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D G Miller

Publications and source records attributed to D G Miller.

At least 37 records · Page 2Linked to original sources
PubMed1994

Cell-surface receptors for gibbon ape leukemia virus and amphotropic murine retrovirus are inducible sodium-dependent phosphate symporters.

Cell surface receptors for gibbon ape leukemia virus (Glvr-1) and murine amphotropic retrovirus (Ram-1) are distinct but related proteins having multiple membrane-spanning regions. Distant homology with a putative phosphate permease of Neurospora crassa suggested that these receptors might serve transport functions. By expression in Xenopus laevis oocytes and in mammalian cells, we have identified Glvr-1 and Ram-1 as sodium-dependent phosphate symporters. Two-electrode voltage-clamp analysis indicates net cation influx, suggesting that phosphate is transported with excess sodium ions. Phosphate uptake was reduced by > 50% in mouse fibroblasts expressing amphotropic envelope glycoprotein, which binds to Ram-1, indicating that Ram-1 is a major phosphate transporter in these cells. RNA analysis shows wide but distinct tissue distributions, with Glvr-1 expression being highest in bone marrow and Ram-1 in heart. Overexpression of Ram-1 severely repressed Glvr-1 synthesis in fibroblasts, suggesting that transporter expression may be controlled by net phosphate accumulation. Accordingly, depletion of extracellular phosphate increased Ram-1 and Glvr-1 expression 3- to 5-fold. These results suggest simple methods to modulate retroviral receptor expression, with possible applications to human gene therapy.

3T3 Cells↗
PubMed1994

Breast-gut connection: origin of chenodeoxycholic acid in breast cyst fluid.

The notion that a breast-gut connection might modulate the microenvironment of breast tissue was supported by the finding that breast cyst fluid contains bile acids that are characteristically found in the intestines. To establish that the gut, rather than circulating steroid precursors, is the source of bile acids in breast cyst fluid, we gave two patients deuterium-labelled chenodeoxycholic acid (three 200 mg doses by mouth), starting 9 days before aspiration of breast cysts. The chenodeoxycholic acid concentration of seven samples of aspirated cyst fluid ranged from 42 to 94 mumol/L. The corresponding serum concentrations of chenodeoxycholic acid on the same day were 0.8 and 2.9 mumol/L, of which the labelled compound comprised 13.0% (0.38 mumol/L) and 28.2% (0.23 mumol/L). The deuterated chenodeoxycholic acid concentrations in cyst fluid were 0.79 and 1.26 mumol/L in two samples from patient 1 and 3.22 mumol/L in patient 2; these values are equivalent to 11-17% of the serum concentrations [corrected]. This study shows that intestinal bile acids rapidly gain access to cyst fluid. Further studies should investigate the mechanisms that govern the exchange processes and the maintenance of the high cyst fluid to plasma concentration gradients, and the biological half-lives of individual constituents.

Adult↗
PubMed1994

Cloning of the cellular receptor for amphotropic murine retroviruses reveals homology to that for gibbon ape leukemia virus.

The host and tissue specificity of retrovirus infection is largely determined by specific cellular receptors that mediate virus entry. Genes encoding these receptors are widely distributed in the genome, and the receptors identified to date show no sequence similarity. We have identified the cellular receptor for amphotropic murine retroviruses, Ram-1, by screening a rat cDNA expression library introduced into amphotropic virus-resistant hamster cells. The 656-amino acid receptor is homologous to the gibbon ape leukemia virus receptor at both hydrophobic termini but is highly divergent in the central hydrophilic region. Both receptors appear to be integral membrane proteins having multiple membrane-spanning regions. Identification of this family of receptors will help define the evolutionary relationship between retroviruses and their cellular receptors.

Amino Acid Sequence↗
PubMed1994

A structured approach to voice range profile (phonetogram) analysis.

A new method to analyze voice range profiles (phonetograms) is described. The structured analysis is based on quantitatively determining the features: shape, area, and "speaking range" dynamics, without distorting the shape of phonetograms. The parameter sets describing these features are calculated independently of fundamental frequency, which makes it possible to compare phonetograms. Two phonetograms representing a normal and a pathological example are used to illustrate the proposed method. The process provides a tool for establishing normative data for specified groups.

Female↗
PubMed1994

A family of retroviruses that utilize related phosphate transporters for cell entry.

The amphotropic murine retrovirus receptor Ram-1 shows significant sequence similarity to the gibbon ape leukemia virus (GALV) receptor Glvr-1, and both of these cell surface virus receptors normally function as sodium-dependent phosphate symporters. However, Ram-1 from humans or rats does not serve as a receptor for GALV, and Glvr-1 from humans does not serve as a receptor for amphotropic virus. Here we show that the murine retrovirus 10A1 can enter cells by using either Glvr-1 or Ram-1. Furthermore, we have constructed Ram-1/Glvr-1 hybrid receptors that allow entry of both GALV and amphotropic virus. While GALV and amphotropic virus are in separate interference groups when assayed on human cells, they do interfere with each other in cells expressing the hybrid receptor. These results indicate a close functional relationship between retroviruses that utilize members of this newly defined receptor family and provide a molecular explanation for nonreciprocal and cell type-specific interference observed for some retrovirus classes.

Amino Acid Sequence↗
PubMed1994

Toward a definition of male 'head' register, passaggio, and 'cover' in western operatic singing.

For male singers in the western operatic tradition the upper part of the frequency range contains a series of pitches called passaggio, the transition between 'chest' and 'head' registers. Although there is no generally accepted objective definition of the distinction between 'head' and 'chest', the distinction is widely recognized among singers and voice teachers, as is the term 'cover', a technique often considered to be helpful in a proper execution of passaggio. On the basis of spectrographic, electroglottographic, and sub- and supraglottal pressure measurements on professional singers' 'correct' and 'incorrect' singing of passaggio, this study offers a definition of the 'chest'/'head' distinction.

Humans↗
PubMed1994

Long-term biological response of injured rat carotid artery seeded with smooth muscle cells expressing retrovirally introduced human genes.

Cultured vascular smooth muscle cells (SMCs) containing retrovirally introduced genes are a potential vehicle for gene replacement therapy. Because the cultured SMCs are selected for their ability to proliferate in vitro, it is possible that the SMCs might be permanently altered and lose their capacity to respond to growth-suppressing conditions after being seeded back into blood vessels. To investigate this possibility we measured SMC proliferation and intimal thickening in balloon-injured Fischer 344 rat carotid arteries seeded with SMCs stained with the fluorescent marker 1,1'-dioctadecyl-3,3,3',3'-tetramethylindo-carbocyanine perchlorate (DiI) and infected with replication-defective retrovirus expressing human adenosine deaminase or human placental alkaline phosphatase. The majority of the seeded SMCs remained in the intima while a few of the cells appeared to migrate into the first layer of the media. Intimal SMC proliferation returned to background levels (< 0.1% thymidine labeling index) by 28 d. At late times (1 and 12 mo) the morphological appearance of the intima was the same for balloon-injured arteries with or without seeded SMC, except that the seeded arteries continued to express human adenosine deaminase or alkaline phosphatase. These results support the conclusion that cultured SMC infected with a replication-defective virus containing human adenosine deaminase or alkaline phosphatase are not phenotypically altered and do not become transformed. After seeding onto the surface of an injured artery, they stop replicating but continue to express the introduced human genes even over the long term.

Adenosine Deaminase↗
PubMed1993

Screening for colorectal cancer with fecal occult blood testing and sigmoidoscopy.

BACKGROUND: The high incidence of and mortality from colorectal cancer (160,000 new cases and 60,000 deaths in the United States each year) are compelling public health concerns. Following the evolution of effective surgery for this disease since the 1960s, the focus has been on improving methods of detection and integrating them into effective screening programs. PURPOSE: This was the first study to evaluate the effectiveness, in a setting of comprehensive medical examinations, of using the fecal occult blood test in conjunction with sigmoidoscopy, rather than sigmoidoscopy alone, to screen for colorectal cancer. Our end points were extent of compliance with fecal occult blood test and sigmoidoscopy, numbers of cancers detected, and mortality rate. METHODS: From 1975 through 1979, a total of 21,756 patients (aged 40 and older) who presented at the Preventive Medicine Institute-Strang Clinic for routine medical examinations were enrolled by calendar period into study and control groups. Study patients were offered annually both rigid sigmoidoscopy examinations and fecal occult blood tests requiring two stool specimens per day for 3 days, while control patients were offered only annual sigmoidoscopy. The majority of fecal occult blood test cards were not rehydrated before assay. Patients with positive tests were referred for double-contrast barium enema and colonoscopy. Two distinct trials were carried out. Trial I was primarily a demonstration of feasibility of using the fecal occult blood test as a supplemental screening method. Of the 9277 participants, 7168 (77%) were assigned to the study group and offered the fecal occult blood test. In trial II, approximately half of the 12,479 patients were assigned to each group. Patients in both trials had follow-up through 1984. RESULTS: Compliance with the fecal occult blood test was initially high in both trials, but diminished such that only 56% of study patients in trial I and 20% of those in trial II returned for second tests. On the initial (prevalence) screen, a substantial number of early-stage cancers were detected by the fecal occult blood test, primarily in trial II. In trial II, survival probability was significantly greater (P < .001) in the study group than in the controls (70% versus 48%), and colorectal cancer mortality was lower (0.36 versus 0.63) with borderline significance (P = .053, one-sided). CONCLUSIONS AND IMPLICATIONS: The screening of average-risk individuals (aged 50 and older) for colorectal cancer through use of the fecal occult blood test in conjunction with sigmoidoscopy can increase the likelihood of early detection of this disease. This practice, coupled with prompt diagnostic work-up following positive tests, will result in treatment of earlier stage cancers and increased survival after treatment.

Aged↗
PubMed1993

Reporting bilaterality status in first-degree relatives with breast cancer: a validity study.

The objective of this study was to validate reports on the bilaterality status of breast cancer in first-degree relatives of women with a strong family history of the disease; i.e., women with 1) two first-degree relatives who have, or have had, breast cancer; 2) one first- and one second-degree affected relative; or 3) one first-degree relative with diagnosis of breast cancer before the age of 50 years and/or bilateral breast cancer. We were able to obtain hospital records for 94 affected relatives of 83 patients who agreed to participate in the study. The accounts of these women were compared to the bilaterality status indicated in the hospital records of the affected relatives. Inconsistencies that might have been attributed to incomplete medical records were resolved through personal interviews with the participants, and when indicated, with other family members or the physician of the affected relative. Overall, 89.4% (84/94) of the reports validated in this manner were correct. Participants who reported unilateral breast cancer in a first-degree relative were correct 94.4% (68/72) of the time. Similarly, 94.0% (47/50) of the accounts concerning affected living relatives were accurate, regardless of whether the participant had indicated unilateral or bilateral disease. However, participants who reported bilateral breast cancer in a deceased relative were accurate only 61.5% (8/13) of the time. Incorrect reports were associated with misunderstanding of medical terminology, especially if the participant was young at the time of the diagnosis of her relative.

Adult↗
PubMed1993

Physical definition of the "flageolet register".

The highest "register" of the female singing voice, often called the "flageolet register" (also called "flute register," "bell register," etc., as well as the misleading term "whistle register"), is broadly recognized by voice pedagogues, but not generally defined in terms that are adequate for objective description. This article presents a description of characteristic patterns of vocal fold movement and of vocal tract formants that are specific for the register. Measurements are made by electroglottograph, pharyngeally placed wide-band pressure transducers, and an external microphone in professional soprano subjects who are adept in using this register.

Female↗
PubMed1993

Belting and pop, nonclassical approaches to the female middle voice: some preliminary considerations.

There is a commonly perceived difference in the sound produced in the approximate range D4-D5 by female singers in the western opera and concert tradition, on the one hand, and certain other styles, including rock, pop, folk, and some Broadway musicals, on the other. The term "belting" is sometimes used to refer to at least one approach to such "nonclassical" singing. In this study, based on spectrographic, electroglottographic, and sub- and supraglottal pressure measurements on representative voices of the "operatic" and "nonclassical" tradition, acoustic and laryngeal differences between the two traditions are described, and an objective, specific definition of "belting" is offered.

Female↗
PubMed1993

Inhibitors of retrovirus infection are secreted by several hamster cell lines and are also present in hamster sera.

We have previously shown that Chinese hamster ovary (CHO) cells are resistant to infection by gibbon ape leukemia virus and amphotropic pseudotype retroviral vectors because of the secretion of factors that inhibit retrovirus infection. Such factors were not secreted by any mouse or human cell lines tested. Secretion of the inhibitors and resistance to infection are abrogated by treatment of CHO cells with the glycosylation inhibitor tunicamycin. Here we show that the inhibitory activities against gibbon ape leukemia virus and amphotropic viruses are partially separable and that glycosylation mutations in CHO cells mimic the effects of tunicamycin treatment. We find that several hamster cell lines derived from both Chinese and Syrian hamsters secrete inhibitors of retrovirus infection, showing that these inhibitors are not unique to the CHO cell line. Inhibitory factors are also present in the sera of Chinese and Syrian hamsters but were not detected in bovine serum. These results suggest the presence of specific factors that function to inhibit retrovirus infection in hamsters.

3T3 Cells↗
PubMed1992

Psychological distress and surveillance behaviors of women with a family history of breast cancer.

Women with a family history of breast cancer are at increased risk for developing the disease. This study investigated the beliefs of women at high risk for breast cancer (one or more first-degree relatives with breast cancer) about their breast cancer risk and the impact of this information on their surveillance behaviors and psychological distress. The Health Belief Model and the Fear Arousing Communications Theory were used in this study. Two hundred and seventeen women, enrolled in a breast protection program, completed a questionnaire regarding health beliefs and behaviors, social support, and psychological distress. While 94% came in for regularly scheduled mammograms, only 69% came in for regular clinical breast examinations. A discriminant function analysis revealed that increased cancer anxiety decreased regular clinical examinations (coefficient = -.65). Only 40% performed breast self-examination monthly, 10% never performed breast self-examination, and 50% did not perform breast self-examination regularly. High breast self-examination performance prior to coming to the program was the best predictor of current breast self-examination, and high anxiety predicted poor adherence to monthly breast self-examination (multiple R = .61). More than 27% of the women at high risk were defined as having a level of psychological distress consistent with the need for counseling. Women reporting more barriers to screening, fewer social supports, and low social desirability had more psychological distress (multiple R = .75). Higher anxiety was directly related to poor attendance at a clinical breast examination and poor adherence to monthly breast self-examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Steroidal nonspecific esterase metabolism of N-hydroxy-2-acetylaminofluorene: evidence for selective activation by the cellular reductant NADPH.

The significance of the nonspecific esterases of human mononuclear leukocytes (HMLs) in arylamine carcinogenesis is suggested by data showing that the metabolically formed hydroxamic acid derivative of 2-acetylaminofluorene, N-hydroxy-2-acetylaminofluorene, is a substrate for this class of enzymes. A viable cell assay for the nonspecific esterases using alpha-naphthyl acetate as substrate is described, and data showing this activity to be sensitive to already known substrates for HML esterases as measured by three previously described assays are presented. All four assays of the same esterase activity are shown to be highly sensitive to up- and down-regulation by addition of NADPH or NADP to viable HML cultures. Selective activation of a purified rabbit nonspecific esterase by NADPH, but not by the other cellular reductants, NADH and glutathione, was demonstrated. Cytosols prepared from normal human tissue samples of liver, breast, colon, and brain were also activated by the presence of NADPH. These data do not indicate that steroidal nonspecific esterases are redox-modulated by the presence of mixed disulfides in their structure. Instead, they support the direct and specific influence of NADPH as a widespread activator of esterase activity by a mechanism not yet understood.

Animals↗
PubMed1992

On the relation between the dimensions and resonance characteristics of the vocal tract: a study with MRI.

The relation between the spatial configuration of the vocal tract as determined by magnetic resonance imaging (MRI) and the acoustical signal produced was investigated. A male subject carried out a set of phonatory tasks, comprising the utterance of the sustained vowels /i/ and /a/, each in a single articulation, and the vowel /epsilon/ with his larynx positioned variously on a vertical axis. Two- and three-dimensional measurements of the vocal tract were performed. The results of these measurements were used to calculate resonance frequencies, according to predictions from acoustical theory. Finally, calculated frequencies were compared with actually measured resonance frequencies in the audio signal. We found a strong relation between the acoustical signal produced and the spatial configuration for the first resonance frequencies of the articulations of the vowel /epsilon/, and first two resonance frequencies of the vowels /a/ and /i/. The capability to determine accurately vocal tract dimensions is a major advantage of this imaging technique.

Humans↗