Search PubMed⌕ Search

Biomedical subjects

A Miller

Publications and source records attributed to A Miller.

At least 433 records · Page 24Linked to original sources
PubMed1989

Will the increased military low-level flying activity in Labrador be detrimental to the hearing of humans in the region?

The Government of Canada has directed the Department of National Defence to encourage our NATO allies to increase use of their facilities at Goose Bay, Labrador. This has already resulted in a substantial increase in the amount of military flying in the area, and more is projected. Much of the flying is done at very low altitude. The aboriginal people in the region (the Innu and, to a lesser extent, the Inuit) are demanding a halt to low-level military flying, and their representatives claim that the noise from the low-flying jet aircraft can cause hearing loss and ear disease. A survey on the ground in the area measured noise levels up to 127.7 dBA with very brief exposure levels. A task force commission to look at the problem concluded that occasionally low-level subsonic overflights might produce noise levels that were potentially damaging to hearing, but that the probability of this happening is at present very low because of the low frequency of flights. This might change if the frequency of flights increases.

Aircraft↗
PubMed1988

Epidermal growth factor (EGF) and hormones stimulate phosphoinositide hydrolysis and increase EGF receptor protein synthesis and mRNA levels in rat liver epithelial cells. Evidence for protein kinase C-dependent and -independent pathways.

Epidermal growth factor (EGF) stimulated the rapid accumulation of inositol trisphosphate in WB cells, a continuous line of rat hepatic epithelial cells. Since we previously had shown that EGF stimulates EGF receptor synthesis in these cells, we tested whether hormones that stimulate PtdIns(4,5)P2 hydrolysis would increase EGF receptor protein synthesis and mRNA levels. Epinephrine, angiotensin II, and [Arg8]vasopressin activate phospholipase C in WB cells as evidenced by the accumulation of the inositol phosphates, inositol monophosphate, inositol bisphosphate, and inositol trisphosphate. A 3-4-h treatment with each hormone also increased the rate of EGF receptor protein synthesis by 3-6-fold as assessed by immunoprecipitation of EGF receptor from [35S]methionine-labeled cells. Northern blot analyses of WB cell EGF receptor mRNA levels revealed that agents linked to the phosphoinositide signaling system increased receptor mRNA content within 1-2 h. A maximal increase of 3-7-fold was observed after a 3-h exposure to EGF and hormones. The phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), which activates protein kinase C also stimulated EGF receptor synthesis. Pretreatment of WB cells for 18 h with high concentrations of TPA "down-regulated" protein kinase C and blocked TPA-directed EGF receptor mRNA synthesis. In contrast, the effect of EGF on EGF receptor mRNA levels was not significantly decreased by TPA pretreatment. Epinephrine-induced increases in EGF receptor mRNA were reduced from 4- to 2-fold. Similarly, 18 h TPA pretreatment abolished the effect of TPA on EGF receptor protein synthesis but did not affect EGF-dependent EGF receptor protein synthesis. The 18-h TPA pretreatment diminished by 30-50% the induction of receptor protein synthesis by epinephrine or angiotensin II. We conclude that in WB cells EGF receptor synthesis can be regulated by EGF and other hormones that stimulate PtdIns(4,5)P2 hydrolysis. In these cells, EGF receptor synthesis appears to be regulated by several mechanism: one pathway is dependent upon EGF receptor activation and can operate independently of protein kinase C activation; another pathway is correlated with PtdIns(4,5)P2 hydrolysis and is dependent, at least in part, upon protein kinase C activation.

Angiotensin II↗
PubMed1988

Human orbital tissue and thyroid membranes express a 64 kDa protein which is recognized by autoantibodies in the serum of patients with thyroid-associated ophthalmopathy.

A 64 kDa protein has been identified in the membrane fraction of human eye muscle, orbital connective tissue and thyroid, by testing sera of patients with thyroid-associated ophthalmopathy in SDS-polyacrylamide gel electrophoresis and Western blotting. Antibodies to this membrane antigen seem characteristic of the early stage of ophthalmopathy. In the thyroid this newly recognized protein seems different from previously known membrane antigens. A thyroid antibody reactive with a 64 kDa membrane antigen in eye muscle could explain the very frequent association of ophthalmopathy with autoimmune thyroid disease.

Adult↗
PubMed1988

A predominant idiotype independent of specificity, or Ig and H-2 allotypes, is found in the primary but not the secondary murine antibody response to lysozyme.

Removal of just the three N-terminal residues Lys-Val-Phe (TIP) on hen egg white lysozyme (HEL), by aminopeptidase cleavage, eliminates an antigenic determinant which is a recurrent and dominant focus of primary but not secondary antibody responses to HEL in a variety of mouse strains. We have generated an anti-idiotypic rabbit antiserum against such a TIP-dependent monoclonal antibody (mAb). This antiserum reacts with many different primary anti-HEL mAb, but fails to react with all of a variety of secondary anti-HEL mAb. The idiotype defined by this antiserum, termed IdXE, is a common feature of early anti-HEL antibody responses but does not appear in secondary responses. Although the presence of IdXE and TIP dependence is correlated in primary responses, studies of idiotype expression on mAb and on plaque-forming cells (PFC) using mixed erythrocyte monolayers clearly show that at the single-cell level the properties are separable, i.e., not all TIP-recognizing PFC display IdXE and a sizable proportion of cells producing non-TIP-dependent antibodies are IdXE+. The restricted idiotypy and specificity of early antibody responses to HEL occur in each of eight diverse mouse strains tested: it is not associated with a particular MHC haplotype, heavy chain allotype or light chain allotype. The finding of such strain-independent restriction in the early response pattern to a typical protein antigen is novel and suggests the involvement of highly conserved, potent regulatory mechanisms which are manifested as a limitation in the initial expression of the available repertoire.

Animals↗
PubMed1988

Phase I and pharmacokinetic studies with the pentacyclic pyrroloquinone mitoquidone.

Mitoquidone (MTQ) is the first member of a new group of pentacyclic pyrroloquinones developed for clinical evaluation as a potential anticancer agent. MTQ demonstrated good activity in a range of experimental solid tumour models, but was weakly active against standard prescreens such as the P388 murine leukaemia. Bone marrow suppression or other significant toxicity was not observed in preclinical studies. Twenty-seven patients were treated with MTQ given as a 4-h infusion either once every 21 days (150-600 mg/m2), once a week (200 mg/m2 per week), or as 5 daily doses repeated every 28 days (60-180 mg/m2 per day). The major adverse events encountered included nausea and vomiting (in virtually all patients), dyspnoea, tumour-related pain, and thrombocytopenia in several patients with pretreatment bone-marrow impairment. Phase I studies were suspended without a maximum tolerated dose being reached because of formulation difficulties. There were no major responses, although stable disease was observed in a number of patients with gastrointestinal malignancies. Temporary remission of B-symptoms occurred in two patients with lymphoma. The plasma pharmacokinetics of MTQ were investigated using an HPLC assay with fluorescence detection. Linear pharmacokinetics were observed with a terminal plasma half-life of 2.9 +/- 2.1 h (n = 18 doses). The volume of distribution was 3.4 +/- 2.6 l/kg and plasma clearance was 629 +/- 469 ml/min per m2. Several soluble analogues with similar antitumour activity are currently under investigation.

Carcinoma↗
PubMed1988

In vitro analysis of germ cell genotoxicity in testis explant cultures: spermatid micronucleus assays.

Explant cultures of testes from the frog Xenopus laevis have been employed to evaluate the application of testis culture to the routine screening of potential germ cell genotoxicants. Testis explants were incubated with varied concentrations of 3 model mutagens (9,10-dimethyl-1,2-benzanthracene, cyclophosphamide, adriamycin) and solvent controls. Round spermatids were isolated from testes cultured 2-30 days after exposure to each mutagen. The spermatids were then stained with Hoechst 33258 and spermatid micronuclei were scored with a fluorescence microscope. Acute exposure of testes to each mutagen resulted in a dose-dependent increase in spermatid micronuclei that was stage specific and proportional to the length of the exposure period. The assay sensitively detected clastogenic effects by 10(-7) M adriamycin (4-h exposure period) and 10(-6) M cyclophosphamide and dimethylbenzanthracene (24-h exposure). The results demonstrate the feasibility of in vitro approaches to the routine screening and investigation of genotoxicity in the premeiotic S through meiotic division stages of vertebrate spermatogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Diagnosis and correction of twin pregnancy in the mare.

Reproductive Physiology 1. Twin pregnancies result in high rates of abortion, stillbirth, and neonatal mortality. 2. Twins develop subsequent to multiple ovulations. Multiple ovulations are related to breed, parity, and mare history. Multiple ovulations are most frequently seen in Thoroughbred and Draft mares. Multiple ovulations are more common in barren and perhaps maiden mares than in lactating mares, and they are more common in certain individual mares. 3. Equine embryos are motile in the uterus from the time of first detection (Days 9 to 10) until fixation (Day 16). They are frequently located in the uterine body on Days 9 and 10. 4. Twin embryos have a pattern of motility and fixation similar to that of single embryos, and fixation is more frequently unilateral than bilateral (70 per cent versus 30 per cent, respectively). 5. Mares have an efficient natural embryo-reduction mechanism to eliminate excess (greater than 1) embryos resulting from multiple ovulations. Natural embryo reduction is more successful in unilateral than bilateral twin pregnancies (89 per cent versus 11 per cent successful reduction, respectively). 6. After the establishment of endometrial cups (Days 35 to 40), mares that are aborted will frequently not cycle for several months. Management of Twin Pregnancy 1. Breed all mares regardless of the number of preovulatory follicles. Withholding mares with preovulatory follicles from breeding does not decrease the incidence of twin pregnancy, but it decreases the overall pregnancy rate and results in a loss of breeding time. 2. Check all mares for twins, regardless of the number of detected ovulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Veterinary↗
PubMed1988

Induction of helper and suppressor T cells by nonoverlapping determinants on the large protein antigen, beta-galactosidase.

The fine specificity of the T cell repertoire directed against T helper (Th)-inducing and T suppressor (Ts)-inducing determinants was examined with cyanogen bromide and tryptic peptides of Escherichia coli beta-galactosidase (GZ), a large tetrameric protein (monomer molecular weight = 116 kDa). Immunization with cyanogen bromide fragment 2 [CB-2, amino acids (a.a.) 3-92] induced both specific Th and Ts cells. Study of the induction of these functionally opposite T cell subpopulations with tryptic peptides of CB-2 indicated that Th and Ts were activated by separate, nonoverlapping determinants. Th-inducing activity resided in a nonapeptide, T6 (a.a. 44-52), whereas T4 (a.a. 27-37) induced Ts cells. The presence of distinct helper and suppressor determinants suggests that the specificity repertoire in these T cell subpopulations may differ, perhaps owing to the expression of antigen-recognizing receptors that are coded by unique gene families. Alternatively, antigen presentation structures may be physicochemically quite different, and bind to distinct parts of the peptide antigen.

Animals↗
PubMed1988

Damage to jejunal intrinsic autonomic nerves in HIV infection.

Jejunal biopsies from 11 HIV-infected male homosexuals, without secondary enteropathogen infection, were examined at ultrastructural and light microscope level. Subjects were clinically categorized into four groups: asymptomatic (3), AIDS-related complex (4), persistent generalized lymphadenopathy (1), and AIDS (3). All 11 biopsies, including the three from asymptomatic HIV-infected individuals, showed extensive damage to autonomic nerve fibres in the lamina propria. These findings show that HIV infection damages the enteric autonomic nerves. Since asymptomatic HIV-infected individuals had similar damage, this appears to be an early event in the course of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Transitional epithelial lesions of the ureter in renal transplant rejection.

The spectrum of ureteric lesions of human renal allografts, long attributed exclusively to postsurgical complications such as ischemia, has recently been shown to include the types of rejection seen in the kidney. Since the rejected ureter also exhibits transitional epithelial lesions that may impact on renal and ureteral function, we studied, by light, immunohistochemical, immunofluorescent, and electron microscopic techniques, ureters of 65 irreversibly rejected kidneys. Seven unused cadaver kidneys served as controls. Urothelial lesions, noticed in 57 of 65 ureters (88%), ranged from minimal basal vacuolization to complete sloughing with or without necrosis of the epithelial lining. Epithelial exfoliation was noticed in 31 cases (54.4%), and basal vacuolization, severe enough to produce cleavage of the epithelial junctions and thus create bullae, was noticed in 21 cases (36.8%). Immunofluorescent and immunoperoxidase stains, performed in 16 cases, were all positive for immunoglobulins but yielded varied results ranging from granular to linear staining, particularly in the region of the basal cells and the basement membrane. Electron microscopic findings confirmed the light microscopic alterations. By contrast, control ureters showed no lesions. Urothelial ureteric lesions might impede ureteral functions and result in obstruction or infection, thus compounding the consequences of renal allograft rejection. Moreover, elucidation of the pathophysiology of the process will advance the understanding of various cutaneous and transitional epithelial autoimmune conditions.

Autoimmune Diseases↗
PubMed1988

Clinical respiratory abnormalities in Michigan. Prevalence by sex and smoking history in a representative sample of the adult population.

A stratified random sample of a large state (Michigan) was studied by respiratory questionnaire, medical history, and physical examination. Data were obtained on 1,169 white adults. The prevalence of chronic bronchitis and chronic wheezing varied with sex (greater in men) and smoking history (greatest in current smokers). The prevalence of chronic bronchitis varied depending on whether it was (1) defined simply as chronic production of sputum, (2) diagnosed by the examining physician, or (3) previously diagnosed by a physician. Dyspnea was more common in women; in men, it was least common in nonsmokers but was of similar prevalence in ex-smokers and current smokers. Angina was more commonly reported by women, but previously diagnosed heart attack was consistently more common in men. Wheezing was by far the most common physical sign, present in 5.1 percent of the total population and 9.2 percent of male current smokers. Clubbing and rales were each noted in 1.2 percent of the total population. The prevalences of clinical findings in this cross section of a large state should be useful for comparison with other populations.

Adolescent↗
PubMed1988

[Cutaneous lymphangitic-nodular sporotrichosis with multiple portals of entry].

A human case of cutaneous sporotrichosis with three chancriform primary lesions and regional lymphangitis is presented in a male patient infected during the hunting of armadillos. The clinical picture shows very well the usual mechanism of infection for the disease in Uruguay, which is a direct contact of man with armadillos and their burrows.

Adult↗