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Biomedical subjects

R C Smith

Publications and source records attributed to R C Smith.

At least 145 records · Page 8Linked to original sources

Effect of epidermal growth factor on prostate cancer cell line PC3 growth and invasion.

Elevated levels of epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) have been demonstrated in prostate cancer cell lines and clinical specimens suggesting a role for polypeptide growth factors in prostate tumor cell growth and invasion. To more clearly define the role of EGF in prostate cancer invasion, we undertook a series of studies utilizing the PC3 prostate cancer cell line, an aggressive, hormone-independent cell line derived from a metastatic lesion. No statistical differences were noted in the growth of PC3 cells under serum-free conditions when EGF (10(-10) M-10(-8) M) or monoclonal anti-EGF-R antibody (10(-11) M-10(-8) M) were added. Utilizing the Boyden chamber microinvasion assay, EGF supplemented cells demonstrated a statistically significant augmentation in invasion (P < 0.05) when compared to control cells at each time point in the study. With increasing length of exposure to EGF, the number of concentrations that produced significant invasion increased: day 1 (10(-8) M), day 3 (10(-8), 10(-9) M), and day 5 (10(-7), 10(-8), 10(-10) M). Northern blot analysis of EGF supplemented cells revealed an increase in expression of urokinase plasminogen activator (uPA) RNA, a serine protease involved in the regulation of pericellular proteolysis and membrane degradation. Protein analysis confirmed these findings. Statistically significant inhibition of invasion by anti-uPA antibodies was demonstrated for EGF-stimulated and PC3 control cells. Our results demonstrate that certain concentrations of EGF augment invasion in the PC3 cell line. This enhancement of invasion occurs in part by an overproduction of uPA, an extracellular protease. These findings suggest that the autocrine production of EGF may potentiate tumor cell invasion.

Antibodies, Monoclonal↗

The maternal histone H1 variant, H1M (B4 protein), is the predominant H1 histone in Xenopus pregastrula embryos.

The Xenopus laevis H1M protein (formerly called B4) is a maternally inherited histone H1 subtype restricted in its expression to early development. Levels of H1M, as well as of the somatic histones H1A, H1B, and H1C, were determined during early embryogenesis using subtype-specific anti-peptide antisera. H1M accumulates late in oogenesis to a titer of approximately 1 ng/unfertilized egg. Following fertilization, H1M persists at slowly decreasing titers for 3 days of development. In contrast, somatic H1 histones are virtually absent from eggs and cleavage-stage embryos (< 80 pg/egg for H1A, < 2 pg/egg for H1B and H1C). H1M thus represents the predominant histone H1 variant in embryos until the beginning of gastrulation, when the amount of newly synthesized H1A increases beyond the 1 ng level. By in situ immunofluorescence, H1M is detected in association with egg and embryonic chromosomes. When expressed at high levels by transient transfection in a Xenopus cell line, H1M competes for chromatin binding with resident H1A. High-level expression of either H1M or H1A causes aberrant chromatin condensation in the transfected cells.

Amino Acid Sequence↗

Overexpression of XMyoD or XMyf5 in Xenopus embryos induces the formation of enlarged myotomes through recruitment of cells of nonsomitic lineage.

The myogenic regulatory factors (MRFs) MyoD and Myf5 are the earliest described muscle-specific genes to be expressed in Xenopus development. To study the in vivo effects of overexpressing Xenopus MyoD and Myf5, synthetic RNAs were microinjected into single blastomeres of 2- to 32-cell stage Xenopus embryos. In vivo overexpression of these MRFs initiates the precocious and ectopic expression of actin and myosin. The effects of unilateral injection of either mRNA were indistinguishable; embryos injected at the 2-cell stage showed ipsilaterally enlarged cranial and anterior trunk myotomes composed of increased numbers of primary myotome myocytes. In addition, formation of ectopic muscle in lateral plate and neural tissue was observed. The MRF-induced effects persist through secondary myogenesis, with the enlarged cranial myotomes failing to undergo the normal program of degeneration. Experiments combining MRF RNA and lineage tracer injections showed that myotomal enlargement is due in part to the contribution of cells of nonsomitic lineage to the myotome, rather than to an increase in muscle precursor cell division. Overexpression of XMyoD and XMyf5 also affected the morphogenesis of the skin and the nervous system. These results reveal that overexpression of XMyoD or XMyf5 in vivo clearly influences the regulation of early myogenesis and the morphogenesis of skin and nervous tissue.

Animals↗

The efficacy of intensive biopsychosocial teaching programs for residents: a review of the literature and guidelines for teaching.

OBJECTIVE: To review research evaluations of intensive biopsychosocial training programs for nonpsychiatry residents, and determine whether this research showed sufficient rigor and consistent beneficial impact to allow initial research-based teaching guidelines. DATA SOURCES: An English-language literature search used MEDLINE (1966-93), Psychological Abstracts (1967-93), and Educational Resource Information Clearinghouse (1966-93) as well as bibliographic reviews from prominent peer-reviewed articles and consultation with an expert. STUDY SELECTION: From among several hundred articles about biopsychosocial training, only 12 studies met the selection criteria: at least 100 contact hours of training for nonpsychiatry residents and an evaluation of efficacy. DATA EXTRACTION: The three authors independently assessed these 12 studies and made a consensus decision based on explicit criteria. Successful and unsuccessful programs were distinguished from among those classified as quasi-experimental or experimental to identify programs of sufficient rigor to meet the study objective; success was defined as learning beyond knowledge and residents' acceptance of teaching. DATA SYNTHESIS: Four successful quasi-experimental or experimental programs showed the following uniquely beneficial features: 1) protected time for residents; 2) teaching that was required, structured, multidimensional, and balanced between learner-centered and teacher-centered approaches; 3) teaching methods that used normal as well as psychosocially disturbed patients, nonpsychiatrist teachers, and special teaching techniques; and 4) inclusion in the curriculum of interviewing, interpersonal skills, doctor-patient relationship, and patient education. Two unsuccessful quasi-experimental or experimental programs were unidimensional and unstructured, and used predominant or isolated teacher-centered approaches. Features found in both successful and unsuccessful programs were experiential teaching, psychiatrist and other mental health professional teachers, use of disturbed patients, training to manage patients' psychosocial problems, teaching directed toward knowledge acquisition, teaching about treatment, and university affiliation. CONCLUSIONS: Four rigorously studied, successful programs showed a common pattern of intensive biopsychosocial teaching that produced, in aggregate, improvement in residents' knowledge, attitudes, skills, and self-awareness. Although there is need for more definitive research, these data are sufficiently compelling and consistent to provide initial, research-based teaching guidelines.

Curriculum↗

Denture tooth selection: size matching of natural anterior tooth width with artificial denture teeth.

This project, conducted by the Removable Prosthodontic faculty, compared the mesiodistal widths of the six maxillary anterior teeth with the widths of denture teeth from six different denture tooth manufacturers. Four hundred eighty-eight casts of dental students were measured from the distal aspect of each canine across the facial surfaces of the six anterior teeth with a flexible plastic millimeter rule. Denture teeth from six manufacturers were compared (370 molds). The results indicated that denture teeth are predominantly smaller and natural teeth are larger.

Cuspid↗

The effect of dipeptide structure on dipeptide and amino acid clearance in rats.

The kinetics of disappearance from the blood of GlyTyr, TyrArg, AlaTyr, TyrAla, GlnGly, GlyGln, GlnAla, and AlaGln and their constituent amino acids was assessed in anesthetized (pentabarbitone) Sprague-Dawley rats (n = 5 for each peptide). Catheters were inserted into both internal jugular veins. A bolus injection of dipeptide was administered into one catheter, and rapid blood samples were taken from the other catheter for measurement of dipeptide and amino acid concentrations. Kinetic parameters for the disappearance of dipeptides and of the amino acids released from the dipeptides from the blood were calculated using standard equations. All dipeptides were cleared rapidly from the blood (clearances ranged from 42.9 +/- 3.28 mL/min/kg body weight for GlyGln to 278 +/- 70.7 for GlnAla, mean +/- SD). Glutaminyl dipeptides with alanine or glycine in the C-terminal position or dipeptides with alanine in the N-terminal position had the greatest clearance values and the shortest half-lives (t1/2). There were significant differences (P < .001) in the volume of distribution of the dipeptides. Many dipeptides had volumes of distribution greater than the blood volume of the animals. The amino acids released from the dipeptides had a longer t1/2 (P < .001) than their parent dipeptides. The t1/2 and the weight-corrected area under the blood concentration-versus-time curve (AUC) of the same amino acid released from different dipeptides differed (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Gallstone ileus: post cholecystectomy.

A case of gallstone ileus occurring 5 months after laparoscopic cholecystectomy is presented. The possible aetiology is discussed and the literature regarding consequences of intraperitoneal stone spillage reviewed.

Cholecystectomy, Laparoscopic↗

Predictive value of symptom profiles in patients with suspected oesophageal dysmotility.

The main aim of the study was to determine prospectively, in patients referred for oesophageal manometry, whether certain combinations of oesophageal symptoms are more likely than others to predict the presence of oesophageal dysmotility or a positive response to acid perfusion testing. In 524 consecutive patients, presenting predominantly with (non-cardiac) chest pain (n = 277), dysphagia (n = 186), or heartburn (n = 61), a standardized symptom assessment was completed before oesophageal manometry and acid perfusion testing. Half the patients in each group reported additional ('secondary') oesophageal symptoms as well as the predominant symptom. Oesophageal dysmotility was categorized in accordance with standard manometric criteria for achalasia, diffuse oesophageal spasm, nutcracker oesophagus, hypertensive lower oesophageal sphincter, or non-specific oesophageal motility disorder. In the predominant chest pain group, the prevalence of abnormal manometry was 33%; in the presence of secondary symptoms, especially dysphagia rather than heartburn, however, the prevalence was significantly (p < 0.01) increased. Also in the predominant chest pain group the prevalence of positive acid perfusion testing (44%) was significantly greater (p < 0.05) in those with than in those without secondary symptoms. In the predominant dysphagia group, the prevalence of abnormal manometry was higher than in the other two groups (56%; p < 0.001) but was not affected by the presence or absence of secondary symptoms; this latter finding was also true for the predominant heartburn group. The distribution of specific manometric disorders in any group was not related to the presence or type of secondary symptoms, although a combination of dysphagia and chest pain discriminated achalasia from other manometric disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Aphasia↗

MR of the head and neck: comparison of fast spin-echo and conventional spin-echo sequences.

PURPOSE: To compare conspicuousness of head and neck lesions on fast spin-echo sequences and conventional spin-echo sequences. METHODS: Forty consecutive patients with 61 head and neck lesions were evaluated. Lesion conspicuousness was qualitatively compared on conventional spin-echo and fast spin-echo sequences, using both spin-density and T2-weighted images. Thirty-six lesions had surgical or pathologic confirmation, and 25 were assigned a presumptive diagnosis based on clinical evaluation and imaging findings seen on conventional spin-echo T1- and T2-weighted sequences. Forty lesions were related to neoplasms; 21 lesions consisted of infectious, vascular, or inflammatory abnormalities. RESULTS: Fast spin-echo sequences provided improved lesion conspicuousness in 91% of spin-density images, in 77% of T2-weighted images, and in 84% of the combined spin-density and T2-weighted images. CONCLUSION: By providing shorter imaging times and equal or superior lesion conspicuousness, long-repetition-time fast spin-echo sequences can replace long-repetition-time conventional spin-echo sequences in evaluation of the head and neck.

Adipose Tissue↗

Magnetic resonance staging of neoplasms of the uterus.

The treatment of patients with uterine neoplasms may be significantly altered by the stage of disease at the time of diagnosis. A noninvasive and accurate means of staging these tumors is therefore desirable. This article discusses the magnetic resonance imaging techniques and findings that are essential for the accurate staging of uterine neoplasms. The imaging findings are presented following a discussion of the histopathologic findings, clinical presentation, diagnosis and staging, pathways of tumor spread, and treatment of each neoplasm. A comparison of magnetic resonance and other imaging techniques is also provided.

Combined Modality Therapy↗

Reversal of copper(II)-induced methemoglobin formation by thiols.

Oxyhemoglobin is oxidized to methemoglobin by copper(II) in a two-stage reaction that results in conversion of Fe(II) to Fe(III) in heme of the beta subunits, but not the alpha subunits. Glutathione and other thiols, which are slowly oxidized by Cu(II), protect oxyhemoglobin from Cu(II)-induced oxidation. In the present studies, when oxyhemoglobin was first oxidized to methemoglobin by Cu(II) and thiols such as glutathione added to the sample, methemoglobin was reduced to oxyhemoglobin. Once reduction of methemoglobin stopped, as the thiol was oxidized, the oxyhemoglobin formed was reoxidized by Cu(II). The addition of the same thiols to methemoglobin formed by autoxidation did not reduce it to oxyhemoglobin. The addition of thiols such as cysteine, which are rapidly oxidized by Cu(II), to methemoglobin formed by incubation with Cu(II) also resulted in reduction of methemoglobin, but the period of reversal was much shorter than that seen with glutathione and other less reactive thiols. When cysteine and glutathione were added together to Cu(II)-induced methemoglobin, the rate of reduction and reoxidation was intermediate to that seen when either was added separately. When EDTA was added to a system in which oxyhemoglobin was undergoing Cu(II)-induced oxidation, oxidation of oxyhemoglobin ceased and there was no reduction of the methemoglobin to oxyhemoglobin. When both glutathione and EDTA were added to this system, the response was the same as with EDTA alone, suggesting that Cu(I) or (II) may be required for the reduction of copper-induced methemoglobin by thiols. These studies show that thiols that are slowly oxidized by Cu(II) both protect oxyhemoglobin from Cu(II)-induced oxidation, and reduce the methemoglobin formed to oxyhemoglobin.

Copper↗

Use of in vitro fertilization for production of calves from involuntary cull cows.

PURPOSE: The main purpose of the study was to assess the feasibility of a combined system for in vitro maturation of oocytes, in vitro fertilization, and in vitro culture of embryos for production of calves from cows that have to be removed prematurely from production units. RESULTS: Eighteen cows that were to be culled from experimental dairy production units were ovariectomized. An average of 45.7 oocytes per cow was collected from the ovaries. After in vitro maturation and fertilization of the oocytes, an average of 40.8 presumptive zygotes was placed into in vitro culture, with an average of 16.1 cleaving by day 2 and an average of 5.7 developing to morulae/blastocysts by day 6 or 7. A greater mean quantity of oocytes was collected from cows that were ovariectomized between day 5 and day 13 of the estrous cycle than from those that were ovariectomized between day 0 and day 3 of the estrous cycle. Correspondingly larger mean numbers of cleaved zygotes and morulae/blastocysts were produced from the cows that were ovariectomized between day 5 and day 13 of the cycle. Transferable embryos were produced from 17 of the 18 cows. Eighteen embryos from six oocyte donor cows were transferred to recipients. Six of the eighteen recipients were confirmed to be pregnant after 40 days. Three of the pregnant recipients delivered live calves at term. Two others remain pregnant but have not reached term. The sixth recipient aborted at approximately 120 days of gestation. CONCLUSIONS: Results from the preliminary study indicate that this system can be used for production of calves from cull cows. Although transferable embryos were produced from all except one cow, there was a high degree of variability among cows in total number of oocytes recovered and embryos produced. More donors need to be evaluated to determine the effects of age, breed, reason for culling, and source of semen.

Animals↗

Organ clearance of tyrosyl-arginine and its effect on amino acid metabolism in young sheep.

In a long-term multiple-catheter sheep model (n = 5), organ clearance of the dipeptide tyrosyl-arginine (TyrArg) and its effects on interorgan amino acid metabolism were investigated. Clearance by hindlimb and splanchnic tissues was measured during infusion into the external iliac artery and superior mesenteric artery, respectively. The hindlimb, intestine, and total splanchnic region removed 32% +/- 9.2% (mean +/- SE), 23% +/- 15%, and 33% +/- 24%, respectively, of the amount of TyrArg infused. There was a large release of tyrosine and arginine when TyrArg was infused into either the hindlimb or intestine, which was quantitatively similar to the TyrArg taken up by these organs. However, across the total splanchnic region, the baseline influx of tyrosine and arginine was not altered by infusion of TyrArg. During either clearance study, only trace amounts of TyrArg or its constituent amino acids were excreted in urine. Infusion of TyrArg produced the following effects on interorgan amino acid metabolism: (1) a reduction in the initial efflux of phenylalanine, leucine, isoleucine, and valine from the hindlimb; (2) a reduction in net efflux of citrulline by the intestine and total splanchnic tissues; and (3) a reduction in efflux of arginine and uptake of citrulline from the kidney. In conclusion, we have shown that TyrArg is cleared from the bloodstream by hindlimb (predominantly muscle) and splanchnic tissues. These results indicate that TyrArg taken up by the hindlimb and intestine was hydrolyzed to its constituent amino acids, which were released quantitatively into the circulation. Of the tissues studied, only the liver appeared to use the amino acids liberated from hydrolysis of TyrArg.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Continuous hepatic artery infusion of 5-fluorouracil for metastatic colorectal cancer localised to the liver.

Continuous regional delivery of chemotherapeutic agents offers the prospect of maximising dose intensity at the site of localised disease, while minimising systemic toxicity. This prospective phase II study evaluates the efficacy and toxicity of hepatic arterial infusion of 5-Fluorouracil (5-FU) via an implantable Infusaid pump in previously untreated patients with localised but unresectable hepatic metastases from colorectal cancer. In 25 patients the response rate was 56% and median survival was 15 months, comparable to previous reports utilising fluorodeoxyuridine (FUDR). Twenty per cent of patients (all responders) survived longer than three years. Systemic toxicity was trivial, and the practice of reducing the intensity of therapy when nausea or a rise in alkaline phosphatase occurred avoided the previously described local toxicity of biliary sclerosis seen frequently with FUDR. In selected patients, particularly those with more limited disease, this form of therapy is effective and well tolerated and warrants further evaluation as an alternative to FUDR.

Colorectal Neoplasms↗

Inversion-recovery fast spin-echo MR imaging: efficacy in the evaluation of head and neck lesions.

To compare the efficacies of fast spin-echo (FSE) and inversion-recovery FSE (IRFSE) magnetic resonance (MR) imaging in evaluating head and neck disorders, the authors evaluated 46 lesions in 23 consecutive patients. Twenty-seven lesions were related to neoplasms; 19 lesions resulted from infectious, allergic, or radiation-induced inflammation. Conventional T1-weighted, FSE, and IRFSE images were obtained in all patients. The FSE and IRFSE images were qualitatively compared in an unblinded manner for conspicuity of lesion margins and extent. IRFSE imaging improved conspicuity of 22 lesions (48%) and showed equal conspicuity of 18 (39%). IRFSE imaging proved most useful for small lesions with long T2 relaxation times that were surrounded by fat. IRFSE imaging improved visibility of small optic nerve gliomas, salivary gland inflammation, peripheral nerve tumors, and small lymph nodes. Early changes secondary to spread of tumor across fascial planes were also well visualized with IRFSE sequences. In six lesions (13%) that did not have long T2 relaxation times, the FSE images provided better conspicuity. The authors conclude that by improving conspicuity of small lesions adjacent to or surrounded by fat, IRFSE sequences can supplement FSE sequences in imaging the head and neck.

Adolescent↗

Evidence for absorption of silicon and aluminum by hens fed sodium zeolite A.

The mechanism of action of zeolite A (ZA) on eggshell quality could be related either to its ion-exchange properties or to individual ZA elements (Al or Si). Two experiments were conducted to determine 1) whether any ZA passes through the digestive system in its original form; and 2) whether any Al and Si absorption occurs. In Experiment 1, unfed hens were intubated with either 0 or 5 g ZA at oviposition. In Experiment 2, fed and unfed hens were intubated at oviposition with 0, 1, or 2 g ZA. At the subsequent oviposition, liver and kidney tissues, excreta, urine, bile, and plasma were collected and analyzed for Al, Si, Na, K, and P. The results indicated that approximately 7% of the intubated ZA passed through the digestive system in its original form (Experiment 1). As the intubated level of ZA increased, excreta Al and Si (P < .0001), urine Si (P < .005), and urine Al (P < .07) also increased (Experiment 2). Aluminum recovery from excreta ranged from 75 to 93% of the quantity intubated in all treatments. Corresponding values of Si from excreta of unfed and fed hens ranged from 76 to 81% and 58 to 60%, respectively. The P content of excreta was not influenced by ZA. However, excreta P was greater (P < .0001) in unfed than in fed hens. Neither plasma electrolytes (Na, K, and P) nor Al or Si levels in either liver or kidney were influenced by ZA.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗