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Biomedical subjects

R H Miller

Publications and source records attributed to R H Miller.

At least 127 records · Page 7Linked to original sources
PubMed1994

Correlation of vitamin K-dependent clotting factors with cholesterol and triglycerides in healthy young adults.

The plasma level of factor VII activity was a risk factor for the development of ischemic heart disease (IHD) in a prospective epidemiological study of hemostatic factors. We have previously reported significant correlations between factor VII clotting activity or antigen and lipid fractions in a group of 132 young men (< 30 years old) at low risk for IHD and concluded that control of the plasma factor VII level may be linked to lipid metabolism in normal male physiology. Because factor VII is one of four vitamin K-dependent procoagulant proteins, we hypothesized that plasma levels of all these proteins would be similarly controlled in normal physiology. In an extension of this study, we have measured two additional vitamin K-dependent clotting factors (prothrombin [factor II] and factor X activity), as well as factor VII activity and antigen and fasting serum lipid fractions in healthy young men and women (< 30 years old) at low risk for IHD. In the women, we found significant positive correlations of factor VII antigen with total or HDL cholesterol and of prothrombin or factor X with total or LDL cholesterol. In the men, factor VII activity or antigen correlated with total cholesterol, triglycerides, HDL cholesterol, or LDL cholesterol; prothrombin or factor X correlated with total cholesterol, triglycerides, or LDL cholesterol. In contrast, we found no significant correlations of fibrinogen with any of the lipid fractions in our groups of men or women. Our data support the hypothesis that control of the levels of the vitamin K-dependent procoagulant proteins is linked to lipid metabolism in the normal physiology of both men and women.

Adult↗
PubMed1994

Regulation of oligodendrocyte differentiation: a role for retinoic acid in the spinal cord.

During development, oligodendrocyte precursors undergo sequential stages of differentiation characterized by expression of distinct cell surface properties and proliferative responses. Although both PDGF and bFGF are mitogenic for these cells, the factors that regulate the progression of oligodendrocyte precursors through their differentiative program remain unclear. One factor present in the embryonic spinal cord that may regulate differentiation of oligodendrocyte precursors is retinoic acid. Here we show that retinoic acid inhibits the maturation of embryonic spinal cord oligodendrocyte precursors in vitro at an early, highly motile stage of differentiation, characterized by the expression of A2B5 immunoreactivity. Basic FGF acts both as a mitogen and an inhibitor of spinal cord oligodendrocyte precursor maturation, but at a significantly later stage of differentiation, characterized by the expression of O4 immunoreactivity. In the presence of RA both the mitogenic and differentiation inhibiting effects of bFGF are abolished, consistent with RA acting as an early regulator of oligodendrocyte differentiation. During embryonic development, oligodendrocyte precursors arise initially from a distinct group of cells at the ventral ventricular zone of the spinal cord. Myelination of the entire spinal cord is dependent on the migration of immature precursor cells to peripheral developing white matter. Since the embryonic spinal cord has the capacity to release relatively high levels of retinoids, we propose that RA inhibits oligodendrocyte differentiation during early embryonic development permitting their dispersal throughout the entire spinal cord.

Animals↗
PubMed1994

Influence of pulsationless milking on teat canal keratin and mastitis.

Twenty-four Holstein cows, producing at least 21 kg of milk/d, were used in two replicate experiments to determine the effect of presence or absence of pulsation on loss of teat canal keratin during machine milking. Left quarters were milked without pulsation and right quarters were milked with pulsation. On d 0 and 10, keratin was collected from one left and from one right teat canal of each cow prior to milking and from the remaining two teat canals after milking. Milk was collected for assessment of SCC and bacteriological status on d 0 and approximately every 3 d until d 18. Quantity of keratin recovered before milking on d 10 did not differ between teats milked with or without pulsation, but loss of keratin because of milking was greater from teats milked with pulsation. By d 7, 30% (12 of 43) of quarters milked without pulsation had become infected, but no (0 of 47) quarters milked with pulsation were infected. By d 14 to 16, new infections had increased to 68% (28 of 41) of quarters milked without pulsation and 2% (1 of 43) in quarters milked with pulsation; mean SCC in pulsationless quarters increased sevenfold relative to pulsation quarters. Protein and water content of keratin did not differ because of treatment, and changes in lipid composition were minor. Histological analysis of the teats of 4 cows indicated that the mean diameter of the teat canal, within 2 h after milking, was greater without pulsation than with pulsation (680 vs. 483 microns).

Animals↗
PubMed1994

Deaths and disposals in lines selected for milk yield and control lines of Jersey cattle.

Deaths and disposals of Jerseys from birth to 120 d of first lactation during a selection experiment were summarized. Cows were randomly assigned to the high milk yield and young sire lines. Service sires were bulls with the highest estimated breeding value for milk for the high milk line and a collection of all young unproven bulls available in AI in 1967. Cattle that were unsuitable for conditions of normal herd management were candidates for culling. Culling of uncalved heifers and of lactating cows was also permitted to maintain group sizes. Culling for herd reduction was random. Culling for low milk yield was permitted after cows reached 120 d of first lactation. Death and disposal data were analyzed through 120 d of first lactation. By 120 d of first lactation, 29.6% of females born to the young sire line had died or been involuntarily removed compared with 29.8% born to the high milk yield line. Deaths were 54.8% of total losses for the high milk yield line compared with 58.4% for the young sire line. Stillbirths were a larger proportion of total losses for animals in the high milk yield line (21.4%) than for those in the young sire line (15.3%). The most frequent cause of death was scours and pneumonia during 1st mo of life for animals in both lines. Selection of sires for high milk yield does not decrease total survival rates through the early first lactation.

Animal Husbandry↗
PubMed1994

Glial cell heterogeneity in the mammalian spinal cord.

The vertebrate spinal cord is comprised of a complex array of different populations of neurons and axon tracts. Recent studies suggest that this complex neuronal cytoarchitecture is complemented by a similarly complex glial cytoarchitecture. Cultures of neonatal rat spinal cord contain multiple different classes of astrocytes. These distinct classes of astrocytes have particular morphologies and arise from separate precursors that proliferate in response to different mitogens. It seems likely that the individual classes of astrocytes will have regional localization and will be involved in specific functions in the intact spinal cord. In contrast to the significant diversity seen among astrocytes, spinal cord oligodendrocytes in the embryonic animal appear to be a relatively homogenous population of cells that proliferates in response to known growth factors at particular stages of maturation. An important future challenge in glial cell biology is to define clearly the functional roles of individual populations of astrocytes in the developing adult, and injured spinal cord. Such information may ultimately lead to the ability to modulate astrocytic function at a cellular level during aberrant development and following injury to the adult spinal cord.

Aging↗
PubMed1994

Diagnosis and management of primary hyperparathyroidism.

Since the introduction of biochemical autoanalyzers primary hyperparathyroidism is no longer an uncommon diagnosis. The diagnosis is established by clinical evaluation and persistently elevated serum calcium and parathyroid hormone levels. Management of symptomatic primary hyperparathyroidism is relatively straightforward and the disease can be effectively treated with surgery. Most surgeons agree patients without previous neck operations need not undergo preoperative localization studies; in addition, they feel that bilateral neck exploration should be the rule. However, the management of primary hyperparathyroidism in the asymptomatic patient is controversial. In this paper the natural history, diagnosis, and management of primary hyperparathyroidism is reviewed.

Combined Modality Therapy↗
PubMed1994

Effect of in vitro and in vivo migration of bovine neutrophils on binding and expression of Fc receptors for IgG2 and IgM.

Binding of endogenous and exogenous homologous IgG2 and IgM to bovine neutrophils before and after in vitro migration through micropore filters, and in vivo migration through mammary tissues after intramammary injection of endotoxin was evaluated by use of flow cytometry. Immunoglobulin binding to neutrophils at 4 and 37 C was also evaluated. Before and after in vitro migration, neutrophils with endogenously bound IgG2 and IgM averaged 1 and 2% and 23 and 7%, respectively. Before and after in vivo migration, IgG2 and IgM binding averaged 1 and 7% and 26 and 15%, respectively. Before and after in vitro migration, binding of purified IgG2 and IgM averaged 75 and 67% and 8 and 24%, respectively. Before and after in vivo migration, percentage of neutrophils binding purified IgG2 and IgM averaged 92 and 98% and 54 and 70%, respectively. When serum was used as a source of exogenous immunoglobulins, binding of total IgG after in vitro migration increased from 5% to 28% and of IgM from 4% to 20%. After in vivo migration, binding increased from 21% to 47% and from 24% to 56%, respectively. Exogenous binding of IgG2 at 4 and 37 C averaged 75 and 84%, and binding of IgM averaged 8% at either temperature. Endogenous IgG2 was unaffected by temperature, however, binding of IgM decreased from 23% at 4 C to 2% at 37 C. These data indicate that endogenous binding was higher for IgM before migration than after migration, in vitro and in vivo. Furthermore, migration in vivo through cellular matrices induced receptor upregulation for IgG and IgM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Mutant woodchuck hepatitis virus genomes from virions resemble rearranged hepadnaviral integrants in hepatocellular carcinoma.

Although hepadnaviruses are implicated in the etiology of hepatocellular carcinoma, the pathogenic mechanisms involved remain uncertain. Clonally propagated integrations of hepadnaviral DNA into cellular DNA can be demonstrated in most virally induced hepatocellular carcinomas. Integration occurs at random sites in cellular DNA, but the highly preferred sites in viral DNA are adjacent to the directly repeated sequence DR1, less often DR2, or in the cohesive overlap region. Integrants invariably contain simple deletions or complex rearrangements that have been thought to occur after integration. We report here the detection of mutant woodchuck hepatitis virus (WHV) genomes cloned from virions in serum that are strikingly similar to the rearranged hepadnaviral genomes found previously as integrated sequences in cellular DNA. Of 102 cloned genomes studied, 2 had large inverted duplications, 1 a 219-nucleotide direct duplication, and 1 a 219-nucleotide deletion. Virus-virus DNA junctions occurred either adjacent to DR1 or DR2 or in the cohesive overlap region at preferred topoisomerase I cleavage sites. Since these sites are located in the single-stranded regions of the genome, cleavage by topoisomerase I would produce linear molecules that would be expected to be highly recombinogenic since this enzyme, possessing nicking and ligating activities, would remain covalently attached. Sucrose density gradient centrifugation coupled with polymerase chain reaction studies confirmed that the mutant WHV DNA forms resided in virions and did not represent free viral DNA released from infected cells or were unlikely to be an artifact of the cloning process. Thus, the finding in virions of mutant WHV DNA similar to WHV DNA integrated into cellular DNA suggests that the processes of mutation and integration are linked in some instances. Furthermore, the mutant genomes that are preferentially integrated into cellular DNA may have an etiologic role in hepatocarcinogenesis.

Animals↗
PubMed1993

At least 12 genotypes of hepatitis C virus predicted by sequence analysis of the putative E1 gene of isolates collected worldwide.

In a previous study we sequenced the 5' noncoding (NC) region of 44 isolates of hepatitis C virus (HCV) and identified heterogeneous domains that provided evidence for additional genetic groups of HCV not previously recognized. In this study we have determined the complete nucleotide sequence of the putative envelope 1 (E1) gene in 51 HCV isolates from around the world and found that they could be grouped into at least 12 distinct genotypes. The E1 gene sequence of 8 of these genotypes has not been reported previously. Although the genetic relatedness of HCV isolates determined by the previous analysis of the 5' NC region predicted the relationships observed in the E1 gene, analysis of the 5' NC sequence alone did not accurately predict all HCV genotypes. The nucleotide and amino acid sequence identities of the E1 gene among HCV isolates of the same genotype were in the range of 88.0-99.1% and 89.1-98.4%, respectively, whereas those of HCV isolates of different genotypes were in the range of 53.5-78.6% and 49.0-82.8%, respectively. The latter differences are similar to those found when comparing the envelope gene sequences of the various serotypes of the related flaviviruses as well as other RNA viruses. We found that some genotypes of HCV were widely distributed around the world, whereas others were identified only in discreet geographical regions. Four genotypes were identified exclusively in Africa and comprised the majority of HCV isolates on that continent. The E1 gene was exactly 576 nucleotides in length in all 51 HCV isolates with no in-frame stop codons. Analysis of the predicted E1 protein identified several conserved domains that may be important for maintaining its biological function: (i) eight invariant cysteine residues, (ii) three potential N-linked glycosylation sites, (iii) a domain of nine amino acids (GHRMAWDMM), and (iv) an amino acid doublet (GV) near the putative cleavage site at the C terminus of the protein. In conclusion, the discovery of at least 12 genotypes of HCV has important implications for HCV diagnosis and vaccine development.

Amino Acid Sequence↗
PubMed1993

Markedly prolonged incubation period of hepatitis B in a chimpanzee passively immunized with a human monoclonal antibody to the a determinant of hepatitis B surface antigen.

The protective efficacy of a human monoclonal antibody directed against the a determinant of hepatitis B virus (HBV) surface antigen was studied in a chimpanzee. A single high dose of 5 mg/kg (body weight) of monoclonal antibody SDZ OST 577 was intravenously administered to a chimpanzee, followed by intravenous challenge with 10(3.5) chimpanzee infectious doses of a wild-type HBV, the MS-2 strain (ayw subtype). The passively acquired antibody to HBV surface antigen could be detected for 40 weeks. Serum HBV DNA tested by a "nested" polymerase chain reaction assay was negative through the 36th week after virus challenge but became positive by the 38th week. The chimpanzee subsequently developed acute hepatitis B approximately 1 year after challenge. The nucleotide sequence of the a determinant of the surface gene of the replicated virus was identical with that of the inoculated wild-type virus. Thus, a human monoclonal antibody directed against the a determinant of HBV surface antigen delayed but did not prevent experimental infection of HBV and hepatitis in the chimpanzee. Our results indicate an incomplete ability of this antibody to protect against HBV infection in vivo after a single infusion.

Amino Acid Sequence↗
PubMed1993

Hepatitis C virus RNA in southern African blacks with hepatocellular carcinoma.

We used a sensitive and specific cDNA polymerase chain reaction assay to detect hepatitis C virus (HCV) RNA in serum samples from 128 unselected southern African Blacks with hepatocellular carcinoma (HCC) and found HCV RNA in 26 (20.3%) of these patients. Antibodies to HCV (anti-HCV) were detected in 59 patients (46.1%) with a first-generation ELISA test, and only 19 of these patients were HCV RNA-positive. Anti-HCV was detected in 25 patients (19.5%) with a second-generation ELISA test, and 17 of these patients were HCV RNA-positive. Among the second-generation ELISA- and HCV RNA-positive patients, 14 were anti-HCV positive, 2 were indeterminate, and 1 was anti-HCV negative in a second-generation recombinant immunoblot assay, whereas all patients who were second-generation ELISA positive, but HCV RNA negative, were anti-HCV negative in this immunoblot assay. A total of 5 patients were negative in both ELISA tests but were HCV RNA positive. Seventy-one patients (55.5%) had evidence of a current HBV infection, 50 (39.1%) had evidence of a previous infection, and 7 (5.5%) had no evidence of a current or previous HBV infection. The prevalence of current HBV infection was significantly lower in patients who were positive for HCV RNA than in those who were negative (P = 0.001). This difference was not dependent on sex, age, or geographical location of the patients. The mean age of HCC patients positive for HCV RNA (52.3 years) was significantly higher (P < 0.001) than that of negative patients (40.3 years), and the difference was not dependent on HBV status or geographical location. Patients positive for HCV RNA were more likely to be urban than were negative patients. Thus, a significant number of southern African Blacks with HCC had a current HCV infection but not a current HBV infection, further suggesting that infection with HCV plays a role, albeit minor, in the development of HCC in this population.

Adult↗
PubMed1993

Water spout injection into the neck.

Work-related high-pressure injection injuries to the extremities are well publicized, and treatment plans are well established. However, water spout injection injuries to the oral cavity are rare. To our knowledge, there have been no reports of water injection injuries in the oral cavity. We describe one case in which a child suffered an intraoral low-pressure injury to the floor of the mouth, which resulted in water dissection to the neck and subcutaneous tissues. Management and eventual outcome are detailed.

Anti-Bacterial Agents↗
PubMed1993

A cell surface antigen expressed by astrocytes and their precursors.

Increasing evidence suggests that astrocytes of the mammalian CNS are a heterogeneous population of cells that express a number of common characteristics. In most cases, astrocytes or their precursors contain a class of intermediate filaments, composed in large part of glial fibrillary acidic protein (GFAP). While the expression of GFAP immunoreactivity is a specific characteristic of astrocytes in the vertebrate CNS, not all astrocytes contain detectable levels of glial filaments, particularly during early development. We have isolated a monoclonal antibody termed 7B11 which binds to the surface of astrocytes and glial precursors, but not to other major types of neural cells. The 7B11 antigen is expressed by astrocytes in the adult CNS in vivo and in cultures of developing CNS tissue, but not on cells of the peripheral nervous system. During early development, 7B11 immunoreactivity appears prior to the expression of GFAP and is retained as punctate staining on the surface of most classes of astrocytes. During CNS maturation, however, 7B11 immunoreactivity is lost from the surface of Bergmann glia in the cerebellum, suggesting that differentiative events lead to functionally and antigenically distinct classes of CNS glial cells. In the adult spinal cord, biochemical analysis suggests that the epitope recognized by 7B11 is associated with a group of polypeptides of apparent molecular weights 200-160, 140, and 92 kD. The cellular distribution of 7B11 expression suggests that astrocytes and their precursors share a distinct cell surface antigenic property and that the expression of 7B11 immunoreactivity may be a useful operational marker for astrocytes in the absence of detectable GFAP expression.

Aging↗
PubMed1993

The complete nucleotide sequence of a pre-core mutant of hepatitis B virus implicated in fulminant hepatitis and its biological characterization in chimpanzees.

Hepatitis B virus (HBV) with an in-frame stop codon within the pre-core region of the virus genome caused fulminant hepatitis in two individuals. Serum from a chronically infected patient who was the source of the virus was inoculated into three chimpanzees at dilutions of 10(-1), 10(-3), and 10(-7). All three chimpanzees developed acute hepatitis B with relatively high peak values of liver enzymes in their serum. The complete nucleotide sequence of virus DNA recovered from the chimpanzee serum by enzymatic amplification was identical with that from the human serum. By comparing the sequence of this strain (HT) with that of 32 published HBV genomes, changes in nucleotides and predicted amino acids that were rarely or never found in other HBV isolates were identified. Thirteen such nucleotides were found within the cis-acting regulatory elements, of which 6 were within the enhancer II-core promoter region. Twenty-four rare or unique changes in amino acids were found in open reading frames, of which 15 occurred in the region that spanned the 3' half of the X gene, through the pre-core/core gene, to the 5' end of the polymerase gene. Thus, an HBV pre-core stop mutant implicated in fulminant hepatitis is highly infectious, induces severe hepatitis in chimpanzees, and possesses significant genetic variation from reported HBV isolates.

Animals↗
PubMed1993

Importance of the polymerase chain reaction in the study of hepatitis C virus infection.

Recently, the principal etiological agent of parenterally transmitted non-A, non-B hepatitis was molecularly cloned from the plasma of an experimentally infected chimpanzee and has been named hepatitis C virus. Determination of the complete nucleotide sequence of the hepatitis C virus genome was a crucial step in preparing the way for future study of this medically important human pathogen. Due to the very low concentration of virus in serum, amplification of viral RNA sequences by reverse transcription and polymerase chain reaction is the only practical method currently available for demonstrating viremia in patients with hepatitis C virus infection. This review examines the pivotal role of the polymerase chain reaction in understanding the biology of hepatitis C virus.

Acute Disease↗