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N Miller

Publications and source records attributed to N Miller.

At least 145 records · Page 8Linked to original sources
PubMed1990

Digestion of proteins associated with the Z-disc by calpain.

The Z-disc of striated muscle is degraded by the Ca2(+)-activated proteinase, calpain, during autolysis of muscle fibres. The effect of calpain on proteins in preparations of Z-discs isolated from Lethocerus flight muscle has been studied. Calpain releases alpha-actinin from the Z-disc and digests two hydrophobic proteins associated with the Z-disc, zeelin 1 (35 kD) and zeelin 2 (23 kD). The Ca2+ sensitivity of zeelin digestion is shifted to lower Ca2+ concentrations (within the physiological range) in the presence of the phospholipids phosphatidyl inositol or phosphatidyl choline and diacylglycerol. The release of alpha-actinin is not affected by phospholipid. Preparations of isolated Z-discs have five times as much associated phospholipid (w/w) as myofibrils and the composition of the lipid differs from that of myofibrils. In muscle fibres the action of calpain on zeelins may be controlled by the composition of phospholipid in the fibres as well as by Ca2+.

Actinin↗
PubMed1990

Effects of recombinant human interferon gamma on human thyroid tissues from patients with Graves' disease and normal subjects transplanted into nude mice.

We have attempted to determine whether interferon gamma (IFN gamma) would enhance, sustain or induce autoimmune thyroid disease (AITD) in xenotransplanted thyroid tissue from patients with Graves' disease or normal persons (actually paranodular tissue) in nude athymic mice, in the absence of an intact immune system. A dosage of 4000 U/mouse of human IFN gamma (hIFN gamma) was injected intraperitoneally daily for six consecutive weeks into the xenotransplanted mice. The parameters measured included the free T4 index, thyroid autoantibodies and TSH during the course of hIFN gamma injections. Thyroid epithelial cell (TEC) HLA-DR expression was measured in the thyroid tissue before xenotransplantation and at sacrifice; in addition, light and electron microscopic studies were carried out at those times. There were no significant differences in thyroid function between the control results and those obtained with hIFN gamma in either group of tissues. TEC HLA-DR expression was significantly increased by hIFN gamma in the normal group, but insignificantly in the Graves' group. In both light and electron microscopic observations, Graves' tissue (whether or not treated with hIFN gamma) was indistinguishable at sacrifice from normal thyroid tissue. The appearance had markedly altered from the same Graves' tissue examined at the time of the initial human surgery, which then showed the usual histological appearance of this disorder. We conclude that IFN gamma induced HLA-DR expression alone is not sufficient to sustain the ongoing process of AITD in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of situational aggression cues: a quantitative review.

Meta-analytic procedures were used to assess the degree to which aggression-related cues present in the environment facilitate aggressive responding among negatively aroused subjects. The first study, which examined the so-called weapons effect, the effect of name-mediated cues, and other cue effects, showed clear evidence that aggression cues augment aggressive responses in negatively aroused subjects. This was true for the overall analysis and for name-mediated cues, but confirmation of the weapons effect was restricted to cases wherein subject sophistication and evaluation apprehension were low. A second study used partial correlation analysis to assess independently the effects of seven potential mediators of aggression cue effects. Of these, target-based facilitation and harm capacity of the aggressive response were found to mediate the magnitude of cue-facilitated aggression. A third study showed that these mediators augmented cue effects among neutral as well as negatively aroused subjects. These outcomes are interpreted as emphasizing the role of cognitive factors in the expression of both impulsive and nonimpulsive aggression.

Affect↗
PubMed1990

Autologous CD4 T-cell responses to ectopic class II major histocompatibility complex antigen-expressing single-cell islet cells: an in vitro insight into the pathogenesis of lymphocytic insulitis in nonobese diabetic mice.

We investigated by flow cytometric analysis the expression of class II major histocompatibility complex (MHC) molecules by viable single-cell islet cells (SCICs) prepared from male and female 4- and 10-week-old nonobese diabetic (NOD) mouse islets. With anti-I-Ak monoclonal antibody (specific for I-Ak,f,r,s beta and produced by clone 11-5-2), and fluorescein isothiocyanate-conjugated goat anti-mouse IgG as second-step antibody, we found that SCICs from both sexes aberrantly expressed class II MHC molecules, which was not altered after SCICs were cultured for 24 hr or 120 hr in the presence of 10 ng of recombinant murine interferon gamma per ml. Double-indirect immunofluorescence of male SCICs indicated that the expression of class II MHC molecules was a property of beta cells. Control experiments documented that macrophages and mononuclear cells did not contaminate the SCIC preparations. Coculture experiments with responder splenic CD4 T cells isolated from diabetic NOD mice and stimulator male SCICs indicated a recognition event evidenced by a 12-fold increase in proliferative response. Monoclonal antibodies to class II MHC and CD4 antigens blocked the proliferative response. Results from control autologous and allogeneic mixed lymphocyte reactions suggest that the responder CD4 T cells are autoreactive self-class II MHC restricted. We tentatively conclude that the ability of SCICs from both sexes of NOD mice to express class II MHC molecules as early as 4 weeks of age may represent a mechanism for targeting immune reactions to beta cells and initiate lymphocytic insulitis.

Animals↗
PubMed1990

Variation at the apolipoprotein (apo) AI-CIII-AIV gene cluster and apo B gene loci is associated with lipoprotein and apolipoprotein levels in Italian children.

We have used RFLPs of the apolipoprotein (apo) B gene and apo AI-CIII-AIV gene cluster to estimate the genetic contribution of variation at these loci to the variability of plasmid lipid, lipoprotein, and apolipoprotein levels in 209 children from Sezze in central Italy. The sample was randomly divided into group I (107 children) and group II (102 children). Four site polymorphisms (PvuII, XbaI, MspI, and EcoRI) of the apo B gene and five site polymorphisms (XmnI, PstI, SstI, PvuII-CIII, and PvuII-AIV) of the apo AI-CIII-AIV gene cluster were examined in group I children. After adjustment for gender, age, and body-mass index, polymorphisms at both gene loci (PvuII-B, PvuII-CIII, and PvuII-AIV) were associated with significant effects on the levels of plasma apo AI, apo B, or high-density lipoprotein-cholesterol. RFLPs that showed significant effects in group I were genotyped in group II. All three polymorphisms were associated with similar effects on apolipoprotein levels, though for all RFLPs the magnitude of the effects was smaller in the group II children and only statistically significant for the effect of the PvuII-B genotype on apo AI levels. In the total sample of 209 children 7.4% of the sample variance in apo AI levels was explained by variation associated with the apo B PvuII-B RFLP. In addition, the PvuII-B RFLP was associated with significant effects on plasma apo B levels and explained 5.7% of the sample variance. The PvuII-CIII and PvuII-AIV polymorphisms were both associated with differences in apo AI levels, explaining 3.7%-5.7% of the sample variance. Taken together, the three PvuII polymorphisms explained 17.7% of the phenotypic variance in apo AI levels. There was significant evidence for an effect of nonlinearity of the PvuII-CIII genotypes on apo AI levels, with the individuals heterozygous for the polymorphism having the highest apo AI levels. No evidence of interaction between genotype and gender, age, and body-mass index was shown by covariance analysis. The molecular explanation of this effect is unclear. Our data show that variation at both the apo AI-CIII-AIV and apo B loci are associated with lipoprotein and apolipoprotein levels in this sample of Italian children.

Alleles↗
PubMed1990

G to A substitution in the promoter region of the apolipoprotein AI gene is associated with elevated serum apolipoprotein AI and high density lipoprotein cholesterol concentrations.

We have determined the sequence of 250 bases 5' of the transcriptional start site of the apolipoprotein AI gene in a human individual with high serum concentrations of apo AI. One of the alleles contained a G to A substitution at position -75, between the CACAT sequence and the TAAATA box, creating a tandem repeat, CAGGGC-CA*GGGC. The substitution destroys an MspI cutting site, and the polymerase chain reaction and MspI digestion were used to identify the presence of the A or G base. The frequency of the A substitution in 96 healthy men from Bristol was 0.11 and this was increased to 0.25 in men with serum apo AI concentrations greater than 180 mg/dl. Men with the A allele had significantly higher serum concentrations of apo AI, high density lipoprotein (HDL) cholesterol and HDL2 than those with the G allele. In this sample, variation associated with the G to A substitution accounted for 6% and 4.6% of the total variance in apo AI and HDL cholesterol concentrations, respectively. Although there is as yet no functional proof, it is possible that the A substitution may be having a direct positive effect on the rate of apo AI gene transcription and thus be associated with increased apo AI and HDL cholesterol concentrations because of increased production of apo AI protein from the liver or intestine.

Alleles↗
PubMed1990

Autoantibodies in the sera from newly diagnosed diabetic nod mice: evidence against cross-reactivity with a putative beta-cell surface autoantigen.

In insulin-dependent diabetes mellitus in humans, the BB rat and the NOD mouse, serum has been reported to contain autoantibodies that precipitate a 64,000 Mr protein from (32S) methionine labeled histoincompatible non-autoimmune rat or mouse islet cell proteins. Because experimental data reported recently have brought into question the role of the 64,000 Mr protein in targeting autoantibodies and hence initiate beta-cell destruction, we report differently designed experiments to clarify the apparent 64,000 Mr autoantigen enigma. Using an in vitro model of NOD mouse origin mimicking diabetic insulitis we found that target beta-cells induced a 6-fold increase in proliferative response of splenic L3T4+, Thy-1,2+ T cells. The magnitude of the proliferative response was not affected when target beta-cells were pretreated with 50% (vol/vol) partially purified immunoglobulins ((NH4)2SO4 precipitation at 33% saturation) from sera from newly diagnosed (less than 4d after onset) diabetic NOD mice. Cytofluorimetric analysis of beta-cells pretreated with partially purified immunoglobulins plus FITC-conjugated goat antimouse IgG as a second-step antibody were negative and thus gave no indication of an autoantigen-autoantibody complex formed on the surface of the beta-cells. We conclude from the experimental data that it remains still in question whether an autoantigen is targeted by an islet cell surface specific autoantibody and plays a role as a triggering event in the pathogenesis of diabetes in NOD mice.

Animals↗
PubMed1990

The impact of corporate culture on nurse retention.

This article concerns the impact of the corporate culture of today's hospitals on the hospital's ability to attract and retain nurses. Several sources are used to illuminate recent sociohistoric changes that have had a profound impact on the business of health care and the professional world of staff nurses. Organizational characteristics that are associated with successful nurse retention strategies are offered.

Hospitals↗
PubMed1989

Plasma concentrations of delta-9-tetrahydrocannabinol in dams and fetuses following acute or multiple prenatal dosing in rats.

Delta-9-tetrahydrocannabinol (THC) was administered by gastric intubation to pregnant rats to study the effects of dose-level and dosing regimen on plasma concentration in dams and fetuses. Two multiple-dose groups were administered either 15 or 50 mg/kg of delta-9-THC once daily during the last two weeks of gestation. Two acute groups were administered the same dose as above but only once on the last day of gestation. Sixty min after receiving the last dose all dams and their fetuses were sacrificed by decapitation, blood collected, centrifuged and plasma removed. Quantitative measurement of delta-9-THC in plasma was carried out using GS/MS. Among the dams, plasma concentrations covaried with dose and multiple dosing produced higher concentrations than acute, especially at the high dose. Among the fetuses, plasma concentrations were approximately 10% of those found in the dams. The fetuses from the high, multiple-dose dams similarly yielded significantly higher concentrations. These findings are discussed with respect to other studies of the placental transfer of delta-9-THC and effects of postnatal developmental.

Animals↗
PubMed1989

Site and mechanism of enhanced gastrointestinal absorption of aluminum by citrate.

Clinical and experimental studies have shown that citrate markedly enhances the intestinal absorption of aluminum (Al), but the site and mechanism of enhanced absorption are unknown. To determine where in the gastrointestinal tract aluminum citrate (Alcitr) was absorbed. Alcitr was gavaged with D-[1-3H] glucose in male Sprague-Dawley rats. Plasma Al levels increased rapidly and simultaneously peaked with D-[1-3G] glucose, suggesting early proximal bowel absorption. In in vitro duodenal and jejunal everted gut preparations, Alcitr incubation resulted in increased tissue Al levels and markedly enhanced transmural transport of Al and citr. Unlike citr, the transmural movement of Al was independent of temperature (37 degrees C vs. 4 degrees C). On the other hand, Al lactate (al Lac) increased tissue associated Al levels but had no effect on transmural Al movement. To determine if this large flux of Al following Alcitr administration was due to paracellular movement, ruthenium red and Ussing chamber studies were used to evaluate the morphologic and functional integrity of cellular tight junctions. Alcitr, as opposed to AlCl3, markedly increased ruthenium red deposits in intercellular spaces, especially around goblet cells, and induced a prolonged significant reduction in transmural resistance. Alcitr also resulted in rapid and nearly complete (99.7%) chelation of free calcium, an event known to disrupt cellular tight junction integrity. Taken together, these data suggest that enhanced Al absorption following administration of Alcitr occurs in the proximal bowel via the paracellular pathway due to the opening of cellular tight junctions.

Aluminum↗
PubMed1989

Histopathology of breast cancer in young women in relation to use of oral contraceptives.

A detailed review was made of the histopathology of 227 tumours taken from 261 women under 45 years of age with breast cancer. The tumours were classified as follows: whether oral contraceptives had been used at any time; and whether oral contraceptives had been used before first term pregnancy. All analyses were adjusted for the effects of age. Overall, 201 (88.5%) of tumours were infiltrating ductal in type, 19 (8.4%) were infiltrating lobular, and seven (3.1%) were in situ ductal. Of the infiltrating ductal tumours, 28 (14%) were grade I 88 (44%) grade II, and 84 (42%) grade III. Various other tumour characteristics were also examined (per cent of carcinoma in situ, lymphatic permeation, necrosis, lymphoplasmocytic reaction and tumour edge). None of the histopathological features assessed showed any significant association with oral contraceptive use. Some characteristics of the areas of breast tissue adjacent to the tumours were also studied. The degree of cyst formation was considerably less pronounced in those using oral contraceptives before first term pregnancy than in those not doing so.

Breast↗