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.

Inhibitory effects of tenilsetam on the Maillard reaction.

It has been hypothesized that advanced Maillard reaction in vivo could explain some of the age- and diabetes-related changes. Furthermore, involvement of the Maillard reaction with Alzheimer's disease has also been suggested, as advanced glycation end products, such as pyrraline and pentosidine, were demonstrated to localize in lesions of the disease. Although aminoguanidine has been studied extensively and established as an inhibitor of the Maillard reaction, other candidates have not been investigated thoroughly. In the present study, we examined the inhibitory effect of tenilsetam [(+/-)-3-(2-thienyl)-2-piperazinone], an antidementia drug, on the Maillard reaction. Tenilsetam inhibited glucose- and fructose-induced polymerization of lysozyme in a concentration-dependent manner in vitro. Reduced enzymatic digestibility of collagen incubated with 100 mM glucose for 4 weeks was also restored to a control level by coincubation with 100 mM tenilsetam. To determine whether tenilsetam inhibits the Maillard reaction in vivo, streptozotocin-induced diabetic rats were treated with tenilsetam (50 mg/kg x day). Elevated levels of advanced glycation end-product-derived fluorescence and pyrraline in renal cortex and aorta of diabetic rats were suppressed by the administration of tenilsetam for 16 weeks. These inhibitory effects of this agent on advanced glycation in diabetic rats suggested its potential therapeutic role in controlling diabetic complications.

[A case of idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia associated with chronic nephritis].

A 48-year-old female who had general fatigue was admitted to our hospital. She had swelling of the axillary, inguinal, and paraaortic lymph nodes and mediastinal lesions. Laboratory examinations showed anemia, polyclonal hyperimmunoglobulinemia with IgG 5570 mg/dl, renal dysfunction and interstitial changes of the lungs. Microscopic findings of hematoxylin-eosin staining in biopsy specimens of the left inguinal and axillary lymph nodes revealed increased levels of infiltration of mature plasma cells without evidence of malignancy. Immunoperoxidase staining showed intracytoplasmic polyclonal immunoglobulin. These findings were identical to those of idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL) described by Mori et al. (1980). The specimens also showed evidence of chronic nephritis with infiltration of lymph cells and a slight invasion of plasma cells. Accordingly this case was diagnosed as IPL with renal involvement, which is associated with chronic nephritis. Recently, five cases of IPL with renal dysfunction have been reported. In particular, two cases of IPL with renal dysfunction, which included our case, revealed an increased level of IL6. These findings suggest that the occurrence of renal involvement with IPL may be related to changes in IL6, which is an important factor in the pathogenesis of IPL.

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.

[Mitomycin C associated hemolytic uremic syndrome--a case report and review of the Japanese cases].

A 36-year-old man who developed hemolytic uremic syndrome (HUS) associated with mitomycin C (MMC) after the radical operation for early gastric cancer was reported. He was successfully treated with hemodialysis and transfusion of fresh frozen plasma. However, the pathogenesis and the effective treatment of this syndrome are still undetermined. The literature on MMC-induced HUS in Japan was reviewed, and the relationship between the prognosis and the patients conditions, such as sex, age, site of primary cancer, total dose of MMC, latent period from MMC administration, laboratory findings at the time of diagnosis and treatment with steroids or plasma exchange, were analysed. Patients less than 60 years old or treated with plasma exchange were found to be associated significantly with a favorable outcome. The most frequent cause of death was pulmonary edema or respiratory failure. In conclusion, early treatment with plasma exchange appeared to result in a better prognosis.

Pericholangitis with ulcerative colitis following autoimmune hepatitis over 12 years.

A 35-year-old woman was diagnosed as autoimmune hepatitis 12 years ago by abnormal findings of liver tests including lupus erythematosus (LE) cell phenomenon and liver biopsy. She was admitted in May 1990 with a history of lower gastrointestinal bleeding. Colonoscopy with biopsy and barium enema revealed chronic ulcerative colitis along the entire colon. Since liver tests did not respond well to prednisolone treatment, liver biopsy was again performed and it revealed periductal inflammation with small duct proliferation, a finding compatible with pericholangitis. We herein report this patient who was initially diagnosed as autoimmune hepatitis and thereafter found to be pericholangitis associated with ulcerative colitis.

Detection of Epstein-Barr virus genome in benign polyclonal proliferative T cells of a young male patient.

Epstein-Barr virus (EBV) DNA was detected in polyclonal T cells that proliferated transiently in a 21-year-old male (referred to as H.J.) who underwent an apparently benign lymphocytosis (white blood cells, 31 x 10(6)/microL; lymphocyte, 79%) with fever, tonsillar swelling, lymphadenopathy, and hepatosplenomegaly. The symptoms and signs subsided mostly within a month of hospitalization. The major population of the lymphocytes at admission was positive for CD3, CD8 (4/8 ratio, 0.16), WT31, and DR antigen. Eight percent of the leukocytes were too blastoid to be classified as atypical lymphocytes of infectious mononucleosis (IM). The blastoid lymphocytes and the duration and degree of the lymphocytosis and hypergammaglobulinemia appeared inconsistent with IM, whereas the EBV serology indicated either EBV primary infection or a secondary alteration of normal seropositive EBV immunity. The genomic analysis of T-cell receptor beta chain in the peripheral blood mononuclear cells (PBMC) at admission with a C beta probe did not show a monoclonal rearrangement. EBV genome was detected in these cells, using the BamHI W and K probe, but not in the cells after discharge. Analysis of the EBV terminal repeat junctional sequence, using Xho I fragment of the latent membrane protein (LMP) probe binding with the terminus, did not show monoclonal or oligoclonal populations. EBV-associated nuclear antigen (EBNA) was detected in 36% of the PBMC at admission, but not in the later cells. These EBNA-positive cells were found to form rosette with sheep erythrocytes. The PBMC of six acute IM patients contained neither EBV DNA nor EBNA-positive cells. The observations in this case show a unique type of EBV infection in T cells that has not been previously reported.

[The effect of neuropeptide Y on the hypothalamic-pituitary-adrenal axis in the dog].

There is increasing evidence that neuropeptide Y (NPY) affects the release of pituitary hormones, including adrenocorticotropic hormone (ACTH). The present study was designed to clarify the mechanism by which NPY activates the hypothalamic-pituitary-adrenal (HPA) axis in the dog. Mongrel dogs were equipped with a chronic cannula allowing intra-third (i.t.v.) or intra-lateral (i.l.v.) cerebroventricular administration. A 1.19 nmol, i.t.v. dose of NPY produced as great an ACTH and cortisol response as did equimolar ovine corticotropin releasing factor (CRF). This action of NPY was dose-dependent and shared by peptide YY (PYY) and pancreatic polypeptide (PP), other members of the PP family peptide. Intravenously (i.v.) administered NPY (1.19-11.9 nmol) was much less potent than i.v. CRF in stimulating ACTH and cortisol secretion. However, i.v. NPY significantly increased plasma ACTH and cortisol concentrations, raising the possibility that NPY may modulate the activity of corticotrophs. We next investigated the possible relationship between NPY and CRF on the HPA axis. Pretreatment with a novel CRF antagonist, alpha-helical CRF9-41 (130.9 nmol i.t.v. or 261.5 nmol i.v.), partly but significantly attenuated the ACTH and cortisol responses to i.t.v. NPY (1.19 nmol). Furthermore, adding a subthreshold dose of i.t.v. NPY (0.119 nmol) to i.t.v. CRF (1.19 nmol) or i.v. NPY (2.38 nmol) to i.v. CRF (0.595 nmol) resulted in the potentiation of CRF-induced ACTH secretion. These results indicate that NPY may activate the HPA axis in concert with CRF probably at hypothalamic and/or pituitary levels. The present findings that NPY evokes ACTH secretion and potentiates the effectiveness of CRF as a secretagogue, together with high concentrations of NPY in the hypothalamus and pituitary portal blood, suggest the NPY is involved in the multihormonal control of ACTH release.

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.

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.

Effect of cholecystokinin octapeptide analogues on food intake in the dog.

Cholecystokinin octapeptide, administered into the third cerebral ventricle (icv), suppresses feeding in sheep, pigs, chicken, rats, and dogs. Because of the species differences in the feeding response to cholecystokinin (CCK), we studied the pharmacological characterization of this peptide on feeding in 16-h-fasted dogs. We examined the effects of CCK-(26-33)-NH2 (CCK-8) and a variety of its analogues, nonsulfated CCK-(26-33)-NH2 (desulfated CCK-8), CCK-(26-33)-OH (deamidated CCK-8), (Nle28,31)-CCK-(26-33)-NH2 [(Nle28,31)-CCK-8], succinyl-CCK-(27-33)-NH2 (Suc-CCK-7) succinyl-Thr28, Leu29, MePhe33-CCK-(27-33)-NH2 [Suc-Thr28, Leu29, MePhe33)-CCK-7], CCK-(29-33)-NH2 (CCK-5), and CCK-(30-33)-NH2 (CCK-4) on food intake after iv injection. Systemic dose-response studies appeared to reveal the following rank order of potencies: Suc-CCK-7 = Suc-(Thr28, Leu29, MePhe33)-CCK-7 greater than CCK-8 = (Nle28,31)-CCK-8 greater than desulfated CCK-8 greater than deaminated CCK-8 greater than CCK-5 = CCK-4 = 0. Smaller COOH-terminal fragments acted as antagonists to the satiety effects of CCK-8. These data demonstrate in the dog that the structural requirements for the behavioral activity of CCK-8 are the COOH-terminal amide group, the sulfate ester of the tyrosine moiety, and the conformational constraints observed in CCK-7.

Effects of pancreastatin on insulin and pancreatic polypeptide secretion in the dog.

Porcine pancreastatin (1.19 nmol) was administered into the peripheral vein (i.v.) or the third cerebral ventricle (i.t.v.) of dogs and its effect on the secretion of insulin and pancreatic polypeptide (PP) studied. Neither means of administration had any effect on basal and glucose-induced insulin or PP secretion. However, i.v. pancreastatin did inhibit the i.v. CCK-8-induced insulin but not PP release. Pancreastatin may thus play a role in the regulation of insulin secretion in the canine pancreas.

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.