Wegener's granulomatosis with intracerebral granuloma and mammary manifestation. Report of a case.

A 48-year-old woman was examined who had a limited form of Wegener's granulomatosis with neurologic manifestations. Despite the relative frequency of neurologic manifestations, we found only two other cases in the literature in which intracerebral granulomas were involved. Moreover, mammary manifestations with necrotizing granulomas developed in this case. Glucocorticoid treatment was effective because the case showed both brain and mammary involvement. This case was uncommon in that the intracerebral and mammary granulomas developed in an area remote from that usually affected by Wegener's granulomatosis.

Hemoglobin A1 properties of diabetic and uremic patients.

Patients with diabetes mellitus as well as those with renal failure had high hemoglobin A1 (HbA1) levels. However, the portion of HbA1a+b fractions was larger in patients with renal failure than in diabetic patients. Thus, if renal disorder is advanced, caution should be exercised in evaluating HbA1 data. Furthermore, not only is the collective determination of Hb minor components such as HbA1 required, but also investigation of changes in HbA1a+b in patients with renal failure or diabetic nephropathy.

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.

Response of serum creatine phosphokinase to steroid hormone.

Serum creatine phosphokinase activity increased significantly four or six hours after the administration of prednisolone in patients with muscular dystrophy of various types, whereas it did not increase in other muscular disorders. The extent of the response correlated inversely with the grade of disability. The prednisolone test may help to differentiate muscular dystrophy from polymyositis.

Increased cholesterol concentration in intermediate density lipoprotein fraction of normolipidemic non-insulin-dependent diabetics.

There is increasing agreement about the atherogenicity of intermediate density lipoprotein (IDL). In order to determine whether normocholesterolemic diabetics are at a higher risk of atherosclerosis, cholesterol concentrations in three subclasses of triglyceride-rich lipoprotein fraction (Sf 12-400) were examined. Their plasma triglyceride and cholesterol levels were limited to below 150 and 250 mg/dl, respectively. They were divided into 3 groups according to their treatment: insulin injection (group I), sulphonylurea (group S) and diet alone (group D). Age-matched healthy normolipidemic non-obese subjects served as controls (group C). Triglyceride-rich lipoproteins were separated by ultracentrifugation: very low density lipoprotein (VLDL), Sf 60-400; intermediate density lipoprotein (IDL1), Sf 20-60; IDL2; Sf 12-20. Cholesterol concentrations in total plasma, VLDL, IDL2 and high density lipoprotein (HDL) were all identical in every group. A significant increase in cholesterol concentration was found in IDL1 of groups S and D. Low density lipoprotein-cholesterol of group I was also increased. These findings indicate an increased risk factor in normolipidemic diabetics.

Carbamylation of hemoglobin in renal failure and clinical aspects.

It was revealed that in renal failure hemoglobin A1 (HbA1) was formed by the binding of substances other than glucose to Hb. It was elucidated that the formation of HbA1 increased in urea-added medium and further increased in media containing urea either stored at 37 degrees C for 1 week or heated at 100 degrees C for five minutes. The increment of HbA1 was proportional to the amount of cyanic acid produced by the treatment of the medium after the addition of urea. We found that there was the best correlation between the HbA1 level and the BUN level of 1 to 2 weeks before. Therefore, it appeared that HbA1 could be an indicator of the state of renal failure of 1 to 2 weeks earlier in patients with renal failure without impaired glucose tolerance, especially in patients on hemodialysis.

Physiological antagonism between prostaglandin E2 and neuropeptide Y on thermoregulation in the dog.

These experiments were undertaken to determine whether neuropeptide Y (NPY) could suppress a prostaglandin hyperthermia in conscious dogs. Prostaglandin E2 (PGE2) (5 micrograms), injected into the lateral cerebral ventricle (ILV), evoked a hyperthermia of approximately 1 degrees C. Addition of ILV NPY (5 micrograms) significantly attenuated the PGE2-induced hyperthermia, whereas pancreatic polypeptide (PP), another member of the PP family peptide, did not. These results provide evidence for a role of NPY on thermoregulation in the dog.

A specific method of glycosylated hemoglobin using furosine measurement.

In order to get an accurately specific determination of glycosylated hemoglobin (GHb-f), the furosine assay method, which can detect epsilon-amino-lysine-bound glucose, was investigated. A good correlation was found between GHb-f values obtained by this method and HbA1 values by conventional ion exchange column chromatography. It was, therefore, considered that this technique would be a new useful method for determining glycosylated hemoglobin.

Evaluation of periflux blood flow measurement in diabetic patients with autonomic neuropathy.

The periflux blood flow (PBF) response pattern in the fingertips determined with a periflux laser Doppler flowmeter was analyzed in a standing test in which the subject was instructed to stand up from the sitting position and in Valsalva's maneuver in which respiration was held for 10 s at the maximum inspiration, and indicators such as reaction time (RT), orthostatic dysreaction rate (ODR) and PBF decreasing velocity (PDV) were established for determining autonomic abnormality. RT and ODR were significantly correlated with the change in blood pressure and pulse rate, respectively, in the standing test, and PDV was significantly correlated with beat-to-beat variation. Abnormalities were found in about half of the diabetics in the standing test and Valsalva's maneuver. These results suggested that the analysis of PBF changes in the standing and Valsalva's tests may be an easy and useful approach for clinical examination of the autonomic nervous system.

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.

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.

Accelerated glycation of the aorta in diabetic rats.

Glycation of the aorta in rats with streptozotocin-induced diabetes was estimated by determining the early-stage product and the advanced product of the Maillard reaction. The early-stage product of the Maillard reaction was determined using furosine, which is derived from glycated lysine residues by acid hydrolysis. The advanced product was determined by fluorescence high-performance liquid chromatography. The levels of both early-stage and advanced products in diabetic rats were significantly higher than those in non-diabetic rats at the age of both 20 and 50 weeks. The levels of both early-stage and advanced products at 50 weeks in rats tended to be higher than those at 20 weeks. However, the level of glycated hemoglobin in both non-diabetic and diabetic rats showed no significant change between 20 and 50 weeks of age. These results suggest that tissue glycation may be involved in the development of diabetic complications and may be related to the aging mechanism.

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 have 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 261.8 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 that NPY is involved in the multihormonal control of ACTH release.

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.

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.

Familial hypercholinesterasemia.

A case of familial hypercholinesterasemia was presented. Cholinesterase isoenzyme study revealed the extra C5 band nearer to the cathode than C4 on the gradient polyacrylamide gel electrophoresis in 6 out of 8 subjects in the family. No significant difference in the effect of inhibitors and activator on serum cholinesterase activity of the family with hypercholinesterasemia was found compared to that of the normal control. It was considered to be clinically useful for differential diagnosis of patients with elevated serum cholinesterase to find subjects with familial hypercholinesterasemia.

Endoscopic studies on the superficial spreading type of early gastric cancer.

Twenty eight cases out of 230 cases of early gastric cancer showed the superficial spreading type of early gastric cancer. Seventeen stomachs (60.7%) were compatible to the endoscopic finding of spreading cancerous regions, even to macroscopic and microscopic ones. Other 11 cases were not corresponded clinicopathologically to the infiltrated lesions. These 11 cases were studied on the superficial spreading lesions respectively. They were divided into three groups and compared each other micro- and macro-scopically and endoscopically. Group I contained 6 cases, compatible to micro- and macro-scopic findings but not to endoscopic ones. Endoscopic overdiagnosis may be redness and overflow of white fur and underestimate by a few cancer cells superficially in the mucosae, slight difference in height at the margin of II c and cancer without exposure. Group II was similar microscopic and endoscopic findings but not compatible macroscopically. Both cases in group II were overestimated macroscopically at the infiltrated edge because of color change in mucosae but endoscopically diagnosed by changes of color and gastric area. Group III contained 3 cases of microscopic characteristics and not compatible to macroscopic and endoscopic ones. Endoscopic underdiagnosis may be based on a few cancer cells superficially in normal mucosae and on less depressed lesions. These clinicopathological studies might be worthy to clarify the endoscopic and pathologic discrepancies of infiltrating areas by early gastric cancer, and might improve endoscopic techniques of the gastric mucosal observation.

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.

Skin blood flow in diabetic patients during cold loading.

We measured periflux blood flow (PBF) in people's fingers and its response to cold loading with a laser Doppler flowmeter. As an index in the cold loading test we used cold recovery time (CRT). Among normal people, CRT increased with age. Diabetics had significantly longer CRTs than did age-matched controls. CRT seems to be useful for evaluating the skin microcirculation in diabetics and the aged.

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.