Multi-university residency training.
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District of Columbia↗
Biomedical subjects
M S Smith
Publications and source records attributed to M S Smith.
The regulation of regional hemodynamics by alpha-1 adrenoceptor subtypes in the conscious rat.
The role of alpha-1 adrenoceptors sensitive and resistant to chloroethylclonidine (CEC) in the regulation of peripheral hemodynamics in the conscious rat has been examined. CEC treatment (15, 25 or 30 mg/kg i.p.) resulted in a sustained decrease in systemic arterial blood pressure and heart rate. These same concentrations reduced, but did not eliminate, [3H]prazosin binding sites in vascular smooth muscle homogenates. The effect of CEC administration on blood flow and regional vascular resistance was assessed using pulsed-Doppler flow probes implanted around the superior mesenteric and iliac arteries. CEC treatment resulted in a significant decrease in mesenteric and hindlimb resistance. Prazosin (3 or 5 mg/kg) reduced systemic arterial blood pressure and vascular resistance to a greater degree than did CEC. The dose-response curve for phenylephrine-induced increases in mesenteric or hindlimb vascular resistance was shifted only 2- to 10-fold to the right by CEC. Prazosin, by contrast, shifted the phenylephrine dose-response curve over 100-fold to the right. These data indicate that multiple alpha-1 adrenoceptor subtypes, both CEC sensitive and insensitive, participate in the regulation of blood flow to the gut and the hindlimb. Finally, CEC sensitive sites do not appear to play as prominent a role as insensitive sites in mediating the pressor response to phenylephrine.
Animals↗
Viral association with Crohn's disease.
Crohn's disease is an inflammatory disorder of the gastrointestinal tract, the cause of which remains unknown. Since the first description by Dalziel in 1913 (1), similarities between Crohn's disease and intestinal mycobacterial infection, particularly Johne's disease in ruminants, have been widely recognized (2, 3). After Mitchell and Rees demonstrated the transmission of granulomata from Crohn's disease by injecting intestinal homogenates into the footpads of mice (4), there followed many studies attempting to identify infective agents within the bowel of patients with Crohn's disease. Although Mycobacterium paratuberculosis has been identified in intestinal tissue from a proportion of patients with Crohn's disease, a convincing role for this agent in the aetiology of Crohn's disease has not been established (5). Likewise, extensive studies into bacterial (6-9) and viral (10) agents potentially associated with Crohn's disease have been inconclusive, although recent ultrastructural observations of viral particles within submucosal granulomata have added a new impetus to the search (11, 12). This review examines the evidence for an association between Crohn's disease and viral infection from epidemiological studies, transmission and cell culture, specific immunological responses, ultrastructure and from molecular biological techniques.
Antibodies, Viral↗
c-Fos and Fos-related antigens as markers for neuronal activity: perspectives from neuroendocrine systems.
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Animals↗
Ranitidine has no effect on postbreakfast ethanol absorption.
The effect of ranitidine, the H2-receptor antagonist, on the systemic bioavailability of ethanol (0.3 g/kg body weight) taken orally 1 h after breakfast, was investigated in a randomized, placebo-controlled, double-blind cross-over study. Twenty normal male subjects (age, 19-26 yr) were studied on the morning of the 8th day of twice-daily dosing with either 150 mg ranitidine or placebo. Plasma ethanol concentration was measured by the alcohol dehydrogenase method from 0 to 240 min after oral ingestion of ethanol (100% ethanol made up to 200 ml orange juice). Compared with placebo, dosing with ranitidine resulted in nonsignificant changes in either the mean integrated 4-h plasma ethanol concentration (27.8 vs. 32.4 mg.h/dl), the peak plasma ethanol concentration (18.0 vs. 21.1 mg/dl), or the time to peak (43 vs. 40 min). There is no clinically important interaction between ranitidine and a low dose of ethanol taken orally 1 h after breakfast.
Administration, Oral↗
Ganglionic and arterial release of neuropeptide Y by bullfrog sympathetic neurons.
Sympathetic C neurons in lumbar paravertebral ganglia of the bullfrog have previously been shown to be vasomotor in function and to express neuropeptide Y (NPY). In the present experiments, a sensitive radioimmunoassay was used to measure the NPY content of ganglia and the descending abdominal aorta and to measure the overflow of NPY evoked by depolarizing concentrations of K+. Paravertebral ganglia 9 and 10 contain 3.1 pg NPY/micrograms protein and the aorta contains 0.18 pg NPY/micrograms protein. During 20-min depolarizations in high K+ (58 mM) Ringer, the ganglia released approximately 5% of their NPY content and the aorta released approximately 2% of its NPY content. Pretreatment of the tissues with Ringer containing 0.18 mM Ca2+, 8 mM Mg2+, and 1 mM Co2+ blocked the NPY release elicited by high K+. These findings provide further evidence that NPY is a postganglionic co-transmitter in sympathetic C neurons of the bullfrog.
Animals↗
Functional neurolobectomy induced by controlled compression of the pituitary stalk.
Degeneration of magnocellular nerve terminals in the neurohypophysis was induced by compressing the pituitary stalk of anesthetized rats for 30 s using a triangle-shaped wire. Immediately after stalk compression (SC), rats exhibited markedly increased water intake characteristic of diabetes insipidus, followed by a triphasic pattern of fluid intake. In SC rats, arginine vasopressin (AVP) and oxytocin (OT) contents of the neurointermediate lobe (NIL) of the pituitary gland were significantly reduced to approximately 2.5% and approximately 10% of sham-operated controls, respectively. In contrast, OT, but not AVP, content of the stalk-median eminence (SME) of SC rats was significantly increased. Histological examination of the pituitaries showed substantial degeneration of the neural lobe with very scarce AVP-neurophysin and OT-neurophysin immunoreactivity, while both the anterior and the intermediate lobes appeared to be intact. Plasma AVP and OT responses to infusion of hypertonic NaCl were significantly blunted in SC rats compared to sham-operated controls. However, two days after surgery the secretory patterns of LH in SC rats were similar to those in the controls. These results indicate that controlled compression of the pituitary stalk results in selective degeneration of the neural lobe without causing permanent ischemic damage to the anterior pituitary, and produces marked sustained functional deficits in pituitary AVP and OT secretion. Consequently, SC provides an alternative means to achieve selective neurolobectomy in rats.
Animals↗
Studies of the role of the N-methyl-D-aspartate (NMDA) receptor in the hypothalamic control of prolactin secretion.
To further examine the role of excitatory amino acids in the control of prolactin (PRL) secretion, the effects of administering a specific agonist and an antagonist of the N-methyl-D-aspartate (NMDA) receptor on plasma PRL concentrations were examined in the adult male rat. Animals of the Sprague-Dawley strain weighing 250-300 g were implanted with an indwelling cardiac catheter via the right jugular vein. Blood samples were collected through the catheter at 5 min intervals for 40 min, beginning 5 min before the iv administration of drug or the saline vehicle (V). Plasma PRL and luteinizing hormone (LH) concentrations were estimated using RIAs. Groups of animals (n = 5-7) received N-methyl-D,L-aspartate (NMA), D,L-2-amino-5-phosphonopentanoic acid (AP5), AP5 and NMA, norvaline (NOR), or V. The effects of administering the NMDA receptor antagonist alone were studied on two separate occasions. Injection of NMA (4.5 mg/rat) resulted in unambiguous PRL and LH discharges. Treatment with AP5 (9 mg/rat) 1 min prior to NMA administration completely blocked the LH releasing action of NMA, but did not significantly alter the discharge of PRL. Injection of AP5, alone, generally elicited a distinct and robust discharge of PRL, although plasma LH levels in these animals remained unchanged. NOR, an amino acid structurally related to AP5, administered at a dose (5.3 mg/animal) isomolar to that of AP5, was without effect on PRL and LH secretion, as was injection of V alone. These findings suggest that neuroexcitatory amino acids acting at the NMDA receptor may play a role in modulating the activity of neuronal systems that govern the release of both PRL releasing factor (PRF) and PRL inhibiting factor (PIF) into hypophysial portal blood.
Animals↗
Acute myocardial infarction in chest pain patients with nondiagnostic ECGs: serial CK-MB sampling in the emergency department. The Emergency Medicine Cardiac Research Group.
STUDY OBJECTIVES: This study tested the hypothesis that serial creatine phosphokinase (CK)-MB sampling in the emergency department can identify acute myocardial infarction (AMI) in patients presenting to the ED with chest pain and nondiagnostic ECGs. DESIGN: Patients more than 30 years old who were evaluated initially in the ED and hospitalized for chest pain were studied. Serial CK-MB levels were analyzed prospectively using a rapid serum immunochemical assay for identification of AMI patients in the ED. Presenting ECGs showing new, greater than 1-mm ST elevation in two or more contiguous leads were considered diagnostic for AMI. All other ECGs were considered nondiagnostic ECGs. CK-MB levels were determined at ED presentation and hourly for three hours (total of four levels). Patients with at least one level of more than 7 ng/mL were considered to have a positive enzyme study. The in-hospital diagnosis of AMI was determined by the development of typical serial ECG changes or separate standard cardiac enzyme changes after admission. SETTING: Eight tertiary-care medical center hospitals. METHODS AND MAIN RESULTS: Of the 616 study patients, 108 (17.5%) were diagnosed in the hospital as AMI; 69 of these AMI patients (63.9%) had nondiagnostic ECGs in the ED. Of the patients with nondiagnostic ECGs, 55 (sensitivity, 79.7%) had a positive ED serial CK-MB enzyme study within three hours after presentation. Combining serial ED CK-MB assay results with diagnostic ECGs yielded an 88.4% sensitivity for AMI detection within three hours of ED presentation. The predictive value of a negative serial ED enzyme study for no AMI was 96.2% (specificity, 93.7%). CONCLUSION: Serial CK-MB determination in the ED can help identify AMI patients with initial nondiagnostic ECGs. Use of serial CK-MB analysis may facilitate optimal in-hospital disposition and help guide therapeutic interventions in patients with suspected AMI despite a nondiagnostic ECG.
Adult↗
Tissue-specific expression of kallikrein family transgenes in mice and rats.
To define the regulatory strategy for the transcriptional control of the kallikrein multigene family, we analyzed the expression of several kallikrein/SV40 T-antigen (TAg) fusion genes in transgenic mice and rats. Kallikrein family members are normally expressed at a high level in the submandibular gland and are expressed in a wide range of tissues that vary among individual family members. A total of 1.7 kb of proximal 5'-flanking DNA from the tissue kallikrein gene (rKlk1) was sufficient to confer much of the correct tissue-specific pattern on a TAg reporter gene. TAg mRNA was detectable in tissues that normally express rKlk1 and TAg-induced tumors arose in brain and pancreas. However, absolute levels of transgene mRNA were very low relative to the expression of the normal endogenous tissue kallikrein gene. In particular, expression in the salivary glands, normally very high for endogenous rKlk1, was either low or absent. An intact rKlk1 transgene with extensive flanking DNA (4.5 kb 5' and 4.7 kb 3') and complete intragenic (4 kb) sequences was expressed similarly to the fusion transgene, demonstrating that regulatory elements necessary for comprehensively correct expression are not contained within these additional gene regions. Two additional kallikrein/SV40 fusion transgenes were derived from other family members, one from the rKlk2 gene, which encodes tonin, and another from the rKlk8 gene, which encodes a prostate kallikrein. Whereas the endogenous rKlk2 and rKlk8 genes normally are expressed at high levels in rat salivary glands, they were not expressed in the salivary glands as transgenes. The results for these transgenes of three different family members indicate that control elements that direct the particular nonsalivary gland expression pattern characteristic of each family member may be present within the proximal 5'-flanking region of each gene, whereas regulatory sequences necessary for normal levels of expression in these tissues and for maximal salivary gland expression are not. We propose that the gene-associated regulatory sequences are complemented by a dominant control region that imposes salivary gland expression on the extended kallikrein family locus.
Animals↗
Subclinical central nervous system infection with JC virus in patients with AIDS.
Immunocompromised patients, particularly those with AIDS, develop progressive multifocal leukoencephalopathy (PML) due to central nervous system infection with JC virus (JCV). It is unknown whether JCV infection in the central nervous system can occur in the absence of PML symptoms. To address this question, autopsy specimens from patients with AIDS were examined. The brains of a group of patients without AIDS or central nervous system disease were also examined. JCV DNA was detected by the polymerase chain reaction in brain tissue from 4 (31%) of 13 human immunodeficiency virus (HIV)-positive patients. JCV was also detected in 1 elderly HIV-negative patient but not in the 11 other control brains. JCV was not detected in 22 myocardial specimens obtained at autopsy from HIV-negative patients nor 10 peripheral blood specimens from HIV-positive patients. The presence of JCV in brains of patients without clinically evident PML suggests that JCV may be present in the central nervous system without clinical disease.
Acquired Immunodeficiency Syndrome↗
The induction of neural tube defects by maternal hyperthermia: a comparison of the guinea-pig and human.
In our recent studies on the effects of maternal hyperthermia on the embryonic guinea-pig, we have demonstrated two 'teratogenic windows' at embryonic days 13 and 21 (E13 and E21). E13 encompasses the period of the closure of the neural groove and anterior neuropore, and E21 the commencement of the cortical plate. The approximate equivalent developmental times in the human are E23-E25 and E49-E56 respectively. In the guinea-pig, maternal hyperthermia at E13 results in a high incidence of neural tube defects (NTD), many open, and associated with other defects such as microphthalmia, and scoliosis or kyphosis. The NTD were most common in the developing hindbrain and all demonstrated considerable infoldings of neural tissue, rosettes of neuroepithelial cells, outpocketings of neural tissue and large cystic cavities beneath the defect. In human examples from the Kyoto Human Embryo Collection, 16 had verified hyperthermic insults at E23-E25 and all had NTD which showed similar deformities to the guinea-pig. Most embryos with such gross defects are aborted in the early fetal period in both species.
Animals↗
Competition between Two Isolates of Denitrifying Bacteria Added to Soil.
We examined the competitive relationship between two isolates of denitrifying bacteria, both of which grow well under aerobic conditions but differ in their ability to grow under denitrifying conditions. The growth and persistence of the two isolates, added to sterile soil or added to soil previously colonized by the other isolate, were monitored under aerobic and denitrifying (anaerobic) conditions. When isolates were added together to sterile soil, the isolate added at the higher density reduced the growth of the isolate added at the lower density. The magnitude of the growth reduction varied depending on the competitive abilities of the individual isolates and the aeration state of the soil. Prior colonization of soil with one of the isolates conferred a competitive advantage on the colonized isolate but did not lead to the disappearance of the challenging isolate. Fluctuations in aeration state caused large changes in the population density of one isolate and altered the competitive relationship between the two isolates. The competitive effectiveness of each isolate varied with cell density, the degree of prior colonization of the soil by the other isolate, and the aeration state of the soil.
Journal Article↗
LHRH neurons express cJun protein during the proestrous surge of luteinizing hormone.
LHRH neurons express cFos on the afternoon of proestrus in association with the ovulatory LH surge. This study determined whether LHRH neurons express another proto-oncogene product, Jun, during the estrous cycle. By using immunocytochemical double staining techniques, localization of Jun proteins and LHRH was compared with expression of cFos in LHRH neurons. LHRH neurons expressed Jun proteins on the afternoon of proestrus with detection of Jun through the morning of estrus. The time course of Jun expression in LHRH neurons during proestrus suggests a common stimulus for both Jun and cFos expression in LHRH neurons, with Jun proteins persisting somewhat longer than cFos. Pentobarbital, which blocks the preovulatory LH surge and cFos expression in LHRH neurons, blocked Jun expression in LHRH neurons; the LHRH neurons similarly expressed Jun and cFos on the following afternoon at the time of the expected delayed LH surge. There was a similarity in the patterns (in terms of numbers and distribution) of Jun-positive and cFos-positive LHRH neurons. Both were localized in the preoptic area and anterior hypothalamus; LHRH neurons above the anterior commissure or rostral to the OVLT did not express Jun or cFos. For the first time, these data provide direct evidence that both proto-oncogene products, Jun and cFos, are expressed in LHRH neurons in association with the proestrous LH surge. Taken together, these results suggest that changes in gene expression mediated by Jun-cFos heterodimers may accompany LHRH activation on the afternoon of proestrus.
Animals↗
The biomethylation of sodium arsenate by rat liver cytosol determined by mass spectrometry.
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Animals↗
Myelopathy in a patient dually infected with HIV-1 and HTLV-I.
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Acquired Immunodeficiency Syndrome↗
Immunity to rabies after administration of prophylactic human diploid-cell vaccine.
The immune status to rabies of 14 volunteers was determined using the commercially available Trousse Platelia Rage (Diagnostics Pasteur) enzyme immunoassay test system. Twelve subjects were evaluated before and between 6 months and 60 months after prophylactic intramuscular (deltoid) administration of rabies human diploid-cell vaccine, while the effect of booster doses on a further 2 volunteers was evaluated over an 11-year period. Optical density values were converted to international units to allow correlation with World Health Organisation seroneutralisation references. Values of greater than or equal to 0.5 IU are considered protective. The results showed that most individuals were still immune 2 years after vaccination; there was a tendency for serum antibody levels to decrease over a 5-year post-vaccination period. Antibody levels rose sharply after booster immunisation, after which they decreased at a much slower rate. In general, results revealed that after the first booster, additional booster vaccinations at 5-yearly intervals would provide adequate prophylactic immunity. There was, however, much individual variation, which emphasises the need to evaluate each individual at regular and shorter intervals to determine the need for booster vaccine doses. The test method employed is economical and well suited to such evaluations.
Antibodies, Viral↗
Mexiletine versus quinidine as first-line antiarrhythmia therapy: results from consecutive trials.
The efficacy of mexiletine and quinidine in controlling ventricular couplets (VC) and ventricular tachycardia (VT) was compared in 156 trials (78 for each drug) in 114 consecutive patients. Forty-two patients received both drugs, whereas 36 patients were given mexiletine, and 36 patients received quinidine only. During acute drug testing, mexiletine was more effective than quinidine in controlling VC and VT (54 vs. 32 patients, respectively, P less than .001) and resulted in fewer proarrhythmic events (4 vs. 13, respectively, P less than .05). Mean duration of follow-up for mexiletine (27 +/- 14 mo) and quinidine (21 +/- 14 mo) did not differ. Long-term success was more frequent with mexiletine administration than quinidine administration (33/47 vs. 10/30 patients, respectively, P less than .01). The incidence of sudden death during follow-up with the two drugs did not differ overall, but more patients with ejection fraction greater than or equal to 40% died suddenly while taking quinidine than while receiving mexiletine (4/17 vs. 0/24, P less than .02). Mexiletine is as effective as quinidine for treating VC and VT and appears to be less proarrhythmic. It should be considered as an initial choice in the management of VC and VT.
Aged↗