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Biomedical subjects

R H Miller

Publications and source records attributed to R H Miller.

At least 181 records · Page 10Linked to original sources

Nucleotide sequence and mutation rate of the H strain of hepatitis C virus.

Patient H is an American patient who was infected with hepatitis C virus (HCV) in 1977. The patient became chronically infected and has remained so for the past 13 years. In this study, we compared the nucleotide and predicted amino acid sequences of the HCV genome obtained from plasma collected in 1977 with that collected in 1990. We find that the two HCV isolates differ at 123 of the 4923 (2.50%) nucleotides sequenced. We estimate that the mutation rate of the H strain of HCV is approximately 1.92 x 10(-3) base substitutions per genome site per year. The nucleotide changes were exclusively base substitutions and were unevenly distributed throughout the genome. A relatively high rate of change was observed in the region of the HCV genome that corresponds to the non-structural protein 1 gene region of flaviviruses, where 44 of 960 (4.6%) nucleotides were different. Within this region there was a 39-nucleotide domain in which 28.2% of the nucleotides differed between the two isolates. In contrast, relatively few nucleotide substitutions were observed in the 5' noncoding region, where only 2 of 276 (0.7%) nucleotides were different. Our results suggest that the mutation rate of the HCV genome is similar to that of other RNA viruses and that genes appear to be evolving at different rates within the virus genome.

Amino Acid Sequence↗

Immature type-1 astrocytes suppress glial scar formation, are motile and interact with blood vessels.

Previous studies have shown that immature but not mature astrocytes have the capacity to suppress glial scar formation and enhance axon outgrowth when transplanted into the adult mouse brain. We report here that glial scar formation is suppressed following transplantation of purified immature but not mature cultured type-1 rat cortical astrocytes into the adult rat brain. To examine the fate of transplanted cells, cultured astrocytes were labeled with either fluorescent beads or BSA-conjugated colloidal gold and traced after transplantation using both light and electron microscopy. While both immature and mature astrocytes survived transplantation, mature astrocytes appeared more susceptible to phagocytosis by cells of the immune system than immature astrocytes. Furthermore, while mature astrocytes were restricted to the region of the implant, immature astrocytes migrated into the surrounding CNS and became closely associated with host blood vessels. Such blood vessels were impermeable to the diffusion of systematically applied Evans blue dye. To determine whether immature astrocytes were intrinsically more motile than mature astrocytes, their rate of translocation was compared in vitro. Immature astrocytes translocated more than twice as fast as mature astrocytes. This ability of immature astrocytes to translocate throughout the host CNS and become associated with blood vessels may be a major factor in their ability to suppress glial scar formation in the adult animal.

Animals↗

Usefulness of d, I sotalol for suppression of chronic ventricular arrhythmias.

Sotalol is a unique beta-blocking drug, possessing significant class III antiarrhythmic activity. The efficacy and safety of 2 doses of sotalol (320 and 640 mg/day, divided in 2 doses) were compared to placebo in a 6-week randomized, double-blind, multicenter study of 114 patients with chronic ventricular premature complexes (VPCs) at frequencies of greater than or equal to 30/hour. Sotalol significantly reduced VPCs in patients receiving both low (n = 38) and high (n = 39) doses, compared with patients (n = 37) receiving placebo (by 75 and 88%, respectively, vs 10%; p less than 0.001, sotalol vs placebo; p less than 0.05, high vs low dose). The individual efficacy criterion (greater than or equal to 75% VPC reduction) was achieved in 34% of low-dose and 71% of high-dose sotalol versus 6% of placebo-treated patients (p less than 0.003, sotalol vs placebo; p = 0.007, high vs low dose). Repetitive beats were suppressed 25% by placebo (difference not significant), 80% by low-dose (p less than 0.003) and 78% by high-dose sotalol (p less than 0.005). Sotalol decreased heart rate (by 24 to 25%, p less than 0.001) and increased PR (by 4 to 6%, p less than 0.001) and corrected JT intervals (by 12 to 13%, p less than 0.001), but did not change ejection fraction. Proarrhythmia (nonfatal) occurred in 3 sotalol and in 2 placebo patients. Nine discontinued therapy because of adverse effects (1 low dose and 8 high dose, p less than 0.02). In summary, sotalol is an efficacious antiarrhythmic drug for VPC suppression; in lower doses, it is somewhat less effective but better tolerated.

Adult↗

Pediatric sinusitis. The role of endoscopic sinus surgery in cystic fibrosis and other forms of sinonasal disease.

Functional endoscopic sinus surgery has altered the surgical treatment of sinus disease in adults. We report our experience with functional endoscopic sinus surgery in the pediatric population. Functional endoscopic sinus surgery was safe and effective and compared favorably with traditional surgery with regard to operative time, blood loss, and parental opinion.

Adolescent↗

Cost analysis of microsurgical reconstruction in the head and neck.

In a cost-conscious environment, pressure exists to justify the use of expensive techniques such as reconstructive microsurgery in head and neck patients. Therefore, the costs and effectiveness of 39 consecutive free tissue transfers in patients with head and neck defects due to neoplasia (77%), trauma (13%), or congenital causes (10%) were assessed by reviewing clinical and billing records. The technical success rate was 95% with a 29% rate of complications. Most patients returned to preoperative levels of social activities, and none admitted dissatisfaction with their results. Average cost was $27,000 per case with 16 days of hospitalization. Average cost for aerodigestive tract tumors was $37,400 with 21 days of hospitalization. Costs were directly related to the etiology of the defect and incidence of complications. Applying cost-effectiveness principles we believe that these costs are justified by the high level of patient satisfaction and enhanced quality of life.

Adult↗

Altered phosphorylation state of branched-chain 2-oxo acid dehydrogenase in a branched-chain acyltransferase deficient human fibroblast cell line.

The abundance and phosphorylation state of the polypeptide constituents of the human branched-chain 2-oxo acid dehydrogenase complex were examined in mitochondria from normal and maple syrup urine disease (MSUD) fibroblasts. In normal fibroblast mitochondria two forms of the E1 alpha subunit were observed: non-phosphorylated (E1 alpha) and phosphorylated (E1 alpha-P). About 40-50% of E1 alpha was present as E1 alpha-P. The ability to quantitate the two forms of E1 alpha permitted examination of the association between decreased capacity of oxidize branched-chain 2-oxo acids and the phosphorylation state of E1 alpha. Changes in phosphorylation state of E1 alpha were observed in MSUD fibroblasts as compared to control cells. Of particular interest was the absence of E1 alpha-P in an MSUD fibroblast line which lacked the dihydrolipoyl acyltransferase (E2) subunit of the dehydrogenase complex. In two MSUD cell lines deficient in E1 alpha, the abundance of E1 alpha-P appeared to be preferentially reduced. A fourth MSUD cell line contained normal quantities of E3, E2 and both forms of the E1 alpha polypeptide. Our results indicate that alterations in the abundance of dehydrogenase complex polypeptides in MSUD fibroblasts may influence the phosphorylation state of the E1 alpha polypeptide. They demonstrate the potential for examining simultaneously mutations which affect both the catalytic and regulatory components of the dehydrogenase complex.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

The nature of genetic variation among viruses.

Genetic variation among viruses may seem unimportant and academic--related only to pedagogical classification of things--but accurate determination of genetic relationships can have important implications, from characterizing the molecular basis of attenuation of viral vaccines to furthering knowledge about origins of viruses and even of life itself. It can even help to establish priority in the discovery of viruses when properly applied. The purpose of this brief review is to demonstrate how viruses change and what implications these changes can have on the delicate balance between the viral parasite and its host. Examples will be drawn from the hepatitis viruses when possible.

Animals↗

Effects of pyruvate and dihydroxyacetone consumption on the growth and metabolic state of obese Zucker rats.

Female obese Zucker rats (aged 6 wk) were randomly assigned to one of two control or one of three experimental-diet groups. Experimental diets contained 6% pyruvate (Pyr). 6% dihydroxyacetone (Dha), or 3% each pyruvate and dihydroxyacetone (Pyr-Dha). Control-group 1 was fed a normal diet ad libitum and control-group 2 was pair fed according to the experimental group with the lowest consumption. After 5 wk the rats receiving Pyr (357.5 +/- 12.7 g) were significantly lighter than pair-fed (385.9 +/- 4.9 g) and ad libitum-fed (404.3 +/- 10.1) controls. Resting oxygen consumption (mL.min-1.kg0.65) was significantly higher in Pyr-fed rats than in pair-fed controls and food-conversion efficiency was significantly decreased. Rats fed Pyr had a lower resting respiratory-exchange ratio than did ad libitum- and pair-fed controls (0.81 +/- 0.01 vs 0.88 +/- 0.01 and 0.87 +/- 0.01, respectively). Results suggest that pyruvate consumption reduced the weight gain and food-conversion efficiency of obese Zucker rats, in part by increasing resting metabolic rate and fatty acid oxidation.

Animals↗

Development and use of statistical survey criteria for release of materials at a former uranium processing facility.

To minimize the amount of waste and to recover reusable resources during demolition of radioactively contaminated facilities, building construction material and equipment can be efficiently and successfully surveyed using statistical methods described in this article. A radioactive contamination survey strategy aimed at reducing survey technician labor while still providing assurance that only uncontaminated material is released for salvage is discussed. Provided is the survey method, rationale, and results of three case studies where this method was successfully employed at a former uranium processing facility.

Construction Materials↗

Retropharyngeal space infection: changing trends.

Retropharyngeal space infection, now a rare entity since the introduction of modern antibiotic chemotherapy, has traditionally been described to occur in children less than 4 years of age with suppurative disorders of the ear, nose, and throat. Recent reports suggest a changing trend in the epidemiology, bacteriology, diagnostic imaging, treatment, and clinical course of this entity. However, the medical literature concerning this topic over the last two decades has consisted mainly of case reports. We reviewed eight cases of retropharyngeal space infection at our institutions over a 15-year period, representing one of the largest clinical series of its kind in the last 20 years. Patient ages ranged from 3 months to 41 years. Findings of these cases and 13 cases from similar reports obtained by a MEDLINE computer search of the recent literature were analyzed. Results show a trend toward occurrence in older age groups, polymicrobial infections, successful use of CT scan as a diagnostic modality, and fewer patients requiring incision and drainage. These findings will be discussed and contrasted to conventional wisdom.

Adolescent↗

Histiocytic non-Hodgkin's lymphoma of Waldeyer's ring.

The most common extranodal site for non-Hodgkin's lymphoma in the head and neck is the lymphoid tissue of Waldeyer's ring. Diffuse histiocytic non-Hodgkin's lymphoma is the most frequent type occurring at all head and neck extranodal sites. The rarity of histiocytic lymphoma in the areas comprising Waldeyer's ring tends to make assembly of a large series of patients for retrospective study quite difficult. Of the 804 patients treated for malignancies in Waldeyer's ring during the years 1948 to 1985 at the Charity Hospital of Louisiana, 26 had lesions classified as histiocytic non-Hodgkin's lymphoma. We present, to our knowledge, the largest series of diffuse histiocytic lymphomas involving Waldeyer's ring.

Adolescent↗

Clonal analysis of astrocyte diversity in neonatal rat spinal cord cultures.

Within the mammalian CNS, astrocytes appear to be a heterogeneous class of cells. To assay the number of distinct types of astrocytes in the rat spinal cord, cell lineage and phenotypic analyses were carried out on cultures from newborn rat spinal cord and five distinct types of astrocytes were observed. Proliferating precursors for each class of astrocyte were isolated by low density culture and shown to give rise to 5 distinct and morphologically homogeneous clusters of GFAP + astrocytes. Immunocytochemical analysis with antibodies A2B5 and Ran-2, which identify different glial lineages in optic nerve cultures, demonstrated that many clusters included both A2B5+ and A2B5- cells. Similarly, many clusters also possessed a mixture of Ran-2+ and Ran-2-cells, suggesting that in spinal cord cultures, in contrast to optic nerve cultures, expression of these antigens is regulated by individual cells rather than by cell lineage. Single-cell cloning studies, revealed that the abundance and proliferative capacity of individual astrocyte precursors differed depending on the type of astrocyte. To assay the effects of a complex cellular environment on the composition of astrocyte clones, lineage analysis was performed in complete spinal cord cultures using a replication deficient retrovirus. Although similar morphologically homogeneous clones of cells to those seen with single-cell clones were observed, the proliferative capacity and relative abundance of the distinct astrocyte precursors differed from that seen in single-cell cloning studies. Together these observations suggest that in spinal cord, gliogenesis is considerably more complex than in the optic nerve and that cultures of newborn rat spinal cord contain multiple, distinct populations of astrocytes.

Animals↗

Lipid composition of teat canal keratin collected before and after milking from Holstein and Jersey cows.

In three experiments, keratin was collected from individual teats of 40 Holstein and 20 Jersey cows immediately before and after milking. In Experiments 1 and 2, keratin collected from teats of 20 Holstein cows before milking was compared with keratin collected after milking. In Experiment 3, keratin was collected from two teats of 20 Jersey and 20 Holstein cows before milking and compared to the other two teats of the same cows after milking. All three experiments yielded similar results. In Holsteins, keratin weight before milking was 1.6 times greater than keratin weight after milking (3.1 vs. 1.9 mg). In Jerseys, only small amounts of keratin were removed during milking (3.5 mg before vs. 3.1 mg after) In Holsteins and Jerseys, neutral lipid concentration was 1.6 times greater after milking than before, suggesting that when keratin was removed during milking, only moderate amounts of lipid were removed. In Holsteins, total lipid collected per teat was similar before or after milking (59.2 vs. 48.5 micrograms). Results demonstrate that keratin collected after milking had a different lipid composition than keratin collected before milking.

Animals↗

Direct response in yield and correlated response in components accompanying selection for milk yield in Jerseys.

In 1967, the Jersey herd at the Dairy Experiment Station, Lewisburg, TN was divided into two groups on the basis of ancestry, type, and breeding value for milk as part of a project to determine effects of single trait selection for high milk yield on yield and correlated traits. Control group was mated randomly to 20 unproven young sires selected randomly from those available from breeding studs in 1967. Selection group was mated to sires selected solely on the basis of their high transmitting ability for milk. Selection sires were selected at intervals and used for 4 yr. By the end of the project (1984), lactation information was available on 672 daughters (520 selection and 152 control) of 37 bulls (17 selection and 20 control). Differences in breeding values for milk, fat, and fat test as calculated from the PTA reported in the July 1989 USDA genetic evaluations and differences in first lactation mature equivalent production of milk, fat, fat test, and 4% FCM were examined. Linear mixed models were used for all analyses and contained the fixed effects group, generation within group, and year. Sires were random, nested within group, and used to test for group differences. Groups differed for all traits. Selection was superior to control in breeding value for milk and fat (828 and 31 kg) and for production of milk, fat, and 4% FCM (1066, 42, and 1061 kg). Control was superior to selection in breeding value and production fat test (.15 and .12%). Group differences existed within generation class for all yield traits but not for fat percentage. Realized response closely matched or exceeded expected response as estimated from pedigree information.

Animals↗

Variation in milk somatic cells of heifers at first calving.

To evaluate variation in milk somatic cells, 24 primiparous cows (paired by calving date) were sampled during the first 75 d of lactation. Milk somatic cell counts were lowest at 9 to 10 wk. For differential cell counts in milk, only percentage of macrophages changed significantly during first 75 d (33% at 1 wk, 25% at 6 wk, and 34% at 11 wk). Epithelial cells were identified and ranged from 11 to 20% of total. For milk somatic cell count, variation between cows within pairs sampled contemporaneously was small (3 to 24%). However, variation between cows was much greater for the differential cell counts (46% of total for lymphocytes and 34% for epithelial cells). Of 1021 quarter foremilk samples, 26 were positive for major pathogens, but 326 were positive for various species. Prevalence of bacteria was significantly higher during first 10 d after calving. Rear quarters had significantly higher bacterial presence: 47% for left rear versus 21% for left front and 37% for right rear versus 24% for right front. Total milk somatic cell count after first calving appears to depend primarily on differences in temporary factors and is not a stable characteristic of individual cows. Proportions of the different somatic cell types in milk may vary consistently by cow in early first lactation.

Analysis of Variance↗