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Y Akagi

Publications and source records attributed to Y Akagi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Role of the tumor microenvironment in mediating response to anti-angiogenic therapy.

Despite the development of innovative anti-angiogenic strategies, early clinical trials have not replicated the results observed from preclinical models. One reason for this apparent discrepancy is the fact that tumor endothelium is phenotypically distinct from normal tissue endothelium. Moreover, it has recently become apparent that each individual tumor may display a different angiogenic phenotype. The expression of angiogenic factors in tumors is controlled by both intrinsic factors in the tumor cell and the influence of the host microenvironment. The diversity of angiogenic factor expression in tumors growing at different sites, combined with the fact that endothelial cells in different organs and tumors are phenotypically distinct, constitutes a formidable challenge for the development of effective anti-angiogenic regimens. This review provides an overview of how the microenvironment regulates tumor angiogenesis and affects the efficacy of anti-angiogenic therapy.

Angiogenesis Inhibitors↗
PubMed2000

Gene transfer targeting interstitial fibroblasts by the artificial viral envelope-type hemagglutinating virus of Japan liposome method.

BACKGROUND: Tubulointerstitial inflammation and fibrosis are commonly associated with most human glomerular diseases. The degree of tubulointerstitial damage, rather than the glomerular injury, could correlate with the degree of renal functional impairment and accurately predict long-term prognosis. In an effort to understand the pathogenesis of the progressive interstitial fibrosis, we developed a new strategy of gene transfer to the interstitial fibroblasts. METHODS: Either fluorescein isothiocyanate (FITC)-labeled oligodeoxynucleotides (ODNs) or pEBAct-NlacF expression vector was introduced into the kidney of normal rats retrogradely via ureter by using the artificial viral envelope (AVE)-type hemagglutinating virus of Japan (HVJ) liposome method. RESULTS: FITC-labeled ODNs were accumulated diffusely in the nuclei of the interstitial cells in the transfected kidney 10 minutes after transfection, and the interstitial cells were identified as interstitial fibroblasts by immunostaining with ER-TR7. To examine the gene expression in the interstitium, pEBAct-NlacF gene-conjugated HVJ liposome was injected retrogradely through the ureter, and in consequence, nuclear beta-galactosidase activity was continuously observed in interstitial cells at least two weeks after transfection. CONCLUSION: This new strategy of gene transfer to the interstitial fibroblasts is useful for the investigation of the pathophysiology of tubulointerstitial lesion, and furthermore, it may be a promising new therapeutic method for the progression of interstitial fibrosis.

Animals↗
PubMed2000

Nitric oxide inhibits growth of glomerular mesangial cells: role of the transcription factor EGR-1.

UNLABELLED: Nitric oxide inhibits growth of glomerular mesangial cells: Role of the transcription factor Egr-1. BACKGROUND: In previous studies, we found a close link of early growth response gene-1 (Egr-1) expression to mesangial cell (MC) proliferation. Antiproliferative agents inhibited mitogen-induced Egr-1 expression. Here we investigated the effect of S-nitrosoglutathione (GSNO) on the proliferation of MCs, specifically asking how GSNO regulates the transcription factor Egr-1, which we have previously shown to be critical for the induction of MC mitogenesis. METHODS: The proliferation of MCs was measured by thymidine incorporation and cell counting. Egr-1 mRNA and protein levels were detected by Northern and Western blots. Electrophoretic mobility shift assays (EMSAs) and chloramphenicol acetyltransferase (CAT) assays were performed to test whether GSNO modulates DNA binding and transcriptional activation of Egr-1. RESULTS: GSNO strongly inhibited serum-induced MC proliferation (-84% at 1 mmol/L). A mild inhibition of serum-induced Egr-1 mRNA was observed at GSNO concentrations from 50 to 200 micromol/L, whereas mRNA levels increased again at concentrations above 500 micromol/L. This increased mRNA expression, however, was not translated into Egr-1 protein. Instead, Egr-1 protein induction was inhibited (-40%). EMSAs indicated that GSNO inhibited specific binding of Egr-1 to its DNA consensus sequence. Moreover, transcriptional activation by Egr-1 in CAT assays using a reporter plasmid bearing three Egr-1 binding sites was strongly suppressed by GSNO. CONCLUSIONS: Our data identify GSNO as a potent inhibitor of MC growth with potential beneficial effects in proliferative glomerular diseases. This antimitogenic property is mediated at least in part by inhibitory effects of GSNO on Egr-1 protein levels and by reducing the ability of Egr-1 to activate transcription by impairing its DNA binding activity.

Animals↗
PubMed2000

A clinicopathological study of IgA nephropathy in renal transplant recipients: beneficial effect of angiotensin-converting enzyme inhibitor.

BACKGROUND: Prolonging the survival of transplant kidneys is a major task of modern nephrology. It has recently been shown that deteriorating renal function and substantial graft loss were observed in 55% of renal allograft recipients with recurrent IgA nephropathy (IgAN) at long-term follow-up. To gain a useful insight into the therapeutic approach towards protecting allograft kidneys from deteriorating graft function, we compared the histological characteristics of post-transplant IgAN to primary IgAN and investigated the effects of an ACE inhibitor. METHODS: Twenty-one patients with post-transplant IgAN and 63 patients with primary IgAN were included in the histopathological study. The effectiveness of angiotensin-converting enzyme (ACE) inhibitor treatment in post-transplant IgAN was also studied in 10 patients. RESULTS: The prevalence of glomeruli with adhesions and/or cellular crescents in primary IgAN was significantly greater than in post-transplant IgAN (P<0.05), but the proportion of glomeruli with segmental sclerosis was similar in both groups. The rate of global obsolescence, and the degree of interstitial fibrosis in post-transplant IgAN were significantly greater than in primary IgAN (P<0.05). The degree of glomerular obsolescence and the severity of interstitial fibrosis correlated with the severity of glomerular lesion in primary IgAN, but not in post-transplant IgAN. In primary IgAN, glomerular diameter significantly correlated with the proportions of glomerular obsolescence, but not in post-transplant IgAN, suggesting that allograft kidneys may be in a hyperfiltration state. Both the blood pressure and the urinary protein excretion significantly improved after ACE-inhibitor treatment (P<0.001). CONCLUSION: In post-transplant IgAN, histopathological lesions indicative of acute inflammatory insults were suppressed, and glomerular hypertrophy, which may relate to haemodynamic burden such as hyperfiltration, was prominent. Preliminary study of ACE-inhibitor treatment in 10 patients showed favourable effects. A future long-term follow-up study is required to establish the effectiveness of ACE inhibitors in treatment of post-transplant IgAN.

Adult↗
PubMed2000

[Immunohistochemical study of apoptosis of lens epithelial cells in human and diabetic rat cataracts].

PURPOSE: To evaluate apoptosis of lens epithelial cells with immunohistochemical methods. METHODS: We performed terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assays on capsulotomy specimens (68 eyes in 53 patients) from patients who had undergone cataract surgery and an epithelium of diabetic cataracts in rats (144 eyes in 72 rats). The animal model of diabetic cataracts was prepared by injection of streptozotocin in three-week old rats. The rats were also examined using the proliferating cell nuclear antigen (PCNA) immunohistochemical staining method. RESULTS: Although some TUNEL-positive cells were detected in capsulotomy specimens, we recognized little correlation between its distribution and morphological classification of cataracts. In the animal model of diabetic cataracts, TUNEL-positive cells were seen around the region where epithelial cells had accumulated. In the accumulated region, PCNA labeled cells undergoing DNA synthesis were also detected. CONCLUSION: These results suggest the possibility that apoptosis occurs in human lens epithelial cells and apoptosis and proliferation may be induced by factors such as hyperglycemia.

Aged↗
PubMed2000

Distinct mechanisms of transport of ascorbic acid and dehydroascorbic acid in intestinal epithelial cells (IEC-6).

Ascorbic acid (AsA) is an essential nutrient for humans as they lack its biosynthesizing key enzyme. Its absorption mechanism in small intestinal epithelial cells still remains to be resolved. In this study, the transport mechanisms functioning on the uptake of AsA and its oxidized form, dehydroascorbic acid (DHA), were investigated using rat small intestinal epithelial cell line IEC-6. Both AsA and DHA were accumulated in the cells in time- and concentration-dependent manners, but their absorption kinetics were apparently different. The saturability of AsA uptake was shown at a considerably lower concentration in IEC-6 cells as well as other mammalian cells, indicating that this absorption was mediated by a specific transporting carrier. The absorption efficiency of AsA was about 1/5-1/10 that of DHA at the same concentration range and, moreover, the uptake of DHA was almost comparable to that of 2-deoxy-D-glucose, an alternative of glucose. The uptake of AsA was diminished by the removal of sodium ion, but not by the addition of glucose, whereas that of DHA was sodium ion-independent and effectively inhibited by glucose. In addition, phlorizin and cytochalasin B, which are blockers of glucose transporters, interfered the uptake of DHA more efficiently than that of AsA. These results indicate that there are at least two distinct transport systems of vitamin C in rat small intestinal epithelial cells; AsA is transported by a specific transporter and DHA is mainly transported by glucose transporter(s).

Animals↗
PubMed1999

Interstitial brachytherapy for stage I and II squamous cell carcinoma of the oral tongue: factors influencing local control and soft tissue complications.

PURPOSE: Our aim was to study the treatment parameters that influence local control and soft tissue complications (STC) in a series of 207 Stage I and II squamous cell carcinomas of the oral tongue treated by interstitial brachytherapy (BRT) alone (127 patients), or by a combination using external beam irradiation (EBI) (80 patients) between 1980 and 1993. METHODS AND MATERIALS: The patient distribution was 93 T1, 72 T2a, and 42 T2b. The prescribed BRT dose at the plane 5 mm from the plane of the radioactive sources was 65-70 Gy in BRT alone, and 50-60 Gy in the combined treatment using EBI. Generally, an EBI dose of 30 Gy was used. No prophylactic neck treatment was performed. RESULTS: The 5-year local recurrence-free rate for T1, T2a, and T2b was 92.9%, 81.9%, and 71.8%, respectively (p < 0.05). The lesions of endophytic appearance and those located in the posterior half of the mobile tongue had a significantly lower local control rate than those of other macroscopic appearances (p = 0.02) and those in other localizations (p < 0.01). Most local recurrences (66.7%) occurred within 2 years after treatment. However, 8 of 14 recurrences of T1 and 6 of 15 recurrences among patients treated by BRT alone occurred after 5 years. Statistical analysis showed that, in BRT alone treatment, a dose rate < = 1.0 Gy/h was related to better local control (p = 0.04). There was no significant relationship between BRT dose and local control; however, the incidence of local recurrence was lowest in a BRT dose 65-70 Gy. In the combined treatment, a total dose > 85 Gy (p = 0.01), BRT dose > 55 Gy (p = 0.04), and a dose rate < 0.55 Gy/h (p = 0.03) were significantly related to better local control. The incidence of more severe STC were 11.5% and was significantly higher in T2a (p = 0.03) and T2b (p < 0.01) than in T1. Statistical analysis revealed that a dose rate > = 0.6 Gy/h was significantly related to more STC in BRT alone (p = 0.03), and that a dose rate > = 0.55 Gy/h (p < 0.03) and a BRT dose > 70 Gy ( < 0.05) and a total dose > 100 Gy (p < 0.05) were significantly related to more STC in the combined treatment. Neck metastases occurred in 25% in T1N0, 27% in T2aN0, and 31% in T2bN0 (NS). Eighty-eight percent were found within 12 months. Thirty-three secondary cancers including 12 head and neck, 8 esophageal, and 3 gastric were found after treatment. The 5-year crude survival rate for T1, T2a, and T2b was 83.4%, 66.0%, and 70.9%, respectively. CONCLUSION: To acheive better local control and fewer STC, we recommend the following relationships between dose and dose rate. In BRT alone, dose rate should be maintained at < 0.6 Gy/h with a preferable BRT dose 65-70 Gy. In the combined treatment, total dose, BRT dose and dose rate should be kept between > 85 Gy and < = 100Gy, between > 55 Gy and < = 70 Gy, and < 0.55 Gy/h, respectively. We also recommend longer follow-up periods; more than 5 years might be necessary for late local recurrences and for secondary cancers.

Adult↗
PubMed1999

Optimum fractionation for high-dose-rate endoesophageal brachytherapy following external irradiation of early stage esophageal cancer.

PURPOSE: To establish the optimum fractionation for high-dose-rate (HDR) endoesophageal brachytherapy (EBT) for early stage esophageal cancer from retrospective data of patients treated with different HDR schedules following external beam irradiation (EBI). METHODS AND MATERIALS: The study population consisted of 35 consecutive early stage esophageal cancer patients who received EBI to the mediastinum, plus EBT, between May 1992 and November 1995 at the Hiroshima University Medical Center and Hiroshima City Hospital. All patients were treated with EBI, with doses ranging from 50 to 61 Gy. The spinal cord was spared after 44-45 Gy. HDR EBT was performed using a double-balloon applicator in conjunction with an Ir-192 remote afterloading system. One group of 10 patients was given a weekly endoesophageal boost of 4 or 5 Gy at a distance of 5 mm from the applicator surface over a period of 1-2 weeks. Another group of 25 patients was treated with 4 or 5 endoesophageal boosts with a fraction dose of either 2.5 or 2 Gy for 1 week. The linear quadratic (LQ) formula was used to calculate the biologically effective dose (BED) for tumor (Gy10) and esophageal mucosa (Gy3); Gy10 means alpha/beta equals 10 Gy, and Gy3 means alpha/beta equals 3 Gy. The Kaplan-Meier method was used to calculate the local control and late complication rates, while the Cox-Mantel test was used to evaluate statistical significance (p < 0.01). RESULTS: Nine (26%) of the 35 patients recurred locally and 7 (20%) had late complications (esophageal ulcer grade by RTOG/EORTC criteria > 1). The 5-year overall survival, local control, and late complication rates were 38%, 57%, and 26%, respectively. The probability of local recurrence was not affected by the treatment parameters. Results from the LQ formula significantly correlate with data on late complications. A BED > 134 Gy3 and a fraction number = < 3 were associated with late complications (grade > 1). BED analysis showed that the fractionation dose should be decreased to 2.5 or 2.0 Gy at a distance of 5 mm from the applicator surface, and the number of doses increased to 4 or 5, respectively, to yield a satisfactory BED (< 134 Gy3). CONCLUSION: A significant reduction in endoesophageal brachytherapy dose per fraction is necessary to reduce late complications. Our current treatment protocol for early-stage esophageal cancer consists of EBI of 60 Gy followed by 4 EBT doses at a fraction dose of 2.5 Gy applied over 1 week.

Adult↗
PubMed1999

Cataract formation through the polyol pathway is associated with free radical production.

The relationship between sugar cataract formation and radical production was investigated. The in vivo formation of free radicals in the lenses of rats fed on a diet containing 25% and 50% galactose was studied using the electron spin resonance (ESR) spin trapping method. Effects of treatment with aldose reductase inhibitor (ARI) SNK-860 on free radical formation were determined in 25% and 50% galactose fed rats. Hydroxyl radical (*OH) adduct of the spin trap 5,5'-dimethyl-1-pyrroline- N -oxide (DMPO) was directly detected in the superficial cortical cataract obtained from 25% and 50% galactose-fed rats. *OH production was completely inhibited by ARI SNK-860 in both galactose groups. Polyol accumulated in rat lenses given 50% galactose with a peak within the first 2 weeks, and was significantly inhibited by SNK-860. The increase in *OH production was considered with the polyol accumulation in both galactose groups. The dose of SNK-860 to inhibit *OH by 50% level was estimated at 3 m by the method of kinetic competition in vitro experiment. SNK-860 is not an effective *OH scavenger compared to other *OH scavengers. The results of the present study suggest that *OH is indirectly inhibited by SNK-860 resulting from decreasing polyol and *OH formation is related to sugar cataract formation in early stages, possibly via the Fenton reaction involving H2O2 produced from the activated polyol pathway. We suppose that *OH may accelerate damage to the cell membrane of lens fibers resulting from polyol accumulation *OH may play an important role in the early stage of sugar cataract process.

Aldehyde Reductase↗
PubMed1999

Inhibitory effect of orally administered aldose reductase inhibitor SNK-860 on corneal polyol accumulation in galactose-fed rats.

BACKGROUND: Diabetic keratopathy, frequently observed after vitreous surgery, has been thought to be related to the aldose reductase-catalyzed reaction. However, few reports have been published on the chronological changes in polyol accumulation and the effect of the aldose reductase inhibitor in the corneal epithelium or endothelium of galactosemic rats. Consequently, the polyol accumulation in corneal epithelium and endothelium with stroma of 50% galactose-fed rats and the preventive effect of an aldose reductase inhibitor, SNK-860, were biochemically analyzed. METHODS: Four-week-old male Sprague-Dawley rats were fed a 50% galactose diet without supplement or supplemented with a low (3 mg/kg b.w.) or high (30 mg/kg b.w.) dose of SNK-860 (Sanwa Kagaku Kenkyusho, Japan), or a normal diet. Polyol contents in the corneal epithelium or endothelium with stroma were individually measured using gas-liquid chromatography. RESULTS: Polyol in corneal epithelia accumulated quickly in the 1st week, reached a maximum at the 3rd week of feeding and then gradually decreased. Low- and high-dose SNK-860 treatment significantly inhibited polyol accumulation in the epithelium and endothelium with stroma, respectively. Changing to the normal or SNK-860 supplemented diets significantly inhibited polyol accumulation. CONCLUSION: This finding indicates that oral administration of a new aldose reductase inhibitor, SNK-860, or systematic treatment of diabetes may be effective in preventing polyol pathway-induced corneal damage by quickly reducing the polyol level.

Administration, Oral↗
PubMed1999

Markedly elevated levels of vascular endothelial growth factor in malignant ascites.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that also has the ability to increase vascular permeability. Malignant ascites has significant morbidity, but the mechanism of its development is unknown. Because of the permeability-inducing properties of VEGF, we hypothesized that malignant ascites formation is associated with high levels of VEGF. The purpose of our study was to determine the role of VEGF in malignant ascites formation. METHODS: Ascites from 25 patients with gastric (n = 6), colon (n = 7), or ovarian (n = 12) cancers was collected by paracentesis or surgery. VEGF protein levels were determined by enzyme-linked immunosorbent assay. The effect of ascites on endothelial cell permeability was assessed by evaluating propidium iodide uptake by human umbilical vein endothelial cells (HUVECs) exposed to ascites. Neutralizing antibodies to VEGF added to ascites were used to determine the causal effect of VEGF in permeability induction. RESULTS: VEGF protein levels were markedly increased in malignant ascites compared with levels in nonmalignant cirrhotic ascites (controls). VEGF protein levels in ovarian, gastric, and colon cancer ascites were found to be increased 45, 23, and 12 times, respectively, compared with levels in cirrhotic ascites. Malignant ascites from patients with colon and gastric cancer caused an increase in permeability in HUVECs in all cases. Neutralizing VEGF activity in colon cancer ascites decreased in-vitro HUVEC permeability in three of four cases. CONCLUSIONS: VEGF protein levels are markedly elevated in malignant ascites. VEGF may play a role in malignant ascites formation by increasing endothelial cell permeability.

Angiogenesis Inducing Agents↗
PubMed1999

Regulation of vascular endothelial growth factor expression in human colon cancer by interleukin-1beta.

Expression of vascular endothelial growth factor (VEGF), an important angiogenic factor in colon cancer, is tightly regulated by factors in the microenvironment. However, specific factors indigenous to the organ microenvironment of colon cancer growth that regulate VEGF expression in human colon cancer are not well defined. We investigated interleukin-1beta (IL-1beta) induction of VEGF expression in colon cancer cells and the mechanism by which this occurs. HT29 human colon cancer cells were treated with IL-1beta for various periods. Induction of VEGF mRNA by IL-1beta peaked at 24 h (> fivefold) and returned to baseline by 48 h. SW620 human colon cancer cells also reached a peak induction of VEGF mRNA 24 h after treatment with IL-1beta. VEGF was induced at a dose range between 1 and 20 ng ml(-1) of IL-1beta. IL-1beta induction of VEGF was also confirmed at the protein level. To examine the mechanism for VEGF induction by IL-1beta, we transiently transfected VEGF promoter-reporter constructs into HT29 cells. IL-1beta increased the activity of the VEGF promoter-reporter construct. Pretreatment of HT29 cells with dactinomycin abrogated the induction of VEGF mRNA by IL-1beta. The half-life of VEGF mRNA was not prolonged by treatment with IL-1beta. These findings suggest that IL-1beta regulates VEGF expression in human colon cancer cells by increasing transcription of the VEGF gene.

Colonic Neoplasms↗
PubMed1999

Evaluation of alpha1-adrenoceptors in the rabbit iris: pharmacological characterization and expression of mRNA.

Subtypes of alpha1-adrenoceptor in rabbit iris have been examined in functional, binding and molecular biological experiments. In functional studies, exogenous and endogenous noradrenaline produced contractions of the iris dilator muscle. The contractile responses to noradrenaline were competitively antagonized by a range of alpha1-adrenoceptor antagonists (pA2 values): prazosin (8.1), WB4101 (8.2), BMY7378 (5.9), YM617 (9.5), JTH-601 (8.8), HV723 (7.8) and KMD-3213 (9.8). The same order of inhibitory potency was seen in the adrenergic responses to electrical stimulation. This affinity profile corresponds well to that of the putative alpha1L-adrenoceptor, which has been proposed in lower urinary tract tissues. In binding studies on rabbit iris membrane however, prazosin, KMD-3213 and WB4101 displayed high affinity (pKd or pKi: 9.6, 10.3, 9.6, respectively), and BMY7378 displayed low affinity (pKi: 6.9). These results show that the binding sites typically correspond to alpha1A-adrenoceptor subtype in character, and we could not detect the significant amount of alpha1L-adrenoceptor subtype. The expression of the three distinct mRNAs that encode proteins of alpha1a-, alpha1b- and alpha1d-adrenoceptors was studied using reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR demonstrated the strongest expression of the alpha1a-adrenoceptor, weak expression of the alpha1b-adrenoceptor and undetectable expression of the alpha1d-adrenoceptor. The present study suggests that alpha1A-adrenoceptor is a major subtype detectable in binding and RT-PCR studies in rabbit iris, but that the adrenergic contractions of iris dilator muscle are mediated via activation of alpha1-adrenoceptor subtype having low affinity for prazosin and WB4101.

Adrenergic alpha-Agonists↗
PubMed1999

Gene therapy by transforming growth factor-beta receptor-IgG Fc chimera suppressed extracellular matrix accumulation in experimental glomerulonephritis.

BACKGROUND: The evidence that transforming growth factor-beta (TGF-beta) is a key mediator in the pathogenesis of fibrotic diseases is now supported by several lines of investigation. This evidence provides a certain base for targeting TGF-beta as an antifibrotic agent. METHODS: We generated a chimeric cDNA, termed TGF beta RII/Fc, encoding an extracellular domain of the TGF-beta type II receptor fused to the IgG-Fc domain, and tested whether TGF beta RII/Fc could be a novel strategy for treating glomerular diseases. RESULTS: In cultured BNul-7 cells, recombinant TGF beta RII/Fc reversed the antiproliferative response induced by TGF-beta 1. In addition, TGF beta RII/Fc diminished the TGF-beta 1-induced production of EIIIA-positive fibronectin in cultured normal rat kidney cells. We then introduced the chimeric cDNA into the muscle of the nephritic rats by the hemagglutinating virus of Japan liposome-mediated gene transfer method in order to block the TGF-beta activity in nephritic glomeruli through systemic delivery of chimeric molecules. Treatment with TGF beta RII/Fc gene transfection could suppress the glomerular TGF-beta mRNA in nephritic rats with a comparable effect in the reduction of extracellular matrix accumulation. CONCLUSION: TGF beta RII/Fc successfully inhibited the action of TGF-beta in vitro and in vivo, and gene therapy by chimeric TGF beta RII/Fc might be feasible for the therapy of glomerulosclerosis.

Animals↗
PubMed1999

Enhanced interstitial expression of caldesmon in IgA nephropathy and its suppression by glucocorticoid-heparin therapy.

BACKGROUND: With progressive renal disease, structural derangement increasingly encompasses the tubulointerstitial compartment. Tubulointerstitial injury is a critical determinant of renal functional reserve and prognosis in renal disease. Interstitial cells acquiring characteristic of myofibroblasts are an important contributor to interstitial fibrosis. Caldesmon, a calmodulin or actin binding protein, is a molecular marker of differentiation in smooth muscle cells and has recently been shown by us to be a good marker of mesangial cell activation in IgA nephropathy patients. METHODS. We studied whether the expression of caldesmon in interstitium of the kidney was enhanced in the process of glomerular disease and whether it would be a marker of interstitial activation in specific disease states. We performed immunohistochemical staining with anti-caldesmon antibodies in 38 biopsy specimens from IgA nephropathy patients and analysed them quantitatively with a computer-aided manipulator. Interstitial caldesmon expression were compared with histological changes and clinical parameters. RESULTS: Caldesmon expression was enhanced where interstitial cell infiltration and fibrosis were found. Immunoelectron microscopy revealed that caldesmon staining in the renal interstitium was cytoplasmic, and in the processes of myofibroblast-like cells. Caldesmon expression was more prominent in the intense CD68 infiltrated group than in the low positive cells infiltrated group. Patients showing high intensity of interstitial caldesmon expression had significantly higher urinary protein excretion than those showing low intensity of caldesmon expression. Next, 15 patients were treated with glucocorticoid and heparin for 4-8 weeks and re-biopsies were performed. Caldesmon expression was reduced in concomitant with decreased interstitial cell infiltration. Follow-up of these patients (average 24 months) revealed a significant suppression of urinary protein excretion and significant improvement of creatinine clearance. CONCLUSION: These results suggest that the interstitial caldesmon expression is associated with the progression of IgA nephropathy, and glucocorticoid--heparin therapy may reverse the phenotypic change of interstitial cells during the disease process of glomerulonephritis.

Actins↗
PubMed1999

Successful treatment of cytomegalovirus retinitis in a patient with malignant lymphoma: a case report and review of the literature.

A 52-year-old Japanese woman was diagnosed as having angioimmunoblastic T-cell lymphoma (stage IV-B). She received 6 courses of chemotherapy including cyclophosphamide, doxorubicin, vincristine, and prednisolone every two weeks (biweekly CHOP), and was considered to be in partial remission. She complained of loss of visual acuity in her right eye during her last cycle of chemotherapy. Cytomegalovirus (CMV) retinitis was suspected from the characteristic ophthalmoscopic appearance. This diagnosis was further supported by the detection of CMV DNA in blood and antigens in polymorphonuclear leukocytes, a sign of CMV reactivation. Although DNAemia and antigenemia became negative, retinitis remained slightly active despite a 4-week systemic treatment of ganciclovir. Intraocular injection of ganciclovir was started and continued until the retinitis became inactive ophthalmoscopically. The patient received high-dose chemotherapy with peripheral blood stem cell transplantation and achieved complete remission. During the after this therapy no recurrence of CMV infections was observed. This case shows that 1) a quick and accurate diagnosis of CMV retinitis was possible by applying DNAemia and antigenemia and 2) intensive treatment for the CMV infection enabled the accomplishment of cure-oriented chemotherapy of the lymphoma without the recurrence of CMV retinitis.

Cytomegalovirus Retinitis↗
PubMed1999

[Migratory pneumonitis similar to bronchiolitis obliterans organizing pneumonia after conservative treatment of breast cancer: a case report].

We report the case of a 63-year-old woman who developed cough and fever with migratory lung infiltrates three months after completion of right breast irradiation following conservative surgery. Lung infiltrates were initially localized in the irradiated area, but later spread to unirradiated areas in both lungs. No cause of migratory pneumonitis other than irradiation was found, and we clinically diagnosed this case as radiation-induced migratory pneumonitis similar to BOOP, without lung biopsy. Steroid therapy resulted incomplete resolution of lung infiltrates. The reported case clearly differed from typical radiation pneumonitis. We suggest that lung irradiation might trigger the development of migratory pneumonitis with a clinical pattern similar to that of BOOP.

Anti-Inflammatory Agents↗