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Biomedical subjects

J K Miller

Publications and source records attributed to J K Miller.

At least 37 records · Page 2Linked to original sources
PubMed1996

A comparison of recurrent and primary herpes simplex keratitis in NIH inbred mice.

Herpes simplex virus (HSV) infection is one of the leading causes of corneal blindness. This study compared the clinical, virologic, and immunopathologic features of primary and recurrent murine models of herpes simplex keratitis (HSK) in the National Institutes of Health (NIH) inbred mouse strain. Primary infection resulted in multiple epithelial dendrites, followed by diffuse stromal opacification, symptoms that do not mimic what is seen in human HSK. In contrast, recurrent infection presented clinical features that included microdendrites, focal stromal opacities, disciform endotheliitis, and corneal neovascularization, which were similar to those observed in human disease. Immunohistochemical characterizations indicated that the number and duration of T cells and macrophages in recurrent HSK resemble those observed in primary disease. Results also indicated that the amount of infectious virus detected in the cornea during primary and recurrent disease was similar. However, when corneas were stained for HSV-1 antigens, mice with primary HSK displayed diffuse HSV antigen expression throughout the cornea, whereas HSV antigens were more focally distributed in recurrent disease. These data suggest that the clinical differences between the recurrent and primary herpetic keratitis may, in part, reflect the different distribution of HSV-1 antigens within the cornea.

Animals↗
PubMed1994

A structural and functional comparison of the latency-associated transcript promoters of herpes simplex virus type 1 strains KOS and McKrae.

The promoters of the latency-associated transcripts (LATs) of herpes simplex virus type 1 (HSV-1) strains KOS and McKrae were compared to examine their influence upon the reactivation phenotypes of these two strains. Unlike strain KOS, McKrae is readily reactivable using in vivo reactivation models. We found greater than 96% sequence conservation between KOS and McKrae in the LATs promoter region, and both promoters showed equivalent basal and inducible activities. An inter-strain recombinant (termed MK13) was constructed in which the LATs promoter of HSV-1 McKrae was recombined into the background of HSV-1 strain KOS. In a murine u.v. light-induced reactivation model, virus shedding was detected by eye swabbing in two of 44 (5%) mice infected with KOS, 20 of 42 (48%) mice infected with McKrae and none of 45 (0%) mice infected with MK13. These data show that the LATs promoters of these viruses are structurally and functionally similar and that transfer of the LATs promoter from McKrae into KOS is insufficient to confer a reactivatable phenotype.

Animals↗
PubMed1994

Antioxidant status of dairy cows supplemented prepartum with vitamin E and selenium.

Possible relationships among dietary antioxidants, oxidative status, and placental retention were investigated in periparturient dairy cows. During 6 wk prepartum, 16 cows each were given daily by capsule 1000 IU of vitamin E, 3 mg of Se, both vitamin E and Se, or neither (control). alpha-Tocopherol in serum and fast-acting antioxidants in plasma increased, but, in red blood cells, thiobarbituric acid-reactive substances decreased during the last 6 wk before parturition in cows given vitamin E. These measurements were unaffected by supplementation of Se. Cows that had retained placenta > or = 12 h had lower fast-acting antioxidants in plasma and glutathione peroxidase in red blood cells up to 2 wk before calving than did cows that shed fetal membranes in < 12 h. Results suggest that inadequate dietary antioxidants may increase oxidative stress, production of lipid peroxides, and incidence of retained fetal membranes in dairy cows.

Animal Feed↗
PubMed1993

In vivo characterization of site-directed mutations in the promoter of the herpes simplex virus type 1 latency-associated transcripts.

Transient expression assays in PC12 cells showed that the cAMP response element (CRE) and the TATA box of the herpes simplex virus type 1 latency-associated transcripts (LATs) promoter are essential for basal expression. Recombinant viruses were generated containing site-specific mutations in these motifs. The abilities of these recombinants to replicate, express LATs and reactivate from latency were compared with wild-type and marker-rescued viruses in a murine ocular model. The acute replication of these TATA and CRE mutant viruses was at a level equivalent to their respective marker-rescued viruses. The reactivation of virus was unaffected by mutation in the TATA box as compared with wild-type or marker-rescued viruses. In situ hybridization of TATA box mutant virus-infected ganglia, however, showed threefold fewer LAT-positive neurons than wild-type virus-infected ganglia, with consistently weaker hybridization signals. Thus, this TATA box is required for normal expression of the LATs but not for efficient reactivation. The LATs CRE mutant reactivated with slightly but reproducibly reduced frequency and delayed kinetics relative to marker-rescued virus. By in situ hybridization, however, the percentage and intensity of LATs-positive neurons were found to be comparable for the CRE mutant- and wild-type virus-infected ganglia, suggesting that the CRE is dispensable for abundant LATs expression but that a reactivation function of the LATs may depend upon the presence of the CRE. Finally, using a modified assay for examining the timing of reactivation, we showed that the induction of viral reactivation by addition of exogenous cAMP can occur independently of the LATs.

Animals↗
PubMed1993

Oxidative stress, antioxidants, and animal function.

Reactive oxygen metabolites generated during normal metabolism and metabolism stimulated by xenobiotics can enter into reactions that, when uncontrolled, can impair performance of dairy cows. Direct effects include peroxidative changes in membranes and other cellular components. Indirectly, competitive consumption of reducing equivalents can interfere with important metabolic functions and divert glucose from other pathways by inducing the monophosphate shunt. Normally, the body is protected by a wide range of antioxidant systems working in concert. Metal catalysts of oxidative reactions are removed in intracellular fluids by metal-binding macromolecules. Superoxide dismutases, glutathione peroxidase, and catalase within cells remove superoxide and peroxides before they react with metal catalysis to form more reactive species. Finally, peroxidative chain reactions initiated by reactive species that escaped enzymatic degradation are terminated by chain-breaking antioxidants, including water-soluble ascorbate, glutathione, and urate and lipid-soluble vitamin E, ubiquinone, and beta-carotene. To optimize performance, oxidative stress in high producing cows must be controlled by supplying all known antioxidant nutrients and by minimizing effects of substances that stimulate reactive oxygen metabolites.

Animals↗
PubMed1993

Corneal Langerhans cell dynamics after herpes simplex virus reactivation.

PURPOSE: The authors investigated the progressive changes in the distribution of corneal Langerhans cells (LC) after reactivation of latent herpes simplex virus type 1 (HSV-1) in mice. METHODS: After corneal inoculation of National Institutes of Health inbred mice with HSV-1 and the establishment of latency, viral reactivation was induced by irradiating the ocular surface with 250 mJ/cm2 of ultraviolet B (UV-B) light. RESULTS: Subsequent viral replication in the cornea was followed by the migration of the LC toward the paracentral and central corneal epithelium. These areas are normally devoid of LC. The number of LC in the paracentral and central regions of the eye reached a peak at day 14 post-UV-B irradiation. After UV-B irradiation of mice latently infected with HSV-1, the development of corneal stromal opacification and neovascularization closely followed the migration of LC toward the central cornea and paralleled the influx of T-cells into the corneal stroma. This pattern was not observed in irradiated uninfected mice. CONCLUSIONS: LC migrate centrally in the corneal epithelium after viral reactivation. There is a direct correlation between the number of LC in the cornea and the degree of persistent stromal opacification.

Animals↗
PubMed1992

The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team.

BACKGROUND: Chronic liver disease develops in more than half of patients with post-transfusion hepatitis C, but little is known about the natural history of community-acquired hepatitis C. METHODS: In 1985 and 1986 we identified adults with acute non-A, non-B hepatitis in four counties in the United States and followed them prospectively. We used three markers to detect hepatitis C virus (HCV) infection in stored samples of serum: antibody to HCV (anti-HCV) detected by second-generation serologic assays; HCV RNA detected by polymerase-chain-reaction assay; and antibody to HCV antigen (anti-HCVAg) detected by fluorescent-antibody-blocking assay. RESULTS: Of 130 patients with non-A, non-B hepatitis, 106 (82 percent) had HCV infection, 93 were positive for anti-HCV, and 13 were positive only for HCV RNA or anti-HCVAg. Chronic hepatitis developed in 60 (62 percent) of 97 HCV-infected patients followed for 9 to 48 months, with no relation to the risk factors for infection. Ten of the 30 patients who had liver biopsies had chronic active hepatitis. In samples collected 42 to 48 months after the onset of hepatitis, HCV RNA was detected in 12 of 13 tested patients with chronic hepatitis and in all 15 tested patients with hepatitis that had resolved. Anti-HCV persisted in all but two of the initially positive patients, for a rate of antibody loss of 0.6 per 100 person-years. CONCLUSIONS: Patients with community-acquired hepatitis C have a high rate of chronic hepatitis. HCV may be a major cause of chronic liver disease in the United States, and in most patients HCV infection seems to persist for at least several years, even in the absence of active liver disease.

Adolescent↗
PubMed1992

Reactivation of latent herpes simplex virus by excimer laser photokeratectomy.

We tested whether excimer laser photorefractive and phototherapeutic keratectomy may reactivate latent herpes simplex and cause recurrent keratitis in mice. Two of ten latently infected mice that were treated with ten excimer laser pulses to the corneal epithelium shed herpes simplex virus type 1, as did four of ten mice that were treated with 50 excimer laser pulses. Ocular shedding of herpes simplex virus was detected in four of ten mice that were treated with ethylenediamine-tetraacetic acid (EDTA) scraping of the corneal epithelium without laser keratectomy, and in six of ten mice on which combined EDTA-facilitated epithelial removal was performed followed by the application of ten excimer laser pulses. In both EDTA-treated groups, viral shedding was prolonged and 18 of 20 mice developed marked corneal opacification or neovascularization, or both. Corneal photoablation with the excimer laser may induce reactivation of latent herpes simplex virus, even in mice with clear and smooth-appearing corneas, and should be considered in the differential diagnosis of humans with persistent corneal epithelial defects after refractive or therapeutic excimer procedures.

Animals↗
PubMed1991

Addition of chloride to a prepartal diet high in cations increases 1,25-dihydroxyvitamin D response to hypocalcemia preventing milk fever.

In this study, we present evidence that cows fed highly cationic diets are less responsive to parathyroid hormone than those fed a highly anionic diet. Forty-seven Jersey cows (55 mo of age) were fed an alfalfa haylage-based diet supplemented with either anions (Cl-) or cations (Na+). Cows fed the high cationic diet suffered significantly more cases of milk fever (6 out of 23) than those fed the high anionic diet (1 out of 24). Concentrations of Ca at parturition and the first 2 d of lactation were significantly higher in cows fed the anionic diet. Secretion of parathyroid hormone in response to developing hypocalcemia was similar in cows fed either diet. Plasma hydroxyproline concentration (an index of bone Ca resorption activity) was greater in cows fed the anionic diet, suggesting better utilization of bone Ca. Plasma 1,25-dihydroxyvitamin D concentration was correlated inversely with plasma Ca and related directly to plasma parathyroid hormone in both groups of cows. However, the magnitude of the response (the amount of 1,25-dihydroxyvitamin D produced per unit increase in parathyroid hormone) was reduced greatly in cows fed the high cation diet. Because parathyroid hormone regulates both bone Ca resorption and renal 1,25-dihydroxyvitamin D production, these data suggest that prepartal diets high in cations decrease the ability of bone and renal tissues to respond to parathyroid hormone. Addition of anions to prepartal diets can reduce the excess cation balance of diets, increasing tissue response to parathyroid hormone and enabling the cow to better adapt to the Ca demands of lactation.

Animal Feed↗
PubMed1991

Effect of wet or dry corn gluten feed on nutrient digestibility and milk yield and composition.

A 22-wk trial was conducted to determine variations in nutrient concentrations of wet and dry corn gluten feed and their effect on nutrient digestibility and milk yield and composition. Holstein cows (n = 48) were blocked at parturition by parity and assigned randomly within block to one of three diets. All cows were fed a control TMR containing corn silage, ground corn, and commercial concentrate plus 2.3 kg/d of alfalfa hay during the 2-wk adjustment period. Thereafter, control diet was fed as wet or dry corn gluten feed substituted for 27% of dietary DM supplied by the control diet. Each cow received TMR for ad libitum consumption. Variations in nutrient concentrations of corn gluten feed were observed throughout the trial. The coefficient of variation was highest for ADIN, and standard deviation was highest for NDF. Intake of CP and NDF and apparent digestibility of DM were greatest when wet or dry corn gluten feed was fed. No differences in DMI, milk yield, and percentages of milk protein, lactose, or SNF were observed, but milk fat percentage was lowest when dry corn gluten feed was fed. Results indicate that corn gluten feed can replace 27% of dietary DM without altering milk yield, but new deliveries should be sampled regularly and amounts fed adjusted to compensate for varying nutrient concentrations.

Animal Feed↗
PubMed1991

A prospective analysis of inter-rater agreement between a physician and a physician's assistant in selecting QMR vocabulary terms.

We prospectively identified a cohort of 19 hospital inpatients to serve as a test set to determine the agreement between a physician and a physician's assistant in selecting and entering Quick Medical Reference (QMR) vocabulary terms for use in QMR case analysis mode. For positive findings, there was good agreement between data entered by the physician's assistant and data entered by the physician. Overall matches for positive findings were 0.66 concordance for the initial state, and 0.67 for the final state. Concordance for negative findings was substantially lower. The QMR generated differential diagnoses lists of the physician and physician's assistant were judged as similar in 14 (74%) of the 19 cases when QMR critique and assert functions were used.

Artificial Intelligence↗
PubMed1991

Luque interpeduncular segmental fixation of the lumbosacral spine.

Interpeduncular segmental fixation of the lumbar and lumbosacral spine with Luque screws and plates is becoming increasingly popular. In this retrospective study, 52 consecutive patients treated with this technique were followed for 16 to 44 months (average, 21). Indications for surgical arthrodesis included lumbar instability from degenerative disease (16 cases), spondylolisthesis (25 cases), pseudarthrosis (eight cases), fracture (two cases), and tumor (one case). Fusion with instrumentation spanned one level in nine patients, two in 38 patients, three in four patients, and four in one patient. Patients wore a rigid lumbar orthosis for an average of six months (range, two to 16). Ten complications occurred in nine patients: two superficial wound infections, four neurologic complications, three loosened screws, and one broken screw. An overall fusion rate of 96% was achieved; pseudarthrosis is suspected in one case and failed arthrodesis secondary to trauma in a second patient. At four months postoperatively, solid unions had resulted in most of the cases, as seen roentgenographically. All patients reported decreased back pain; however, one patient is addicted to narcotics. Twenty-five of the 29 patients employed were able to return to work at an average of six months postoperatively.

Adolescent↗
PubMed1990

Risk factors for acute non-A, non-B hepatitis in the United States and association with hepatitis C virus infection.

The Centers for Disease Control conducted intensive surveillance for acute non-A, non-B hepatitis in four sentinel counties over a 7-year period. Testing for antibody to hepatitis C virus was performed with the newly developed enzyme immunoassay. The incidence of non-A, non-B hepatitis remained relatively stable (average, 7.1 cases per 100,000, but there were significant changes in disease transmission patterns. The proportion of patients with a history of blood transfusion declined from 17% to 6%, but the proportion with a history of parenteral drug use increased from 21% to 42%. The proportion of patients with histories of sexual exposure (6%), household exposure (3%), occupational exposure to blood (2%), or hemodialysis (0.6%) did not change over time. Antibody to hepatitis C virus was found in 45% of patients within 6 weeks of onset of illness and in 68% of patients followed up for at least 6 months. Patients with no history of transfusions were just as likely to be positive for antibody to hepatitis C virus as patients with transfusion-associated hepatitis, indicating that hepatitis C virus is the major causative agent of all non-A, non-B hepatitis in the United States.

Acute Disease↗
PubMed1990

Structure of interleukin 1 alpha at 2.7-A resolution.

The interleukin 1 (IL-1) family of proteins has a central role in modulating immune and inflammatory responses. Two major IL-1 proteins, designated alpha (IL-1 alpha) and beta (IL-1 beta), are produced by activated macrophages and other cell types. In an effort to understand the similarities and differences in the physicochemical and functional properties of these two proteins, a program was initiated to determine their structures. Crystals of IL-1 alpha were grown, and the three-dimensional structure at 2.7-A resolution was solved. The technique of multiple-wavelength anomalous dispersion (MAD) with the selenomethionine form of IL-1 alpha was utilized in combination with a single mercury derivative to provide the starting phases. Partial refinement of the IL-1 alpha model has been performed as well. The overall structure is composed of 14 beta-strands and a 3(10) helix. The core of this structure is a capped beta-barrell that possesses 3-fold symmetry and displays a topology similar to that observed for IL-1 beta [Priestle, J. P., et al. (1988) EMBO J. 7, 339-343] and soybean trypsin inhibitor (STI) [McLachlan, A. D. (1979) J. Mol. Biol. 133, 557-563]. In this paper, the overall structure of IL-1 alpha and the nature and fidelity of the internal 3-fold symmetry are discussed. Comparisons with IL-1 beta and STI are made within these contexts.

Amino Acid Sequence↗
PubMed1990

The changing epidemiology of hepatitis B in the United States. Need for alternative vaccination strategies.

To determine trends in the incidence and epidemiology of acute hepatitis B in the United States we conducted intensive surveillance for viral hepatitis in four sentinel counties from October 1, 1981, to September 30, 1988. The overall incidence of hepatitis B remained relatively constant throughout the study period (average, 13.2 cases per 100,000 population), but disease transmission patterns changed significantly. The proportions of hepatitis B cases accounted for by homosexual activity and health care employment decreased 62% and 75%, respectively; the proportions of cases accounted for by parenteral drug use and heterosexual exposure increased 80% and 38%, respectively. The percentage of patients for whom no risk factor was identified (30% to 40%) did not change over time. These patients tended to belong to minority populations, and their socioeconomic level was low. The decline in the number of hepatitis B cases among homosexual men probably results from the modification of high-risk sexual behavior; the decline among health care workers is due mostly to hepatitis B immunization. The current strategy for prevention of hepatitis B, which targets high-risk groups for immunization, has failed to have a significant impact on the incidence of disease.

Acute Disease↗