Human recombinant erythropoietin directly stimulates B cell immunoglobulin production and proliferation in serum-free medium.

The effect of human recombinant erythropoietin (Epo) on B cell responses was studied in a serum-free medium. Epo enhanced IgM production and thymidine uptake by a human IgM-producing lymphoblastoid cell line, CBL. This effect was specific to Epo since enhancement was blocked by anti-Epo antibody but not by control antibody. Among the various cytokines, interleukin-4 (IL-4) enhanced IgM production and thymidine uptake while IL-6 enhanced IgM production without affecting thymidine uptake. In contrast, other cytokines including IL-1 beta, IL-2, IL-5, interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), or granulocyte/macrophage colony-stimulating factor (GM-CSF) were without effect. However, the enhancing effect of Epo is different from that of IL-4 or IL-6, since Epo effect was not blocked by anti-IL-4 antibody or anti-IL-6 antibody. Moreover, specific binding of Epo was detected on CBL cells. Epo also enhanced immunoglobulin (IgG, IgM and IgA) production and thymidine uptake by purified tonsil small resting B cells stimulated by Staphylococcus aureus Cowan strain I (SAC) or by large activated B cells. In contrast, Epo had no effect on unstimulated small resting B cells. These results indicate that Epo could directly stimulate activated and differentiated B cells and could enhance B cell immunoglobulin production and proliferation.     

Kinetic study of glomerular epithelial cells associated with segmental glomerular sclerotic lesions with adhesion in spontaneously diabetic WBN/Kob rats

Background We previously found that glomerular epithelial cells play an important role in the formation of adhesive lesions. Glomerular sclerotic lesions develop after the inital adhesive lesions. Methods Two series of experiments were done with spontaneously diabetic WBN/Kob rats. These rats develop segmental glomerular sclerotic lesions with aging. The first series of experiments was intended to clarify the kinetics of glomerular cells on progressive glomerular damage in these rats. The second series of experiments was designed to study the relationship between proliferation (judged by % bromodeoxyuridine-positive cells) of glomerlar epithelial cells and sclerotic lesions with adhesions. Results In the first series, rats having increased proteinuria showed segmental glomerular sclerotic lesions with adhesions. At the same time, increased labeling indices of tuft cells and epithelial cells of Bowman's capsule were observed. In the second series, no significant increase in the labeling indices of tuft cells with sclerotic lesions was observed, compared to tuft cells without sclerotic lesions. In sclerotic lesions with adhesion, bromodeoxyurdine-positive cells were observed that were not distinguishable as podocytes or epithelial cells of Bowman's capsule. The highest labelling index was noted in the epithelial cells of Bowman's capsules with sclerosis. Conclusion This study shows that the proliferation of glomerular epithelial cells (mainly epithelial cells of Bowman's capsule) occurs in glomerular sclerotic lesions with adhesions.     

Periodic alternating nystagmus and rebound nystagmus in spinocerebellar ataxia type 6.

We report on a family with ataxia type 6 (SCA6) showing peculiar oculomotor symptoms. The proband presented with periodic alternating nystagmus (PAN), and her 2 brothers had rebound nystagmus and gaze-evoked nystagmus. They carried the identical mutation (the number of expanded CAG repeat, 24) in the CACNA1A gene. The intrafamilial variability of oculomotor symptoms may be ascribed to factors other than CAG repeat expansion size in SCA6.     

Endogenous tumor necrosis factor functions as a resistant factor against hyperthermic cytotoxicity.

One of the mechanisms of cytotoxicity by tumor necrosis factor (TNF) is the induction of reactive oxygen molecules. Cells producing endogenous tumor necrosis factor (enTNF) show resistance to the cytotoxicity of exogenous TNF by scavenging the reactive oxygen molecules. The intracellular hydroxyl radical production is also known to be involved in the heat-induced cytotoxicity. In the present study, we therefore examined the possibility that enTNF may act as a protective protein against the heat-induced cytotoxicity in a manner similar to that of exogenous TNF. Heat-sensitive L-M (mouse tumorigenic fibroblast) cells, originally expressing no enTNF, were transfected with a human TNF expression vector to produce enTNF. The stable transfectants showed apparent resistance to heat treatment. Conversely, when HeLa (human uterine cervical cancer) cells, originally producing an appreciable amount of enTNF, were transfected with an antisense TNF mRNA expression vector to inhibit enTNF synthesis, their heat sensitivity was enhanced. Furthermore, L-M cells which were transfected with nonsecretory human TNF expression vector also acquired resistance to heat treatment. In these cells, heat resistance correlated well with expression of enTNF and intracellular levels of manganous superoxide dismutase. These results indicate that enTNF exerts its intracellular protective effect against the heat-induced cytotoxicity by scavenging reactive oxygen with induced manganous superoxide dismutase in a manner similar to that found in cells treated with exogenous TNF.     

Comparison of screening methods for diabetes mellitus, based on fasting glucose, HbA1C and fructosamine levels

Screening methods for diabetes mellitus, based on fasting glucose (FPG), HbA1C and fructosamine (FRA) levels were compared with regard to their screening power. The subjects studied were 699 health examinees. A significant elevation of the mean level of each screening index was observed in diabetic subjects, but not in borderline cases compared with that of normal subjects. The FPG, HbA1C and FRA levels in diabetic subjects distributed over a wide range overlapping largely with the distributions of non-diabetic subjects. No appreciable difference in the screening power was observed between FPG and HbA1C but specificity was low in FRG for the comparable sensitivity level. In the screening methods based on the combination of two or more indices, elevation of the sensitivity was noted, but the specificity declined, resulting in an increase of re-examination rate. Among them, the combination of FPG and HbA1C indicated the highest sensitivity.     

A case of primary ureteral carcinoma in the duplicated renal pelvis and ureter diagnosed by transurethral uretero-renoscopy

We present a case of primary ureteral carcinoma in the duplicated renal pelvis and ureter diagnosed by transurethral uretero-renoscopy. The case was of a 78-year-old man with the complaint of sudden asymptomatic macrohematuria. An excretory urogram strongly suggested the presence of duplication of the right collecting system, and cystoscopy revealed a gross hematuria from the right ureteral orifice. A retrograde ureteropyelogram revealed incomplete duplication of the right renal pelvis and ureter fused at about the ureter crossing over the iliac vessels, and a polyp-like filling defect in the lower segment of duplicated ureter at about 4 cm from the fusion of the ureters. Transurethral uretero-renoscopy was employed to investigate the filling defect, and a papillary tumor extended into the lower segment of duplicated ureter was revealed. Tumor was resected by a rigid operating instrument under transurethral uretero-renoscopy. The pathological diagnosis was grade I-transitional cell carcinoma of the ureter, so that right total nephroureterectomy with partial cystectomy was carried out subsequently. Surgical specimen after right total nephroureterectomy with partial cystectomy showed no other tumor in the pelvis or ureter macroscopically, and histopathological studies of surgical specimens were no evidence of malignancy. We believe that transurethral uretero-renoscopy significantly increases the diagnostic accuracy in determining the nature of upper urinary tract lesions, and this procedure is indispensable in the diagnosis of ureteral tumors. The present case was the 7th case of primary ureteral carcinoma in the duplicated renal pelvis and ureter in the Japanese literature.     

Sister chromatid exchange induction by benzo(a)pryene in cultured peripheral blood lymphocytes of lung cancer patients and healthy individuals with or without familial history of neoplasms

The inducibility of sister chromatid exchanges (SCEs) by benzo(a)pyrene (BP) was studied in cultured peripheral blood lymphocytes of 15 untreated lung cancer patients and 25 healthy persons including 11 high- and 14 low-cancer-risk individuals tentatively classified by the familial history of lung cancer and other neoplasms. The baseline SCE frequency in cultured lymphocytes was significantly high in lung cancer patients, as compared with all healthy persons or low-cancer-risk individuals. Following exposure to BP, the lymphocytes of lung-cancer patients and high-cancer-risk individuals exhibited significantly greater SCE yields than those of persons at low risk, although no significant difference was observed in the lymphocyte SCE yields when the levels of lung cancer patients were compared with those of all healthy persons. A comparison of the net SCE increase (delta SCE) in BP-exposed lymphocytes among the study groups, however, revealed a significant difference in delta SCE values only between high- and low-cancer-risk individuals. The present findings on both the observed SCE yields and delta SCE values suggest that lymphocytes of high-risk individuals may be more susceptible to BP-induced DNA damage than those of persons at low risk, and that such a chromosomal hypersensitivity to genotoxins may be associated with a high risk of neoplasms.     

Cross-sectional study of allergic disorders associated with breastfeeding in Japan: The Ryukyus Child Health Study

Uncertainties remain as to whether breastfeeding is protective against childhood allergic disorders. Positive relationships of breastfeeding with asthma and atopic eczema were observed in two previous Japanese studies. This cross-sectional study investigated the association between the feeding pattern after birth and the prevalence of allergic disorders during the past 12 months in Japanese schoolchildren. Study subjects were 24,077 children aged 6-15 yr in Okinawa. The outcomes were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Allowance was made for age, sex, number of siblings, smoking in the household, paternal and maternal history of asthma, atopic eczema, and allergic rhinitis, and paternal and maternal educational level. Breastfeeding, regardless of exclusivity, for 13 months or longer and exclusive breastfeeding for 4-11 months were independently associated with a higher prevalence of atopic eczema, particularly among children without a parental allergic history. A clear positive dose-response relationship was observed between prolonged duration of breastfeeding, regardless of exclusivity, but not exclusive breastfeeding, and the prevalence of atopic eczema. We found a significant positive trend for atopic eczema across the three categories (formula milk, partial and exclusive breastfeeding) in the first 4 months of life although the odds ratio for exclusive breastfeeding was not statistically significant. No material association was found between the feeding pattern after birth and the prevalence of wheeze or allergic rhinoconjunctivitis. Prolonged breastfeeding may be associated with a higher prevalence of atopic eczema in Japanese children.