, creatinine was 9.0 mg/dl and alkaline phosphatase was 571 IU/l. As bone scintigraphy revealed localized asymmetric lesions, Paget's disease of bone was suspected at first. However, neither osteosclerosis nor hypertrophy was seen in radiographs. Based on a bone specimen histology we diagnosed as mixed-type renal osteodystrophy including osteomalacia and osteitis fibrosa. Mosaic pattern of cement lines was not present. This case was not compatible with either Paget's disease or typical renal osteodystrophy as seen in dialysis patients. Etidronate disodium was effective in alleviating bone symptoms. The patient's bone disorder may be a new disease at least partly related to Chinese herbs independently of nephropathy.

Aged↗
PubMed2002

[Neurotoxicity in sodium azide poisoning].

The effects of sodium azide administration on the central cholinergic functions were investigated utilizing mice to evaluate the neurotoxicity in the acute poisoning. Seven oral doses of the toxicant, ranging in dosage from 12.3 to 59.3 mg/kg, based upon a multiple of 1.3 x 27 mg/kg (an empirical LD50 for mice) or 27 mg/kg divided by 1.3 to calculate the lower three doses, were administered to facilitate the acute signs and to observe behavior. The behavior included locomotor activity, rectal temperature and rotarod performance which are convenient for the evaluation of central cholinergic involvement even if it may be partial, since no behavioral methods to study totally the cholinergic system have been known. Measurements of the activities of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT), enzymes that hydrolyze and synthesize acetylcholine (ACh) and high-affinity choline uptake (HACU), a rate-limiting step in the synthesis of ACh, were determined in the presence of various concentrations of sodium azide in vitro. Adult (12-15 weeks) female ICR strain mice were utilized in this study. Mice were orally given sodium azide in doses from 27 to 59.3 mg/kg and appeared sedated within 5 min. Next we observed hyperpnea and dyspnea, which were followed by seizure and death for mouse groups which received more than 35.1 mg/kg. Oral administration of the sodium azide solution produced an increase in locomotor activity for the 12.3 mg/kg group and a decrease for the higher doses (ranging from 16.0 to 27.0 mg/kg). The sodium azide administration suppressed rectal temperature dose-dependently as well as rotarod performance at high doses (20.8 and 27.0 mg/kg). Such behavioral changes elicited by sodium azide administration suggest an involvement of the central cholinergic system. Sodium azide also caused a measured decrease in the activity of AChE, but an increase in the activities of ChAT and HACU, dose-dependently, in vitro. From the results obtained from the behavioral and the in vitro experiments, we concluded that acute sodium azide poisoning significantly affects the central cholinergic system.

Acetylcholine↗