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Biomedical subjects

C Lee

Publications and source records attributed to C Lee.

At least 523 records · Page 29Linked to original sources
PubMed1996

Lack of effect of methotrexate on the expression of constitutive hepatic cytochromes P450 in the male rat.

1. The effects of methotrexate (MTX) on the expression of selected constitutive cytochrome P450 (CYP) isozymes in the liver of male rats at the catalytic activity and mRNA levels were examined. 2. Male rats received a single intraperitoneal injection of MTX (4 mg/kg) or vehicle and were killed, 1, 2, 7 or 14 days following drug administration. 3. Hepatic microsomes were used for determination of total CYP content, NADPH-CYP reductase activity, aminopyrine N-demethylase activity, and androstenedione (AD) hydroxylation activity; total RNA was also isolated from liver and was used for hybridization analysis of CYP isozyme expression at the mRNA level. 4. MTX did not affect any of the following parameters at any time-point in comparison with the corresponding vehicle control: body weight, liver weight, hepatic microsomal protein content, total CYP content, NADPH-CYP reductase activity, aminopyrine N-demethylase activity, AD 6 beta- and 7 alpha-hydroxylase activity, and CYP3A2 mRNA content. 5. The major male-specific CYP isozyme, 2C11, was down-regulated by MTX treatment as revealed by a marginal (25%), but statistically significant decrease in AD 16 alpha-hydroxylase activity at day 14 and a marginal (18%), but statistically significant decrease in CYP2C11 mRNA content at day 14. 6. In comparison with other antineoplastic drugs that have been examined, MTX appears to possess a lesser capacity for modulation of hepatic CYP enzymes.

Animals↗
PubMed1996

Role of androgen in prostate growth and regression: stromal-epithelial interaction.

The prostate is a secretory gland in which secretions produced by its cells are transported through the ductal system and discharged into the urethra. Each prostatic ductal system can be traced from the opening in the urethra as a single tubular structure from which branches and sub-branches are formed in a manner like the branching pattern of a tree. Owing to the distance from the urethral orifice, regions of the prostatic ductal system can be classed into the proximal, intermediate, and distal regions. In the distal region, the tips of the ductal system (equivalent to the top of the tree), the epithelial cells are tall and columnar in shape, and active in cell division. Cells of the intermediate region (equivalent to the majority of the body of the tree) are also of tall and columnar type but are mitotically quiescent. Cells in this region are the only ones that have the ability to secrete. Cell death is not evident in these two regions. Cells in the proximal region, a region that is immediately adjacent to the urethra (equivalent to the tree trunk) are low cuboidal or flat in shape and are actively undergoing cell death. These observations indicate that cells in different regions of the prostatic ductal system are not the same, even though they are exposed to the same circulating level of androgen. The recognition of this regional heterogeneity in cell shape and activity in the ductal system has advanced our understanding of the basic biology of the prostate. For example, our understanding of the cellular mechanism of action of androgen in the prostate should be re-evaluated. In the past, the convention concept of androgen action has been a stimulatory one, and a depletion of this androgenic support leads to prostatic cell death. The recognition of a regional heterogeneity in cellular activity has created a situation in which all prostatic cells in the same prostatic ductal system are exposed to the same level of circulating androgen. However, these cells are not responding to the same amount of androgen in the same manner: some are multiplying while others are dying. These observations indicate that the effect of androgen vary according to the location of prostatic cells in the ductal system. A new concept of the role of androgen in prostatic growth, differentiation, and cell death is discussed.

Androgens↗
PubMed1996

Partially mismatched related donor transplants as salvage therapy for patients with refractory leukemia who relapse post-BMT.

Patients who relapse post-ABMT are usually resistant to conventional therapy, and a potentially curative therapy with allogeneic BMT is limited due to availability of a matched donor. To assess whether such patients can be salvaged using partially mismatched related donors (PMRD), eight patients age 6-50 years old underwent PMRD-BMT. All patients ALL (n = 3) and AML (n = 5) were in relapse 7-31 months after first BMT. Donors (1-3 Ag mismatch) were selected from family members. Conditioning included TBI, etoposide, Ara-C and cytoxan (n = 3), or busulfan, thiotepa, and etoposide (n = 5). GVHD prophylaxis consisted of partial T cell depletion followed by systemic immunosuppression. All evaluable patients established sustained engraftment by day 18. Severe regimen-related toxicity was evident in the gastrointestinal and hepatic systems (6/8 and 4/8, respectively), the latter associated with poor outcome (P < 0.014). Acute but not chronic GVHD, grade > or = II occurred in 3/7 patients. Four of eight patients are disease-free, maintaining longer remission than following their first BMT (14 vs 9 months). In conclusion, our data shows that PMRD-BMT is a feasible option for patients who relapse post-BMT and use of such alloreactive grafts may be appropriate earlier in the disease course of high risk patients.

Adolescent↗
PubMed1996

Modulation of the expression on constitutive rat hepatic cytochrome P450 isozymes by 5-fluorouracil.

The objective of this study was to determine the effects of 5-fluorouracil (5FU) on the expression of individual cytochrome P450 (CYP) isozymes in rat liver at the catalytic activity and apoprotein levels. Male Fischer 344 rats (9 to 10) weeks old) received a single intraperitoneal injection of 5FU (120 mg/kg) or vehicle. Rats were euthanized 1, 2, 7, or 14 days following drug administration. Hepatic microsomes were isolated and used for determination of spectral CYP and heme content and steroid hydroxylation activity, and immunoblot analysis of CYP apoproteins. 5FU treatment did not alter the levels of total microsomal CYP and heme. The major male-specific CYP isozyme, CYP2C11, was downregulated by 5FU treatment, as revealed by a significant decrease in CYP2C11 immunoreactive protein and catalytic activity (progesterone 2 alpha-hydroxylase) levels at day 14. Members of the CYP3A subfamily also appeared to be modulated by 5FU treatment in a complex manner. Two days following 5FU exposure, CYP3A immunoreactive protein was increased compared with vehicle control; however, 7 days after treatment, both CYP3A immunoreactivity and catalytic activity (progesterone 6 beta-hydroxylase) were suppressed by 5FU. 5FU appears to modulate the expression of constitutive CYP isozymes in the liver of male rats. The modulation of the catalytic activity of CYP2C11 and CYP3A by 5FU appears to be due to changes in the expression of the corresponding proteins.

Animals↗
PubMed1996

MR evaluation of developmental venous anomalies: medullary venous anatomy of venous angiomas.

PURPOSE: To present characteristic MR findings of developmental venous anomalies (DVAs) in terms of location of caput and draining veins, to correlate these findings with normal medullary venous anatomy, and to suggest an approach to the evaluation of DVAs by means of MR imaging. METHODS: We reviewed the contrast-enhanced MR examinations of 61 patients with DVA, which were selected from 4624 consecutive cranial MR examinations. Site of the DVA and size and direction of draining veins were recorded. RESULTS: Seventy-two DVAs with 78 draining veins were located: 18 were juxtacortical, 13 were subcortical, and 41 were periventricular or deep. Twenty-six of the DVA caputs were frontal, 16 were parietal, 13 were in the brachium pontis/dentate, seven were in the temporal lobe, three were in the cerebellar hemisphere, three were in the occipital lobe, three were in the basal ganglia, and one was in the pons. The draining veins were superficial in 29 cases and deep in 49. Of the 36 supratentorial deep draining veins, 16 were in the trigone/occipital horn, 11 were in the mid-body of the lateral ventricle, seven were in the frontal horn, and two were in the temporal horn. Among the 14 infratentorial deep draining veins, five were in the lateral recess of the fourth ventricle, four were anterior transpontine veins, three were lateral transpontine veins, and two were precentral cerebellar veins. CONCLUSION: The DVA caputs and their draining veins occurred in typical locations that could be predicted from the normal medullary venous anatomy, with the frontal, parietal, and brachium pontis/dentate being the most common locations. Drainage can occur in superficial cortical veins or sinuses or in deep ventricular veins or in both, no matter where the caput is located. Whether drainage was superficial or deep could not be predicted on the basis of the site of the DVA caput. Contrast-enhanced T1-weighted MR images showed the DVAs best, but diagnosis could be made from T2-weighted MR images.

Adolescent↗
PubMed1996

Fatigue evaluation of lumbar muscles during repeated dynamic trunk exercise.

Muscle fatigue in the lumbar muscles for five normal subjects was investigated during repeated dynamic trunk exercise using a lumbar extension machine which is designed to isolated lumbar extension functions. The electromyogram (EMG) signal from erector spinae muscles at lumbar 1 (L1), lumbar 3 (L3) and lumbar 5 (L5) spinal level was detected by bipolar Ag-AgCl surface electrodes. Subjects were required to perform one set of variable resistance lumbar extensions through a 72 degrees range of motion (ROM) with a weight load (50% maximal voluntary contraction) that allowed 13 repetitions of fatigue contraction. Median frequency (MF) of EMG power spectrum was analyzed to compare the difference of fatigability between each lumbar muscle. The experimental results indicated: 1) each lumbar muscle has characteristic MF, especially at the beginning of the trunk exercise (i.e., L1 = 86 Hz, L3 = 96 Hz and L5 = 106 Hz); 2) Significant differences (P < 0.001) in MF between the beginning and the end of trunk exercise for all lumbar muscle sites; 3) Significant differences in the decreasing ratios of MF between L1, L3 and L5. Based on the theory that the decreasing ratio of MF is proportional to fatigability, L5 was more fatiguable than L1 and L3.

Adult↗
PubMed1996

Acute rejection of marrow grafts in patients transplanted from a partially mismatched related donor: clinical and immunologic characteristics.

Bone marrow transplantation (BMT) from a partially mismatched related donor (PMRD) provides a treatment option for patients lacking a matched sibling donor. T lymphocyte depletion of the graft reduces the risk of severe graft-versus-host disease, but may increase the risk of graft failure. We evaluated the pattern of acute graft rejection in eight patients receiving PMRD BMT with respect to the conditioning therapy, diagnosis, age and sex of donor and recipient, degree of HLA mismatch, and peripheral blood immunophenotype at the time of graft failure. All grafts were partially depleted of T lymphocytes. Marrow grafts infused into patients who experienced acute rejection did not differ significantly in nucleated cell dose, degree of T lymphocyte depletion, T cell dose, or CFU-GM/kg infused, from those received by 31 patients who showed durable engraftment. In three of four patients who rejected their grafts, and had sufficient peripheral blood cells for immunophenotyping, a CD3+CD8+ T lymphocyte phenotype was predominant at the time of acute rejection. In one patient rejection was associated with a predominant population of CD3+CD4+ T lymphocytes. Rejection was significantly associated with chronic myelogeneous leukemia and in patients mismatched by more than two antigens.

Adult↗
PubMed1996

Bile acid synthesis: 7 alpha-hydroxylation of intermediates in the sterol 27-hydroxylase metabolic pathway.

The recognition that the 7 alpha-hydroxylation of 27-hydroxycholesterol is catalyzed by an enzyme that is different from cholesterol 7 alpha-hydroxylase raises the question as to the number of similar enzymes that may be present in liver and subserve bile acid synthesis. Thus, both 3 beta-hydroxy-5-cholestenoic acid and 3 beta-hydroxy-5-cholenoic acid, further oxidation products derived from 27-hydroxycholesterol, are also 7 alpha-hydroxylated during their metabolism to chenodeoxycholic acid. Using a microsomal fraction of hamster liver and competition plot analysis, we found that the 7 alpha-hydroxylase activity for the acid substrates was approximately one-tenth that found for 27-hydroxycholesterol. Mixtures of the different substrates did not depress the total rate of 7 alpha-hydroxylation. The evidence supports the view that these substrates share the same catalytic site on a single enzyme.

Animals↗
PubMed1996

Malignant melanoma in American black females: an unusual distribution of primary sites.

BACKGROUND: Since the inception of the Charity Hospital Tumor Registry in 1948, 80 cases of malignant melanoma in blacks were treated at the Tulane University School of Medicine, Department of Surgery. Among black people, melanoma occurs on acral dermal sites. The histologic type is primarily acrallentiginous melanoma (ALM), found on acral, volar-subungual skin and junctional mucocutaneous sites. STUDY DESIGN: The registry records of 80 black patients with malignant melanoma were reviewed. The clinical data for 41 female patients were compared to those of 39 male patients. These data were analyzed according to the sex of the patient as well as the histologic type, site, and stage of disease at diagnosis. RESULTS: Among women, 44 percent of primary lesions were found on extradermal sites compared with only 10 percent among men. Only 32 percent of primary lesions among women were located on the foot, whereas 73 percent of the primary lesions in men were found on the foot. Of the seven patients with vulvar, cervical, and vaginal melanoma, none lived more than two years after diagnosis. Two female patients with anorectal melanoma succumbed to their disease within 22 months. However, 50 percent of the female patients with head and neck lesions and 75 percent of those with eye lesions lived more than five years. Forty and 26 percent of the female patients with limb lesions lived five and ten years, respectively. CONCLUSIONS: Black females have a higher rate of extracutaneous melanoma than black men or white men and women, which accounts for a distinct negative impact on survival rates among black women with melanoma. In addition, the worst prognosis of melanoma among black women is not entirely related to delays in diagnosis, as has been suggested, but to their higher rates of extracutaneous melanoma.

Adolescent↗
PubMed1996

Pharmacokinetic in vivo comparison using 1-stage and chromogenic substrate assays with two formulations of Hemofil-M.

In a study to demonstrate the safety and pharmacokinetics (half-life and recovery) of two different method M purified AHF (Hemofil-M) concentrates processed in the USA and Spain, two different methods of factor VIII assay (one-stage clotting and chromogenic) have been compared in vivo. The study was a single centre blinded, randomised, crossover study. Twelve patients with severe haemophilia A (VIII:C < 2 u/dl) were divided into two subgroups of six. None had received factor VIII concentrate within 48 h preceding the study. Twenty-four pharmacokinetic studies were performed in the 12 patients. Each subgroup received two different lots of study material (US and Spanish) at a dose of 50 u/kg seven days apart. A second randomisation was nominal potency, high: 1000 u or mid: 500 u per vial. The potency label was a one-stage clotting assay using the mega I standard. A standard pharmacokinetic study was performed over 24 h and each blinded sample was analysed in duplicate by a one-stage clotting (aPTT) and a chromogenic (Chromogenix AB; CS) assay at the Royal Free and NIBSC. Pharmacokinetic modelling was performed. The mean label for Hemofil-M using the chromogenic substrate assay was 79% that using the one stage assay (Mega I standard). The recovery was 17-28% higher measured by chromogenic compared to the clotting assay. Since most clinicians use the clotting assay, potency labelling using the chromogenic assay, will overestimate predicted Hemofil-M recovery by as much as 25%.

Biological Assay↗
PubMed1996

Loss of expression of transforming growth factor beta type I and type II receptors correlates with tumor grade in human prostate cancer tissues.

Transforming growth factor beta1 (TGF-beta1) is a potential regulator of prostate cancer cell growth that signals through a heteromeric complex composed of type I and type II receptors. In the present study, an attempt was made to establish a correlation between expression of TGF-beta receptors and tumor grade in archival human prostate cancer tissues. To this end, immunohistochemical studies for TGF-beta receptors were carried out on 32 cases of human prostate cancer and 8 samples of benign human prostate. In both benign and malignant human prostate tissues, immunoreactivity for both type I and type II receptors was detected predominantly in epithelial cells. In addition, there was an inverse correlation between the loss of expression of TGF-beta1 type I and type II receptors and the tumor grade. Of the 32 prostate cancer cases screened, staining was completely absent in four samples for type II receptor (P < 0.05) and eight samples for type I receptor (P < 0.025). In contrast, all eight samples of benign prostate tissues investigated in this study showed strong staining for both type I and type II receptors. These results, taken together, indicate that human prostate cancer cells frequently have loss of expression of TGF-beta type I and/or type II receptors. Furthermore, these observations provide a potential mechanism for prostate cancer cells to escape the growth-inhibitory effect of TGF-beta.

Activin Receptors, Type I↗
PubMed1995

Transcriptional induction of the PML growth suppressor gene by interferons is mediated through an ISRE and a GAS element.

PML is a nuclear matrix protein with growth suppressing properties, whose expression is deregulated during oncogenesis. Moreover, in the t(15;17) translocation of acute promyelocytic leukaemia (APL), PML fusion to the retinoic acid receptor alpha (RAR alpha) is the likely molecular basis of leukaemogenesis. Here we show that interferons (IFNs) alpha, beta, and gamma upregulate PML mRNA expression. Analysis of 5' genomic sequences of the PML gene revealed an IFN-alpha/-beta stimulated response element (ISRE) and an IFN-gamma activation site (GAS) in the untranslated first exon. Binding of IFN signal transducers and activators of transcription (STATs) was demonstrated to be weak for the PML GAS, but strong for the PML ISRE which also seemed to contribute substantially to the IFN-gamma response. Thus, PML is a primary target gene of IFNs and would appear as a suitable candidate for mediating some of their antiproliferative effects. Abnormalities of PML structure, localisation or expression in human malignancy, constitute examples of how an IFN target gene may be altered in oncogenesis.

Amino Acid Sequence↗