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Biomedical subjects

R W Miller

Publications and source records attributed to R W Miller.

At least 91 records · Page 5Linked to original sources
PubMed1989

Dominantly transmitted hematologic dysfunction clinically similar to Fanconi's anemia.

We report a family with a dominantly transmitted syndrome resembling Fanconi's anemia and spanning two generations. This syndrome was characterized by an ill-defined hematologic stem cell disorder, immune dysfunction, poor dentition, hyperpigmented skin, warts, and multiple second trimester spontaneous abortions and included one case of acute myelomonocytic leukemia (acute non-lymphocytic leukemia, M4). This family lacks the characteristic chromosomal aberrations of Fanconi's anemia. We believe this constellation of findings represents an entity not previously described.

Abortion, Habitual↗
PubMed1989

Keloids and neoplasms in the Rubinstein-Taybi syndrome.

In a series of 574 individuals with the Rubinstein-Taybi syndrome, 28 had keloids, and 19 had one or more neoplasms. The array of malignant neoplasms does not suggest an etiology or pathogenesis in common. One possible exception is that four cases of leukemia were observed. When the data for malignant and benign neoplasms were combined, at least nine of the 22 could have arisen from developmental errors. The apparent excess of keloid formation indicates overreaction to mild injury, with no known relevance to neoplasia but of potential interest in future studies of scar formation.

Abnormalities, Multiple↗
PubMed1989

Effect of experimental bedding treatments on the density of immature Musca domestica and Stomoxys calcitrans (Diptera: Muscidae) in outdoor calf hutches.

Experimental bedding materials and a novel delivery method of cyromazine (Larvadex) were evaluated as replicated treatments in outdoor calf hutches for effect on the density of immature Musca domestica L. and Stomoxys calcitrans (L.). In 6-wk trials, overall density of Musca domestica L. and Stomoxys calcitrans (L.) in straw bedding averaged 36.2 and 52.6 maggots/liter, respectively, compared with respective average densities of 9.0 and 16.2 for wood chips and 10.4 and 20.0 for wood chips over a hydraulic fabric filter system. These values represent average reductions of 80 and 69% and 77 and 68%, respectively. Densities of M. domestica and S. calcitrans in ground corncob over the filter system averaged 13.3 and 4.1 maggots/liter in 3.2-mm size corncob particles, and 1.7 and 1.2 for 6.4-mm size corncob particles (average reductions of 62 and 87% and 90 and 96%, respectively) relative to straw bedding. Densities of these two species in sand bedding averaged 2.8 and 0.4 maggots/liter (average reductions of 93 and 99%), but sand became compacted and soiled with calf urine and feces after several weeks. Cyromazine excreted in calf urine limited density of both species in straw to an average of 11.0 and 15.6 maggots/liter, respectively (a 58 and 79% suppression relative to untreated straw). These data confirm that straw bedding promotes muscoid maggot growth and illustrate that alternative calf hutch bedding systems and urine delivery of cyromazine may improve muscoid fly management on dairy farms by limiting the development of muscoid maggots.

Animals↗
PubMed1989

Costs of existing and recommended manure management practices for house fly and stable fly (Diptera: Muscidae) control on dairy farms.

Costs of fly control practices were estimated for 26 New York and Maryland dairy farms. Objectives were to characterize existing practices, compare them with the cost of more frequent and complete manure removal to reduce fly breeding, and to compare costs of manure removal and insecticide application. Information was collected in scouting visits and personal interviews of farm operators. Equipment, labor, and bedding costs were included for manure removal. Insecticide application costs included chemicals and labor for application. A typical farm with a stanchion barn had manure removal costs of $0.348 per cow per day. Recommended changes would increase costs by $0.016-0.033 per cow per day. Insecticide costs averaged $0.021 per cow per day. It may be possible to eliminate many of the insecticide applications on the farms by using the recommended 7-d manure removal practice. Even if insecticides are not eliminated entirely, increased manure removal costs would be offset by some reduction in insecticide cost. This also would have the additional benefit of greatly slowing the development of insecticide resistance by the flies.

Animals↗
PubMed1988

Molybdenum and vanadium nitrogenases of Azotobacter chroococcum. Low temperature favours N2 reduction by vanadium nitrogenase.

A comparison of the effect of temperature on the reduction of N2 by purified molybdenum nitrogenase and vanadium nitrogenase of Azotobacter chroococcum showed differences in behaviour. As the assay temperature was lowered from 30 degrees C to 5 degrees C N2 remained an effective substrate for V nitrogenase, but not Mo nitrogenase, since the specific activity for N2 reduction by Mo nitrogenase decreased 10-fold more than that of V nitrogenase. Activity cross-reactions between nitrogenase components showed the enhanced low-temperature activity to be associated with the Fe protein of V nitrogenase. The lower activity of homologous Mo nitrogenase components, although dependent on the ratio of MoFe protein to Fe protein, did not equal that of V nitrogenase even under conditions of high electron flux obtained at a 12-fold molar excess of Fe protein.

Azotobacter↗
PubMed1988

The vanadium nitrogenase of Azotobacter chroococcum. Purification and properties of the Fe protein.

1. Nitrogenase activity of a strain of Azotobacter chroococcum lacking the structural genes of Monitrogenase (nifHDK) was associated with a V + Fe-containing protein and an Fe-containing protein [Robson, Eady, Richardson, Miller, Hawkins & Postgate (1986) Nature (London) 322, 388-390; Eady, Robson, Richardson, Miller & Hawkins (1987) Biochem. J. 244, 197-207]. 2. The Fe protein was purified to homogeneity by the criterion of Coomassie Blue staining after electrophoresis in 10% or 17% (w/v) polyacrylamide gels in the presence of SDS. One type of subunit, of Mr 32,000 +/- 2000, was found. 3. The native protein had an Mr of 62,500 +/- 2500 and contained approximately 4 Fe atoms and 4 acid-labile sulphide groups per molecule. The amino acid composition was similar to those of other purified Fe proteins, and, characteristically, tryptophan was absent. The specific activities (nmol of protein/min per mg of protein) when assayed under optimum conditions with the VFe protein from this strain were 1211 for H2 evolution under Ar, 337 for NH3 from N2 formation and 349 for C2H2 reduction. Activity of the Fe protein was O2-labile with a t1/2 of 36 s in air. At low temperatures the dithionite-reduced protein exhibited e.p.r. signals consistent with the presence of both S = 1/2 and S = 3/2 spin states. These signals were similar to those given by other nitrogenase Fe proteins, as were the changes in their line shape that occurred in the presence of MgATP or MgADP. The absorbance spectra showed that an increase in absorption occurred in the visible range on reversible oxidation of the dithionite-reduced protein. The oxidized-minus-reduced epsilon 420 was 6000 M-1.cm-1.

Amino Acids↗
PubMed1988

A cancer family syndrome in twenty-four kindreds.

A search of the Cancer Family Registry of the National Cancer Institute revealed 24 kindreds with the syndrome of sarcoma, breast carcinoma, and other neoplasms in young patients. Cancer developed in an autosomal dominant pattern in 151 blood relatives, 119 (79%) of whom were affected before 45 years of age. These young patients had a total of 50 bone and soft tissue sarcomas of diverse histological subtypes and 28 breast cancers. Additional features of the syndrome included an excess of brain tumors (14 cases), leukemia (9 cases), and adrenocortical carcinoma (4 cases) before age 45 years. These neoplasms also accounted for 73% of the multiple primary cancers occurring in 15 family members. Six of these patients had second cancers linked to radiotherapy. The diversity of tumor types in this syndrome suggests pathogenetic mechanisms which differ from hereditary cancers arising in single organs or tissues. The syndrome is presently diagnosed on clinical grounds; laboratory markers are needed to identify high-risk individuals and families and to provide insights into susceptibility mechanisms that may be shared by a wide variety of cancers.

Adult↗
PubMed1988

Cyanamide: a new substrate for nitrogenase.

(1) Cyanamide (N identical to C-NH2) has been shown to be a substrate for purified Mo-nitrogenases of Klebsiella pneumoniae and Azotobacter chroococcum, with apparent Km values near 0.8 mM. (2) Reduction products were CH4, CH3NH2 and NH3 formed by pathways requiring 6 or 8 electrons: N identical to CNH2 + 6e + 6H+----CH3NH2 + NH3; N identical to CNH2 + 8e + 8H+----CH4 + 2NH3 (3) Acetylene reduction and hydrogen evolution were inhibited more than 75% by cyanamide (10 mM). Cyanamide also inhibited total electron flux at nitrogenase protein component ratios (Fe/MoFe) near 10. (4) Cyanamide was also a substrate for the recently isolated Va-nitrogenase of A. chroococcum, but with an apparent Km of 2.6 mM showed weaker binding and an 8-fold lower Vmax than did either Mo-nitrogenase. (5) The component ratios of nitrogenase proteins favouring CH4 formation was 3.5 Fe/MoFe protein and 1 Fe/VaFe protein.

Acetylene↗
PubMed1988

Simultaneous infection with respiratory syncytial virus and other respiratory pathogens.

The presentation and subsequent course of respiratory syncytial virus (RSV) bronchiolitis may be atypical and unusually severe when simultaneous infection due to other pathogenic agents is present. During the past two years, nine of the 189 pediatric patients hospitalized with documented RSV infection were found to have the following simultaneous isolates from initial respiratory tract specimens: four adenovirus, four pneumococcus, one cytomegalovirus, and one Pneumocystis carinii. Noted complications attributable to the second pathogen included thrombocytopenia and anemia (cytomegalovirus), hepatitis and disseminated intravascular coagulation (adenovirus), and sepsis and osteomyelitis (pneumococcus). Three of the four patients with RSV and adenovirus died of severe respiratory failure despite mechanical ventilation; two of these patients received ribavirin therapy. Rapid identification of RSV is important but should not be a substitute for more comprehensive viral and bacterial evaluation.

Adenoviruses, Human↗
PubMed1988

Respiration supported nitrogenase activity of isolated Rhizobium meliloti bacteroids.

Bacteroids having a high level of respiration-supported nitrogenase activity were isolated from nitrogen-fixing alfalfa root nodules. Gentle maceration under anaerobic conditions in the presence of sodium succinate and a fatty acid scavenging agent were employed in this method. A large proportion of isolated bacteroids retained a triple membrane structure as shown by transmission electron microscopy. Dicarboxylic acids of the TCA cycle (malate, fumarate, succinate), but not glutamate or aspartate, supported sufficient respiratory activity to supply the nitrogenase system with ATP and reducing equivalents and to protect the nitrogenase system from inactivation by 4% oxygen over a period of 20-30 min. Sugars did not support nitrogenase activity in intact bacteroids. The properties of the isolated bacteroids were ascribed to minimal damage to the cytoplasmic membrane and peribacteroidal membrane during isolation. With succinate as substrate and oxygen as terminal electron acceptor, initial nitrogenase activity was determined at 4% oxygen in the gas phase of the assay system employed. At this oxygen concentration, the sustained rate of acetylene reduction by respiring bacteroids was linear up to 30 min. Bacteroid activity declined rapidly with time of exposure to oxygen above 4% in the gas phase. The optimum temperature range for this activity was 10-20 degrees C. Nitrogenase activity was measurable at incubation temperatures below 10 degrees C under 4% oxygen. Functionally intact bacteroids had little nitrogenase activity under anaerobic conditions in the presence of an external source of ATP and reductant. Treatment of the bacteroids with chlorpromazine eliminated respiration-supported activity and rendered the bacteroid cell membrane permeable to external ATP. Bacteroids treated with chlorpromazine had high acetylene reducing activity with external ATP and dithionite in the absence of oxygen.

Carboxylic Acids↗
PubMed1988

Intrauterine radiation exposures and mental retardation.

Small head size and mental retardation have been known as effects of intrauterine exposure to ionizing radiation since the 1920s. In the 1950s, studies of Japanese atomic-bomb survivors revealed that at 4-17 wk of gestation, the greater the dose, the smaller the brain (and head size), and that beginning at 0.5 Gy (50 rad) in Hiroshima, mental retardation increased in frequency with increasing dose. No other excess of birth defects was observed. Otake and Schull (1984) pointed out that the period of susceptibility to mental retardation coincided with that for proliferation and migration of neuronal elements from near the cerebral ventricles to the cortex. Mental retardation could be the result of interference with this process. Their analysis indicated that exposures at 8-15 wk to 0.01-0.02 Gy (1-2 rad) doubled the frequency of severe mental retardation. This estimate was based on small numbers of mentally retarded atomic-bomb survivors. Although nuclear accidents have occurred recently, new cases will hopefully be too rare to provide further information about the risk of mental retardation. It may be possible, however, to learn about lesser impairment. New psychometric tests may be helpful in detecting subtle deficits in intelligence or neurodevelopmental function. One such test is PEERAMID, which is being used in schools to identify learning disabilities due, for example, to deficits in attention, short- or long-term memory, or in sequencing information. This and other tests could be applied in evaluating survivors of intrauterine exposure to various doses of ionizing radiation. The results could change our understanding of the safety of low-dose exposures.

Brain↗
PubMed1987

The vanadium nitrogenase of Azotobacter chroococcum. Purification and properties of the VFe protein.

1. Nitrogenase activity of a strain of Azotobacter chroococcum lacking the structural genes for conventional nitrogenase (nifHDK) was separated into two components: an Fe-containing protein and a vanadoprotein. 2. The larger protein was purified to homogeneity by the criterion of electrophoresis of 10% (w/v) acrylamide gels in the presence of SDS. Two types of subunit, of Mr 50,000 and 55,000, were present in equal amounts. 3. The protein had an Mr of 210,000 and contained 2 V atoms, 23 Fe atoms and 20 acid-labile sulphide groups per molecule. The Mo content was less than 0.06 g-atom/mol. All the common amino acids were present, with a predominance of acidic residues. Ultracentrifugal analysis gave a maximum sedimentation coefficient of 9.7 S and a symmetrical boundary at 5 mg of protein X ml-1; dissociation occurred at lower concentrations. The specific activities (nmol of product/min per mg of protein), when assayed under optimum conditions with the complementary Fe protein from this strain, were 1348 for H2 evolution, 350 for NH3 formation and 608 for acetylene reduction. Activity was O2-labile, with a t1/2 of 40 s in air. At low temperatures the dithionite-reduced protein showed e.p.r. signals at g = 5.6, 4.35, 3.77 and 1.93, consistent with an S = 3/2 ground state with an additional S = 1/2 centre giving rise to the feature at g = 1.93. The u.v. spectra of dithionite-reduced and thionine-oxidized protein were very similar. Oxidation resulted in a general increase in absorbance in the visible region. The shoulder at 380 nm in the spectrum of reduced protein was replaced with shoulders near 330 nm and 420 nm on oxidation.

Amino Acids↗
PubMed1987

Evaluation of incorporated iododeoxyuridine cellular radiosensitization by photon activation therapy.

Halogenated pyrimidines such as iododeoxyuridine (IdUrd), when incorporated into cellular DNA, sensitize cells to radiation. A technique known as photon activation therapy (PAT) has recently been proposed to further enhance IdUrd radiosensitization. This approach relies on the emission of high linear energy transfer Auger electrons as a result of photoelectric absorption of photons with energies slightly above the K shell binding energy for iodine. Thus, additional IdUrd radiosensitization has been predicted for this technique using photons either generated externally from orthovoltage units or with implants of radioisotopes with emissions of the appropriate energy range. We have tested this prediction by comparing the radiosensitization of Chinese V79 cells, which have incorporated IdUrd (16% replacement of thymidine with IdUrd), to megavoltage (15 MV) versus orthovoltage (100 KVp) radiation. Enhancement ratios at 1% survival levels for 15 MV vs. 100 KVp radiation were 1.8 and 1.95, respectively. This modest 10-15% additional enhancement was much less than that predicted by PAT. The discrepancy between experimental data and the theoretical predictions of PAT are discussed.

Animals↗