Leptin regulates leukocyte recruitment into the brain following systemic LPS-induced inflammation.

The appetite suppressing hormone leptin has emerged as an important modulator of immune function and is now considered to be a critical link between energy balance and host defense responses to pathogens. These 'adaptive' responses can, in situations of severe and sustained systemic inflammation, lead to adverse effects including brain damage that is partly mediated by neutrophil recruitment into the brain. We examined the contribution of leptin to this process in leptin-deficient (ob/ob), -resistant (db/db) and wild-type (WT) mice injected intraperitoneally with a septic dose of lipopolysaccharide (LPS). This treatment induced a dramatic increase in the number of neutrophils entering the brain of WT mice, an effect that was almost totally abolished in the mutant mice and correlated with a significant reduction in the mRNA levels of interleukin-1beta, intracellular adhesion molecule-1 and neutrophil-specific chemokines. These effects were reversed with leptin replenishment in ob/ob mice leading to recovery of neutrophil recruitment into the brain. Moreover, 48 h food deprivation in WT mice, which decreased circulating leptin levels, attenuated the LPS-induced neutrophil recruitment as did a single injection of an anti-leptin antiserum 4 h before LPS treatment in WT mice. These results provide the first demonstration that leptin has a critical role in leukocyte recruitment to the brain following severe systemic inflammation with possible implications for individuals with altered leptin levels such as during obesity or starvation.

Coexpression of microsomal-type prostaglandin E synthase with cyclooxygenase-2 in brain endothelial cells of rats during endotoxin-induced fever.

Fever is triggered by an elevation of prostaglandin E(2) (PGE(2)) in the brain. However, the mechanism of its elevation remains unanswered. We herein cloned the rat glutathione-dependent microsomal prostaglandin E synthase (mPGES), the terminal enzyme for PGE(2) biosynthesis, and examined its induction in the rat brain after intraperitoneal injection of pyrogen lipopolysaccharide (LPS). In Northern blot analysis, mPGES mRNA was weakly expressed in the brain under the normal conditions but was markedly induced between 2 and 4 hr after the LPS injection. In situ hybridization study revealed that LPS-induced mPGES mRNA signals were mainly associated with brain blood vessels, especially vein or venular-type ones, in the whole brain area. Immunohistochemical study demonstrated that mPGES-like immunoreactivity was expressed in the perinuclear region of brain endothelial cells, which were identified as von Willebrand factor-positive cells. Furthermore, in the perinuclear region of the endothelial cells, mPGES was colocalized with cyclooxygenase-2 (COX-2), which is the enzyme essential for the production of the mPGES substrate PGH(2). Inhibition of cyclooxygenase-2 activity resulted in suppression of both PGE(2) level in the CSF and fever (Cao et al., 1997), suggesting that the two enzymes were functionally linked and that this link is essential for fever. These results demonstrate that brain endothelial cells play an essential role in the PGE(2) production during fever by expressing COX-2 and mPGES.

Significant correlation between the immunofluorescence of alpha 2-plasmin inhibitor in glomeruli and the effects of urokinase therapy in patients with IgA nephropathy.

Correlation between the deposition of alpha 2-plasmin inhibitor (alpha 2-PI), which is one of the inhibitory factors of fibrinolytic activities, in the glomeruli and the effects of urokinase therapy in patients with IgA nephropathy is described. Urokinase (UK) is a plasminogen activator derived from fresh human urine. Urinalysis and measurements of renal function tests, i.e., serum creatinine, blood urea nitrogen, glomerular filtration rate and phenolsulfonphtalein, were performed before and at 8 and 48 weeks after the administration of urokinase. There was marked improvement of proteinuria after UK therapy in patients without deposition of alpha 2-PI in the glomeruli. In contrast, the improvement of proteinuria after UK therapy was not observed in patients with positive deposition of alpha 2-PI in the glomeruli. It was concluded that the administration of UK may be useful for treatment of proteinuria in patients with IgA nephropathy.

[Leiomyoma of the scrotum: a case report].

A case of intrascrotal leiomyoma is reported. A 62-year-old male was admitted to our hospital with the chief complaint of a painless intrascrotal mass, which had been gradually increasing in size during the past 25 years. Physical examination revealed impervious to light and elastic firm mass of 5 cm in diameter in the left scrotum. Although the serum level of some tumor markers such as alpha fetoprotein and human chorionic gonadotropin-beta were normal, since the border on the left testis was unclear on the ultrasonogram of the scrotum, a testicular tumor was suspected, and radical orchiectomy was performed. The tumor was 6 x 4 x 4 cm, 55 g, and well-defined with testis, epididymis and tunica dartos. It was histopathologically diagnosed as leiomyoma arising from the tunica vaginalis. The post operative course has been uneventful for 9 months after the surgery, and no recurrence has been recognized. An intrascrotal tumor is relatively rare, and is generally defined as one arising between tunica dartos and tunica vaginalis testis, which is independent of testis, epididymis, and funiculus spermaticus. This is the 25th case of intrascrotal leiomyoma reported in the literature in Japan.

Levels of fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (FPB beta) in urine and plasma after urokinase administration in patients with chronic glomerulonephritis.

A study on the significance of the measurement of fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (FPB beta) in urine and plasma before and after urokinase (UK) administration in patients with chronic glomerulonephritis is described. FPA and FPB beta in urine and plasma were measured by radioimmunoassay. The levels of fibrinogen degradation product (FDP) in urine and sera were also determined before and after the UK administration. UK was administered at a dose of 48,000 IU/20 ml in saline intravenously, followed by an intravenous infusion of 250 ml of 5% glucose for one hour. It was demonstrated that the levels of FPB beta in urine and plasma showed a significant increase after UK administration in patients with chronic glomerulonephritis. However, there was no significant difference in the levels of FDP in urine and sera before and after UK administration. It was concluded that the measurement of FPB beta in urine and plasma may be useful for evaluating the efficacy of UK therapy in patients with chronic glomerulonephritis.

Detection of alpha 2-pregnancy associated-glycoprotein (alpha 2-PAG) in cultured human peripheral blood mononuclear cells.

A study of the detection of alpha 2-pregnancy associated-glycoprotein (alpha 2-PAG) by double immunofluorescence in cultured human peripheral blood mononuclear cells (MNC) was performed. MNC was obtained from four healthy adults and isolated on a Ficoll-Hypaque density gradient. MNC was incubated with RPMI-1640 with or without pokeweed mitogen in 5% CO2/air at 37 degrees C for six days. MNC was initially stained with rhodamine-conjugated antihuman IgA, IgM, and IgG antisera, and then stained with FITC-conjugated antihuman alpha 2-PAG antisera. It was concluded that alpha 2-PAG was not produced by IgA, or by IgM and IgG producing cells in healthy adults.

Detection of immunoglobulins and/or complement in kidney tissues from non-obese diabetic (NOD) mice.

Immunofluorescent studies were performed on kidney tissues from non-obese diabetic (NOD) mice. Tissues from twenty-two NOD mice ranging in age from 8 to 33 weeks were examined by immunofluorescence and light microscopy. It was shown that the immunofluorescent pattern of immunoglobulins and complement deposition in glomeruli from NOD mice were changed from diffuse linear, focal and/or local fine granular to diffuse coarse granular depending on the age. These findings in NOD mice were consistent with those in human diabetic nephropathy. It was suggested that the immunofluorescent studies in NOD mice are useful for evaluation of the pathogenesis of renal involvement in patients with diabetes mellitus.

A case of insulin-secreting tumor successfully treated with diazoxide.

A 72-year-old patient was referred to our hospital because of a hypoglycemic crisis possibly due to an insulin secreting-tumor. Although its localization was assumed to be at the head of the pancreas as assessed by transhepatic venography with sampling, no mass lesion was detected by selective angiography, ultrasound, computerized axial tomography, magnetic resonance imaging and 67Ga-citrate scan. The patient was treated with diazoxide, because of poor localization and his age, insulin secretion was improved after both 30 and 60 min in the 75 g oral glucose tolerance test. The total amount of urinary C-peptide excretion decreased from 70.8 to 29.2 mcg/day. Thereafter, no hypoglycemic symptoms were observed during his admission. No side effects except mild liver damage were observed.

Eosinophilic peritonitis responding to treatment with glycyrrhizin.

A 63-year-old man with diabetes mellitus for 15 years was admitted to our hospital in 1990 because of end-stage renal failure. Five days after beginning continuous ambulatory peritoneal dialysis (CAPD) he developed an eosinophilic peritonitis (EP). With protein loss in the dialysate and a decreased serum albumin level, the patient developed ankle edema. The patient was treated with glycyrrhizin, and his EP resolved. It is suggested that an allergic background may play an important role in the development of EP in patients on CAPD.

Parameters of altered plasma glucose levels during short intervals in diabetic patients.

The percentages of glycosylated proteins or albumin, or glycohemoglobin A1 (HbA1) in sera from patients with noninsulin dependent diabetes mellitus (NIDDM) were measured to elucidate whether such measurements are useful for evaluation of the mean levels of blood glucose during short intervals in these patients. Forty patients with NIDDM and twenty healthy adults were examined. The percentages of glycosylated proteins or albumin were quantitated by a Glyc-Affin system and those of HbA1 were measured by electrophoresis. It was indicated that the percentages of glycosylated proteins or albumin, and HbA1 in sera from patients with NIDDM were significantly higher than those in sera from healthy adults. There was a significant correlation between the percentages of HbA1 in sera and the mean levels of fasting blood sugar (FBS) during short intervals in patients with NIDDM. It was concluded that the measurement of HbA1 is a useful method for evaluation of the mean levels of blood glucose during short intervals in patients with NIDDM compared with those of glycosylated proteins or albumin.

A case of Fabry's disease.

A case of Fabry's disease in a 22-year-old male patient who had mild proteinuria and dark-red eruptions is reported. He had been treated as a case of a so-called "chronic glomerulonephritis" for one year. However, histopathological findings of the renal biopsy specimens showed the presence of numerous vacuolated cells in the glomeruli. These vacuolated cells contained numerous electron dense bodies observed by electron microscopy. Skin lesions of this patient were consistent with those of angiokeratoma corporis. The levels of serum alpha-galactosidase were significantly lower than those of healthy controls. The mother of this patient also showed decreased levels of serum alpha-galactosidase. The pedigree of this patient showed a familial history of various types of renal diseases. It was postulated that Fabry's disease occurring in older patients has a worse clinical course. it is concluded that early detection of this disease through biopsy and the assay of serum alpha-galactosidase levels is important in managing the future course of patients with Fabry's disease.

Solubilization of intraglomerular deposits of serum proteins by fresh human sera or gamma-globulin in patients with diabetic nephropathy.

The solubilization of renal deposits of IgG and other serum proteins by fresh human sera or human gamma-globulin was studied in patients with diabetic nephropathy. Renal biopsy specimens were from 10 patients with diabetic nephropathy. These specimens were incubated with fresh sera obtained from the same patients and healthy adults or human gamma-globulin at 37 degrees C for 1 hr in plastic test tubes. The sections were stained with FITC-labeled heavy chain specific anti-human IgG, alpha 1-antitrypsin, haptoglobin and beta-lipoprotein antisera, and then examined with a fluorescent microscope. It was demonstrated that fresh human sera or gamma-globulin significantly solubilized glomerular deposits of IgG and other serum proteins in patients with diabetic nephropathy. It was postulated that solubilization of protein deposits in glomeruli requires the same substances detected in vitro in the kidney tissues from patients with diabetic nephropathy.

[Predictability of Gleason score and reduction time (tau) of prostatic volume after castration for the prognosis of prostatic cancer].

PURPOSE: The efficacy of the reduction time (tau) after castration as a prognostic factor was examined by comparing to Gleason score. MATERIALS AND METHODS: The change of prostatic volume after castration was observed from the castration to 3 months after in 24 cases of prostatic cancer. Prostatic volume was examined by transrectal ultrasonography of the prostate. Survival curves was calculated by Kaplan-Meier method. Differences among survival curves were analyzed using Cox-Mantel test. RESULTS: tau had a close relationship to the prognosis of each case (Wilcoxon test: p < 0.05, Cox-Mantel test: p < 0.05). Gleason score had a weak relationship to prognosis (Wilcoxon test: N. S., Cox-Mantel test: p < 0.05). CONCLUSIONS: tau was efficient as prognostic factor compared to Gleason score.

Immunopathological analysis of acute phase reactant (APR) proteins in glomeruli from patients with diabetic nephropathy.

The levels of immunoglobulins, complement components and APR proteins including alpha 1-antitrypsin (alpha 1-AT), alpha 1-acid glycoprotein (alpha 1-AG), alpha 2-macroglobulin (alpha 2-MG) and haptoglobin (Hpt) in the sera, as well as glycosylated or nonglycosylated protein fractions of these proteins in the sera, were examined by laser nephelometry in 49 patients with diabetes mellitus. Immunofluorescence studies of immunoglobulins, beta-lipoprotein (beta-Lp), complement components and APR proteins in the kidney and skin tissues of patients with diabetic nephropathy were performed to elucidate whether such factors might play a role in the development of the vascular changes in this disease. The levels of alpha 1-AT and alpha 2-MG in the sera as well as glycosylated or nonglycosylated protein fractions of these proteins in the sera from patients with diabetic nephropathy, were significantly greater than those in healthy adults. Marked linear deposition of these proteins in the glomerular or dermal vascular walls was observed in the same patients. In particular, IgG and alpha 1-AT were accumulated in the glomeruli of patients with the nodular type of this disease. The intensity of alpha 1-AT or IgG deposition in glomerular capillary walls treated with a high concentration (4 mol) of NaCl was markedly decreased in such patients. It appeared that serum APR proteins with or without glycosylation underwent exudation into the glomerular and dermal vascular walls, and then accumulated in these walls in patients with diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Individual differences in encoding and decoding of nonverbal expressions].

The purpose of this experiment was to examine correlations among encoding ability, decoding ability, and individual differences. Thirty undergraduates were measured on the CP110 (short version of California Personality Inventory), Y-G Personality Inventory, and assessed for their ability to encode and decode facial and vocal expressions depicting six different emotions. The main findings were as follows: (a) encoding scores were positively correlated with both CP110 and Y-G; (b) decoding score was correlated with CP110 and negatively correlated with Y-G; (c) there was no correlation between encoding and decoding score on vocal expression or facial expression; and (d) there was no sex difference.

Detection of glomerular sialic acids in patients with diabetic nephropathy.

A study on immunofluorescence of sialic acids in glomeruli from patients with diabetic nephropathy is described. Measurement of sialic acid in sera from 25 patients with diabetes mellitus was also performed. Renal biopsy specimens from 12 patients with diabetic nephropathy were stained with FITC-labeled antihuman IgG antiserum and rhodamine-labeled Triticum vulgaris (WGA) or Limulus polyphemus (LPA). These specimens were also stained with such reagents after treatment with neuraminidase, trypsin or citrate buffer. Both deposition of IgG and binding of WGA in the glomerular capillary walls were observed in all patients with diabetic nephropathy. The binding of WGA in the glomerular capillary walls in diabetic nephropathy was significantly increased compared with that in four normal renal tissues. However, the binding of LPA was hardly observed in the glomerular capillary walls of patients with diabetic nephropathy. The binding of WGA in the glomeruli was markedly decreased after treatment with neuraminidase although it was hardly decreased after treatment with trypsin or citrate buffer. The levels of sialic acid in sera from patients with diabetic nephropathy were markedly increased. It is suggested that accumulated substances in the glomerular capillary walls with an affinity for WGA are mainly composed of N-acetyl glucosamine and/or N-acetyl neuraminic acid in patients with diabetic nephropathy.

Detection of immunoglobulins and other serum proteins in the dermal and glomerular capillary walls from patients with diabetes mellitus.

Deposition of immunoglobulins or acute phase reactant (APR) proteins in the dermal and glomerular capillary walls from patients with diabetes mellitus was examined to determine whether development of microangiopathy in such patients was related to exudation and/or entrapment of these proteins. Skin and renal biopsy specimens were obtained from patients with diabetic nephropathy and diabetes mellitus without nephropathy. These biopsy samples were stained with FITC-labeled anti-human IgG, IgA, IgM, C3, APR proteins, and beta-lipoprotein antisera. Linear depositions of IgA, IgG, and/or APR proteins were observed in the dermal and/or glomerular capillary walls from some patients with diabetic nephropathy or diabetes mellitus without nephropathy. It is indicated that deposition of such immunoglobulins in the dermal and glomerular capillary walls might be due to exudation and/or entrapment of these substances in patients with diabetes mellitus.

Correlation of renal histopathology duration of diabetes, and control of blood glucose in patients with type II diabetes.

Correlations of renal histopathologic changes, duration of diabetes, and the degree of control of blood glucose in patients with diabetic nephropathy were determined. Biopsies from 17 patients with diabetic nephropathy due to Type II diabetes were examined. Mild histopathologic changes in renal tissues were observed in patients with good blood glucose control, even if their disease was of more than 5 years' duration. Moderate to severe renal histopathology was found in patients with poor blood glucose control regardless of the duration of diabetes. It is concluded that strict control of blood glucose during the course of diabetes is important in inhibiting the progression of renal involvement in patients with Type II diabetes.

The American Urological Association symptom index for benign prostatic hyperplasia as a function of age, volume and ultrasonic appearance of the prostate.

PURPOSE: Our study was conducted to reveal quantitatively the relative effects of age and ultrasonic appearance of benign prostatic hyperplasia (BPH) on urinary symptoms as evaluated by the American Urological Association (AUA) symptom index score. MATERIALS AND METHODS: In 929 examinees (732 with a normal prostate and 197 with BPH) on a mass screening program for prostatic diseases using transrectal ultrasonography in Japan, the AUA symptom score was compared to age, prostatic volume and presumed circle area ratio using simple and multiple regression analyses. RESULTS: Simple regression analysis demonstrated the symptom score to correlate significantly with age (R = 0.162, p < 0.0001), prostatic volume (R = 0.072, p = 0.0281) and presumed circle area ratio (R = 0.150, p < 0.0001). However, multiple regression analysis demonstrated that age and presumed circle area ratio were significant independent determinants of the total symptom score. Among 7 symptoms included in the AUA symptom index weak stream and hesitancy scores were not influenced by age, prostatic volume or presumed circle area ratio. CONCLUSIONS: As a parameter representing the degree of BPH in terms of the severity of urinary symptoms, presumed circle area ratio was preferable to prostatic volume. Regression analyses confirmed again that the AUA symptom index was influenced considerably by age and was not specific to BPH.