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Biomedical subjects

C A Miller

Publications and source records attributed to C A Miller.

At least 181 records · Page 10Linked to original sources

"De novo" aneurysms. A clinical review.

The authors present seven cases drawn from 620 consecutive cases over 30 years, in which previously undemonstrated (hence "de novo") intracranial aneurysms formed and ruptured at intervals of 3-20 years, after clipping of an initial aneurysm. Six patients were treated for rupture of a second aneurysm. All six had undergone successful treatment of a previous aneurysm; pre- and postoperative angiography showed not only successful clipping of the first aneurysm but also no incidence of multiple aneurysms. In no case was a major artery occluded at the time of the initial surgery. The implications as to natural history and the advisability of repeated arteriography in some patients with aneurysms are discussed.

Adult↗

Polymorphism of theophylline metabolism in man.

To determine whether genetic mechanisms control large interindividual variations in theophylline elimination in normal uninduced human subjects, and, if so, to test the possibility that these genetic factors are transmitted as a simple Mendelian trait, theophylline was administered to 79 unrelated adults, six sets of monozygotic twins, six sets of dizygotic twins, and six two-generation families. Thereafter, in urine collected from each subject at regular intervals for 48 h, concentrations of theophylline and its three principal metabolites were measured and rate constants of formation of these metabolites calculated. The twin study, designed to determine the relative contributions of genetic and environmental factors to large interindividual variation in theophylline elimination, revealed predominantly genetic control. Values for this genetic component, designated heritability (H1(2)), of interindividual variation in rate constants of metabolite formation were 0.61, 0.84, and 0.95 for 3-methylxanthine, 1-methyluric acid, and 1,3-dimethyluric acid, respectively. H1(2) for the overall theophylline elimination rate constant (kel) was lower (0.34). In the 79 unrelated adults, each distribution curve for rate constants of formation of each theophylline metabolite appeared to be trimodal. By contrast, the distribution curve for the overall theophylline elimination rate constant appeared to be either unimodal or bimodal. The extent of interindividual variation was fourfold for theophylline kel and 6-8-fold for the three principal metabolites. High correlations among the three rate constants in individual subjects suggested their regulation by a single shared factor. In six families carefully selected to be under near basal environmental conditions so that hepatic theophylline metabolism of each family member would be neither markedly induced nor inhibited, phenotypes for theophylline metabolite rate constants were assigned. This assignment of phenotype was made by the position of each family member's rate constant on the three distribution curves that were generated from the 79 unrelated subjects. In each family, pedigree analysis of the three phenotypes for each rate constant was consistent with their control by two alleles at a single genetic locus and with autosomal codominant transmission. Frequencies of the two alleles at each genetic locus controlling rate constants of formation of theophylline metabolites were similar (p = 0.49, 0.53, and 0.52). In the three families studied with antipyrine (AP) as well as with theophylline, AP k(el) correlated (r approximately 0.7) with each rate constant of theophylline metabolite formation, as well as with theophylline k(el). While these results are compatible with a common regulatory element in the AP and theophylline polymorphisms, other evidence suggests more than a single genetic polymorphism. This additional evidence includes different gene frequencies for the AP (p approximately 0.1) and theophylline (p approximately 0.5) polymorphisms, different genotype assignments in several families for some theophylline metabolites, different distribution curves for theophylline k(el) from those for the three theophylline metabolites in 79 unrelated subjects, and finally low correlations between AP metabolite rate constants and theophylline metabolite rate constants in the three families receiving both drugs.

Acetylation↗

Hypomelanosis of Ito: association with a chromosomal abnormality.

We report the clinical and neuroradiologic findings and the association of a chromosome abnormality, t(2,8), with a case of hypomelanosis of Ito (incontinentia pigmenti achromians). Chromosome anomalies have not been previously recognized in this genetically determined, neurocutaneous disorder.

Chromosome Aberrations↗

1984 update on the world economic crisis and the children: a United States case study.

A previously published report by these authors on the impact in the United States of recession on children's health emphasized four points: available monitoring systems are not adequate for reporting on the health of children in a timely fashion; the monitoring of maternal and child health must emphasize data on population subgroups, i.e., minorities, the poor and those hardest hit by recession; the health of poor children is adversely affected and their numbers dramatically increased during the recession of 1981-82; and comparisons between the recession of 1974-75 and that of 1981-82 suggest that expansion of health services and social support systems during the recession of 1974-75 had a cushioning effect that protected the health of children, while the curtailment of many of these programs during the 1981-82 recession is associated with adverse health trends, especially among the most vulnerable population subgroups. Data on these issues are appreciably better now than they were nine months ago, thus further validating the points made above. As with the previous report, officially released current data are abundant for economic indicators (even for early 1984), but are sparse for health status indicators. The previous report also observed that the health status of children is influenced by interdependent and interlocking factors that include economic well-being and access to health services and social supports. A new analysis attempts to unlock those relationships and measure the impact of lost welfare benefits, implemented as a result of the Omnibus Reconciliation Act of 1981 (OBRA), and the separate impact of the serious recession of 1981-82. That analysis shows the poverty rate for children increased by 7.6 percentage points between 1981 and 1982. Approximately 60 percent of the increase is attributable to the recession and 40 percent to social policy changes effected after 1981.

Child↗

The world economic crisis and the children: United States case study.

This is a review of the United States experience with issues of child health and services as they relate to changes in economic trends. No existing data systems are entirely adequate for reporting on the current health status of children. An important consideration for the monitoring of children's health in the United States is the status of subgroups such as those who are disadvantaged for reasons of poverty, discrimination or geographic isolation. Ample evidence confirms that children living in poverty suffer adverse health consequences and that the proportion of children living in poverty in the United States has increased steadily since 1975 and dramatically since 1981. Most measures of health status and health risks for children show steady improvements throughout the 1970s. The exercise of public responsibility for financing and providing essential services and supports held constant or improved during this period, especially during the recession of 1974-75. The health status and risks for children since 1981 appear to be adversely affected which must be attributed to a combination of circumstances that include serious recession, increased poverty rates for households with children and diminished health benefits and social support services. These findings suggest that when either local or widespread economic reversals are anticipated, health services and social supports for children need to be expanded rather than contracted.

Adolescent↗

Selective phosphorylation of cytosol proteins associated with transformation and restoration of normal phenotype in AKR mouse embryo fibroblasts.

Phosphoproteins from cytosol preparations of methylcholanthrene-transformed AKR mouse (AKR-MCA) cells were compared to those of their untransformed counterparts, AKR-2B cells, by two-dimensional electrophoresis following an in vitro 32P phosphorylation procedure using endogenous kinases and substrates. Five proteins were phosphorylated in the AKR-MCA cells which were not observed in the AKR-2B cells, while six proteins were phosphorylated in the untransformed cells which were not observed in the malignant cells. Treatment of AKR-MCA cells with 1% N,N-dimethylformamide induced the reversion of the malignant cells to a phenotype similar to that of untransformed AKR-2B cells (S. Chakrabarty et al., Cancer Res., 44: 2181, 1984). Treatment of AKR-MCA cells with dimethyl formamide resulted in the restoration of five of the AKR-2B-associated phosphorylations and abolished 2 of the AKR-MCA-associated phosphorylations. AKR-2B cells have been shown to respond to transforming growth factors with reversible phenotypic transformation (R. F. Tucker et al., Cancer Res., 43: 1581, 1983). Transforming growth factor treatment of AKR-2B cells induced all five of the AKR-MCA-associated phosphoproteins and the loss of all six of the AKR-2B phosphoproteins. Epidermal growth factor treatment of AKR-2B cells resulted in the phosphorylation of several proteins which were not observed in either AKR-MCA or untreated AKR-2B cells. Some, but not all, of the AKR-2B-associated phosphorylations were also observed in epidermal growth factor-treated cells. The results of these studies demonstrated qualitative and/or quantitative changes in cytosolic protein kinase-phosphatase activities between transformed and normal AKR-2B cells. Treatment of AKR-MCA cells with dimethylformamide resulted in the restoration of some of the normal AKR-2B cell-associated protein kinase-phosphatase activities.

Animals↗

Selective protein phosphorylation in heterogeneous subpopulations of human colon carcinoma cells.

Endogenous membrane and cytosolic and nuclear protein phosphorylations were compared among three well-characterized subpopulations of human colonic carcinoma cells that were originally isolated from a single human primary colon tumor. These intratumoral subpopulations of cells were found to differ significantly in their biological properties. Analysis of phosphoproteins by two-dimensional electrophoresis following 32P phosphorylation of subcellular fractions in a cell-free system or labeling intact cells in vivo revealed significant differences in the selective phosphorylation of membrane, cytosol, and nuclear proteins. The two-dimensional membrane, cytosol, and nuclear phosphoprotein profiles distinguished the three subpopulations of colonic carcinoma cells from each other. Silver-staining proteins from the three subpopulations were also compared. The two-dimensional, silver-stained electrophoretic profiles of nuclear proteins were essentially the same for all three subpopulations. The silver-stained electrophoretic profile of membrane and cytosolic proteins revealed only minor differences in the expression of polypeptides. Nevertheless, these changes could also distinguish the three subpopulations. The results of this study suggest that minor differences in the expression of cytosolic and membrane proteins exist in intratumoral subpopulations of colonic cells. However, a significantly greater degree of heterogeneity was found to be associated with post-translational modification of proteins by phosphorylation and/or dephosphorylation. These modifications could play an important role in determining the expression of different biological properties among subpopulations of malignant cells.

Cell Line↗

Detection of only JH III in several life-stages of Nauphoeta cinerea and Thermobia domestica.

We have conducted a reinvestigation into both the identification and quantification of juvenile hormone (JH) from several developmental stages of the cockroach, Nauphoeta cinerea, and the firebrat, Thermobia domestica, using a gas chromatography-mass spectrometric (GC/MS) method. We detected only JH III in these animals in contrast to prior studies in which JH I, II, and/or III had been reported using a different scheme relying on HPLC purification and subsequent GC/MS analysis under chemical ionization (CI) conditions. Very high levels (approximately 800 ng/g) of JH III were found in N. cinerea embryos at stages after dorsal closure whereas first stadium nymphs and female penultimate stadium nymphs contained only low levels (approximately 1 ng/g and approximately 7 ng/ml respectively); in adult females at the stage of rapid oocyte growth approximately 150 ng JH III per ml of hemolymph was measured. T. domestica nymphs and egg laying adults contained only low levels (approximately 1 ng/g) of JH III. The results emphasize the caution which must be used in interpreting results of procedures for analysis of JH at parts-per-billion levels, and also enforce prior observations that the higher JH homologs are not present except in the Lepidoptera.

Animals↗

Characterization of human granular lymphocyte subpopulations expressing HNK-1 (Leu-7) and Leu-11 antigens in the blood and lymphoid tissues from fetuses, neonates and adults.

Three subpopulations of human granular lymphocytes from blood and lymphoid tissues were characterized using combinations of the monoclonal antibodies (mAb) HNK-1 (Leu-7), Leu-11 and VEP13. Each subpopulation was confirmed to possess natural killer (NK) cell functional capability, but a different level of cytotoxic efficiency (HNK-1+leu-11- less than HNK-1+Leu-11+ less than HNK-1-Leu-11+). In adult from 23 healthy donors, the subpopulations with HNK-1+Leu-11-, HNK-1+Leu-11+ and HNK-1-Leu-11+ phenotypes comprised 4.7 +/- 3.0, 8.0 +/- 6.4 and 3.9 +/- 3.5% of mononuclear cells, respectively. Despite their distinct surface marker phenotypes and NK functional ability, all 3 subpopulations exhibited granular lymphocyte morphology. One of these subpopulations, HNK-1+Leu-11-, also expressed the pan-T cell antigen Leu-4. Different patterns were observed in fetal bone marrow and cord blood, where the vast majority of HNK-1+ cells lacked the Leu-11 antigen (HNK-1+Leu-11+ cells). The HNK-1 antigen was not expressed on granulocytes and their precursors, whereas both Leu-11 and VEP13 antigens were expressed on these myeloid cells from fetal bone marrow and cord blood as well as adult bone marrow and spleen. Cell lines of granular lymphocytes cultured in the presence of interleukin 2 all possessed the HNK-1+Leu-4+ phenotype and NK functional capability but lacked the Leu-11 and VEP13 antigens on their surface after 15 days of culture. Although granular lymphocytes expressing the Fc receptors reacting with the mAb Leu-11 and VEP13, are the most functionally active NK cells, the HNK-1+ subpopulation lacking the Leu-11 and VEP13 antigens appears to be an important population (possibly an immature form of granular lymphocytes) for delineating the cell lineage(s) and differentiation of human granular lymphocytes. Although none of the currently available mAb react both inclusively and exclusively with human granular lymphocytes, the combination usage of these antibodies permits a more precise and comprehensive analysis of these subsets.

Adolescent↗

Structural and functional analysis of the par region of the pSC 10 1 plasmid.

Three distinct segments (the partition-related, or PR segments) within the 370 bp par region of pSC101 have been shown by deletion analysis to be involved in partitioning of the plasmid to daughter cells. The two lateral segments are direct repeats, each of which potentially can pair with an inverted repeat located between them to form a hairpin-loop structure. Deletion of either lateral segment, together with the middle segment, results in plasmid instability (the Par- phenotype). Deletion of one PR segment yields a stable plasmid that nevertheless shows reduced ability to compete with a coexisting wild-type derivative of the same replicon (the Cmp- phenotype). Deletion of all three segments results in a rate of plasmid loss far in excess of that predicted from the observed copy number of the plasmid. Analysis of the segregation properties of these mutants and of temperature-sensitive and high copy number derivatives of the pSC101 replicon suggests a model in which the par function allows the nonreplicating plasmids of the intracellular pool to be counted as individual molecules, and to be distributed evenly to daughter cells. In the absence of par, the multicopy pool of plasmids behaves as a single segregation unit.

Base Composition↗

Isolation and primary structure of two peptides with cardioacceleratory and hyperglycemic activity from the corpora cardiaca of Periplaneta americana.

Two cardioacceleratory peptides from the corpora cardiaca of Periplaneta americana have been purified by gel filtration and reversed-phase liquid chromatography, Based on analysis of the intact factors and their chymotryptic fragments, we have assigned the primary structure of these octapeptides as pGlu-Val-Asn-Phe-Ser-Pro-Asn-Trp-NH2, designated periplanetin CC-1, and pGlu-Leu-Thr-Phe-Thr-Pro-Asn-Trp-NH2, designated periplanetin CC-2. They represent new members of a family of invertebrate peptides that includes locust adipokinetic hormone and crustacean red-pigment concentrating hormone. Both peptides show adipokinetic activity in grasshoppers and hyperglycemic activity in cockroaches. One of these peptides (CC-2) has provocative sequence homology with the NH2-terminal portion of glucagon.

Amino Acid Sequence↗

Differences in use of health services by children according to race. Relative importance of cultural and system-related factors.

Black children make substantially less use of health services than do their white counterparts, despite their demonstrably poorer health status. This relationship is true regardless of income. Various authors have suggested that such differences are due to system-related barriers to access to care by black children. Alternatively, others have noted that blacks have cultural patterns related to health and illness, and these culturally determined beliefs and behaviors may account for the observed differences. The present study compared use of health services by black and white children within a system of care that has sought to decrease barriers to access to care by black children. Within this system, black and white children used health services in a similar fashion, suggesting that system-related factors that assure equity of access to health services may be more important than client-related cultural factors, or that these cultural factors may be overcome.

Adolescent↗

Reconstruction of the skull base.

Tumor surgery of the skull base has been increasingly undertaken in recent years. This report involves a series of 18 consecutive patients who have undergone 22 operations at Ohio State University from July 1980 to January 1983 for removal of tumors either adjacent to or through the skull base. A variety of reconstructive techniques such as pericranial flaps, muscle flaps, temporalis fascial grafts, split-rib grafts, fat grafts, and bone grafts have been found to be reliable. This series also included the successful use of a temporalis myocutaneous flap. The conclusion of this study is that these techniques provide a safe approach to the resection of tumors involving the base of skull.

Adenocarcinoma↗

Pediatric neck injuries. A clinical study.

This review of pediatric neck injuries includes patients admitted to Children's Hospital of Columbus, Ohio, during the period 1969 to 1979. The 122 patients with neck injuries constituted 1.4% of the total neurosurgical admissions during this time. Forty-eight patients had cervical strains; 74 had involvement of the spinal column; and 27 had neurological deficits. The injuries reached their peak incidence during the summer months, with motor-vehicle accidents accounting for 31%, diving injuries and falls from a height 20% each, football injuries 8%, other sports 11%, and miscellaneous 10%. There is a clear division of patients into a group aged 8 years or less with exclusively upper cervical injuries, and an older group with pancervical injuries. In the younger children, the injuries involved soft tissue (subluxation was seen more frequently than fracture), and tended to occur through subchondral growth plates, with a more reliable union than similar bone injuries. In the older children, the pattern and etiology of injury are the same as in adults. The entire cervical axis is at risk, and there is a tendency to fracture bone rather than cartilaginous structures.

Adolescent↗