PubMed Health⌕ Search

Biomedical subjects

L D Miller

Publications and source records attributed to L D Miller.

At least 19 recordsLinked to original sources
PubMed1992

Construction of Bordetella pertussis strains that overproduce genetically inactivated pertussis toxin.

Nontoxic analogs of pertussis toxin (PT), produced by in vitro mutagenesis of the tox operon, are immunogenic and protective against infection by Bordetella pertussis. The moderate levels of PT production by B. pertussis, however, make it the limiting antigen in the formulation of multicomponent, acellular, recombinant whooping cough vaccines. To increase production of the highly detoxified Lys9Gly129 PT analog by B. pertussis, additional copies of the mutated tox operon were integrated into the bacterial chromosome at the tox or fha locus by unmarked allelic exchange. Recombinant strains produced in this way secreted elevated levels of the PT analog proportional to gene dosage. The strains were stable during 10-liter fermentations, and yields of up to 80 mg of PT analog per liter were obtained under production-scale conditions. The nontoxic analog was purified and shown to be indistinguishable from material obtained from a B. pertussis strain that contained only a single copy of the toxLys9Gly129 operon. Such strains are therefore suitable for large-scale, industrial production of an acellular whooping cough vaccine containing a genetically detoxified PT analog.

Alleles↗
PubMed1992

Characterization of early pathogenic effects after experimental infection of calves with bovine immunodeficiency-like virus.

The early pathogenic effects of bovine immunodeficiency-like virus (BIV) were studied in calves experimentally inoculated with BIV. All animals inoculated with BIV R29-infected cells seroconverted by 6 weeks postinoculation, and BIV was recoverable from each animal at 2 weeks postinoculation. However, levels of BIV replication in vivo appeared to be low. In situ hybridization studies indicated that during peak periods of viral replication in vivo, less than 0.03% of peripheral blood mononuclear cells were expressing detectable levels of viral RNA. Moreover, the levels of viral RNA in these cells in vivo were less than 1/10 the levels observed in persistently infected cells in vitro. BIV-inoculated calves had significantly higher numbers of circulating lymphocytes, and follicular hyperplasia was observed in lymph nodes, hemal nodes, and spleen. The histopathological changes observed in BIV-infected calves were similar to changes found early after infection with the immunosuppressive lentiviruses, including human immunodeficiency virus type 1.

Animals↗
PubMed1992

Mycobacterium bovis infection in North American elk (Cervus elaphus).

A naturally occurring outbreak of Mycobacterium bovis infection in captive wild elk (wapiti) in Montana was confirmed by mycobacteriologic examination. Twenty-eight of 143 elk responded to M. bovis purified protein derivative (PPD) tuberculin injected intradermally in the cervical region (SCT). The results of comparative cervical tuberculin skin tests conducted within 9 days of SCT revealed greater responses to M. bovis PPD tuberculin than to M. avium PPD tuberculin in 23 of 28 elk responding. At necropsy, several grossly visible tuberculous lesions were observed in the parenchyma of the lung, thoracic lymph nodes, and submandibular lymph nodes. Microscopic examination of appropriately stained tissue sections revealed the presence of granulomatous lesions containing acid-fast bacilli. An enzyme-linked immunosorbent assay (ELISA) was developed using a sarkosyl extract of M. bovis (antigen) and peroxidase-labeled protein G (conjugate); reactions were detected in the sera of 8 of 9 elk responding to M. bovis PPD tuberculin. Lymphocyte blastogenic assay responses were detected using M. bovis antigens in 7 of 9 elk positive on skin tests using M. bovis PPD.

Animals↗
PubMed1991

Case management with homeless mentally ill people.

This article reports the findings of a National Institute of Mental Health (NIMH) services demonstration project that used a mobile case management team to serve homeless mentally ill clients. The project examined three issues: (1) factors associated with client engagement in case management, (2) clients' perceptions of how case management affected their quality of life, and (3) significant differences between clients who remained engaged in case management services and those who discontinued involvement. The results indicated that clients who received more frequent case management contact, had higher assessed independent living skills, were older, were less likely to be substance abusers, and had experienced fewer periods of homelessness and fewer prior psychiatric hospitalizations were more likely to remain engaged in case management services. After six months of case management, clients perceived significant improvement in their global well-being, living situation, use of leisure time, finances, and physical health. Implications for providing case management services to homeless mentally ill people are presented.

Activities of Daily Living↗
PubMed1991

Metabolic changes in blood and liver during development and early treatment of experimental fatty liver and ketosis in cows.

Eighteen cows were assigned in equal numbers to three groups: control, ketosis induction by using feed restriction plus dietary 1,3-butanediol to provide ketone bodies, and glucose treatment with 484 g/d of glucose infused intraduodenally starting 7 d after beginning ketosis induction. Ketosis induction, begun at d 15 postpartum, caused ketonemia and gradual development of clinical ketosis by d 40 to 45. None of the cows in the control or glucose-treated groups became ketotic. Concentrations of NEFA in plasma of cows that became ketotic increased 3.0-, 2.6-, and 1.9-fold at 3 wk before, 2 wk before, and at ketosis, respectively, but increased nonsignificantly for glucose-treated cows. Concurrently, beta-hydroxybutyrate increased 3.5-, 5.8- and 8.4-fold for cows that became ketotic but 1.6-fold or less for glucose-treated cows. Plasma acetate increased dramatically 2 wk before ketosis. Liver glycogen content decreased to nearly 0 by 2 wk before ketosis occurred, but it increased to prepartal values in glucose-treated cows. Liver triglycerides averaged 2.0% of wet weight at d 5 for all cows but increased to 8 to 10% for about 2 wk before ketosis occurred. Microscopy of liver samples demonstrated progressive accumulation of lipid globules, which began in hepatocytes near the central vein and progressed toward the portal triad. Visible lipid content reached a peak 2 wk before ketosis. Hepatic in vitro gluconeogenic capacity decreased significantly for ketosis induction protocol cows when clinical ketosis was detected. Results indicate that experimental ketosis was preceded by metabolic abnormalities up to 2 wk before clinical ketosis occurred. The key events for onset of clinical ketosis, however, were not elucidated.

3-Hydroxybutyric Acid↗
PubMed1991

Comparison of natural transmission of bovine leukemia virus in Holstein cows of two genetic lines selected for high and average milk production.

One hundred and fifty lactating Holstein cows from 2 genetic lines selected for high and average milk production were used in the study. Sera from 6 annual herd tests were analyzed by agar-gel immunodiffusion test for antibodies to bovine leukemia virus. Odds of being seropositive were analyzed by use of stepwise and backward logistic regression procedures. Analysis within birth year revealed that estimated in odds increased by 0.19/year of age among cows of the high genetic line and by 0.43 among cows of the average genetic line. This was accompanied by a more important cohort effect among high producers than among average producers.

Animals↗
PubMed1990

Ocular manifestations of a metastatic pulmonary adenocarcinoma in a cat.

A primary pulmonary bronchogenic adenocarcinoma originating from an intramediastinal accessory lung was diagnosed in a 14.5-year-old cat. The cat had been admitted because of a cloudy right eye. Physical examination revealed a thin cat with severe iritis, aqueous flare, and a fibrin clot in the anterior chamber of the right eye. Right fundic examination revealed bullous retinal detachment superior to the optic disc. Euthanasia and necropsy were requested when FeLV test results were positive. Metastatic neoplastic cells similar to those of the primary tumor were detected in the choroid, ciliary body, and ciliary processes of the right eye. Ciliary and iridic stromal necrosis attributable to neoplastic embolization of uveal vessels had led to severe uveitis. Foci of metastasis were also in the heart, kidney, and cerebral meninges.

Adenocarcinoma↗
PubMed1990

Gene replacement in Bordetella pertussis by transformation with linear DNA.

We replaced the wild-type TOX operon of Bordetella pertussis with in vitro mutated, detoxified alleles by electroporetic transformation using unmarked linear DNA. Uptake of DNA was selected by transient ampicillin resistance and two simultaneous recombination events resulted in gene-replacement at the natural locus with no integration of heterologous DNA. TOX alleles were stable without selection and recombinant strains secreted non-toxic, fully assembled, protective pertussis toxin (PT) analogues with kinetics similar to the parental vaccine strain under production-scale fermentation conditions. Strains generated in this way are suitable for the production of recombinant whole-cell or component whooping cough vaccines that require no chemical modification of PT.

Alleles↗
PubMed1990

Lipopolysaccharide and tumor necrosis factor cause a fall in plasma concentration of lecithin: cholesterol acyltransferase in cynomolgus monkeys.

The effects of intravenous injection of lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF) were investigated in cynomolgus monkeys (Macaca fascicularis). Injection of 20 micrograms/kg of LPS from E. coli (serotype 055:B5) into cynomolgus monkeys fed a monkey chow diet caused a twofold increase in plasma triglyceride and a 25% reduction in plasma cholesterol 48 h after injection. Similar results were found with injection of recombinant human TNF at a dose of 20 micrograms/kg into chow-fed animals. However, injection of the same dose of LPS or TNF into animals fed an atherogenic diet containing saturated fat and cholesterol resulted in a 2.4- to 5-fold increase in plasma triglyceride concentrations and no significant change in plasma cholesterol levels. The fall in plasma cholesterol levels observed in chow-fed animals was associated with a 57% decrease in the cholesteryl ester (CE) content in low density lipoprotein (LDL) and 35% decrease in CE in high density lipoprotein (HDL) in LPS-injected animals, and a decrease of 33% in CE concentration of LDL and 41% in CE of HDL in animals injected with TNF. In animals fed the atherogenic diet containing saturated fat and cholesterol, the injection of both LPS and TNF also resulted in a significant decrease in the CE content of LDL and HDL. However, the plasma total cholesterol levels did not change in the animals fed saturated fat and cholesterol because the decrease in CE content of LDL and HDL was offset by an increase in very low density lipoprotein (VLDL)-CE.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Serum biochemical and hematologic values of normal and Mycobacterium bovis-infected American bison.

Hematologic and serum biochemical tests were used to monitor the health of 3 groups of bison in an experimental study of tuberculosis. Bison were randomly assigned to Mycobacterium bovis-infected, M. bovis-sensitized, and uninfected control groups. Hematologic measurements included total and differential leukocyte counts, hemoglobin (Hb), packed cell volume (PCV), fibrinogen, and plasma proteins. Biochemical tests included serum urea nitrogen, creatinine, aspartate amino transferase, sorbitol dehydrogenase, serum calcium, and serum phosphorus. There were no significant differences (P = 0.05) in any test values between groups of bison. The bison data were combined and compared to similar data of cattle. The mean values for PCV and Hb were higher than values (PCV 24-46%, Hb 8-15 g/dl) for cattle. Mycobacterium bovis-infected bison had a slight increase in the number of blood monocytes and lymphocytes when compared to the uninfected bison but were within the normal ranges for bison and cattle. Other hematologic parameters were within normal ranges reported for cattle. Creatinine levels in all bison were above the normal range (1.0-1.5 mg/dl) for cattle. Phosphorus levels for M. bovis-infected and M. bovis-sensitized bison exceeded the normal range (5.6-8.0 mg/dl) reported for cattle. The level for uninfected bison was near the upper limit of normal for cattle. Mean values for other serum biochemical tests were within the normal ranges reported for cattle.

Animals↗
PubMed1988

Assertive case management in three CMHCs: a controlled study.

At three community mental health centers (CMHCs) in Indiana, 167 clients at risk for rehospitalization were randomly assigned to experimental groups receiving assertive case management (ACM) or to control groups eligible to receive all other aftercare services at the centers. During a six-month follow-up period, experimental clients received an average of one visit a week from the ACM team, usually in the client's home or in community settings. Overall, ACM clients were rehospitalized an average of 9.2 days, significantly less than the 30.8 days for controls. In two of the three centers, significant rehospitalization differences were also found between ACM and control groups. No differences were found between groups in quality of life, medication compliance, involvement in CMHC programs, or contacts with the legal system in any of the centers. The most cost-effective center had savings of about +5,500 for each ACM client.

Adult↗
PubMed1988

Pathogenesis of Mycobacterium bovis infection in American bison.

Eighteen 12-month-old bison were randomly placed in each of 3 groups (6 animals/group): group-1 bison were exposed to live Mycobacterium bovis, group-2 bison were inoculated with killed M bovis in oil, and group-3 bison were noninfected controls. Six, 6-month-old, tuberculin test-negative calves were placed (pen contact) with group-1 bison 30 days after exposure to M bovis. Tuberculin skin test responses (caudal fold and/or comparative cervical) were detected in all bison in groups 1 and 2 at 2, 4, 6, 10, and 12 months. Tuberculin skin test responses were observed in 2 of 6 calves at 9 and 11 months after pen contact with M bovis-exposed bison (group 1). Statistically significant lymphocyte blastogenic responses to M bovis purified protein derivative were detected in group-1 bison exposed to live M bovis at 2 months after exposure (P less than 0.025). Significant ELISA reactions were detected in sera of bison at 2 months after exposure to killed M bovis in oil (P less than 0.005) and in bison 2 months after exposure to live M bovis (P less than 0.01). Significant tuberculin skin responses, ELISA reactions, or lymphocyte blastogenic responses to M bovis purified protein derivative were not observed in the 6 control bison. Grossly visible tuberculous lesions were observed in lymph nodes and/or lung collected at necropsy in 4 of 6 bison at 12 months after exposure to live M bovis. Microscopic granulomas compatible with tuberculosis were detected in 5 of 6 bison; M bovis was isolated from tissues of each of the 6 bison.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗