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Biomedical subjects

D Miller

Publications and source records attributed to D Miller.

At least 505 records · Page 28Linked to original sources
PubMed1987

Effect of permanently charged and uncharged dopaminergic agonists on the potassium-induced release of [3H]acetylcholine from striatal slices.

The effects of chemical analogs of dopamine, which are permanently charged or which lack a net positive charge, on the potassium-evoked release of [3H]acetylcholine from mouse striatal slices were studied in order to determine whether a positive charge on the dopamine agonist molecule is required to activate dopaminergic receptors. The striatal slices were first preincubated with [3H]choline, transferred to a superfusion chamber, and then superfused in physiological medium. [3H]Acetylcholine release was evoked by exposure of the slices to a high potassium medium and potential dopamine agonist drugs were added to the medium 10 min before superfusing with high potassium. A permanently charged quaternary ammonium analog and dimethylselenonium analog of dopamine inhibited the potassium-evoked release of [3H]acetylcholine, and this inhibition was antagonized by sulpiride, a dopamine receptor antagonist. However, this inhibition was not antagonized by reserpine and alpha-methyl-p-tyrosine, which was shown to completely antagonize the inhibitory effect of amphetamine, an indirectly acting amine. This suggests that the charged dopamine analogs are acting directly on dopaminergic receptors. In contrast to the permanently charged dopamine analogs, analogs of dopamine with no net positive charge produced no inhibition of the potassium-evoked [3H]acetylcholine release. These in vitro observations are in agreement with a behavioral model in which a permanently uncharged monomethylsulfide analog of dopamine was ineffective in eliciting circling behavior after its unilateral injection into the striatum of rats in which dopamine neurons were previously lesioned by the injection of 6-hydroxydopamine into the medial forebrain bundle. In contrast, under these same conditions, the intrastriatal injection of the charged quaternary ammonium or dimethylsulfonium analog of dopamine elicited intense contralateral circling. These results suggest that the charged form of a dopamine agonist molecule is required to bind to and activate the dopamine receptor regulating [3H]acetylcholine release and circling behavior.

Acetylcholine↗
PubMed1987

Branhamella catarrhalis keratitis.

Branhamella catarrhalis, formerly known as Neisseria catarrhalis, has structural similarities to Neisseria gonorrhoeae, but is generally considered to be nonpathogenic. We studied the clinical and laboratory data of four previously reported cases and six additional cases of B. catarrhalis keratitis. All patients had a predisposing ocular or systemic condition, or both. There were various clinical characteristics, but in most cases the infiltrate occurred in the central or paracentral cornea. A prompt response to treatment with a cephalosporin and aminoglycoside antibiotic was noted in all cases. Two patients had corneal perforations, which probably resulted from a delay in treatment. Gram-negative diplococci from corneal scrapings may not necessarily represent N. gonorrhoeae.

Adolescent↗
PubMed1987

Antibody to human T-lymphotropic virus type 1 in West-Indian-born UK residents with spastic paraparesis.

Of 13 West-Indian-born UK residents with spastic paraparesis of unknown cause, 11 were tested for serum antibody to human T-cell lymphotropic virus type 1 and all were positive. Their magnetic resonance imaging scans were normal or showed only minor abnormalities in the brain, and the spinal cord was normal in the 5 investigated. Of 48 patients with multiple sclerosis, mainly caucasian, none had antibody to HTLV-1 in the blood.

Adult↗
PubMed1987

The potential relationship of maternal toxicity, general stress, and fetal outcome.

Standard teratology bioassays generally call for a top dose level which is sufficient to induce some form of overt maternal toxicity such as death or weight loss. The presence of such maternal toxicity is often a confound in the interpretation of experimental results, especially at those dose levels producing the toxicity. While the physiological bases for the toxicity vary widely in a compound-related fashion, one underlying factor that remains constant for most induced toxicity is the presence of generalized stress in the affected animals. Previous studies have indicated that pregnant animals treated acutely with toxic levels of a variety of pharmacologically unrelated chemicals produced litters without a recognizable syndrome of defects, except for an increased incidence of supernumerary ribs (SNR). The present study reports on the effects of immobilization stress on the production of SNR in the Sprague-Dawley rat and the CD-1 mouse. Pregnant animals were immobilized in the supine position for 12-hour periods during the day of greatest sensitivity to SNR production (days 9 and 10 in the mouse and rat, respectively). Animals were killed immediately before term and the fetuses were examined. An increase in SNR was noted in immobilized mice but not rats. These results suggest that such fetal effects may be the result of general agent-induced maternal stress.

Abnormalities, Drug-Induced↗
PubMed1987

Unproportionally high concentrations of diadenosine triphosphate (Ap3A) and diadenosine tetraphosphate (Ap4A) in heavy platelets. Consequences for in vitro studies with human platelets.

Platelets from whole blood were separated into five density subpopulations using a discontinuous Percoll gradient. The content of diadenosine triphosphate (Ap3A), diadenosine tetraphosphate (Ap4A), ADP and ATP were determined in the subfractions. The dinucleotides were directly measured in neutralized, acid-soluble extracts of human platelets with a bioluminescence method not requiring any chromatographic step. When comparing the nucleotide contents of the density subpopulations it became evident that all nucleotides steadily increased with increasing density. Ap3A, Ap4A, ADP and ATP were present in 10-, 7-, 4- and 2-fold higher amounts in the heaviest platelets, respectively, as compared to the subfraction with the lowest density. This finding is practically relevant since the most dense platelet subpopulations may be lost during conventional centrifugation to obtain platelet-rich plasma. Therefore we compared a platelet population obtained from PRP with the platelet population, which had been prepared from whole blood by means of a continuous Percoll gradient. All the four nucleotides investigated were represented in 1.5- to 2-fold higher amounts in the whole blood platelet population. This indicates that PRP does not contain a representative population but lacks part of the large heavy platelets containing the highest amounts of nucleotides.

Adenine Nucleotides↗
PubMed1987

Heart rate variability power spectrogram as a potential noninvasive signature of cardiac regulatory system response, mechanisms, and disorders.

This paper attempts to provide evidence that the heart rate variability power spectrum (HRVPS) reflects the presence of neural control of cardiac regulation. A normal individual is seen to have a characteristic HRVPS (comprising a 0.1-Hz peak and a respiratory peak at 0.25-0.34 Hz), which is altered in a predictable manner in response to orthostatic stress and exercise, while in two patients with autonomic neuropathy, the HRVPS failed to demonstrate such a characteristic alteration in response to orthostatic stress. Postinfarct HRVPS signatures were studied in two patients with anterior and inferior infarcts so as to lend insight using non-invasive means into both the healing process and the dominant deliterious sympathetic or protective vagal tone due to the infarct. When subjects with transplanted hearts were studied, their HRVPS did not exhibit the characteristic pattern of a normal individual; rather, the HRVPS energy was spread over a wider and higher frequency range. However, one of the transplanted patients surprisingly but consistently revealed the characteristic HRVPS; the post-transplant time at the time of the study was 33 months and the patient had the typically high resting heart rate of a transplant recipient but a wide standard deviation like that of a normal individual. This could be the first noninvasively demonstrated evidence in humans of reinnervation of a transplanted heart. Thus, the HRVPS constitutes a simple non-invasive method to assess cardiac neuroregulatory response and disorders and it is proposed that it be referred to as the heart rate variability cardiogram (HRVC).

Adult↗
PubMed1987

Serum lipids and lipoproteins after myocardial infarction: associations with cardiovascular mortality and experience in the Aspirin Myocardial Infarction Study.

Serum cholesterol and triglyceride levels were measured at baseline in 4021 men and 503 women (myocardial infarction survivors) participating in the Aspirin Myocardial Infarction Study (AMIS). A cohort of participants (1824 men and 226 women) had, in addition, a determination of high-density lipoprotein (HDL) cholesterol and an estimate of low-density lipoprotein (LDL) cholesterol. In comparison with values obtained for normal Americans by the Lipid Research Clinics Prevalence Study Group, AMIS participants had higher serum cholesterol, higher serum triglyceride, higher LDL cholesterol, and lower HDL cholesterol levels. These values were the most disparate in the women and younger men. The serum total cholesterol, the ratio of LDL to HDL cholesterol, and the serum triglyceride level were significantly related (p less than 0.05) to the 3-year cardiovascular mortality rate for men less than 55 years of age (univariate relationships). For men older than 55 years, these relationships were not statistically significant. After adjustment for multiple risk factors, serum cholesterol and the ratio of LDL to HDL cholesterol remained significant risk factors for cardiovascular death and the combined incidence of cardiovascular death or nonfatal myocardial infarction in men less than age 55 years.

Adult↗
PubMed1987

The binding of an aminoazo dye carcinogen to a specific methionine residue in rat liver alcohol dehydrogenase in vivo.

On the administration of 3'-methyl-N,N-dimethyl-4-aminoazobenzene to rats pure aminoazo dye-bound alcohol dehydrogenase accounting for 45% of the total soluble protein bound aminoazo dye is isolated from the liver soluble supernatant. Tryptic digestion of that purified aminoazo dye-bound enzyme yields an aminoazo dye-bound nonapeptide which has a sequence identical to amino acids 301-309 in the known sequence of alcohol dehydrogenase (H. Jornvall and O. Markovic, Eur. J. Biochem., 29 (1972) 167-174) with the exception of methionine 306 which is replaced by an aminoazo dye modified amino acid. The nature of the aminoazo dye adduct was determined by studying the structure of the related tetrapeptide obtained by Pronase B digestion and shown by proton NMR spectroscopy and fast atom bombardment mass spectroscopy to have the structure 3-(Val. Asn. Pro. Homocystein-S-yl)-4-methylamino-3'-methylazobenzene. This carcinogen-protein adduct is assumed to arise from attack of the ultimate carcinogenic metabolite, N-sulphonyloxy-4-methylamino-3'-methylazobenzene (FF. Kadlubar, J.A. Miller and E.C. Miller, Cancer Res., 36 (1976) 2350-2359) at the sulphur of methionine 306 followed by spontaneous S-demethylation. This highly specific reaction of carcinogen with alcohol dehydrogenase lowers its Vmax and increases its Km with cyclohexanone thereby reducing its catalytic efficiency for this substrate. This highly specific reaction of the carcinogen with alcohol dehydrogenase may be regarded as a major detoxication reaction.

Alcohol Dehydrogenase↗
PubMed1987

Angiographic evidence of basilar artery constriction in the rabbit: a new model of vasospasm.

The main objective of this study was to produce angiographic evidence of basilar artery constriction using the rabbit model. The technique described involves the transdural injection of blood into the cisterna magna on two different days. The results obtained show that vasoconstriction occurs over a time period that is comparable in duration to that seen in patients undergoing vasospasm as a result of subarachnoid hemorrhage. Further investigation should be done to evaluate the usefulness of the rabbit model as a verifiable tool in studying the etiology of vasospasm.

Animals↗
PubMed1987

Central nervous system (CNS) prophylaxis in children with low risk acute lymphoblastic leukemia (ALL).

Five hundred four children with low risk acute lymphocytic leukemia (previously untreated, age 3 to 6 years with white blood counts less than 10,000/mm3 at diagnosis) were randomized into two different central nervous system prophylaxis regimens. One regimen (250 patients) consisted of cranial radiation and intrathecal methotrexate (IT MTX). The second regimen (254 patients) consisted of IT MTX only. Median follow-up time for surviving patients is currently 54 months from randomization. Life table analysis of central nervous relapse, marrow relapse, disease-free survival, and survival shows very similar outcome for both treatment groups. The results indicate that maintenance IT MTX as described in this report can be substituted for cranial radiation in children with low risk ALL.

Central Nervous System↗
PubMed1987

Radionuclide cineangiography in acute myocardial infarction: role in prognostication.

Radionuclide-based procedures have achieved frequent application in acute myocardial infarction (MI). While these methods can be employed in diagnosis and assessment of therapy, diagnosis usually can be made more easily and with less expense when other methods are employed. Assessment of therapy, while potentially of value, has not been evaluated in a manner which can provide practical guidelines for clinical application. Practical utility has been associated with the use of radionuclide-based techniques in prognostication after infarction; this application is crucial to the formulation and optimization of management decisions. While myocardial perfusion scintigraphy and infarct-avid-agent imaging have been employed in prognostication after infarction, the largest body of prognostic data are available in association with radionuclide cineangiography. When determined in the early hours after infarction, a left ventricular ejection fraction (LVEF) less than 30% indicates a high likelihood of in-hospital mortality, irrespective of the site of infarction. When determined shortly prior to hospital discharge, LVEF less than 30% indicates a high likelihood of posthospital mortality, perhaps as high as 25% during the first year, and reaching 30% by the end of 2 years after infarction. Conversely, LVEF greater than or equal to 30% indicates an 8% 2-year postinfarction mortality risk. While LVEF is a highly potent risk descriptor, considerable evidence suggests the LVEF determined during exercise prior to hospital discharge also provides risk stratification, and may be superior to, or at least additive to, LVEF at rest as a prognostic index.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗
PubMed1987

The influence of dose and dose rate of total lymphoid irradiation in the rat cardiac allograft model.

Immunosuppression generated by total lymphoid irradiation (TLI) may be of use in solid organ transplantation. We have investigated the use of TLI in the rat cardiac allograft model. Lewis rats received TLI from a cobalt-60 machine. The daily dose was 1.25 Gy and treatments were administered 4 days per week. We performed experiments to assess the effect of dose rate upon graft survival. The dose rate was varied by changing the source to animal distance and by using a lead attenuator. Cardiac allografts from each ACI donor rat were transplanted to the recipient Lewis rat's abdomen utilizing microvascular surgical technique. Heart graft survival times (GST) were monitored by direct palpation of the cardiac impulse. Immune function was measured by an activity index of the mixed lymphocyte reaction. In the absence of any immunosuppression there was a mean GST of 6.9 +/- 0.3 days. When a graft was placed the day following completion of TLI, there was an increase in GST as the total TLI dose was increased. Mean GST (+/- S.E.) following 5, 10, and 15 Gy were 12.3 +/- 1.3, 14.5 +/- 1.3, and 25.5 +/- 1.1 days, respectively. Following 20 Gy, GST decreased because of irradiation induced pulmonary toxicity and host death. When 3.5 weeks were allowed to elapse between the completion of TLI and transplantation, GST were less than those seen with equivalent doses of TLI and early transplantation. Mean GST following 5, 10, and 15 Gy and a delayed transplant were 7.2 +/- 0.1, 10.7 +/- 1.2, and 19.0 +/- 3.5 days, respectively. We tested the effect of dose rate upon GST.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Corneal ulcer due to Listeria monocytogenes.

We present a patient with a corneal ulcer due to Listeria monocytogenes, which has not previously been considered to be a feature of human listeriosis. The ulcer responded to topical and subconjunctival gentamicin and cephaloridine. Subsequent management was complicated by the development of a fibrinous pupillary membrane leading to pupillary block requiring iridotomy and later vitrectomy with trabeculectomy. Listeria monocytogenes may be confused with diphtheroid contaminants seen in corneal ulcer scrapings and is probably underreported as a cause for microbial keratitis.

Aged↗
PubMed1987

Caustic ingestion and its sequelae in children.

Management of caustic ingestion in children remains a difficult challenge, with the outcome ranging from an asymptomatic state to intractable esophageal strictures. We reviewed the cases of 56 children ranging in age from 10 months to 5 years treated from 1973 to 1984 at the University of Florida. For children seen primarily at our institution, initial management consisted of prompt endoscopy and early institution of steroids and antibiotics. Esophageal burns were confirmed in 37 patients, 21 (56.75%) of whom subsequently had esophageal strictures of varying severity. In seven patients, limited esophageal strictures were managed successfully by dilation, but 14 children with multiple strictures required eventual esophageal replacement. Substernal right colonic interposition was tolerated well by these patients, with few complications, and their growth and development have been satisfactory over follow-up periods ranging from nine months to 13 years. A review of these cases suggests that the character of the ingested caustic material is the most important determinant of the severity of esophageal injury, with preparations containing lye being the most injurious; that in the presence of full-thickness esophageal injury, there is a high potential for stricture formation, regardless of the type of initial management, including early use of steroids; and that multiple esophageal strictures are refractory to dilation, and esophageal replacement should be an early consideration.

Black or African American↗
PubMed1987

Association of serum iron, serum transferrin saturation, and serum ferritin with survival in acute lymphocytic leukemia.

The present investigation was motivated from the consideration that a host environment rich in iron, represented by high serum transferrin saturation (TS) and high serum iron and serum ferritin levels might offer favorable growth conditions for leukemic cells in addition to infection, thus affecting survival. Serum measurements were obtained on 113 pediatric patients with acute lymphoblastic leukemia (ALL), seen at Memorial Sloan-Kettering Cancer Center between May 20, 1981 and August 8, 1983. A significant difference (p less than 0.001) was found between the survival of patients according to whether their first measured TS was greater than 36% or less than 36%, with fewer deaths in the group with TS less than 36. The relationship between TS and survival was still observed when patients were stratified according to length of time from diagnosis, risk group, French-American-British (FAB) classification, or presence of organomegaly at diagnosis (p less than 0.001). Similar differences were observed between survival of patients grouped according to their first measured serum ferritin. These results independently confirm and extend observations presented earlier and support the consideration that motivated this study. The value of serum iron-related measurements as prognostic variables cannot be established from this type of study; however, these findings suggest the need for a prospective study.

Child↗
PubMed1987

Dimethylthetin can substitute for glycine betaine as an osmoprotectant molecule for Escherichia coli.

Glycine betaine is believed to be the most active naturally occurring osmoprotectant molecule for Escherichia coli and other bacteria. It is a dipolar ion possessing a quaternary ammonimum group and a carboxylic acid group. To examine the molecular requirements for osmoprotective activity, dimethylthetin was compared with glycine betaine. Dimethylthetin is identical to glycine betaine except for substitution of dimethyl sulfonium for the quaternary nitrogen group. Dimethylthetin was found to be about equally as effective as glycine betaine in permitting E. coli to grow in hypertonic NaCl, and both compounds were recovered almost completely from bacterial cells grown in the presence of hypertonic NaCl. 3-Dimethylsulfonioproprionate, an analog of dimethylthetin observed in marine algae, and 3-Dimethylsulfonio-2-methylproprionate were found to be less active. Dimethylthetin may prove useful as a molecular probe to study betaine metabolism and as a model for the development of antibacterial agents.

Betaine↗
PubMed1987

Relationship between simian virus 40 large tumor antigen expression and tumor formation in transgenic mice.

A line of transgenic mice containing the simian virus 40 (SV40) large tumor antigen gene under the control of the viral enhancer-promoter expressed this viral protein in the brains of these mice within the first 2 weeks after birth. Multiple foci of anaplastic cells formed in the choroid plexuses of these mice at 36 to 41 days after birth, and normal tissue coexisted with these transformed foci. Immunoperoxidase staining to detect the SV40 T antigen showed tumor-specific expression of nuclear T antigen at late times in tumor development, approximately 90 to 100 days and thereafter. The level of SV40 T antigen, on a per cell basis, appeared to be lower in the great majority of choroid plexus cells at earlier times in tumor development. These results suggest that low levels of tumor antigen (14 to 36 days) are present before detectable pathology (36 to 41 days) and the level of T antigen per cell is higher in rapidly growing late-stage tumors (older than 90 days).

Animals↗