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Biomedical subjects

D Lee

Publications and source records attributed to D Lee.

At least 379 records · Page 21Linked to original sources
PubMed1995

Case report: coincident granular cell tumour of the breast with invasive ductal carcinoma.

Granular cell tumours of the breast are rare lesions which are almost always benign. They are of interest because their clinical, radiological and pathological appearances often closely resemble those of malignancy. A case is described in which screening mammography in an asymptomatic woman led to the diagnosis of simultaneous invasive intraductal carcinoma in one breast and benign granular cell tumour in the other. Granular cell tumour of the breast coincident with other breast tumours is very rarely described and an association with breast carcinoma is unknown.

Breast Neoplasms↗
PubMed1995

Differential control of type-I iodothyronine deiodinase expression by the activation of the cyclic AMP and phosphoinositol signalling pathways in cultured human thyrocytes.

The effects of TSH and the activation of the cyclic AMP (cAMP) and Ca(2+)-phosphatidylinositol (Ca(2+)-PI) cascades on the activity and expression of the selenoenzyme thyroidal type-I iodothyronine deiodinase (ID-I) have been studied using human thyrocytes grown in primary culture. Stimulation of ID-I activity and expression was obtained with TSH and an analogue of cAMP, 8-bromo-cAMP. In the presence or absence of TSH, the addition of the phorbol ester, phorbol 12-myristate 13-acetate (PMA) together with the calcium ionophore A23187, caused a decrease in ID-I activity; a decrease in ID-I expression was also observed as assessed by cell labelling with [75Se]selenite. PMA alone had no effect on ID-I activity in the presence or absence of TSH. A23187 alone produced a small but significant reduction in ID-I activity, but only in TSH-stimulated cells. These data provide evidence that the expression of thyroidal ID-I is negatively regulated by the Ca(2+)-PI cascade, and positively regulated by the cAMP cascade.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Design and development of external prostheses and their function.

This article describes current techniques and materials used in the prosthetic rehabilitation of disfigured patients. The types of patients helped by external prostheses, the importance of accurate sculpting and tinting of prosthetic devices, the type of adhesives, and the new technique of osseous integration for external fixation of appliances are also reviewed in this article.

Ear↗
PubMed1995

Thiopurine methyltransferase pharmacogenetics. Cloning of human liver cDNA and a processed pseudogene on human chromosome 18q21.1.

Thiopurine methyltransferase (TPMT) is a genetically polymorphic enzyme that catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine. This genetic polymorphism is an important factor responsible for individual variation in thiopurine drug response. A cDNA for TPMT has been cloned from T84 human colon carcinoma cells. Northern blot analysis of multiple human tissues was performed with the T84 human colon carcinoma TPMT cDNA open reading frame (ORF) as a probe as one step toward understanding the molecular basis for the TPMT genetic polymorphism. Three mRNA species (approximately 1.4, 2.0, and 3.6 kb in length) were present in all tissues studied, including liver. However, none of these mRNAs matched the length of the 2.7 kb T84 TPMT cDNA. Therefore, it was important to clone a TPMT cDNA from a human drug-metabolizing organ such as the liver to determine whether its sequence matched that of the cDNA cloned from the T84 cell line. A human liver cDNA library was screened with the T84 TPMT cDNA ORF as a probe, and a 1.8 kb cDNA was isolated with a coding region sequence identical to that of the T84 TPMT cDNA. The TPMT cDNA ORF was then used to screen a human lymphocytes genomic DNA library in an attempt to clone the TPMT gene(s) in humans. Three intronless clones were isolated with identical ORF sequences that were 96% identical to that of the TPMT cDNA, but which contained multiple nucleotide substitutions and one deletion. The 3'- and 5'-flanking regions of one of the genomic DNA clones were sequenced.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1995

Reappraisal of cardiac murmurs related to aortic regurgitation.

BACKGROUND: With the advent of color Doppler echocardiography, which can detect even a trivial aortic regurgitation (AR), the spectrum of the audible cardiac murmurs caused by AR which presents specific and characteristic findings should receive further refinement. METHODS: Twenty-eight subjects with isolated AR (21 male and 7 female, mean age 61 +/- 41 yrs) diagnosed by colour Doppler echocardiography (15 mild, 6 moderate, and 7 severe by Nanda's criteria) and 8 normal controls (5 male and 3 female, mean age 38 +/- 15 yrs) were randomly invited for a physical examination to evaluate the systolic and diastolic murmurs in four auscultation areas by two experienced cardiologists who were blind to the clinical profile of each patient. Subsequently, a complete and comprehensive echocardiographic examination was performed to measure the transaortic peak velocity and time velocity integral, aortic root diameter, stroke volume, peak diastolic velocity and pressure half time of the AR jet, fractional shortening, and left ventricular systolic and diastolic internal dimensions. RESULTS: Systolic murmur was present in 62.5%, 66.7%, 100% and 100% of subjects with no, mild, moderate and severe AR, respectively. The corresponding numbers for diastolic murmur were 12.5%, 13.3%, 100% and 100% in subjects with no, mild, moderate and severe AR, respectively. The corresponding numbers for diastolic murmur were 12.5%, 13.3%, 100% and 100%. Multivariate analyses revealed that only the high peak aortic flow velocity was a significant determinant of systolic murmur. High grade AR, low diastolic blood pressure, high peak velocity of the AR jet and high systolic blood pressure were significant determinants of diastolic murmur. CONCLUSIONS: Both systolic and diastolic murmurs can be heard in most patients with moderate to severe AR. In contrast, a large proportion of subjects with mild AR have systolic murmur alone.

Adult↗
PubMed1994

Targeted disruption of the apolipoprotein C-III gene in mice results in hypotriglyceridemia and protection from postprandial hypertriglyceridemia.

Using gene targeting in embryonic stem cells, we have generated mice lacking apolipoprotein C-III (ApoC-III). Homozygous mutant animals show absence of ApoC-III protein and no expression of ApoC-III mRNA in the liver or in the intestine. Expression of the neighboring genes, coding for apolipoprotein A-I and apolipoprotein A-IV, are not altered in the liver but are reduced in the intestine. This suggests that these three genes share a tissue-specific element for intestinal expression and that insertion of an additional promoter for the neomycin-resistant gene into the locus affects interaction between the tissue-specific element and the promoter of the individual gene. Fasted plasma triglyceride levels in the homozygous mutants are reduced to about 70% of normal, while heterozygotes have values intermediate between those of the homozygous mutants and wild types. Plasma levels of total cholesterol and of high density lipoprotein cholesterol in homozygotes are consistently lower than those in normal mices but the reduction does not reach statistical significance. A fat meal test showed that postprandial hypertriglyceridemia is abolished in homozygotes lacking ApoC-III. The homozygous mutants also clear chylomicrons faster than wild type controls. These data indicate that ApoC-III modulates the catabolism of triglyceride-rich lipoproteins and plays a role in the postprandial management of triglycerides.

Animals↗
PubMed1994

Glucocorticoids potentiate the adenylyl cyclase-cAMP system mediated immunoreactive beta-endorphin production and secretion from hypothalamic neurons in culture.

Beta-endorphin(beta EP)1-31, a potent opioid peptide of proopiomelanocortin (POMC) derivatives, is produced and released from neurons at arcuate nuclei of the rat hypothalamus. Although dexamethasone (DM) suppresses the production and secretion of POMC related peptides from rat pituitary corticotrophs, the effect of glucocorticoids on the function of hypothalamic beta EP neurons remains unclear. Employing long term monolayer cultures of neonatal rat hypothalamic cells, we report here that 4 day treatment with 10 microM of forskolin increased ir-beta EP levels in cell content and culture media by approximately 1.7 (P < 0.05) and 4.1 times (P < 0.01) above vehicle treated control cultures (mean +/- S.E.M., 47.3 +/- 2.6 pg/well and 40.4 +/- 3.0 pg/well; n = 3) respectively. Although 4 day treatment with DM alone had little effect on the release and the cell content of ir-beta EP, it significantly enhanced forskolin-induced elevation of ir-beta EP levels in cell content and in culture media. The effect of DM was dose-related and time-dependent, with an EC50 of about 1 nM; at this concentration DM enhanced ir-beta EP secretion about 2.1 times (P < 0.01) above that induced by 10 microM of forskolin alone. Furthermore, the potentiating effect of DM was specifically suppressed by 100 nM of RU38486 (P < 0.01), a glucocorticoid receptor antagonist, but not by an equivalent dose of RU28318, a mineralocorticoid receptor antagonist. In addition, Northern blot analysis showed that forskolin (10 microM) increased the abundance of POMC mRNA 1.4 fold above that of vehicle treated control cultures. Whereas by itself, DM (10 nM) had little effect on the level of POMC mRNA, it enhanced forskolin-stimulated increase of the abundance of POMC mRNA approximately 2.6 times. Moreover, DM also augmented 1.6 times (P < 0.05) forskolin-induced but not 3-isobutyl-1-methylxanthine (IBMX)-induced increase of cAMP production (5.5 +/- 0.4 pmol/well; mean +/- S.E.M., n = 3) in the cultures. Taken together, our findings suggest that in contrast to the inhibitory effect on pituitary corticotrophs, glucocorticoids enhance the production and secretion of beta EP from rat hypothalamic neurons by facilitating the stimulatory effect mediated, in part, through the adenylyl cyclase-cAMP system.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Global form and singularity: modeling the blind spot's role in lateral geniculate morphogenesis.

Optic nerve terminals segregate by functional class into distinct layers in the lateral geniculate nucleus, the thalamic relay nucleus of the visual system. In the rhesus monkey, the number of geniculate layers changes abruptly from six posteriorly (central vision) to four anteriorly (peripheral vision). The plane of transition between these patterns passes through small laminar gaps corresponding to the perceptual blind spot caused by the exit of the optic nerve from the eyeball. However, this plane of transition has no apparent functional link to the blind spot. A thermodynamic model of geniculate morphogenesis supports the hypothesis that the blind spot traps the transition in its stereotypic position by introducing a singularity in an otherwise smooth gradient in forces guiding the development of geniculate morphogenesis. This relation suggests that small-scale anomalies may be important in the determination of large-scale patterns in biological structure.

Animals↗
PubMed1994

D2 receptors mediate dopamine suppression of irANF release and pro-ANF mRNA expression of rat hypothalamic neurons in culture.

Although N-terminal truncated forms of atrial natriuretic factor (ANF) are produced and released from rat hypothalamic neurons, the intrahypothalamic regulation of these processes remains unclear. Employing a well-characterized hypothalamic cell culture system, we report here that dopamine, mediating through D2 receptors, inhibits the synthesis and release of ANF. In long-term cultures of hypothalamic neurons, daily treatment for 4 days with quinpirole, a D2 agonist, significantly suppressed the basal irANF release in a time-related and a dose-dependent manner. The ED50 and Emax of the drugs were 9.1 x 10(-8) M and 10(-5) M, respectively. This effect of quinpirole was mimicked by 10(-7) M of dopamine, a physiological ligand for D2 receptor. Furthermore, the suppressing effects of both quinpirole and dopamine were abolished by sulpiride, a D2 antagonist. Whereas 10(-6) M of forskolin treatment consistently enhanced the release of irANF through activating the adenylyl cyclase-cAMP system, this stimulatory effect was suppressed by quinpirole in a dose-related manner. In addition, the application of pertussis toxin, a bacterial toxin which inactivated G1 protein activity, reversed the suppressing effect of quinpirole or dopamine on irANF release. These immunoassay findings were accompanied by corresponding changes in the abundance of pro-ANF mRNA in the cultures as determined by colorimetric Northern blot analysis. By combining the techniques of in situ hybridization and immunocytochemistry, the mRNA of D2 receptor was colocalized with irANF at a single cell level by double fluorescent staining.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Vitamin D metabolism and bone mineralization in children with juvenile rheumatoid arthritis.

OBJECTIVE: To examine bone mineralization and bone mineral content in a cross-sectional population of children with juvenile rheumatoid arthritis (JRA). METHODS: Bone mineral content was measured by single-photon absorptiometry in 44 children with JRA and 37 control children. Serum concentrations of minerals, vitamin D, parathyroid hormone, osteocalcin, bone alkaline phosphatase, and tartrate-resistant acid phosphatase, and urinary concentrations of minerals, were determined. RESULTS: Bone mineral content was decreased in children with JRA. Significantly lower concentrations of osteocalcin (7.4 +/- 3.4 vs 12.5 +/- 2.5 micrograms/L) and bone alkaline phosphatase (78.8 +/- 36.4 vs 123.0 +/- 46.0 IU/L) suggested reduced bone formation; lower levels of tartrate-resistant acid phosphatase (10.3 +/- 4.1 vs 14.4 +/- 5.8 IU/L) and a lower urinary calcium/creatinine ratio (0.07 +/- 0.06 vs 0.12 +/- 0.09) suggested decreased bone resorption. The serum calcium concentration was significantly lower (9.3 +/- 1.0 vs 10.0 +/- 0.4 mg/dl), as was the parathyroid hormone concentration (19.8 +/- 8.6 vs 26.7 +/- 9.3 ng/L); 1,25-dihydroxyvitamin D values (30.1 +/- 10.5 vs 30.4 +/- 9.3 pg/ml) were normal. CONCLUSION: These data suggest that decreased mineralization in JRA is related to low bone turnover; parathyroid hormone and 1,25-dihydroxyvitamin D levels may be inappropriately normal for the decreased serum calcium concentration in children with JRA.

Adolescent↗
PubMed1994

Chemotherapy for anaplastic oligodendroglioma. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To examine the rate and duration of response of anaplastic oligodendrogliomas to a dose-escalated combination chemotherapy regimen consisting of procarbazine, lomustine (CCNU), and vincristine (PCV) and to evaluate the side effects of this treatment. METHODS: In this single-arm multicentered phase II study, patients with measurable, newly diagnosed or recurrent, contrast-enhancing anaplastic oligodendrogliomas were treated with up to six cycles of PCV. Central pathology and radiology review were mandatory, and rigorous response criteria based on imaging were used. RESULTS: Thirty-three patients entered the trial; nine were excluded subsequently, seven due to ineligible pathology. Eighteen of 24 eligible patients (75%) responded, nine completely (38%), four had stable disease (SD), and two progressed during the first cycle of PCV. Responses were observed in nine of 10 patients (90%) with a preexisting low-grade oligodendroglioma and 10 of 15 (67%) with necrotic tumors, called glioblastoma multiforme by some. Previously irradiated patients were as likely to respond to PCV as those newly diagnosed (11 of 15 [73%] v seven of nine [78%]). The median time to progression will be at least 25.2 months for complete responders, and was 14.2 months for partial responders and 6.8 months for stable patients. Four ineligible patients also responded to PCV; all had gliomas with oligodendroglial differentiation. All responders, eligible or ineligible, were stable or improved neurologically, but nine of 22 (41%) experienced a decline in Eastern Cooperative Oncology Group (ECOG) performance status of one grade while on PCV. Adverse events on treatment included a death from Pneumocystis pneumonia, a severe reversible encephalopathy due to procarbazine, an intratumoral hemorrhage, and a subdural hematoma. All other acute toxicities were anticipated and manageable. CONCLUSION: Anaplastic oligodendrogliomas are chemosensitive brain cancers. Patients with these tumors respond predictably, durably, and often completely to PCV, and many tolerate a dose-escalated formulation. Cooperative group and randomized trials will be necessary to explore fully the role of chemotherapy in the treatment of aggressive oligodendrogliomas.

Adolescent↗
PubMed1994

Implementation of a relational patient record with integration of educational and reference information.

The clinician must identify pertinent diagnostic information and develop appropriate medical management plans in the context of rapidly changing research information, new therapeutic options and expanding diagnostic modalities. To assist in recognition of patterns relevant to diagnostic or therapeutic interventions, the medical record must be presented in a format that emphasizes important data interrelationships. Reference and educational information specifically pertinent to the case being reviewed must be immediately accessible. A system that presents point of care patient centered clinical information, a summarized patient record, in a relational format with linked reference information has been developed. Data is acquired from the VA patient information database and provided over a PC network. At the time of data transfer, preliminary analysis and reorganization of data is performed such that interrelationships between laboratory, pharmacy and diagnostic information can be rapidly recognized. During data compilation reference and educational information is linked with patient data such that it can be accessed with a mouse click ("hotspot") when the record is subsequently reviewed. The medical record and CD-ROM based reference databases are then made available to users on a PC network in a Windows (tm) environment. Initial experience with the system is very favorable and suggests that evaluation of patient data may be significantly enhanced.

Computer Communication Networks↗
PubMed1994

Routine 36-week hemoglobin and hematocrits: are they necessary?

Different schedules for hemoglobin and hematocrit (H&H) screening of pregnant women exist at various hospitals in the Air Force. Charts of women delivering between November 1990 through February 1991 were reviewed for 28-week, 36-week, and labor admission H&H; 111 were included in the study. Statistical analysis of the data obtained showed that 28-week values were significantly lower (p > 0.01) than the 36-week values, which were lower (p > 0.01) than those on admission. This study indicates that screening at 36 weeks does not improve prenatal care and increases both discomfort for the patient and the workload for the laboratory.

Female↗
PubMed1994

The role of intracellular calcium in the cellular response to ionizing radiation.

Calcium is required as a cofactor by primer recognition proteins involved in DNA synthesis and by protein kinase C (PKC), which is activated by ionizing radiation. Because these processes may be involved in radiation-mediated regulation of the progression of cells through the phases of the cell cycle, we studied the effects of the intracellular Ca2+ chelator, acetoxymethyl-1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (AM-BAPTA), on PKC activation, expression of c-jun and Gadd45 and distribution of cells in the phases of the cell cycle after irradiation. AM-BAPTA prevented ionizing-radiation-induced activation of PKC and expression of c-jun in cells of human tumor cell lines. Conversely, calcium chelation had no effect on X-ray-induced expression of the Gadd45 gene. To determine whether changes in the intracellular Ca2+ concentration ([Ca2+]i) occurred during irradiation, we measured [Ca2+]i in single cells using fura-2-based microfluorimetry. There was no increase in [Ca2+]i during or after irradiation of cells of the human tumor cell lines RIT-3, SQ-20B or HL-60 or normal human fibroblast strain IMR-90. The percentage of human tumor cells crossing the G1/S-phase border was reduced by pretreatment with AM-BAPTA. These data indicate that calcium is required for ionizing radiation-induced cell cycle regulation and PKC activation, but that increases in [Ca2+]i do not occur in cells of the cell lines irradiated in this study.

Amino Acid Sequence↗