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Biomedical subjects

K A Miller

Publications and source records attributed to K A Miller.

At least 55 records · Page 3Linked to original sources

Neomorphic agouti mutations in obese yellow mice.

Several dominant mutations of the mouse agouti coat colour gene have pleiotropic effects that include obesity and a yellow coat. The Ay allele is caused by a large deletion that affects the expression of several contiguous genes. We show that three other obesity-associated agouti mutations, Aiy, Asy and Avy, are due to different molecular alterations that result in ubiquitous expression of a chimaeric RNA that encodes a normal agouti protein. The Aiy and Avy alleles are caused by insertion of an intracisternal A particle element 1 kb or 100 kb, respectively, upstream of agouti coding sequences. These results provide a model for other genes that show allele-specific imprinting, and demonstrate that molecular mechanisms typically responsible for activation of proto-oncogenes can also lead to other disease phenotypes.

Agouti Signaling Protein↗

Establishing an internal medicine practice: a model to determine economic feasibility.

To make informed career decisions, physicians must acquire a basic knowledge in medical management and health care economics as they evaluate the potential survival and growth of a primary care practice. Health care providers considering a specific community and local leaders and hospital administrators attempting to recruit internal medicine physicians need a method by which they can evaluate a community's potential for supporting a first or additional primary care physician. To develop this method, we conducted a detailed survey of nonmetropolitan internal medicine generalists and primary care physicians. Data collected from internal medicine physicians and their administrative staff reflected the volume of ambulatory and hospital visits and the direct and indirect costs of the practice over the previous 24 months. Using the fixed and operating cost data, as well as number of patient visits and patient care revenue, we designed a model to project the economic feasibility of establishing an internal medicine practice in a specific community. This model can be used to project the number of adult primary care visits a community can generate for a prospective physician, as well as to estimate the direct and indirect costs, annualized capital costs, gross revenue, and net income of the practice.

Adolescent↗

Influence of cell density and receptor number on the binding and distribution of cell surface epidermal growth factor receptors.

Previous studies have shown that cell density influences the expression of receptors for at least four growth factors. The data presented in this report demonstrate that epidermal growth factor receptors are regulated differently on cells expressing over a million receptors as opposed to cells expressing approximately fivefold fewer receptors. Specifically, we show that BT-20, MDA-468, and A-431-R1 cells, which exhibit a large number of epidermal growth factor receptors, preferentially down-regulate the high affinity class of these receptors as cell density increases. In addition, we show that these cells express cell surface epidermal growth factor receptors that are localized predominantly to the periphery of the cells. In contrast, A-549 and BSC-1 cells, which exhibit fewer cell surface epidermal growth factor receptors and which reduce all affinity classes of epidermal growth factor receptors as cell density increases, exhibit a diffuse cell surface distribution of these receptors at both low and high densities.

Animals↗

Long-term outcome of patients with acute myelogenous leukemia: the role of maintenance therapy, consolidation therapy and the predictive value of two in vitro assays.

Three successive strategies used to treat acute myelogenous leukemia (AML) patients who entered complete remission are compared with respect to their long term efficacy (> 5 years). Additionally, the ability of two in vitro assays to identify patients who would be long term remitters was assessed. With respect to the proportion of patients in long term remission, 5 years of maintenance therapy, intensive consolidation therapy plus 3 years of additional therapy, and 4 courses of consolidation therapy produced equivalent results with 18 to 22% of patients in remission at 7 years. Patients whose leukemia cells retained high levels of cytosine arabinoside triphosphate (araCTP) and who received maintenance therapy were less likely to experience early relapse than comparably treated patients whose leukemia cells failed to retain araCTP. The failure of leukemia cells to clone in vitro was also associated with a lower early relapse rate for patients who received maintenance therapy. Neither the ability of leukemia cells to retain araCTP nor their ability to clone in vitro were of prognostic significance for patients treated with 4 courses of intensive consolidation therapy.

Arabinofuranosylcytosine Triphosphate↗

Dressing in costume and the use of alcohol, marijuana, and other drugs by college students.

This study compared the behavior of college students who wore costumes on Halloween with those who did not. It was designed to examine the degree to which college students disguised their identity at Halloween, whether they masqueraded with a group, and whether these factors were related to alcohol and other drug use behaviors. The sample included 805 females and 448 males from two colleges. They were surveyed over a five-year period. The findings revealed significant associations between dressing in costume and drinking alcohol, and between masquerading with a group and using marijuana and other drugs. No significant associations were found between disguise of identity and the use of alcohol, marijuana, and other drugs.

Adolescent↗

Expression of fibroblast growth factor receptors by embryonal carcinoma cells and early mouse embryos.

We have previously shown that differentiation of embryonal carcinoma (EC) cells leads to both increased binding of FGF (fibroblast growth factor) and suppression of k-FGF expression. In the current study, we examined the expression of FGF receptors by EC cells, EC-derived differentiated cells and early mammalian embryos using the technique of reverse transcription-polymerase chain reaction (RT-PCR). We determined that both mouse, F9, and human, NT2/D1, EC cells as well as their differentiated counterparts express transcripts for two forms of FGF receptors, bek (bacterially expressed kinase) and flg (fms-like gene). In addition, we determined that mouse blastocysts express flg transcripts. The presence of FGF receptor transcripts in early embryos and the previous finding of FGF-related activity in medium conditioned by mouse blastocysts argue that the FGF family plays important roles during early mammalian development.

Animals↗

Moderate and severe reactions in blood donors.

During the period April 1985 to March 1986, 217 blood donors were found to have moderate (syncopal) to severe (convulsive) reactions. This population was compared to 5630 randomly selected donors who did not have reactions. An examination of demographic, physical, and societal/emotional factors was conducted to determine if any were predictive of reactions in donors. The results of the research supported the hypothesis that first-time donors have a higher frequency of reactions (1.7%) than do repeat donors (0.19%). A review of the above predictive factors documented that, with regard to demographic factors, 1) the number of prior donations was inversely proportional to the risk of reaction; 2) the gender of the donor was not predictive; and 3) youth was a predictor of reactions. An analysis of the physical factors revealed that donors who reacted were of lower weight (mean, 153.7 lb) than those who did not (mean, 166.4 lb) and that systolic blood pressure was slightly lower in the group with reactions. Although the difference was significant (3 torr), it was not thought to be significant clinically. In a comparison of a group with systolic blood pressure ranging from 80 to 100 torr and a group with systolic blood pressure ranging from 120 to 140 torr, the first group had a 70-percent higher risk of reaction. Finally, with regard to the last category of societal or emotional factors, the research demonstrates 1) that the ingestion of caffeinated beverages was associated with a reduced risk of reactions; 2) that the food intake of donors who reacred was significantly different from that of those who had no reaction, but this difference was not thought to be clinically significant; and 3) that the duration between registration and the onset of phlebotomy was directly predictive of reaction status. The research indicates that first-time donor status and several specific demographic, physical, and societal or emotional factors are predictors of donor reactions.

Adjustment Disorders↗

Dorsal penile nerve block in neonatal circumcision: chloroprocaine versus lidocaine.

Dorsal penile nerve blocking (DPNB) has been used with success in decreasing neonatal stress during circumcision. This study was designed to confirm the effectiveness of lidocaine in DPNB and to demonstrate that chloroprocaine, a shorter acting anesthetic, is as effective in blocking circumcision stress as lidocaine, but, because of its shorter plasma elimination half-life and time of onset of action, is safer. Five groups of 15 neonates were matched for weight, age, and Apgar scores and randomly assigned to a control group, one lidocaine group and three chloroprocaine groups with 2-, 3- and 5-minute postinjection waiting periods. Each neonate was subjected to six events during circumcision for which heart rate, tissue oxygenation, and cry duration were recorded. We found that, as in previous investigations, DPNB with lidocaine was effective in reducing neonatal stress, as was evident from decreased excursion from baseline heart rate, tissue oxygenation, and cry duration when compared with the control group (nonblocked). Furthermore, chloroprocaine DPNB approximates the effectiveness of lidocaine, as was evident from decreased change from baseline cry duration, tissue oxygenation, and heart rate during the most stressful events, particularly in the 3-minute wait chloroprocaine group. This more rapid onset of regional anesthesia decreases DPNB circumcision time and benefits patients, parents, and physicians.

Anesthetics, Local↗

Localization and synthesis of entactin in seminiferous tubules of the mouse.

Localization and synthesis of entactin in seminiferous tubules of mouse testis was studied by immunocytochemistry. Frozen sections from adult mice testes were subjected to anti-entactin and anti-laminin immunofluorescence. Both entactin and laminin were localized within the seminiferous tubule basement membrane and intertubular region of the testis. The addition of excess amount of entactin (but not fibronectin), premixed with anti-entactin antiserum, abolished the immunostain. Western blotting showed that a protein extract from a seminiferous tubule basement membrane preparation was recognized by anti-entactin anti-serum and comigrated with recombinant entactin. Enriched fractions of isolated primary Sertoli cells and peritubular myoid cells cultured for 6 days on a glass coverslip were able to synthesize and secrete entactin as detected by immunofluorescence microscopy. Entactin was also produced by TM3 (Leydig-like) and TM4 (Sertoli-like) cell lines as detected by both immunofluorescence and Western blotting. The distribution of entactin vs. laminin within both the cultured primary cells and the TM3 and TM4 cell lines differed. Entactin appeared mainly localized extracellularly. In contrast, laminin was mainly localized intracellularly. The above findings suggested that 1) entactin existed in the seminiferous tubule basement membrane and intertubular region of adult mice testis, co-localized with laminin; 2) entactin was synthesized by the cultured primary Sertoli cells and peritubular myoid cells and the TM3 and TM4 cell lines; 3) entactin was exocytosed with little intracellular accumulation, in contrast to an intracellular accumulation of laminin.

Animals↗

Adolescent blood pressure survey: Tulsa, Oklahoma, 1987 to 1989.

The study goals were to document the incidence of elevated blood pressure (BP) values in public high school students in Tulsa, Oklahoma; to determine whether age and sex are risk factors; and to encourage adolescents with abnormal screening BP values to seek medical care. Over a 2-year period, 5537 adolescents aged 14 to 19 years were evaluated by a mass screening method. Blood pressure was measured once between 8:30 and 9:30 AM, with the students seated. Korotkoff phases 1 and 5 were recorded as systolic and diastolic BP. According to the criteria of the Second Task Force on Hypertension in Children and Adolescents, 334 students had elevated BP values (either systolic, diastolic, or both) (an incidence of 6%). Boys had an incidence of elevated systolic BP of 5.8%, while girls had a 2.8% incidence, a difference that might have been expected because of the generally higher incidence among men in the adult population. The incidence of elevated diastolic BP was 2.8% in boys and 2.1% in girls. Statistically significant differences between boys and girls mean systolic and diastolic elevations were found, but were not considered clinically significant. An instructional mailing was done in an effort to stimulate follow-up medical care for those with abnormal findings, but its effect was not measured.

Adolescent↗

Significance of sludge and thickened wall in ultrasound evaluation of the gallbladder.

Ultrasonography is reliable in detecting the presence of cholelithiasis. Isolated findings of a thickened gallbladder wall or intraluminal sludge (echogenic bile), or both, are regarded as less reliable in the diagnosis of primary gallbladder pathologic factors and are often thought to be indicators of some other pathologic or physiologic process. A retrospective analysis of 72 patients with isolated findings of sludge or thickened wall was performed. Thickened wall remains a non-specific finding. The presence of sludge on ultrasound, when coupled with normal liver function and amylase test results and right upper quadrant pain, correlated with a significant incidence of intrinsic pathologic findings of the gallbladder.

Adolescent↗

Establishing a family practice: a model to determine economic feasibility.

The availability of adequate health care is a major concern of urban and rural citizens. Community leaders and hospital administrators attempting to recruit family physicians and health care providers considering a specific community need a method by which they can evaluate a community's potential for supporting a first or additional primary care physician. To develop this method, a detailed survey of family practices geographically dispersed throughout Oklahoma was conducted in 1989. Data collected from family physicians and their administrative staff reflected the volume of ambulatory and hospital visits and the direct and indirect costs of the practice over the previous 12 months. Using the fixed and operating cost data, as well as number of patient visits and patient care revenue, we designed a model to project the economic feasibility of establishing a family practice in a specific community. This model can be used to project the number of visits a community can generate for a prospective family physician, as well as the direct and indirect costs, gross revenue, and net income of the practice.

Adolescent↗

Tissue factor antigen in senile plaques of Alzheimer's disease.

Tissue factor (tissue thromboplastin) is the primary initiator of the extrinsic coagulation pathway, triggering a proteolytic cascade when exposed to circulating coagulation factors. In this study, the distribution of tissue factor was examined immunohistochemically in Alzheimer's disease (AD) and control brains. Tissue factor was expressed diffusely in the neocortex, but in AD there was enhanced immunoreactivity in senile plaques. Although tissue factor might potentially contribute to the formation of senile plaques, it could also accumulate in the plaques as a secondary response to other biochemical perturbations.

Adult↗

A model to determine the feasibility of a pediatric practice.

A major concern of urban and rural citizens of the United States is the availability of adequate pediatric health care in their community. Community leaders attempting to recruit health care providers and pediatricians considering locating their practice in a specific community need a method by which they can evaluate a community's potential for supporting a new primary care practice. A detailed survey was conducted in early 1988 of pediatric practices geographically dispersed throughout the state of Oklahoma. Data collected from the physicians and their administrative staff reflected the volume of office and hospital visits and practice costs over the prior 12 months. Using the capital costs and direct operating cost data with information obtained on the number of patient visits and revenue generated collected in this survey, we designed a model to project the economic feasibility of establishing a pediatric practice in a specific community. This model can be used to project the number of annual pediatric primary care visits a community can generate, the direct and indirect costs to establish and maintain a clinic, and the gross revenue and net income of the practice.

Adolescent↗

Late recurrence (33 years) of a gastric epithelioid stromal tumor (leiomyoblastoma) with low malignant potential.

A recurrence of a gastric epithelioid stromal tumor (leiomyoblastoma) 33 years after incomplete resection and radiation therapy is reported. The original tumor involved the posterior gastric wall and presented with intraperitoneal hemorrhage. A tumor recurrence was found attached to the stomach with invasion through the wall of the splenic flexure of the colon. The histologic features of the tumor had not significantly altered, except for a slight increase in mitotic rate. Neither the original tumor nor the recurrence exhibited smooth-muscle differentiation on ultrastructural or immunohistochemical examination, suggesting an origin from an undifferentiated or primitive mesenchymal cell. The term leiomyoblastoma, although established in the literature, should be reserved for epithelioid tumors in which myoid differentiation can be established. The long interval to recurrence supports the suggestion that all of these tumors have at least a low-grade malignant potential.

Adult↗