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Biomedical subjects

R J Schmidt

Publications and source records attributed to R J Schmidt.

At least 19 recordsLinked to original sources

The effects of various antifungal additives on the fermentation and aerobic stability of corn silage.

In 2 consecutive years, whole plant corn was ensiled in laboratory silos to investigate the effects of various silage additives on fermentation, dry matter (DM) recovery and aerobic stability. In yr 1, chopped forage was treated with 1) no additive (untreated, U), 2) Lactobacillus buchneri 40788, 4 x 10(5) cfu/g of fresh forage (LLB4), 3) L. buchneri 11A44, 1 x 10(5) cfu/g (PLB), 4) Biomax 5 (Lactobacillus plantarum PA-28 and K-270), 1 x 10(5) cfu/g (B5), 5) Silo Guard II (sodium metabisulfite and amylase), 0.05% of fresh forage weight (SG), 6) a buffered propionic acid-based additive, 0.1% (Ki-112), 7), sodium benzoate, 0.1% of fresh weight (SB), or 8) potassium sorbate:EDTA (1:1), 0.1% of fresh weight (PSE). Silage treated with LLB4 had the highest concentration of acetic acid compared with other treatments, and yeasts were undetectable in LLB4 ( 210 h.

Acetic Acid↗

The sensitivity of auditory brainstem response testing for the diagnosis of acoustic neuromas.

OBJECTIVES: To determine the sensitivity of auditory brainstem response (ABR) testing for detecting acoustic neuromas and to determine whether the test is less sensitive for detecting small tumors. DESIGN: Retrospective review of the medical charts of 58 patients with acoustic neuroma who had all of the data necessary for inclusion in the study. SETTING: University-affiliated referral practice of one neurotologist. PATIENTS: Patients with acoustic neuromas who had both ABR tracings and magnetic resonance imaging films available for review. MAIN OUTCOME MEASURES: Positive ABR and negative ABR results correlated with tumor size. RESULTS: Tumor size ranged from 0.4 to 7 cm. The overall sensitivity of ABR in diagnosing acoustic neuromas was 90%. However, ABR was progressively less sensitive with decreasing tumor size. Only 7 (58%) of the 12 tumors 1 cm or smaller were detected by ABR. CONCLUSION: Auditory brainstem response testing cannot be relied on for detection of small acoustic neuromas and should not be used as a criterion to determine whether magnetic resonance imaging should be performed when an acoustic neuroma is suspected clinically.

Evoked Potentials, Auditory, Brain Stem↗

Effects of aging and alterations in dietary sodium intake on total nitric oxide production.

Animal studies suggest that nitric oxide (NO) deficiency is linked to salt-sensitive hypertension and that NO activity decreases during normal aging. This study investigates the impact of increasing age and manipulations in dietary salt intake on biochemical indices of the NO system in healthy humans. We measured NO(2) + NO(3) (NO(X); stable oxidation products of NO) and cyclic guanosine monophosphate (cGMP; major second messenger) in plasma and urine of 30 healthy subjects aged 22 to 77 years. Subjects were maintained on controlled low NO(X) and low-, normal-, or high-salt diets for 3 days. Salt sensitivity of blood pressure was seen only in the oldest subjects. Plasma renin activity was suppressed by a high salt intake in all age groups, and baseline values declined with advancing age. Neither age nor salt intake correlated with indices of NO activity over the third 24-hour period of controlled salt intake. In a subgroup of subjects aged 33 +/- 4 years challenged with ultrahigh sodium intake (400 mEq/24 h), again there was no increase in NO(2) + NO(3) or cGMP measures. In contrast to animal studies, there is no correlation in humans between either salt intake or age and total NO production and activity, indicated by NO(2) + NO(3) and cGMP measures. This does not preclude undetected alterations occurring in NO production and/or activity in strategic locations in the kidney and cardiovascular system. Limitations of blood and urine measurements of NO(2) + NO(3) and cGMP as indices of NO activity are discussed.

Adult↗

Circulating endothelial nitric oxide synthase inhibitory factor in some patients with chronic renal disease.

BACKGROUND: Chronic renal disease (CRD) is associated with hypertension and reduced synthesis of nitric oxide (NO). Here, we investigated whether there is a circulating endothelial NO synthase (eNOS) inhibitory factor(s) in some patients with CRD that might directly influence endothelial NOS. METHODS: Human dermal microvascular endothelial cells (HDMECs) were incubated for six hours with 20% plasma from subjects with normal renal function (PCr = 0.8 +/- 0.2 mg%), and patients with moderate renal insufficiency of various causes (PCr = 4.0 +/- 1.5 mg%) and impact on NOS activity, transport of L-arginine, and abundance of eNOS protein were measured. Plasma concentrations of asymmetric and symmetric dimethyl L-arginine (ADMA and SDMA) were also measured. RESULTS: There was no effect of any human plasma on L-arginine transport. The NOS activity was variable in CRD patients and fell into two subgroups: CRD I, individual values similar to control, and CRD II, individual values lower than control mean. The effect of CRD plasma on NOS activity in cultured cells was not related to the primary disease, but was predicted by plasma ADMA levels since plasma ADMA was elevated in CRD II versus both control and CRD I. Blood urea nitrogen and creatinine levels were uniformly elevated in CRD plasma. The abundance of eNOS protein was unaffected by plasma. CONCLUSION: High plasma levels of ADMA in CRD patients are independent of reduced renal clearance, suggesting an alteration in ADMA synthesis and/or degradation. High ADMA is a marker and is partly responsible for the inhibition of eNOS activity in cultured cells and may also result in reduced eNOS activity in vivo, with consequent hypertension.

Adult↗

Attitudes of patients toward cardiopulmonary resuscitation in the dialysis unit.

Some dialysis units have a policy of performing cardiopulmonary resuscitation (CPR) on all patients who experience cardiac arrest while undergoing dialysis. However, to perform CPR on patients who do not want it is contrary to ethics and the law. We interviewed hemodialysis patients in 12 units in Missouri, New York, and West Virginia to learn their attitudes about CPR. Four hundred sixty-nine of 830 patients (57%) agreed to be interviewed. Eighty-seven percent of patients wanted to undergo CPR if cardiac arrest were to occur while undergoing dialysis. Patients who had seen CPR on television were more likely to report that they knew what CPR was (94% versus 68%; P < 0.001) and to want CPR (88% versus 78%; P = 0.033). Thirteen percent of patients did not want CPR if cardiac arrest were to occur while undergoing dialysis. Compared with patients who wanted CPR, those who did not were older (69 versus 59 years; P = 0.026), had more comorbid conditions (2.0 versus 1.5 comorbid conditions; P = 0.016), and were more likely to have a living will (61% versus 43%; P = 0.01), be widowed (36% versus 20%; P = 0.026), and live in a nursing home (9% versus 3%; P = 0.017). Blacks were significantly more likely to want CPR than whites (adjusted odds ratio, 6.56; 95% confidence interval, 2.57 to 22.27). Only 20 of 58 patients (35%) who did not want CPR were certain they had a do-not-resuscitate order in their dialysis chart. Ninety-two percent of patients who wanted CPR agreed that patients who did not want CPR should have their wishes respected by the dialysis unit. We conclude that most dialysis patients want to undergo CPR, but also want other patients' preferences not to be resuscitated to be respected. Dialysis units need to do a better job of identifying patients who prefer not to be resuscitated and respecting their wishes in the event of cardiac arrest while undergoing dialysis. Most importantly, nephrologists and dialysis unit staff need to educate dialysis patients about the poor outcomes with CPR so that dialysis patients' decisions about CPR are informed.

Aged↗

Molecular and genetic analyses of the silky1 gene reveal conservation in floral organ specification between eudicots and monocots.

The degree to which the eudicot-based ABC model of flower organ identity applies to the other major subclass of angrosperms, the monocots, has yet to be fully explored. We cloned silky1 (si1), a male sterile mutant of Zea mays that has homeotic conversions of stamens into carpels and lodicules into palea/lemma-like structures. Our studies indicate that si1 is a monocot B function MADS box gene. Moreover, the si1 zag1 double mutant produces a striking spikelet phenotype where normal glumes enclose reiterated palea/lemma-like organs. These studies indicate that B function gene activity is conserved among monocots as well as eudicots. In addition, they provide compelling developmental evidence for recognizing lodicules as modified petals and, possibly, palea and lemma as modified sepals.

Adaptor Protein Complex alpha Subunits↗

Plasma from ESRD patients inhibits nitric oxide synthase activity in cultured human and bovine endothelial cells.

Our recent observations of reduced total nitric oxide synthesis in renal failure patients on peritoneal dialysis and haemodialysis suggest that hypertension in end-stage renal disease involves lack of vasodilatory endothelial NO. To directly test this, uraemic plasma was obtained from dialysis patients and incubated with cultured vascular endothelial cells, to determine the effect on nitric oxide synthase (NOS) activity in comparison with plasma from subjects with normal renal function. After incubation for 6 h with 20% uraemic plasma from peritoneal dialysis and immediately prehaemodialysis patients, NOS activity was reduced in human dermal microvascular endothelial cells. Haemodialysis did not remove the NOS-inhibitory activity of uraemic plasma nor did it activate inducible NOS, as NOS activity was always similar in control and dexamethasone pretreated cells. Nitric oxide production (accumulation of nitrite and nitrate) was lower in cells incubated with uraemic vs. normal plasma and excess arginine increased nitric oxide production by cells previously exposed to uraemic medium. This inhibitory effect was not associated with co-factor deficiency but did correlate with plasma concentrations of endogenous NOS inhibitors. These in vitro findings suggest that low endothelial NOS activity may contribute to hypertension in end stage renal disease patients.

Animals↗

Total nitric oxide production is low in patients with chronic renal disease.

BACKGROUND: A deficiency of the endogenous vasodilator nitric oxide (NO) has been implicated as a potential cause of hypertension in chronic renal disease (CRD) patients. This study was conducted to determine whether 24-hour NOX (NO2 and NO3) excretion (a qualitative index of total NO production) is reduced in patients with CRD. METHODS: Measurements were made in 13 CRD patients and 9 normotensive healthy controls after 48 hours on a controlled low-NOX diet. Urine was collected over the second 24-hour period for analysis of 24-hour NOX, and cGMP and blood drawn at the completion. Plasma levels of arginine (the substrate for endogenous renal NO synthesis), citrulline (substrate for renal arginine synthesis), and the endogenous NO synthesis inhibitor asymmetrical dimethylarginine (ADMA) and its inert isomer and symmetrical dimethylarginine (SDMA) were also determined. RESULTS: Systolic blood pressure was higher in CRD patients (12 of whom were already on antihypertensive therapy) than in controls (P < 0.05). Twenty-four-hour urinary NOX excretion was low in CRD patients compared with controls despite similar dietary NO intake, suggesting that net endogenous NO production is decreased in renal disease. In contrast, the 24-hour urinary cGMP did not correlate with UNOXV. Plasma citrulline was increased in CRD patients, possibly reflecting reduced conversion of citrulline to arginine. Plasma arginine was not different, and plasma ADMA levels were elevated in CRD versus controls, changes that would tend to lower NO synthase. CONCLUSION: These results suggest that NO production is low in CRD patients and may contribute to hypertension and disease progression in CRD.

Adult↗

Sarcoidosis after renal transplantation.

This is the case of a 41-year-old renal transplant recipient taking tacrolimus immunosuppressive therapy, who had a large pleural effusion, found on a chest radiograph during the work-up of digital clubbing. The patient had undergone a renal transplant 17 months earlier for end-stage renal disease secondary to immunoglobulin A nephropathy. Analysis of the effusion fluid demonstrated a lymphocytic exudate. Biopsy specimens of pleural and lung tissues showed noncaseating granulomas. Fluid and tissue cultures were negative for viral, fungal, and bacterial pathogens. Diagnosis of sarcoidosis was established by identification of noncaseating granulomas in pleural and lung tissue, the exclusion of other conditions, and rapid resolution of the effusion after the institution of corticosteroid therapy. The patient has remained free of pulmonary symptoms and had normal chest radiographs during the 20-month follow-up period.

Adrenal Cortex Hormones↗

The maize EmBP-1 orthologue differentially regulates opaque2-dependent gene expression in yeast and cultured maize endosperm cells.

In addition to the bZIP protein Opaque2 (O2), there are other maize endosperm nuclear proteins that recognize the O2 box in 22 kDa zein gene promoters. In an effort to understand the effect of these factors on 22 kDa zein expression, we have cloned one of these and identified it as the putative maize (Zea mays L.) orthologue of the wheat bZIP protein EmBP-1 (mEmBP-1). The mEmBP-1 protein exhibits 52% sequence identity and 68% similarity with the wheat protein and recognizes a similar spectrum of DNA sequences, albeit with slightly altered specificity. The mEmBP-1 gene exists as duplicate loci in maize on chromosomes 7S (mEmBP-1a) and 2L (mEmBP-1b). The mEmBP-1 genes are expressed in endosperm, embryo, immature ears, tassel, roots, and seedling shoots at low levels. Although mEmBP-1 binds to the O2 box from the 22 kDa zein gene promoter as a homodimer, it is unable to heterodimerize with O2. The mEmBP-1 protein can activate transcription from a truncated promoter containing a pentamer of the O2 site in yeast cells; however, it inhibited regulated transcription of a 22 kDa zein promoter in a transient expression assay using cultured maize endosperm cells.

Amino Acid Sequence↗

Diversity and similarity among recognition sequences of Dof transcription factors.

Dof proteins are a family of transcription factors that share a unique DNA-binding domain. Dof proteins were found recently in association with diverse promoters of plant-specific genes, suggesting various roles of Dof proteins in plants. Through binding site selection experiments using randomly synthesized DNA, the recognition sequences of four maize Dof proteins were systematically analyzed. All selected oligonucleotides contained an AAAG sequence, suggesting that this sequence is the recognition core of Dof proteins. In fact, a single mutation in this sequence abolished binding of all four Dof proteins. Furthermore, the preference of each Dof protein for the sequence flanking the core motif was also analyzed using oligonucleotides containing a fixed AAAG and random flanking sequences. Similar, as well as distinct, flanking sequences were observed among the optimal binding sites. Changes in the flanking sequences did affect DNA-binding of Dof proteins.

Base Sequence↗

Indices of activity of the nitric oxide system in hemodialysis patients.

Arginine deficiency and/or increased levels of circulating nitric oxide (NO) synthesis (NOS) inhibitors can cause reduced NOS, which may contribute to hypertension in patients with end-stage renal disease (ESRD). To test these hypotheses, NO oxidation products (NO(2) + NO(3) = NO(x)) and cyclic guanosine monophosphate (cGMP), the vasodilatory second messenger of NO, were measured in the blood, urine, and dialysate effluent of hemodialysis (HD) patients and compared with the blood and urine of healthy subjects. The subjects ate a controlled low-nitrate diet (approximately 330 micromol/d) for 48 hours before and during blood, dialysis effluent, and 24-hour urine collection. NO(x) output was significantly reduced in HD patients versus controls (552 +/- 51 v 824 +/- 96 micromol/24 h; P < 0.001), whereas cGMP output was not low versus controls. Plasma arginine level was normal and plasma levels of citrulline and the endogenous NOS inhibitor, asymmetric dimethylarginine (ADMA), were markedly elevated in patients with ESRD versus controls. Systolic blood pressure was greater in HD patients compared with controls despite concurrent antihypertensive therapy in most patients with ESRD. These studies suggest NO production is low in patients with ESRD undergoing HD, possibly because of the increased ratio of plasma ADMA to arginine.

Arginine↗

The activity of the maize Opaque2 transcriptional activator is regulated diurnally.

The maize (Zea mays L.) Opaque2 (O2) protein is an endosperm-specific transcriptional activator whose DNA-binding activity is regulated diurnally by a phosphorylation/dephosphorylation mechanism. We show that the O2 transcript undergoes pronounced oscillations during the day-night cycle. The highest level of the O2 message is present at midday and the lowest level at midnight. The level of O2 transcript follows a diurnal rhythm that appears controlled by the circadian clock. Two different endosperm-expressed DNA-binding proteins, PBF (prolamin box-binding factor) and OHP1 (O2-heterodimerizing protein 1), were also analyzed. While the PBF message levels oscillate diurnally, the steady-state levels of OHP1 transcript were constant through the day and night. We present data showing that the seed is not directly involved in the perception of the light signal, but presumably responds to diurnal fluxes of nutrients into the endosperm. Moreover, we show that the O2 protein is not involved in the regulation of its own transcript levels. These data indicate that O2 activity is down-regulated at night by both a reduction in O2 transcript and by hyperphosphorylation of residual O2 protein, and suggest that regulatory gene activity during endosperm development may be acutely sensitive to a diurnal signal(s) emanating from the plant and passing into the developing seeds.

Circadian Rhythm↗

Nitric oxide production is low in end-stage renal disease patients on peritoneal dialysis.

To test the hypothesis that nitric oxide (NO) deficiency occurs in end-stage renal disease (ESRD), NO oxidation products (NO2 + NO3 = NOx) and cGMP were measured in blood, urine, and dialysate effluent of peritoneal dialysis (PD) patients and compared with blood and urine of healthy subjects. All subjects were on a controlled low-nitrate diet (approximately 330 micromol/day). NOx and cGMP outputs were significantly reduced in PD patients (334 +/- 50 micromol/24 h and 55 +/- 13 nmol/24 h, respectively) vs. controls (823 +/- 101 micromol/24 h and 149 +/- 46 nmol/24 h). Plasma arginine was borderline low, plasma citrulline was elevated and plasma levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine were approximately five time higher in PD patients (2.2 +/- 0.3 microM) vs. controls (0.4 +/- 0.1 microM). Although blood pressure (BP) was not different between groups at the time of study, 10 of 11 PD patients were on medication for hypertension. These studies demonstrate that total NO production is low in ESRD, and with appropriate caution, we conclude that this NO deficiency may contribute to the increased BP that occurs in ESRD.

Adult↗

Effects of LY295427, a low-density lipoprotein (LDL) receptor up-regulator, on LDL receptor gene transcription and cholesterol metabolism in normal and hypercholesterolemic hamsters.

The action of LY295427 [(3alpha,4alpha, 5alpha)-4-(2-propenylcholestan-3-ol)], a compound that derepresses low-density lipoprotein receptor (LDL-R) expression in a cell-based model, was examined in hamsters. It was found that the compound does not have an effect in normal chow-fed hamsters, in which LDL-R levels are not repressed, but exerts a marked hypocholesterolemic effect (>70% decrease) in cholesterol-coconut oil-fed hamsters, in which LDL-R is repressed. In this model, there is a dose-response for cholesterol lowering with an approximate ED50 value of 40 mg/kg/day and an inverse relationship between serum cholesterol and serum LY295427 levels. LDL-R mRNA is increased (2-fold) and liver cholesterol ester content is decreased (>90%). Unlike the 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor lovastatin, the decreased serum cholesterol is confined to the non-high-density lipoprotein fraction. Furthermore, LY295427 does not affect cholesterol biosynthesis, and it does not have a significant effect on cholesterol absorption. These data suggest that LY295427 acts in the hypercholesterolemic hamster by derepressing LDL-R transcription, thereby enhancing cholesterol clearance from the blood. The results with LY295427 suggest that compounds that act to increase LDL-R may represent a novel approach in the pharmacotherapy for hypercholesterolemia.

Acetates↗

Regulation of leaf initiation by the terminal ear 1 gene of maize.

Higher plants elaborate much of their architecture post-embryonically through development initiated at the tips of shoots. During vegetative growth, leaf primordia arise at predictable sites to give characteristic leaf arrangements, or phyllotaxies. How these sites are determined is a long-standing question that bears on the nature of pattern-formation mechanisms in plants. Fate-mapping studies in several species indicate that each leaf primordium becomes organized from a group of 100-200 cells on the flank of the shoot apex. Although molecular studies indicate that the regulated expression of specific homeobox genes plays some part in this determination process, mechanisms that regulate the timing and position of leaf initiation are less well understood. Here we describe a gene from maize, terminal ear 1. Patterns of expression of this gene in the shoot and phenotypes of mutants indicate a role for terminal ear 1 in regulating leaf initiation. The tel gene product contains conserved RNA-binding motifs, indicating that it may function through an RNA-binding activity.

Amino Acid Sequence↗