Acute effect of inhaled beta(2)-agonists with different type of intrinsic activity on airway resistance in healthy volunteers]

Inhaled beta(2)-agonists (long-acting as well as short acting) are used world-wide for the relief of asthma symptoms. However, there are few reports which have evaluated the additive effect of short-acting beta(2)-agonists to long-acting beta(2)-agonists on airway resistance measured by a plethysmography. This study was designed to evaluate the additive effect of inhaled short-acting beta(2)-agonists (protecarol) to long-acting beta(2)-agonists (salmeterol) on airway resistance in normal healthy volunteers (S+P group). In addition, to compare the effects of beta(2)-agonists which have different types of intrinsic activities, acute effect of inhaled procaterol adding to procaterol was also evaluated (P+P group). Seven healthy volunteers (all male and all non-smokers) were entered in this study. Pulmonary function was measured by a body plethysmography. Forced expiratory volume per 1 second (FEV1), the maximum flow rate at 25% (V(.) 25), the maximum flow rate at 50% of forced vital capacity (V(.) 50), and airway resistance were measured before and after inhalation of salmeterol (1 dry powder, 50 microg) or procaterol (2 puffs, 20 microg). Sixty minutes after inhalation of salmeterol, or 15 minutes after inhalation of procaterol, inhalation of procaterol (2 puffs, 20 microg) was added, and then pulmonary function was monitored. FEV1, V(.) 25, and V(.) 50 were significantly increased after inhalation of salmeterol as well as procaterol. In addition, airway resistance decreased significantly after inhalation of salmeterol as well as procaterol. In the S+P group, additional decrease of airway resistance after inhalation of procaterol was relatively small compared with the P+P group. In conclusion, although additional bronchodilatoric effects were observed in the S+P and P+P group, the effects seemed to be different based on the intrinsic activity of each beta(2)-agonist.     

Concentration quenching of photoluminescent Ru(bpy) dispersed in a polysiloxane film containing 2,2′-bipyridine pendant groups in dependence of molecular distribution

The photoluminescent Ru(bpy) complex was dispersed in a polysiloxane film containing 2,2′-bipyridine (bpy) pendant groups. The unusually long photoluminescence lifetime of the Ru(bpy) (1,94 μs at 25°C) and the blue-shifted photoluminescent wavelength suggest a rigid polymer matrix. The fluorescence yield becomes lower with higher probe concentration, indicating concentration quenching. According to the analysis based on Stern-Volmer plots, the quenching obeys a mechanism composed of both static and dynamic processes. A statistical intermolecular distance distribution between the probes was used to interpret the results in terms of static and dynamic quenching. It is shown that in the present system the dispersed complexes diffuse slightly during the excited state.     

Multiple epithelial cysts of the spleen and on the splenic capsule, and high serum levels of CA19-9, CA125 and soluble IL-2 receptor

An 18-year-old woman with abdominal pain was diagnosed as having splenic cysts by computed tomography scan. She had high serum levels of CA19-9 (2886.8 U/mL; normal value, <35 U/mL), CA125 (131.1 U/mL; normal value, <35 U/mL) and soluble IL-2 receptor (1490 U/mL; normal range, 220-530 U/mL). The resected spleen weighed 1050 g, was 14 x 28 cm, and had more than 10 macroscopic cysts up to 10.3 x 9.5 cm. There were numerous microscopic cysts in the spleen and several on the splenic capsule. The levels of CA19-9 and CA125 in the cyst fluid were 2165550 U/mL and 160400 U/mL, respectively. After the surgery, the serum levels of the tumor markers decreased gradually. The inside of the largest cyst was mainly covered by granulation tissue with a focal lining of epithelial cells, and the other macroscopic cysts had stratified squamous epithelium. The microscopic splenic cysts and cysts on the splenic capsule were lined by either attenuated single-layered or multilayered epithelial cells. The lining epithelial cells of these cysts were positive for epithelial membrane antigen and cytokeratins. CA19-9 and CA125 were detected in the lining cells of the splenic cysts. In the present case, it is suspected that the splenic cysts were derived from the capsular lining cells that showed migration from the capsule or formed microcysts on the splenic capsule, as in the case of ovarian inclusion cysts.     

Immunoexpression of the α subunit of a guanine nucleotide-binding protein (Go) in pulmonary neuroendocrine cells and neoplasms

The α subunit of a GTP-blndlng protein, Go, was investigated in pulmonary neuroendocrine neoplasms and fetal tissues of the lung by an immunohistochemlcal method. Positive immunostaining for the α subunit of Go (Goα) was found predominantly on the cell membrane and found occasionally in the cytoplasm. Typical carcinoids were all positively stained (9/9), and small cell carcinoma showed weaker and less frequent staining (5 positive cases in 10). Atypical carcinoids were variously stained (3/4). The tendency for obvious neuroendocrine differentiation to be immunohistochemically determined in typical carcinoids and not in small cell carcinoma is also true of staining for neuron specific enolase (NSE), chromogranin A (CG-A) and synaptophysin. In the lung, Goα-immunostaining was positive not only in nerve tissues but also in the airway epithelium. In the fetal lung, serial sections immunostained for NSE, CG-A and Goα confirmed that Goα-immunoreactive cells belong to the neuroendocrine cell population. The biological significance of Goα is unclear in normal and neoplastic lung tissues, but Goα is a useful marker of neuroendocrine cells and neoplasms of the lung.     

Unique properties of fetal lymphoid progenitors identified according to RAG1 gene expression

RAG1/GFP knockin mice were exploited to isolate and characterize fetal lymphoid progenitors. CD11b and IL-7Ralpha are expressed in a developmental stage-dependent fashion, revealing how substantial numbers of early lymphoid progenitors were discarded or neglected in previous studies. The myeloerythroid potential of fetal progenitors in clonal assays declined in synchrony with activation of the RAG1 locus but was not completely extinguished. Lymphoid differentiation corresponded to patterns of gene expression previously found for adult marrow, but no fraction of fetal liver was enriched with respect to B + T progenitors. Also, unlike adults, fetal lymphoid progenitors transiently expressed endothelial cell markers. These findings help to reconcile discrepancies in previous reports and suggest that the fetal immune system arises via unique mechanisms.     

A locus for posterior polymorphous corneal dystrophy (PPCD3) maps to chromosome 10

Posterior polymorphous corneal dystrophy (PPCD) is an autosomal dominant disorder characterized by corneal endothelial abnormalities, which can lead to blindness due to loss of corneal transparency and sometimes glaucoma. We mapped a new locus responsible for PPCD in a family in which we excluded the previously reported PPCD locus on 20q11, and the region containing COL8A2 on chromosome 1. Results of a 317-marker genome scan provided significant evidence of linkage of PPCD to markers on chromosome 10, with single-point LOD scores of 2.63, 1.63, and 3.19 for markers D10S208 (at (circumflex)theta = 0.03), D10S1780 (at (circumflex)theta = 0.00), and D10S578 (at (circumflex)theta = 0.06). A maximum multi-point LOD score of 4.35 was found at marker D10S1780. Affected family members shared a haplotype in an 8.55 cM critical interval that was bounded by markers D10S213 and D10S578. Our finding of another PPCD locus, PPCD3, on chromosome 10 indicates that PPCD is genetically heterogeneous. Guttae, a common corneal finding sometimes observed along with PPCD, were found among both affected and unaffected members of the proband's sib ship, but were absent in the younger generations of the family. Evaluation of phenotypic differences between family members sharing the same affected haplotype raises questions about whether differences in disease severity, including differences in response to surgical interventions, could be due to genetic background or other factors independent of the PPCD3 locus.     

Functional interleukin 2 receptors on B cells lacking Tac antigens

Human B lymphoblastoid line, SKW 6-4, cells were induced to IgM-secreting cells by high concentrations of interleukin 2 (IL 2). These cells were found to be unreactive with anti-Tac antibody and did not express mRNA detectable for Tac antigen. In Scatchard plot analysis, low-affinity IL 2-binding sites were found on SKW 6-4 cells. Moreover, analysis of the IL 2-binding molecules revealed ones (molecular weight 70,000 and 75,000) distinct from Tac antigen. It is conceivable that IL 2 exerts its effect through its interaction with these novel IL 2-binding molecules in SKW 6-4 cells.     

Intestinal microflora and aging: Age-related change of lipid metabolism in germ-free and conventional rats

The influence of intestinal microflora and aging on the lipid metabolism in germfree (GF) and conventional (CV) rats, 8 and 40 weeks old, was investigated. Serum cholesterol at the age of 8 and 40 weeks and serum triglyceride (TG) at the age of 40 weeks was higher in GF than in CV rats. Serum cholesterol decreased and serum TG and corticosterone tended to increase in both GF and CV rats with aging. In the rats 40 weeks of age, lipase activity of the pancreas and the duodenal, jejunal, and colorectal contents in GF rats increased, but that of the ileal and cecal contents in GF and CV rats decreased. Intestinal microflora tended to depress the age-related increase of serum TG and lipase activity of the pancreas and the duodenal and jejunal contents Lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities of the epididymal adipose tissue were higher in CV than in GF rats at both 8 and 40 weeks of age. The LPL activity increased and the HSL activity decreased in both GF and CV rats with aging. The concentration of cholesterol increased and that of bile acids decreased in the cecal contents of 40-week-old GF rats.     

Immunohistochemical profile of primary sclerosing Iipogranuloma of the scrotum: Report of five cases

Five cases of primary sclerosing scrotal lipogranuloma were examined histologically and immunohistochemically. Every case lacked a history of injection or trauma, and revealed Common histologicat features; a typical granuloma composed of epithelioid cells and multinucleated giant cells, and inflammatory infiltrates of eosinophils, lymphocytes and macrophageimonocytes in the interstitium. lmmunahistochemistry disclosed the epithelioid cells and multinuclaated giant cells of the granuloma to be monocytetr in nature, as bath types of cells were positive for lyso-yme, α-1-antltrypin, α-1-antichymotrypsin, and KP-1. In the interstitium, KP-1 positive monocytes, L-26 positive B lymphocytes, UCHL-1 positive T lymphocytes and 5–100 protein positive Langerhans-like cells were frequently found. 5100 protein positive cells could not be detected in the granuloma. Primary sclerosing lipogranuloma of the scrotum, therefore, is a peculiar inflammation characterized by granulomas consisting of monocytes and marked tissue eosinophilia of unknown etiology.     

Influence of obstructive jaundice on pancreatic growth and on basal plasma levels of cholecystokinin and gastrin in rats

Obstructive jaundice was produced in rats by ligation and transection of bile duct outside the liver; the control group underwent laparotomy alone. Pancreatic wet weight, amylase, lipase, protein, DNA, RNA, RNA/DNA ratio, and weight/100 g DNA were significantly increased in jaundiced rats when compared to control rats. Histologic evaluation of pancreatic tissue obtained from jaundiced rats revealed the appearance of large or multiple nuclei in pancreatic acinar cells. Basal plasma levels of immunoreactive CCK were significantly increased in haundiced rats at two weeks and four weeks but, when compared to the levels obtained in laparotomized controls at those time intervals, CCK levels were not significantly different. In jaundiced rats, plasma immunoreactive gastrin was found to be significantly decreased at two and four weeks. Plasma gastrin levels were also found significantly decreased when the jaundiced group was compared with laparotomized control group. The results suggest that obstructive jaundice induced enlargement of the pancreas, probably due to hyperplasia and hypertrophy of pancreatic cells. Whether or not this phenomenon is related to changes in gastrin and CCK is not known.This work was presented in part at the 36th Kinki Section Meeting of Japanese Gastroenterological Association (January 1982) in Osaka, Japan; at the Annual Meeting of the Japanese Pancreatic Association (March 1982) in Hiroshima, Japan; and at the American Gastroenterological Association (May 1983) in Washington, D.C.; and appeared in abstract form inGastroenterology 84: 1095, 1983.