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Biomedical subjects

N Igaki

Publications and source records attributed to N Igaki.

At least 19 recordsLinked to original sources

Calciphylaxis in a patient with end-stage renal disease secondary to systemic lupus erythematosus associated with acral gangrene and mesenteric ischemia.

A patient with end stage renal disease secondary to systemic lupus erythematosus (SLE) ultimately required amputation of the four extremities and developed mesenteric ischemia. The patient presented with widespread medial calcification involving various small to medium sized arteries, although no noticeable secondary hyperparathyroidism was observed. We speculated that SLE associated with systemic vasculitis and uremic milieu over a number of years may represent the perfect preexisting condition for calcific arteriolopathy to occur following which several factors including chronic administration of corticosteroids, photosensitivity in lupus, and significant weight loss may have contributed to acral gangrene and mesenteric ischemia.

Amputation, Surgical↗

[A case of hepatitis C virus-associated glomerulonephropathy presenting with MPO-ANCA-positive rapidly progressive glomerulonephritis].

We report a case of hepatitis C virus-associated glomerulonephropathy presenting with MPO-ANCA-positive, rapidly progressive glomerulonephritis(RPGN). A 60-year-old woman was admitted to our hospital for evaluation of RPGN. Laboratory evaluation revealed microhematuria, proteinuria(800 mg/day), anemia, renal failure(blood urea nitrogen 27 mg/dl, serum creatinine 2.2 mg/dl), cryoglobulinemia, hypocomplementemia, positive MPO-ANCA(232 EU), and hepatitis C virus infection(GOT 58 IU/l, GPT 38IU/l, HCV-RNA(PCR) 1,200 kcopy/ml, serotype 1). After admission, the patient's renal function and anemia deteriorated rapidly, then prednisolone(30 mg/day) was started. After treatment her renal function gradually improved, then a renal and liver biopsy was performed. The renal biopsy revealed six sclerosing fibrous crescentic glomeruli in twelve glomeruli. Immunofluorescent examination revealed granular deposits of IgG, C3, and fibrinogen along the glomerular basement membrane and mesangial matrix. The pathogenesis of RPGN in this case may relate to the deposition of immune complexes in the glomeruli because immunofluorescent examination was revealed to be the immune-complex type, but not pauci immune type nephritis. Liver histology revealed chronic active hepatitis with mild piecemeal necrosis and did not reveal vasculitis. Although her renal function was improved after treatment with prednisolone, she suffered from pulmonary manifestations(dry cough etc.) on the 120th hospital day. Suddenly she died because of pulmonary hemorrhage on the 180th hospital day. These findings suggest that various HCV-induced immunological abnormalities, such as positive MPO-ANCA, cryoglobulinemia and hypocomplementemia, play an important role in the pathogenesis of this RPGN, although we could not demonstrate deposition within glomeruli of immune complexes containing HCV. The effect of interferon therapy on such immunological abnormalities remains to be documented. Since interferon is known to have immunomodulatory effects, we selected corticosteroid therapy. Future studies need to focus on the optimal treatment strategy for hepatitis C virus-associated glomerulonephritis.

Aged↗

[A case of hepatitis B virus carrier complicated with nephrotic syndrome].

We report a patient, a 23-year-old man, who was a hepatitis B virus(HBV) carrier complicated with nephrotic syndrome. He was admitted to our hospital because of generalized edema and massive ascites. Laboratory data on admission were as follows: proteinuria 9,850 mg/day, Cr 2.7 mg/dl, BUN 73 mg/dl, albumin 1.9 g/dl, cholesterol 501 mg/dl, GOT 23 IU/l, GPT 19 IU/l, HBsAg(+), and HBeAg(222.7). Since his nephrotic symptoms were seriously complicated with renal failure, we selected steroid therapy for nephrosis preference. His renal function was improved and the urinary protein decreased immediately, but his liver function deteriorated. The renal biopsy revealed focal mesangial proliferative glomerulonephritis. Immunofluorescent examination revealed slight deposits of IgG, IgM, and C3 along the glomerular basement membrane and mesangial matrix. He was not compliant and often stopped taking the steroid therapy, thereby causing nephrosis to recur each time. After all, nephrotic symptoms have been well-controlled with cyclosporin and steroid. In spite of the seroconversion of HB virus by formation of HBe antibody, mutant HBV infection continued. The fact that liver biopsy revealed severe lymphoid infiltration at the portal area suggested chronic active hepatitis. His clinicopathologic course suggests that HBV-associated nephropathy does not always remit as there are some cases in whom hepatitis remains in an active state even after seroconversion, due to its mutant status. In these cases, the long-term prognosis of HBV nephropathy has not been defined. Further study is necessary to establish the optimal treatment for HB nephropathy in adults.

Adult↗

Two cases of aorto-gastrointestinal fistula.

We report two cases of aorto-gastrointestinal fistula. Case 1, a 60-year-old man, suffered from repeat hematemesis. He was preoperatively diagnosed as aortoesophageal fistula with thoracic aortic aneurysm and was successfully treated by graft replacement of the aneurysm. Case 2, a 73-year-old man, presented with massive gastrointestinal bleeding, yet repeat endoscopical examination did not reveal the origin of the bleeding. He died of catastrophic hematochezia. The pathological findings at autopsy revealed an aortoduodenal fistula. These two cases suggested the importance to consider an aorto-gastrointestinal fistula in the differential diagnosis of patients presenting gastrointestinal hemorrhage.

Aged↗

Increase in 3-deoxyglucosone levels in diabetic rat plasma. Specific in vivo determination of intermediate in advanced Maillard reaction.

A specific assay of 3-deoxyglucosone (3-DG) was developed in our laboratory to help elucidate the relationship between advanced Maillard reaction and diabetic complications. 3-DG is known as a highly reactive intermediate of the reaction in vitro and a precursor of advanced glycosylation end products such as pyrraline and pentosidine, which have been previously detected in vivo. 3-DG was converted to a stable compound, 2-(2,3,4-trihydroxybutyl)-benzo[g]quinoxaline, by reacting with 2,3-diaminonaphthalene. Since the derivative had a characteristic UV spectrum, it was determined at 268 nm by high performance liquid chromatography. This method was sensitive enough to detect 10 ng/ml (61.7 nM) of 3-DG in vitro. A slight modification to this method allowed in vivo detection of small amounts of 3-DG. Plasma free 3-DG levels were significantly higher in streptozotocin-induced diabetic rats compared with controls (918 +/- 134 nM versus 379 +/- 69 nM, p < 0.001) and were suppressed with the administration of aminoguanidine, an inhibitor of Maillard reaction. Plasma pyrraline levels in diabetic rats also increased in parallel with elevated 3-DG levels but were only marginally suppressed by administration of aminoguanidine. Our results indicate that 3-DG is present in vivo under normal conditions and that its level increases in diabetic subjects. Determination of 3-DG represents a good tool to predict development and progression of diabetic complications and to assess the efficiency of inhibitors to Maillard reaction.

2-Naphthylamine↗

Comparison of lipids, apoproteins and associated enzyme activities between diabetic and nondiabetic end-stage renal disease.

Lipids, apoproteins and associated enzyme activities in type 2 diabetic end-stage renal disease (ESRD) were compared with that in nondiabetic ESRD and normal controls. Of the 40 uremic patients with non-insulin-dependent diabetes mellitus, 20 patients were receiving stable continuous hemodialysis treatment (CHT). Of the 39 patients with nondiabetic ESRD, 21 were undergoing CHT. Patients with nondiabetic ESRD exhibited elevated levels of serum triglyceride and a marked reduction in high-density-lipoprotein (HDL) cholesterol. Concentrations of serum apolipoprotein (Apo) C-3 were higher than in controls, whereas mean levels of serum Apo E were lower. The concentrations of serum Apo A-1 and Apo A-2 decreased with diminished lecithin: cholesterol acyltransferase activity. Lipoprotein lipase activity decreased in undialysed patients, and hepatic triglyceride lipase activity decreased significantly throughout the observation. Patients with diabetic ESRD exhibited elevated serum Apo B and normal serum Apo E levels, besides the lipid and Apo abnormalities observed in nondiabetic ESRD. Moreover, a prominent reduction in serum Apo A-1 was found in dialysed diabetic patients. The Apo B/Apo A-1 ratio was significantly higher in diabetic ESRD than in nondiabetic patients undergoing CHT. These results indicate that lipid abnormalities are accelerated in diabetic ESRD and may constitute a serious risk for the development of atherosclerosis.

Adult↗

Effects of 3-deoxyglucosone on the Maillard reaction.

We investigated the effect of exogenously applied 3-deoxyglucosone, a major carbonyl intermediate, on the Maillard reaction. The fluorescence intensity of the product of the reaction of bovine serum albumin with 3-deoxyglucosone was higher than that with an equivalent amount of glucose. Similarly the rate of polymerization of lysozyme in the presence of 3-deoxyglucosone was also greater than with glucose, and collagen incubated with 3-deoxyglucosone was less digestible than collagen incubated with glucose. By contrast, aminoguanidine inhibited an increase in fluorescence of the Maillard compounds and the polymerization of protein, both of which were stimulated by 3-deoxyglucosone. These results suggest that 3-deoxyglucosone accelerates the advanced stage of the Maillard reaction and that aminoguanidine acts on 3-deoxyglucosone to inhibit its action in the advanced stage of the Maillard reaction.

Collagen↗

Fructose-related glycation.

We investigated in vitro the effect of the polyol pathway on the formation of advanced Maillard reaction products which have fluorescence and cross-links. Bovine serum albumin supplemented with various concentrations of glucose, fructose or sorbitol was incubated for 14 days. The fluorescence intensity was higher after incubation with fructose than after incubation with glucose. However, no significant increase in fluorescence intensity was found after incubation with sorbitol. These results suggest that in the polyol pathway fructose plays an important role in the formation of advanced Maillard products.

Fructose↗

Age- and diabetes-accelerated glycation in the human aorta.

The extent of glycation in pieces of human aorta was estimated by determining the content of furosine, which is derived from fructose-lysine through acid hydrolysis. Glycation of human aorta was found to increase with advancing age. A significant positive correlation was found between the degree of atherosclerosis and the furosine level in the aorta in subjects over 60 years of age. Furthermore, the furosine level in the aortae of diabetic patients was significantly higher than that in normal subjects of the same age. These results suggest not only that glycation in the aorta may increase with aging and with the development of arteriosclerosis, but also that diabetes may be related as well to premature aging as to arteriosclerosis.

Adult↗

Clinical application of hair protein glycation in the assessment of blood glucose control and diabetic neuropathy.

Glycation of hair protein was assessed in diabetic patients by the measurement of furosine, which is derived from fructose-lysine, a glycated lysine residue in protein. The level of furosine in 12-cm-long hair which grew over the course of one year was significantly better correlated with the mean values of four determinations of fasting plasma glucose (FPG) and four determinations of hemoglobin A1c, respectively, at the time of hair sampling. The level of glycation in hair, which corresponds to the time taken for hair growth, may represent the mean level of blood glucose during the time corresponding to the growth period. The values of motor nerve conduction velocity and sensory nerve conduction velocity were better correlated with the level of furosine in hair corresponding in the length to 1 year's growth than the levels of FPG and hemoglobin A1c at the time of the determination of nerve conduction velocity. These results suggest that hair glycation may serve as a valuable indicator both of long-term blood glucose trends and of the relationship between diabetic complications and blood glucose.

Adult↗

The effect of fructose on collagen glycation.

The effect of fructose on the formation of advanced Maillard reaction products which have fluorescence and cross-links was investigated. Type I collagen was added to various concentrations of glucose and fructose which were then incubated at 37 C for 4 weeks. Both the level of furosine and the fluorescence intensity increased in direct proportion to glucose and fructose levels and to the duration of incubation. Incubation with fructose produced less furosine but more intense fluorescence than incubation with glucose. These results suggest that fructose in the polyol pathway plays an important role in the formation of advanced Maillard products.

Animals↗

Effect of aminoguanidine on the glycation.

3-Deoxyglucosone, a carbonyl intermediate compound in the Maillard reaction, acts on bovine serum albumin to increase its fluorescence. Aminoguanidine inhibited the increase of fluorescence intensity formed by bovine serum albumin and 3-deoxyglucosone when 3-deoxyglucosone had been preincubated with aminoguanidine. These results suggested that aminoguanidine inhibits the action of 3-deoxyglucosone in the Maillard reaction.

Animals↗

Hair protein glycation as a long-term index of blood glucose in diabetics.

We used furosine, which is derived from fructose-lysine and is a glycation product, to measure the extent of hair protein glycation in diabetic patients. We took hair samples that were 12 cm long, corresponding roughly to 1 year's growth. While the furosine levels in these samples correlated poorly with fasting plasma glucose (FPG) and with hemoglobin A1c (HbA1c) levels at the time of sampling, better correlations were observed between glycation and the year-long average values of FPG, HbA1c, and the conduction velocities in two peripheral nerves. The glycation levels in these samples may thus reflect the year-long average of the patient's blood glucose. Hair glycation may serve as a valuable indicator both of long-term blood glucose trends and of the relationship between diabetic complications and blood glucose.

Adult↗

Glycation of hair protein in the assessment of long-term control of blood glucose.

Glycation of hair protein was assessed in diabetic patients by the measurement of furosine, which is derived from fructose-lysine, a glycated lysine residue in protein. The level of furosine in 12-cm-long hair which grew over the course of one year was significantly better correlated with the mean values of four determinations of fasting plasma glucose (FPG) and four determinations of hemoglobin A1c (HbA1c) performed at three-month intervals than with FPG and the level of HbA1c, respectively, at the time of hair sampling. The level of glycation in hair, which corresponds to the time taken for hair growth, may represent the mean level of blood glucose during the time corresponding to the growth period. These results suggest that the determination of glycation in hair may be useful as an indicator of long-term control of blood glucose levels if appropriate lengths of hair are taken from the scalp.

Adult↗