Induction of distinct types of spontaneous electrical activities in mammary epithelial cells by epidermal growth factor and insulin.

Electrophysiological measurements of the membrane potentials of mouse mammary epithelial cells in primary culture revealed the presence of spontaneous-oscillating-hyperpolarizing potentials in cells incubated with epidermal growth factor. The hyperpolarizing potentials were 5-20 mV in amplitude and about 10 sec in duration. The peak height of the response was reduced by hyperpolarization, and the input membrane resistance decreased during the response. The response was probably due to activation of K+ channels. The latency period for the epidermal growth factor induction of the hyperpolarizing potential was approximately 3 hr. In contrast, insulin induced spontaneous-depolarizing potentials that were about 5 mV in amplitude and 1 sec in duration. The depolarizing potentials were attributed to activity of ion channels, since the peak height was dependent on the membrane potential and the depolarizing potential was accompanied by a decrease of input membrane resistance. The time lag for the induction of the depolarizing potential was 6-12 hr. Other hormones involved in mammary cell differentiation, such as cortisol and prolactin, neither induced the depolarizing potentials nor changed the induction of depolarizing potential by insulin. In addition, other growth factors, such as nerve growth factor and fibroblast growth factor, elicited no electrical activity.     

Transbronchial biopsy is clinically useful in classifying patients with interstitial pneumonia associated with polymyositis and dermatomyositis

Background and objective: The histological type of intraluminal fibrosis is an important prognostic factor for interstitial pneumonia. We therefore examined whether transbronchial lung biopsy (TBLB) specimens are useful for predicting the clinical course and prognosis of patients with interstitial pneumonia associated with polymyositis and dermatomyositis (PM/DM), with particular attention to the different types of intraluminal fibrosis. Methods: Twenty‐five cases of interstitial pneumonia associated with PM/DM were classified according to the pattern of intraluminal fibrosis as assessed by TBLB, and the clinical course and response to treatment were compared. Interstitial fibrosis was evaluated by sequential thin‐section CT scans. Results: In 19 of 25 (76%) cases, there was sufficient intraluminal fibrosis to perform an evaluation. Intraluminal fibrosis was classified as bud (polyp) type or mural incorporation type (either alone or mixed with bud type). The bud type was seen in five cases and these improved following treatment with corticosteroids only. The mural incorporation type was seen in 14 cases. In 11 of these 14 cases, progressive long‐term fibrosis developed and four cases were fatal, in spite of corticosteroid and immunosuppressive therapy. The response to drugs (P < 0.01) and survival (P < 0.05) were significantly greater in patients with bud‐type than mural incorporation‐type intraluminal fibrosis. Conclusions: Classification of the pattern of intraluminal fibrosis as assessed by TBLB is useful for predicting the response to treatment, clinical course and prognosis of interstitial pneumonia associated with PM/DM.     

Plasma level of asymmetric dimethylarginine (ADMA) as a predictor of carotid intima-media thickness progression: six-year prospective study using carotid ultrasonography

This study was designed to determine the relationship between plasma asymmetric dimethylarginine (ADMA) and the development of carotid atherosclerosis. Cross-sectional studies have revealed that plasma ADMA concentration is correlated with the intima-media thickness (IMT) of the carotid artery, but no prospective studies have appeared. Therefore we prospectively investigated whether or not plasma ADMA level can predict IMT progression. In a community-based cohort, we enrolled 712 subjects who were over 40 years old and who had no apparent cardiovascular diseases according to high-resolution carotid ultrasonography. Blood chemistries including ADMA were measured at baseline. In 575 subjects, IMT was re-measured 6 years later. The value of baseline ADMA for predicting IMT changes was investigated by multivariable analysis. At baseline, there was a significant (beta=0.321; p<0.001) relationship between IMT and ADMA levels. Multiple linear regression analysis revealed that baseline ADMA (beta=0.241; p<0.01) was the only predictor of IMT progression after adjustments for age, sex, baseline IMT, and four major risk factors (hypertension, hypercholesterolemia, diabetes mellitus, and smoking) plus hyperuricacidemia. Plasma ADMA was a predictor of carotid IMT progression.     

Interleukin 15 activity in the rectal mucosa of inflammatory bowel disease

Background & Aims: Interleukin (IL)-15 has been found to share many immunoregulatory activities in lymphocytes with IL-2. The aim of this study was to investigate IL-15 activity in organ cultures, localization of IL-15 messenger RNA (mRNA), and proliferation of lamina propria mononuclear cells (LPMCs) in response to recombinant IL-15 using the mucosal tissues obtained from patients with inflammatory bowel disease (IBD). Methods: The contents of IL-15, tumor necrosis factor α, and IL-2 in the culture supernatant of the rectal mucosal tissues were determined by an enzyme-linked immunosorbent assay. Expression of IL-15 mRNA was analyzed by in situ hybridization, and proliferative response of LPMCs to recombinant IL-15 was determined by [³H]thymidine incorporation into DNA. Results: Significantly greater IL-15 activity was detected in active IBD, and this elevation was also observed in inactive ulcerative colitis. In contrast, greater tumor necrosis factor α activity was observed only in active IBD, and IL-2 was not detected in organ cultures. In situ hybridization showed IL-15 mRNA in macrophages and epithelial cells in active IBD specimens, and recombinant IL-15 induced a dose-dependent proliferative response in LPMCs. Conclusions: Mucosal IL-15 may be involved in the pathogenesis of IBD as one of the important mediators in activation of mucosal immune cells.GASTROENTEROLOGY 1998;114:1237-1243     

A novel leukemia cell line, MR-87, with positive Philadelphia chromosome and negative breakpoint cluster region rearrangement coexpressing myeloid and early B-cell markers

We developed a Philadelphia chromosome (Ph) positive cell line, designated MR-87, from a 4-year-old boy with Ph+-acute leukemia. MR-87 cells grew in single cell suspensions with a doubling time of 120 to 144 hours. Both MR-87 and original leukemia cells were positive for myeloperoxidase (MPO) and myeloid antigen CD13. These cells exhibited the early B-cell phenotype, ie, terminal deoxynucleotidyl transferase+, Ia+, CD19+, and CD10+. Rearrangement of the immunoglobulin heavy chain was confirmed in both. Approximately 80% of MR-87 cells coexpressed CD13 and lymphoid antigens CD10 or CD19, as confirmed by a two-color analysis. Simultaneous expression of MPO and CD19 on a single MR-87 cell was demonstrated at ultrastructural level. Thus, MR-87 is a Ph+ leukemia cell line exhibiting a hybrid phenotype. The breakpoint cluster region (bcr) was not rearranged in the MR-87 cells and subsequent analysis using antisera revealed that these cells expressed a novel protein, P190c-abl, which was immunoprecipitated with anti-abl and anti-phosphotyrosine antibodies. The MR-87 line will be most useful for investigating the biology and pathogenesis of Ph+ bcr- acute leukemia.     

Molecular cloning and characterization of a gonadotropin-releasing hormone receptor in the guinea pig, Cavia porcellus

Guinea pig gonadotropin-releasing hormone (gpGnRH) is predicted to have a unique structure among all known forms of GnRH molecule [Endocrinology 138 (1997) 4123] and it is of great interest to determine whether the unique structure of gpGnRH is manifested in the characteristics of the guinea pig GnRH receptor. In the present study, we isolated a full-length cDNA for a GnRH receptor from the pituitary gland of the guinea pig. The putative guinea pig GnRH receptor protein has an amino acid identity of 79-87% with mammalian type I GnRH receptors. The amino acid residues which have been demonstrated to be important for ligand binding and signal transduction were conserved in the guinea pig GnRH receptor. However, there are several specific amino acid substitutions among mammalian type I GnRH receptors. Moreover, though the guinea pig has generally been classified as a rodent, the putative GnRH receptor protein did not have some rodent-specific characteristics. Total IP assays demonstrated that the cloned guinea pig GnRH receptor is a functional GnRH receptor and that it shows different preference of ligand sensitivities from the rat GnRH receptor.     

Usefulness of measuring electrically evoked auditory brainstem responses in children with inner ear malformations during cochlear implantation

Conclusions: EABR is a reliable and effective way of objectively confirming device function and implant-responsiveness of the peripheral auditory neurons up to the level of the brainstem in cases of inner ear malformation. Objective: To investigate the usefulness of measuring the intra-operative electrically evoked compound action potential (ECAP) and electrically evoked auditory brainstem response (EABR) in patients with and without congenital inner ear anomalies during cochlear implantation. Method: Thirty-eight consecutive children (40 ears) aged 5 or younger with congenital profound hearing loss. Twenty-four (25 ears) lacked congenital inner ear anomalies. The 14 patients (15 ears) with a malformation had common cavities (four ears), incomplete partition type I (three ears), cochlea hypoplasia type III (three ears), enlarged vestibular aqueduct (four ears), and cochlear nerve canal stenosis (one ear). Main outcome measures are ECAP and EABR responses. Results: Of the 25 ears lacking any malformation, 21, three, and one showed ‘Good’, ‘Variable’, and ‘No’ ECAP responses, respectively, and 24 and one showed ‘Good’ and ‘Variable’ intra-cochlear responses, respectively. Of the 15 ears with a malformation, two showed ‘Good’ ECAP responses, nine had ‘Variable’ ECAP responses, and four showed ‘No’ ECAP responses. Moreover, five showed ‘Good’ EABR responses and 10 showed ‘Variable’ EABR responses.