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Biomedical subjects

D L Miller

Publications and source records attributed to D L Miller.

At least 343 records · Page 19Linked to original sources
PubMed1987

A mutation that alters the nucleotide specificity of elongation factor Tu, a GTP regulatory protein.

A single amino acid substitution (Asp to Asn) at position 138 of Escherichia coli elongation factor Tu (EF-Tu) was introduced in the tufA gene clone by oligonucleotide site-directed mutagenesis. The mutated tufA gene was then expressed in maxicells. The properties of [35S]methionine-labeled mutant and wild type EF-Tu were compared by in vitro assays. The Asn-138 mutation greatly reduced the protein's affinity for GDP; however, this mutation dramatically increased the protein's affinity for xanthosine 5'-diphosphate. The mutant protein forms a stable complex with Phe-tRNA and xanthosine 5'-triphosphate, which binds to ribosomes, whereas it does not form a complex with Phe-tRNA and GTP (10 microM). These results suggest that in EF-Tu.nucleoside diphosphate complexes, amino acid residue 138 must interact with the substituent on C-2 of the purine ring. Thus, in wild type EF-Tu, Asp-138 would hydrogen bond to the 2-amino group of GDP, and in the mutant EF-Tu, Asn-138 would form an equivalent hydrogen bond with the 2-carbonyl group of xanthosine 5'-diphosphate. Aspartic acid 138 is conserved in the homologous sequences of all GTP regulatory proteins. This mutation would allow one to specifically alter the nucleotide specificity of other GTP regulatory proteins.

Asparagine↗
PubMed1987

The comparative immunoreactivities of brain amyloids in Alzheimer's disease and scrapie.

An antibody was raised to a synthetic peptide corresponding to a published sequence for the first 24 residues of a cerebrovascular amyloid peptide (CVAP). Immunohistochemical staining of tissue sections revealed that the antibody bound extensively to cerebrovascular amyloid in Alzheimer disease (AD/SDAT) and Down's syndrome cases. The antibody bound less extensively to neuritic plaques (primitive and mature) and indetectably to neurofibrillary tangles. The antibody did not label scrapie plaques, scrapie-associated fibrils, or Gerstmann-Sträussler syndrome plaques. Immunoblotting experiments showed that the cerebrovascular amyloid peptide epitopes contaminating the neurofibrillary tangle preparations could be extracted with urea, leaving the neurofibrillary tangles intact. These data confirm that the cerebrovascular amyloid peptide is a component of cerebrovascular amyloid, and suggest that its epitopes are also components of neuritic plaque amyloid. The reduced level of immunostaining on amyloid cores in tissue sections suggests that either the cerebrovascular amyloid peptide epitopes are a minor component of amyloid cores, or that their mode of packing or state of processing in amyloid cores renders them relatively inaccessible to the antibody. We also conclude that the cerebrovascular amyloid peptide is not a component of neurofibrillary tangles. The synthetic cerebrovascular amyloid peptide possesses amyloid-like properties: at neutral pH it forms insoluble aggregates consisting of 5-7-nm fibrils, which form red-green birefringent adducts with Congo red and fluoresce with thioflavine S.

Alzheimer Disease↗
PubMed1987

Failure of Ivalon to provide permanent hepatic arterial occlusion.

Ivalon (polyvinyl alcohol) is a commonly used embolic agent, generally considered to be permanent. In a patient with the carcinoid syndrome, embolization of hepatic metastases with Ivalon failed to produce permanent occlusion, and recurrent tumor was supplied by many of the same small arteries identified on the original arteriogram. Occasionally, Ivalon may have only a temporary occlusive effect. A possible explanation for this phenomenon is proposed.

Adult↗
PubMed1987

Prospective study of the ability of computed axial tomography to localize gastrinomas in patients with Zollinger-Ellison syndrome.

The ability of routine computed tomography (CT) performed with oral and intravenous contrast to localize gastrinomas in 61 consecutive patients with Zollinger-Ellison syndrome was evaluated prospectively. The results of CT scanning were subsequently evaluated in all patients by either surgery, autopsy, or percutaneous biopsy. Thirteen of 14 patients with CT scans positive for hepatic metastases and 5 of 13 patients with CT scans negative for hepatic metastases were found to have gastrinoma in the liver. For gastrinoma metastatic to the liver, CT scanning had a specificity of 98%, a sensitivity of 72%, a positive predictive value of 93%, and a negative predictive value of 90%. Twenty-two of 23 patients with positive extrahepatic CT scans and 15 of 33 patients with negative extrahepatic CT scans were found to have extrahepatic gastrinomas. For extrahepatic gastrinoma, CT scanning had a specificity of 95%, a sensitivity of 59%, a positive predictive value of 96%, and a negative predictive value of 54%. The ability of CT scan to detect gastrinomas both in the liver and extrahepatically was directly related to tumor size, detecting 0% of tumors less than 1 cm and 83%-95% of tumors greater than 3 cm. The location of the extrahepatic gastrinoma was also an important determinant in that approximately 80% of pancreatic gastrinomas but only 35% of extrapancreatic gastrinomas were detected. The present results indicate that because of its convenience and accuracy, CT scanning with oral and intravenous contrast material should be the initial procedure to evaluate the extent of gastrinoma. A positive CT scan is almost always correct; therefore, a CT scan detecting metastatic gastrinoma to the liver would avoid unnecessary surgery and, if positive for extrahepatic gastrinoma, would assist the surgeon in finding the gastrinoma. A negative CT is less reliable; therefore, patients should undergo other localizing studies before exploratory laparotomy.

Biopsy↗
PubMed1987

Role of selective angiography in the management of patients with Zollinger-Ellison syndrome.

To determine the ability of selective abdominal angiography to localize gastrinoma in patients with Zollinger-Ellison syndrome, selective angiography was performed in 70 consecutive patients and the results were assessed prospectively by either surgery, autopsy, or percutaneous biopsy. In addition, to define the role of angiography in the management of patients with gastrinoma, we compared the results of angiography with those of computed tomography (CT) scanning in 58 patients who underwent both tests. For gastrinoma in the liver, angiography had a specificity of 100% and a sensitivity of 86% with a positive predictive value of 100% and a negative predictive value of 94%. For extrahepatic gastrinoma, angiography had a specificity of 94% and a sensitivity of 68%, a positive predictive value of 97% and a negative predictive value of 53%. Comparison of CT scanning and angiography demonstrated that for hepatic tumor CT demonstrated 72% and angiography 89% of tumors, and the combination detected all tumors with no false-positive results. Outside the liver, CT scanning detected 57%, angiography 70%, and the combination 73% of tumors with a false-positive rate of 7%. These results indicate that if a CT scan is performed first, then the addition of selective angiography will detect a further 28% of hepatic tumors and a further 16% of extrahepatic tumors, but that 24% of extrahepatic tumors will still be missed. Angiography is a useful adjunct to CT particularly in patients in whom surgery is contemplated.

Abdomen↗
PubMed1987

Effects of MHz ultrasound on electrical pain threshold perception in humans.

An electrode system was developed consisting of two 8 mm long 0.2 mm diameter silver-coated copper wires arranged parallel to each other 8 mm apart and held in contact with the skin by means of an acoustically transparent plastic adhesive tape. This system was attached to the upper arms of young adult volunteers who increased the voltage of the rectangular electrical pulses supplied to the electrodes until a reproducible sharp prickling pain sensation was perceived. A one inch diameter physiotherapy transducer was positioned over the electrode site so that ultrasound could be administered throughout the measurement period. The experiments were performed single blind to eliminate any subjective bias on the part of the volunteers. Preliminary experiments established that highly reproducible (+/- 3 to 4%) pain threshold perception values could be obtained, and that these values were not affected by changes in (a) the duration of the "on" time of the electrical pulses between 1.5 and 48 ms, (b) the contact pressure between the transducer and the electrode site, (c) the time interval between successive threshold measurements (providing that an unacceptable level of oedema was not produced around the electrodes), and (d) whether or not a test measurement was preceded by a control. Ultrasound exposure via a direct contact technique consistently produced a statistically significant (p less than 0.05) decrease in the perception threshold for electrical pain. This effect usually developed within 30-60 s and its magnitude increased both with increasing intensity (rising to 20.7 +/- 0.57% at an SATA intensity of 0.43 W/cm2 at 1.1 MHz) and with increasing frequency at the same ultrasonic intensity. Delivering the same amount of ultrasonic energy in the form of 2 ms bursts at several different peak intensities produced exactly the same reduction in pain threshold perception. These results indicate a thermal interaction mechanism, and similar threshold changes could be obtained by heating or cooling the electrode site by nonacoustic means. The inclusion of a thermocouple junction between the electrode wires showed that temperature increases of up to 10 degrees C could be produced when the transducer was in direct contact with the tape over the electrodes. The volunteers were not aware of these temperature increases which were primarily caused by heating of the transducer face. If the temperature of the skin surface is kept constant by interposing a thermostatted water path between the transducer and the electrode system, then similar ultrasound exposures had no detectable effects upon the electrical pain perception threshold.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

A review of the ultrasonic bioeffects of microsonation, gas-body activation, and related cavitation-like phenomena.

Ultrasonic exposures localized to regions smaller than a wavelength minimize the thermal mechanism, but promote nonthermal mechanisms of ultrasonic bioeffects. Microsonation experiments with vibrating needles or wires exploit this situation for the study of nonthermal mechanisms such as acoustic microstreaming flow. Shear stress in microstreaming flow, which is in excess of critical values for biomembranes, leads to cell lysis. Plane wave exposure of small bodies of gas also yields localized exposure, with further amplification of nonthermal mechanisms by resonance activation of oscillation. Gas body activation in vitro causes gathering of suspended cells by radiation forces, aggregation, cellular effects and lysis by microstreaming. When suitable gas bodies are present, these effects may occur at levels below the threshold for ultrasonic cavitation. In vivo, gas body activation generates intracellular microstreaming in Elodea leaves and disrupts the cells for super-critical shear stress levels. Similar phenomena seem to account for cell death, growth and mitotic index reductions in other plant tissues, and developmental abnormalities and delayed death in fruit flies. Only fragmentary and equivocal evidence presently exists on the medically relevant question of whether such subthreshold cavitation-like activity and bioeffects occur in vertebrates.

Animals↗
PubMed1987

Kinetics of light-dependent Ca fluxes across the plasma membrane of rod outer segments. A dynamic model of the regulation of the cytoplasmic Ca concentration.

We measured simultaneously in single toad rods the membrane photocurrent and the Ca concentration in a small volume surrounding the outer segment. Illumination causes a rise in the extracellular Ca concentration. Photocurrents and Ca concentration changes occur over the same range of light intensities. Analysis of the time course of the Ca concentration changes suggests that these concentration changes arise from the difference in the transport rates of light-activated Ca influx and efflux across the outer segment plasma membrane. The Ca influx occurs through the light-sensitive channels of the outer segment membrane and the efflux through Na/Ca exchangers. In 0.1 mM external Ca, approximately 1-2% of the dark current is carried by Ca ions. The Ca efflux in the dark is identical to the influx, approximately 2 X 10(6) ions/s. Upon illumination, the Ca influx decreases with a time course and light sensitivity identical to those of the photocurrent. The Ca efflux, on the other hand, has very different kinetics from those of the photocurrent. Upon illumination, the Ca efflux decreases with a time course and light sensitivity determined by the change in membrane voltage and in the free cytoplasmic Ca concentration near the plasma membrane. In response to bright stimuli, which saturate the photocurrent for prolonged periods of time, the Ca efflux decays with an exponential time course from its value in darkness. The average time constant of this decay is 2.5 s. From the kinetics of the light-activated Ca fluxes, it is possible to predict that illumination causes a decrease in the cytoplasmic Ca concentration. We present a model of the regulation of the cytoplasmic Ca concentration by the dynamic balance of the Ca influx and efflux from the rod outer segment. The model accounts for our experimental observations and allows us to predict the time course and extent of the light-dependent decrease in the free cytoplasmic concentration.

Animals↗
PubMed1987

Localization of parathyroid adenomas in patients who have undergone surgery. Part I. Noninvasive imaging methods.

The authors evaluated computed tomography (CT), ultrasound (US), technetium/thallium scintigraphy, and magnetic resonance (MR) imaging as localization procedures in 53 patients with proved parathyroid adenomas and previous unsuccessful parathyroid surgery. CT had the highest overall sensitivity (47%), followed by US (36%) and scintigraphy (27%). There is still too little data to assess MR imaging. Adenoma size affected the sensitivity of CT, scintigraphy, and MR imaging but not US. When all three studies were used, at least one study depicted a lesion in 78% of patients, but definitive localization (two positive studies) was achieved in only 31%.

Adenoma↗
PubMed1987

Localization of parathyroid adenomas in patients who have undergone surgery. Part II. Invasive procedures.

The authors studied intraarterial digital subtraction angiography (DSA), conventional selective angiography, parathyroid venous sampling (PVS), and intraoperative ultrasound (US) as localization procedures for parathyroid adenomas in 53 patients with proved parathyroid adenomas and previous unsuccessful parathyroid surgery. PVS had the highest overall sensitivity as a single study (80%), followed by intraoperative US (78%), angiography (60%), and DSA (49%). Invasive procedures permitted successful localization of adenomas in 41 of 43 patients studied (95%). False-positive studies were uncommon. The optimum sequence of invasive localization procedures is determined by clinical factors and not by the sensitivity of individual tests. The authors recommend DSA be performed first, followed by angiography, PVS, and intraoperative US, in that order.

Adenoma↗
PubMed1987

Fentanyl and diazepam for analgesia and sedation during radiologic special procedures.

Fentanyl is a synthetic narcotic which, when administered intravenously, has a rapid onset and short duration of action. It produces less cardiovascular depression than either meperidine or morphine. Experience with 100 examinations performed using intravenous fentanyl and diazepam for analgesia and sedation in adults is reviewed. There were no complications, and effective analgesia was obtained in all cases. Fentanyl has distinct pharmacologic advantages over both morphine and meperidine for use in radiologic special procedures.

Adolescent↗
PubMed1987

Liver metastasis detection: comparative sensitivities of MR imaging and CT scanning.

Twenty patients with known liver metastases were evaluated by unenhanced computed tomography (CT), scans enhanced with ethiodized oil emulsion-13 (EOE-13), and magnetic resonance (MR) imaging with three pulse sequences. Spin-echo (SE) 300/26 (repetition time/echo time, in msec) images prospectively demonstrated 95.4% of the detectable liver metastases; inversion recovery (IR) 1,500/100 (repetition time/inversion time, in msec) images revealed 90.8%; and EOE-13-enhanced CT scans showed 87.1%. SE 2,000/80 images showed 51.4%, and unenhanced CT scans 49.6%, of the metastases. The relationship of vascular anatomy to metastatic foci was best seen on SE 300/26 images and EOE-CT scans. SE 300/26, IR 1,500/100, and EOE-CT studies particularly improved detection of lesions in the 1-2-cm range compared with SE 2,000/80 imaging or unenhanced CT scanning. SE 300/26 and IR 1,500/100 sequences appear comparable to EOE-CT scans in demonstrating liver metastases and significantly superior to conventional CT scans. Because EOE-13 is generally not available, these MR sequences should be the procedure of choice for the diagnosis of liver metastases.

Carcinoma↗
PubMed1987

Distribution of iodized oil within the liver after hepatic arterial injection.

Radiography and microscopy were used to investigate the hepatic distribution of iodized oil injected into the hepatic artery in a rabbit VX2 tumor model. Iodized oil accumulates within hepatic metastases and in a ringlike fashion around them. Radiographic and histologic appearances were correlated, and it was concluded that ringlike deposition occurs in peritumoral sinusoids. There was no evidence that iodized oil is cleared by hepatic lymphatics. Early clearance of iodized oil into bile may possibly be caused by localized hepatic ischemia from oil microemboli or by direct phagocytosis by Kupffer cells. The remaining oil is washed through hepatic vasculature, circulates systemically, and is cleared by reticuloendothelial cells in lung, spleen, liver, and bone marrow. This mode of clearance, which has not been considered previously, may be important in the prediction of toxic effects caused by lipid and lipophilic antitumor agents administered via the hepatic artery.

Animals↗
PubMed1987

Identification of ACTH-producing intrathoracic tumors by measuring ACTH levels in aspirated specimens.

Three patients with Cushing syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) production underwent direct 22-gauge needle aspiration of bronchial (two cases) and mediastinal (one case) carcinoid tumors. High levels of ACTH were measured in all three tumors. This technique permits absolute identification of an ectopic source of ACTH before surgery.

ACTH Syndrome, Ectopic↗
PubMed1987

Angiographic ablation of parathyroid adenomas: lessons from a 10-year experience.

Angiographic ablation of parathyroid adenomas with ionic contrast material was performed in 24 patients with persistent hyperparathyroidism who had undergone at least one prior unsuccessful surgical resection; 23 had mediastinal adenomas. The success rate was 83% at 1 month after ablation and 71% at both 5 and 9 years. Ablation was successful in 85% of the patients in whom the catheter could be wedged into the artery feeding the adenoma. Long-term success was achieved in 89% of the patients in whom contrast enhancement persisted in the adenoma on computed tomographic scans obtained 24 hours later. Acute complications were seen only in patients with glands supplied by the inferior or superior thyroid arteries. Long-term complications were limited to permanent hypocalcemia, present in 8% of patients. Even if unsuccessful for ablation, the procedure may provide localization and does not preclude surgical resection. It is recommended for most patients with persistent hyperparathyroidism and mediastinal adenomas, especially adenomas supplied by the internal thoracic artery.

Adenoma↗