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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 685 records · Page 38Linked to original sources
PubMed1994

High passage T47D human breast cancer cells: altered endocrine and 2,3,7,8-tetrachlorodibenzo-p-dioxin responsiveness.

Low passage (L) T47D cells cultured for up to 12 months in media containing fetal bovine serum, fetal bovine serum plus 1 nM 17 beta-estradiol and estrogen-deficient media gave high passage cells denoted H, H(E+) and H(E-) cells, respectively, which exhibited differential responsiveness to 17 beta-estradiol, various growth factors, tamoxifen, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and their combinations. Moreover, the altered mitogen/antimitogen responsiveness was paralleled by changes in hormone receptor levels, cellular architecture and ploidy. Estrogen receptor binding levels in the H, L and H(E+) cells varied from 36 to 155 fmol/mg protein; in contrast, the estrogen receptor binding in H(E-) cells exhibited a time-dependent increase from 81 to 1229 fmol/mg after culturing in estrogen-deficient media for approximately 12 months. Gel mobility shift assays of the nuclear estrogen receptor extracts from high and low passage cells with 32P-labeled estrogen responsive element showed that levels of the estrogen receptor-estrogen responsive element retarded band were lower in all the high passage cells compared to the low passage cells. These studies further illustrate the genetic instability of the T47D human breast cancer cell line and the resulting changes in mitogen and antimitogen responsiveness. In addition, the high passage H(E-) cells which express high estrogen receptor but low estrogen responsive element binding represent a unique model system for investigating the cellular and molecular biology of breast cancer cells which appear to be estrogen receptor-positive but are insensitive to antiestrogens.

Base Sequence↗
PubMed1994

The deliberate misdiagnosis of major depression in primary care.

OBJECTIVE: Because the correct diagnosis of a psychiatric condition can jeopardize reimbursement and other benefits, physicians deliberately substitute alternative diagnoses. We estimated the prevalence of alternative coding for major depression by primary care physicians and the reasons for its occurrence. DESIGN: Cross-sectional mail survey with telephone follow-up of nonresponders. SETTING: Primary care practices in communities across the nation. PARTICIPANTS: Physicians were eligible to participate if they were randomly selected from membership lists of two professional organizations of primary care clinicians. Four hundred forty-four physicians (70.0% of eligible physicians and 89.5% of eligible physicians we could locate) completed the survey by mail or telephone. MAIN OUTCOME MEASURE: Substitution of an alternative code for major depression within a 2-week period. RESULTS: Of our respondents, 50.3% (SE, +/- 2.5%) reported that they had substituted another diagnostic code during a 2-week period for one or more patients whom they recognized met the criteria for major depression in the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. Thirty-one percent of depressed patients received alternative codes. The most common reasons for these substitutions involved physician uncertainty about the diagnosis and problems with reimbursement for services if a diagnosis of major depression was coded. CONCLUSION: The practice of deliberately substituting another diagnostic code for major depression is widespread among primary care providers. Physicians who employ deliberate misdiagnosis circumvent inequitable policies for particular patients, but the impact of substitution on the health care system as a whole deserves more careful consideration.

Adult↗
PubMed1994

Spermophagy in semen in the red wolf, Canis rufus.

The red wolf (Canis rufus) is an endangered species with 194 individuals remaining in the wild and in various captive facilities. Breeding efforts at the Graham, WA site (Point Defiance Zoo and Aquarium) have involved artificial insemination with fresh or frozen semen in an effort to increase population and maximize the genetic potential of the stock. Electron microscopic observations were made in semen specimens obtained by electro-ejaculation from mature males prior to their use in an effort to determine semen parameters that might be useful in guiding breeding procedures. Sperm samples were either fixed immediately or treated with capacitating media and fixed after 4 to 7 hr of incubation. Many of the specimens examined were pyospermic (white cell in semen) and showed evidence of spermophagy, primarily by neutrophils. Of the six animals surveyed, only one showed little evidence of spermophagy, and three had extensive pyospermia and spermophagy but this finding was not correlated with fertility. Samples fixed immediately as well as those incubated for several hours showed evidence of spermophagy, indicating that the phagocytosis was not the result of culture. Gene pool restriction and/or captive stress may be contributing factors of reduced semen quality.

Animals↗
PubMed1994

Skeletal muscle involvement in tropical spastic paraparesis/HTLV-1-associated myelopathy.

The frequency of muscle involvement in TSP/HAM is not known, nor is the precise role that HTLV-1 and the diverse cytokines play in the genesis of HTLV-1-associated diseases. In order to better define the frequency and characteristics of the skeletal muscle involvement in TSP/HAM, we studied 11 affected patients. EMG was performed in 9 patients and muscle biopsy was performed in all 11. Muscle tissue was analyzed using: reverse transcriptase PCR for interleukin-1 in 8; PCR for HTLV-1 proviral DNA in 5; and electron microscopy for viral particles in 3. We found pathologic alterations in all 11 patients. Four patients (36%) had a neurogenic process, while a primary muscle involvement was observed in the rest (64%). Four patients (36%) had polymyositis, and 3 (27%) had a noninflammatory myopathy. Muscle weakness in the upper limbs was significantly associated with inflammation in the muscle biopsy. EMG was abnormal in only 2 of 9 patients. Reverse transcriptase PCR did not demonstrate message for interleukin-1 in any sample examined. PCR did identify HTLV-1 proviral DNA in the muscle of 3 patients. Retroviral-like particles were found, by EM, in only one biopsy. HTLV-1 may play an important role in the pathogenesis of the frequent myopathies associated with HAM/TSP.

Adult↗
PubMed1994

Disruption of fast axonal transport in vivo leads to alterations in Schwann cell gene expression.

Following nerve injury, Schwann cells distal to the site of injury down-regulate genes associated with myelination. We hypothesized that at least some of these alterations were due to the loss of ongoing axon:Schwann cell homeostatic signals, as opposed to loss of physical contact and/or inflammatory responses. To directly test this hypothesis, we perturbed axonal physiology by selectively blocking fast axonal transport via locally cooling the sciatic nerve to 5-8 degrees C (a cold block). Immunostaining with the monoclonal antibody ED1, which recognizes mononuclear phagocytic cells, demonstrated that macrophages did not invade the cold-blocked nerve, indicating the lack of an inflammatory response. Morphological studies demonstrated that the nerve distal to the cold block showed no signs of Wallerian degeneration, with maintenance of normal axon and myelin profiles, and confirmed the absence of invading macrophages. Thus, any effects of a cold-block treatment were not likely due to inflammatory responses or to loss of physical contact between axons and Schwann cells. To determine whether this treatment affected Schwann cell phenotype, we examined expression of the major myelin protein P0, and p75 NGF receptor, both of which are regulated as a function of axon:Schwann cell interactions. Levels of p75 NGF receptor mRNA were unaffected by the cold block, while p75 NGF receptor protein levels were increased in the region of the nerve immediately adjacent to the cold block, presumably reflecting protein accumulation as a consequence of the block to fast axonal transport. In contrast, levels of P0 mRNA were decreased in the distal nerve in a fashion that indicated modulation of Schwann cell phenotype as a function of local axonal microenvironment. These data therefore suggest that P0 and p75 NGF receptor are regulated as a function of two different aspects of Schwann cell:axon communication. Furthermore, these data demonstrate that the presence of axon:Schwann cell contact alone is insufficient to maintain Po gene expression and indicate that at least some myelin-specific Schwann cell responses are dependent upon ongoing biochemical signals generated by the axon and maintained by fast axonal transport.

Animals↗
PubMed1994

Psychological symptom profiles in patients with chest pain.

Five-hundred and thirty-two patients with ischaemic-like chest pain referred for symptom-limited exercise thallium myocardial perfusion studies, were assessed on a range of psychosocial measures. Three groups of patients were identified on the basis of their perfusion studies: (1) normal thallium perfusion; (2) current myocardial ischaemia; and (3) past myocardial infarction (but no current ischaemia). There were no significant psychological differences between these groups on a wide range of measures which included depression, state and trait anxiety, Type A behaviour, personality, suppression of affect, locus of control, alexythymia, and hypochondriasis. Significant differences were identified, however, on measures of anger and coping style. Subjects with no current ischaemia (normal thallium perfusion and those with past myocardial infarction) had higher scores on 'immature coping' and 'anger in', than subjects with current myocardial ischaemia. These findings are discussed in the light of other published research.

Adult↗
PubMed1994

Clinical and histological findings in proteolipid protein-induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Distribution of demyelination differs from that in EAE induced by other antigens.

Proteolipid protein (PLP) is the major protein of central nervous system (CNS) myelin. In some species, intradermal inoculation with PLP and adjuvants causes experimental autoimmune encephalomyelitis (PLP-EAE) characterized by neurological signs of tail and limb weakness and by inflammation and demyelination in the CNS. A previous study found that inoculation of Lewis rats with 100 micrograms of PLP causes PLP-EAE with a low incidence of neurological signs and a highly variable clinical course. In the present study we assessed PLP-EAE produced by inoculation with 1000 micrograms of PLP per rat. Fifty-one of 59 (86%) Lewis rats developed neurological signs 8 to 20 days (mean = 12.0 +/- 2.0) after inoculation with 1000 micrograms of PLP. In such rats, mononuclear cell infiltrates were present in the brain and spinal cord while primary demyelination occurred mainly in the subpial regions of the spinal cord, especially in the dorsal root entry and ventral root exit zones. The histological findings were compared with those in acute EAE induced in the Lewis rat by inoculation with whole CNS tissue or with myelin basic protein: in PLP-EAE, in contrast to these other models, the disease was essentially restricted to the CNS. This form of EAE should be useful in future studies of the consequences of autoimmunity to PLP.

Animals↗
PubMed1994

Analysis of surface layers on bioactive glasses.

FT-Raman spectroscopy proves to be a powerful technique to study surface reactions on bioactive glasses and it eliminates the fluorescence of the organic phase of whole bone, thereby making it possible to compare the reaction layers formed on bioactive glasses with the mineral phase of bone. The spectrum of hydroxycarbonate apatite (HCA) developed on the bioactive glasses is closer to that of bone than synthetic hydroxyapatite (HA) and closely matches that of bone mineral obtained by deproteination of whole human femoral cortical bone.

Apatites↗
PubMed1994

FGF-7 (keratinocyte growth factor) expression during mouse development suggests roles in myogenesis, forebrain regionalisation and epithelial-mesenchymal interactions.

We have isolated cDNA and genomic clones for the murine FGF-7 gene and examined its expression throughout development. Transcripts were transiently detected in the developing myocardium, differentially regulated between the atrium and ventricle. The gene was also expressed in the myotomes of the somites, coincident with FGF-4 and FGF-5 transcripts, and was detected transiently in cleaved muscles. Regional expression was detected in the ventricular zone of the developing forebrain at 14.5 d.p.c. Later in development, FGF-7 RNA was detected in mesenchymal tissues suggesting a role in epithelial-mesenchymal interactions and in the dermis consistent with its proposed role as a keratinocyte mitogen. Our results suggest that FGF-7 is likely to have diverse roles during development.

Amino Acid Sequence↗
PubMed1994

Sodium ion binding in the gramicidin A channel. Solid-state NMR studies of the tryptophan residues.

Gramicidin A analogs, labeled with 13C in the backbone carbonyl groups and the C-2 indole carbons of the tryptophan-11 and tryptophan-13 residues, were synthesized using t-Boc-protected amino acids. The purified analogs were incorporated into phosphatidylcholine bilayers at a 1:15 molar ratio and macroscopically aligned between glass coverslips. The orientations of the labeled groups within the channel were investigated using solid-state NMR and the effect of a monovalent ion (Na+) on the orientation of these groups determined. The presence of sodium ions did not perturb the 13C spectra of the tryptophan carbonyl groups. These results contrast with earlier results in which the Leu-10, Leu-12, and Leu-14 carbonyl groups were found to be significantly affected by the presence of sodium ions and imply that the tryptophan carbonyl groups are not directly involved in ion binding. The channel form of gramicidin A has been demonstrated to be the right-handed form of the beta 6.3 helix: consequently, the tryptophan carbonyls would be directed away from the entrance to the channel and take part in internal hydrogen bonding, so that the presence of cations in the channel would have less effect than on the outer leucine residues. Sodium ions also had no effect on the C-2 indole resonance of the tryptophan side chains. However, a small change was observed in Trp-11 when the ether lipid, ditetradecylphosphatidylcholine, was substituted for the ester lipid, dimyristoylphosphatidylcholine, indicating some sensitivity of the gramicidin side chains to the surrounding lipid.

Amino Acid Sequence↗
PubMed1994

One-stage laparoscopic pelvic lymphadenectomy and radical perineal prostatectomy.

Laparoscopic pelvic lymph node dissection is currently an accepted procedure for staging adenocarcinoma of the prostate. To assess the feasibility and efficacy of performing laparoscopic pelvic lymph node dissection and radical perineal prostatectomy during the same anesthesia, we retrospectively analyzed 98 patients with clinically localized adenocarcinoma of the prostate who were candidates for radical prostatectomy. Of the patients 12 (12%) underwent laparoscopic pelvic lymph node dissection only since they had metastatic disease to the pelvic lymph nodes on frozen section evaluation (the Gleason pathological grade was 2 to 4 in 2 patients, 5 to 7 in 8 and 8 in 2). Of the remaining 86 patients who underwent radical perineal prostatectomy for definitive management 76 (88%) underwent 1-stage radical perineal prostatectomy immediately after laparoscopic pelvic lymph node dissection, while 10 (12%) in the initial stages of our series underwent delayed perineal prostatectomy following laparoscopic pelvic lymph node dissection (2-stage). The average postoperative hospital stay in the 1-stage group was 3.11 days, yet 19 (25%) patients were discharged from the hospital within 48 hours and another 39 (51%) within 72 hours. Thus, 76% of the patients were discharged from the hospital within 72 hours of laparoscopic pelvic lymph node dissection and radical perineal prostatectomy. The advent of laparoscopic pelvic lymph node dissection and radical perineal prostatectomy has found a resurgence at our institutions, with its lower morbidity rate and more rapid return to normal activity for these patients. Based on our results, we recommend laparoscopic pelvic lymph node dissection followed by radical perineal prostatectomy as a 1-stage treatment option for localized adenocarcinoma of the prostate.

Adenocarcinoma↗
PubMed1994

Distal cervical internal carotid artery stenosis.

This report describes a case of distal cervical internal carotid artery (ICA) occlusive lesion managed by saphenous interposition vein graft after exposure of the ICA up to the skull base. The skull base approach described herein emphasizes the mobilization of the mandible without mandibular osteotomy or disarticulation. Instead, the stylomandibular and stylosphenoidal ligaments are resected to allow mandibular mobilization. In addition, the distal ICA lesion represented a form of diffuse intimal thickening without any plaque formation. This required the resection of the thickened, stenotic segment and reconstruction of the distal cervical ICA with a saphenous interposition graft. The surgical management implications of diffuse intimal thickening are discussed.

Case Reports↗
PubMed1994

The real-time dust exposures of sodium borate workers: examination of exposure variability.

As part of an epidemiologic study of acute respiratory irritation, an assessment of the short term (TWA-0.25 hr) and daily (TWA-6 hr) dust and boron exposures of workers in a sodium borate production facility was undertaken. A real-time continuous aerosol monitor was used in an active mode with an in-line filter to collect a TWA-6 gravimetric sample with a datalogger to store the continuous aerosol measurements. Over 430 person-days of personal exposure measurements were made, resulting in more than 10,000 15-minute average (TWA-0.25) dust concentration measurements. The arithmetic mean total dust concentrations for the 13 job groups exposed to sodium borate dust ranged from 0.29 to 18.95 mg/m3. The geometric standard deviation of the TWA-6 total dust exposures within the sodium borate exposed job groups had a median of 2.78. The geometric standard deviation of the TWA-0.25 total dust exposures had a median of 3.97. In most jobs the "within-day" variability accounted for over 50% of the total variability in exposure levels. In jobs with constant exposure to sodium borate, the second most important source of exposure variability was attributable to "between worker" differences. Where there was only intermittent exposure, the second most important source of exposure variability was "within-worker" variability. The implications of these findings for control strategies are discussed. Based on boron measurements, a substantial portion of a total dust air sample is nonborate material such as cigarette smoke, vehicle exhaust, ambient dust, or hydration mass. Thus, even in an environment where sodium borate is being packaged, total dust measurements are an overestimate of the actual borate exposure level.

Air Pollutants, Occupational↗
PubMed1994

Demonstration by two-color flow cytometry that tyrosine kinase activity is required for down-modulation of the oncogenic neu receptor.

Expression of rat oncogenic neu receptor, p185T-neu (a growth factor receptor with constitutive tyrosine kinase activity), causes cells to become transformed. Treatment with anti-neu receptor monoclonal antibodies reverts the transformed phenotype by down-modulation of p185T-neu. Monoclonal antibody treatment of cells expressing normal neu receptor, p185C-neu (which lacks constitutive tyrosine kinase activity), does not result in down-modulation of p185C-neu. To understand further the role the biochemical activity of p185T-neu plays in transformation and endocytosis, we created a series of mutations in p185T-neu. We found that fibroblasts expressing the tyrosine kinase-defective mutants cannot form foci in culture, colonies in soft agar, or tumors in immunocompromised mice. To follow the antibody-induced endocytosis of neu receptors expressed in these transfectants, we developed a novel two-color flow cytometric assay and confirmed receptor localization by electron microscopy. Cells were treated with mAb7.16.4 over time. After 4 hr of antibody treatment, less than 50% of full-length p185T-neu and of mutant T691 remained on the cell surface, whereas internal expression of the neu receptors within these cells initially increased and then decreased to the original internal receptor level. In contrast, the level of kinase-deficient mutated neu receptors remaining on the cell surface initially decreased by 35%, but, after 4 hr of antibody treatment, the cell surface expression level returned to approximately the original level. Concurrently, fluctuations in expression levels were seen internally over time as well. These cell lines were also treated with gold-conjugated mAb7.16.4. Using electron microscopy, we consistently found the gold particles within multivesicular bodies of cell lines expressing full-length or mutated neu receptor. These data strongly suggest that the fate of the neu receptor, once internalized, is directed by its tyrosine kinase activity. When the kinase activity of the neu receptor is disrupted, the receptor is internalized but recycled to the cell surface, whereas neu receptors which have constitutive kinase activity are internalized and presumably degraded when engaged with anti-neu receptor mAb. Understanding the regulation of receptor endocytosis, degradation, and recycling will contribute to the development of novel therapeutic protocols to combat human malignancies, particularly those associated with the overexpression of the human homologue of the neu receptor, c-erbB2.

Animals↗
PubMed1994

Surgery for gynecologic cancer.

Surgery is an integral part of staging procedures for ovarian, endometrial, and vulvar cancers, with a move toward surgicopathologic rather than clinical staging in cervical cancer. Morbidity can be reduced without compromising patient cure by individualizing surgery for patients with early vulvar cancer, and reproductive potential can be maintained in some women with early ovarian cancer. The place of prophylactic oophorectomy and primary and secondary surgery in ovarian cancer remain controversial and await prospective study. Recent developments in laparoscopic techniques have been applied to a number of problems in gynecologic cancer surgery, and the feasibility of laparoscopic lymphadenectomy and radical pelvic surgery has been demonstrated. Care must be taken, however, to ensure that the tenets of surgical oncology are not sacrificed in order to offer minimal-access surgery to women with gynecologic cancer.

Endometrial Neoplasms↗