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Biomedical subjects

M L Smith

Publications and source records attributed to M L Smith.

At least 379 records · Page 21Linked to original sources
PubMed1986

Cardiovascular responses to lower body negative pressure in endurance and static exercise-trained men.

The cardiovascular responses to lower body negative pressure (LBNP) (to -50 torr) were examined in 8 sedentary control (UT), 8 endurance-trained (ET), and 8 weight-trained (WT) human subjects. The results were used to compare and contrast the blood pressure control system of the three subject groups. The primary differences in response included a more effective maintenance of blood pressure, by reason of greater stroke volume and cardiac indices of the WT subjects during LBNP (P less than 0.05). Peripheral vascular resistances were not different (P greater than 0.05) throughout LBN P between the three groups. Therefore, the improved blood pressure maintenance of the WT subjects was attributed to a cardiac effect. The ET subjects were less effective in maintaining blood pressure than UT or WT subjects. This finding was apparently due to an attenuated baroreflex sensitivity, as evidenced by a significantly (P less than 0.05) lower delta heart rate/delta systemic blood pressure ratio, 0.99 for ET vs 1.51 and 1.38 or the UT and WT groups respectively, calculated from the responses observed from 0 to -50 torr of LBNP.

Adult↗
PubMed1985

The vibrational bands of carbon monoxide bound to hemes or metal surfaces.

Infrared spectra of imidazole carbonyl complexes of 2,4-substituted hemes are presented. An increased CO stretch frequency is accompanied by a lowered FeC vibrational energy. Hartree-Fock-Slater electron structure calculations discern pi and sigma contributions to the observed shifts of vibrational energies. We conclude that an enhanced electron availability manifests itself as a lowered ferric/ferrous reduction potential, increased filling of the 2 pi orbital of liganded CO which in turn reduces nu CO and increases nu Fec, and increased basicity of the liganded CO. Analogies between CO liganded to heme and CO adsorbed onto metal surfaces are discussed.

Carbon Monoxide↗
PubMed1985

Spin and electron distributions in heme-cyanide models and hemeproteins.

Proton NMR spectra of low-spin Fe(III) cyanoprotoheme as prosthetic group in a number of proteins are presented. The diagonally positioned 1-, 5- and 3-, 8-methyl groups obey shifts proportional to the Fe(III)/(II) reduction potential Em7, which indicates a pseudo-contact interaction. The correlation with Em7 is understandable if one postulates an enhanced rhombic distortion, dominating the Fe-methyl dipolar interactions. Hartree-Fock-Slater quantum chemical calculations show no significant changes of spin density as a function of the Fe-L5 distance, except at the iron atom and predominantly in the 3dxz and 3dyz orbitals. 4p orbitals, on the other hand, uphold most of the changes of electron density. We also observe a principal difference in the amino acid sequences in the heme-accommodating pocket of oxygen carriers and two-electron transmitters.

Cyanides↗
PubMed1985

Effect of different degrees of brain ischemia and tissue lactic acidosis on the short-term recovery of neurophysiologic and metabolic variables.

The recovery of the EEG and somatosensory evoked responses (SER) as compared with recovery of the cerebral energy state was studied in rats during recirculation following different degrees of brain ischemia with varying tissue lactic acidosis. Reversible complete and incomplete ischemia was induced either by increasing the intracranial pressure (compression ischemia) or by carotid artery clamping combined with arterial hypotension. In incomplete ischemia the degree of tissue lactic acidosis was varied by manipulations of blood and brain glucose levels. Animals with an increase in brain lactate to about 25 mumol X g-1 (whole brain wet weight) during ischemia showed persistent failure of both cerebral energy metabolism and neurophysiologic restitution during the recirculation phase; if less than 20 mumol X g-1 metabolic recovery was almost complete. Despite a similar restitution of tissue energy metabolism in these animals, neurophysiologic recovery was inversely proportional to brain lactate concentrations during ischemia. At similar levels of ischemic tissue lactic acidosis, and despite a similar recovery of cortical energy state, the neurophysiologic restitution was clearly inferior after complete ischemia to that following incomplete ischemia. Three conclusions were drawn: (i) neurophysiologic variables were more sensitive indicators of postischemic persistent cerebral dysfunction than the cerebral energy state; (ii) the degree to which lactate accumulated in the ischemic brain influenced neurophysiologic restitution even if concentrations critical for metabolic recovery were not attained; and (iii) incomplete ischemia was less harmful than complete ischemia provided that tissue lactic acidosis was not excessive.

Acidosis↗
PubMed1985

11C-labeled 4-isopropylantipyrine: preparation and biological evaluation as a blood flow tracer in positron emission tomography (PET).

Radiolabeled 4-isopropylantipyrine (1) has been synthesized and evaluated as a tracer for the measurement of cerebral blood flow (CBF). Methylation of 4-isopropyl-3-methyl-1-phenylpyrazol-5-one (2) with [14C]methyl iodide in acetonitrile gave [14C]-1 in radiochemical yields of 10-20%. Its blood-brain partition coefficient in rats was determined to be 0.62 +/- 0.03 (mean +/- SE). Autoradiographic determination of regional cerebral blood flow under normal flow conditions indicated that [14 C]-1 gives results essentially identical with those obtained with the widely used tracer [14C]-4-iodoantipyrine ( [14C]-IAP). Studies performed in high-flow states indicated that [14C]-1 is not more diffusion limited than [14C]-IAP. A rapid synthesis was therefore developed for the preparation of [11C]-1. Radiochemical yields were increased to 40-50% when the alkylation of 2 with [11C]methyl iodide was performed in dimethyl sulfoxide using solid potassium hydroxide as a base. Since the 11C-labeled compound can easily be produced in large quantities and since the tracer is not diffusion limited at flow rates commonly observed in normal and most pathological states in man, [11C]-4-isopropylantipyrine will be used for in vivo studies of CBF using positron emission tomography.

Animals↗
PubMed1985

Lactic acidosis and recovery of mitochondrial function following forebrain ischemia in the rat.

The effect of different degrees of lactic acidosis on the recovery of brain mitochondrial function, measured as respiratory activity in isolated mitochondria or cortical concentrations of labile phosphates and carbohydrate substrates, was studied during 30 min of recirculation following 15 min of near-complete forebrain ischemia in rats. During ischemia, there was a marked decrease in mitochondrial State 3 respiration in vitro and a depletion of energy stores (i.e., phosphocreatine, ATP, glucose, and glycogen) in vivo that was similar in the high- and low-lactate ischemia groups. However, lactate concentrations differed markedly (20 and 10 mumol g-1, respectively). During recirculation, there was a near-complete recovery of both respiratory activity in vitro and adenylate energy charge (EC) in vivo regardless of the differences in lactic acidosis during ischemia. Respiratory activity and EC were well correlated. The changes in Ca2+ homeostasis during ischemia, an increase in tissue and a decrease in mitochondrial Ca2+ content, were reversed rapidly after ischemia in both high- and low-lactate ischemia animals and did not hinder an early recovery of mitochondrial function. It is concluded that lactic acidosis, with lactate levels reaching 20 mumol g-1 during 15-min ischemia, does not adversely affect early postischemic recovery of mitochondrial function.

Acidosis↗
PubMed1985

Lysosomal cystine storage in cystinosis and mucolipidosis type II.

Cultured fibroblasts from mucolipidosis II (ML-II) patients demonstrated an elevated cystine content which increased with time in culture compared to fibroblasts from cystinotic patients or normal controls under the same conditions. In both cystinotic and ML-II cells the increased levels of cystine could be derived either from endogenous proteolysis or from in vitro supplementation of the cultured cells with cysteine-glutathione mixed disulfide. Cystine was depleted from both cell types by cysteamine. When cysteamine was replaced with complete medium, the cystine reaccumulated in both cystinotic and ML-II cells within 24 h, although a lag of 4 h was seen with ML-II cells. The intracellular location of the increased cystine in cultured fibroblasts was examined utilizing free-flow electrophoresis and found to be in the purified population of secondary lysosomes of both cystinotic and ML-II cells. White blood cell and hepatic cystine, which was greatly increased in cystinotic patients, was not elevated in ML-II patients. Compared to normal control fibroblasts the efflux of cystine from isolated granular fractions was virtually absent in cystinotic fibroblasts and considerably reduced in ML-II fibroblasts. The examination of such similarities and differences in cystine accumulation and transport in tissues from cystinotic and ML-II patients has provided some insight into the defects in these diseases.

Cells, Cultured↗
PubMed1985

Frontal lobes and the temporal organization of memory.

Evidence for a major involvement of the frontal cortex in various aspects of the temporal organization of memory has emerged from the study of patients who had sustained a unilateral frontal- or temporal-lobe excision for the control of cerebral seizures. It has now been established that the frontal cortex participates in judgements of the temporal order of recent events and of their frequency of occurrence, as well as in the planning and monitoring of the execution of self-determined sequences of responses. Some differential effects related to the side of the lesion were observed, these depending both on the nature of the stimulus material used and on the special demands of the task.

Discrimination, Psychological↗
PubMed1984

Mutant hemoglobin stability depends upon location and nature of single point mutation.

The temperature dependence of the rates of heme release from the beta subunits of methemoglobin A and 5 beta mutant methemoglobins has been determined. The rates were largest for two hemoglobins with mutations distal to heme, previously known to be unstable. The other 3 mutants also released heme faster than A. These hemoglobins, with single point mutations at the alpha 1/beta 2 interface, were previously thought to be stable. The low reported yields of the 5 mutant proteins covaries with the relative rates of heme release from the met species.

Heme↗
PubMed1984

Improved lesion detection with dimethyl-amino-diphosphonate: a report of two cases.

In two patients with metastatic disease more lesions were detected on scintigraphs obtained with the 'low uptake' bone-scanning agent dimethyl-amino-diphosphonate. The results in these two patients provide practical support for the suggestion that bone-scanning agents with low uptake in normal bone, but high tumour-to-normal bone ratios, will allow better delineation of focal bone abnormalities.

Aged↗
PubMed1984

The density and distribution of ischemic brain injury in the rat following 2-10 min of forebrain ischemia.

The density and distribution of brain damage after 2-10 min of cerebral ischemia was studied in the rat. Ischemia was produced by a combination of carotid clamping and hypotension, followed by 1 week recovery. The brains were perfusion-fixed with formaldehyde, embedded in paraffin, subserially sectioned, and stained with acid fuchsin/cresyl violet. The number of necrotic neurons in the cerebral cortex, hippocampus, and caudate nucleus was assessed by direct visual counting. Somewhat unexpectedly, mild brain damage was observed in some animals already after 2 min, and more consistently after 4 min of ischemia. This damage affected CA4 and CA1 pyramids in the hippocampus, and neurons in the subiculum. Necrosis of neocortical cells began to appear after 4 min and CA3 hippocampal damage after 6 min of ischemia, while neurons in the caudoputamen were affected first after 8-10 min. Selective neuronal necrosis of the cerebral cortex worsened into infarction after higher doses of insult. Damage was worst over the superolateral convexity of the hemisphere, in the middle laminae of the cerebral cortex. The caudate nucleus showed geographically demarcated zones of selective neuronal necrosis, damage to neurons in the dorsolateral portion showing an all-or-none pattern. Other structures involved included the amygdaloid, the thalamic reticular nucleus, the septal nuclei, the pars reticularis of the substantia nigra, and the cerebellar vermis.

Animals↗
PubMed1984

Renal cell culture using autopsy material from children with cystinosis.

Renal cell cultures were initiated using fresh autopsy material from two individuals with cystinosis, ages 5 and 8 yr. Cells obtained from collagenase treated autopsy material were grown in a selective kidney medium containing Coon's modified F12, 2.5% fetal bovine serum, transferrin, insulin, selenium, hydrocortisone, PGE1, and fibronectin. These cells had an epithelial appearance, formed domes, and were periodic acid-Schiff positive. Both tight junctions and microvilli were seen by electron microscopy. Fibroblasts had a cloning efficiency of zero in the selective medium and grew poorly compared to their growth in Coon's F12 with 10% fetal bovine serum. The lysosomal cystine content of the renal cells was greatly elevated and comparable to that of fibroblasts from cystinotic patients. Renal cell lysosomal cystine levels were only partially reduced by exposure to either pantethine or the aminothiol, cysteamine. However, exposure to either compound effectively depleted cystinotic cultured fibroblasts of their lysosomal cystine. Study of cultured renal material may have practical significance in pharmacologic considerations.

Autopsy↗
PubMed1984

Differential effects of frontal-lobe lesions on cognitive estimation and spatial memory.

Patients with unilateral frontal- or temporal-lobe excisions and normal control subjects were tested on the recall of objects and of their location in an array. An incidental-learning situation was used, in which the task was presented as a test of the ability to estimate the prices of the objects. Patients with right frontal-lobe lesions were the only group impaired on price estimation, but a correlation was obtained between error-score in price estimation and lesion-size for the left frontal-lobe group. In contrast to patients with extensive right hippocampal excisions, both frontal-lobe groups were accurate on location-recall when tested immediately and again 24 hr later.

Adolescent↗
PubMed1984

Antiemetic efficacy of high-dose corticosteroids and droperidol in cisplatin-induced emesis: a controlled trial with droperidol and metoclopramide.

The nausea and vomiting associated with cisplatin chemotherapy make care of the patient more difficult for nurses and physicians, can cause severe metabolic and pathologic sequelae, and preclude further courses of chemotherapy. Current reports suggest that the two most efficacious agents for antiemetic prophylaxis are metoclopramide and corticosteroids. These two agents in combination with droperidol have been compared in a randomized controlled prospective fashion. Patients had less nausea and vomiting on the steroidal regimen than the nonsteroidal regimen (P less than 0.05), and the duration of nausea and vomiting was significantly less on the steroidal regimen (P less than 0.05). Patients expressed a preference for the steroidal regimen over the nonsteroidal one and the steroidal regimen retained its antiemetic effectiveness through repeated courses of chemotherapy. The results of the study suggest that corticosteroids and droperidol are superior antiemetic agents for cisplatin-induced nausea and vomiting.

Adrenal Cortex Hormones↗
PubMed1984

Transvaginal absorption of estrogens through irradiated mucosa.

Serum concentrations of unconjugated estrone (E1) and 17 beta-estradiol (E2) have been measured in eight patients before and after 1.25 mg of conjugated estrogens administered intravaginally. The measurements were repeated using 2 mg of micronized estradiol administered intravaginally 1 week later to six of the women and 7 months later in one. All the patients had completed a full course of irradiation for pelvic malignancy at least 8 months prior to the study. Baseline, 1/2, 1-, 2-, 4-, 8-, and 24-hr samples were analyzed. After conjugated estrogens mean serum E2 increased 4.5-fold to peak at 163 pg/ml at 2 hr while serum E1 increased 3.2-fold to peak at 222 pg/ml at 2 hr. After micronized E2 mean serum E2 increased 89.3-fold to peak at 1250 pg/ml at 1 hr while E1 increased 3.1-fold to peak at 416 pg/ml at 2 hr. These data indicate that rapid absorption of E1 and E2 occurs through irradiated vaginal mucosa.

Absorption↗
PubMed1984

Correlation of skeletal uptake of 99mTc-diphosphonate and alkaline phosphatase before and after oral diphosphonate therapy in Paget's disease.

In Paget's disease of bone, quantitation of skeletal uptake of radiolabeled diphosphonate has been proposed as a means of monitoring response to therapy. However, the validity of such techniques has been questioned during oral diphosphonate therapy because of possible interaction between oral and radiolabeled diphosphonate. In the present study 18 patients with Paget's disease received a 6 month course of oral diphosphonate therapy. Measurements of 24 h whole body retention (WBR) of 99mTc-labeled hydroxyethylidene diphosphonate (HEDP), serum alkaline phosphatase (SAP), and urinary hydroxyproline excretion were obtained before, during, and after treatment. WBR correlated well with SAP and urinary hydroxyproline throughout the course of therapy. In addition, the relationship between WBR and SAP was maintained after cessation of oral diphosphonate. It would thus appear that in Paget's disease 24 h WBR of HEDP, a quantitative measure of skeletal uptake of diphosphonate, will reflect disease activity even in the presence of an oral diphosphonate load.

Administration, Oral↗