The aging stomach: implications for NSAID gastropathy.
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Aged↗
Biomedical subjects
M Lee
Publications and source records attributed to M Lee.
TGF-beta isoforms differentially attenuate EGF mitogenicity and receptor activity in fetal lung mesenchymal cells.
To evaluate signaling interactions, combinations of epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) isoforms were applied to primary fetal mouse lung mesenchymal cells isolated at 16 days of gestation. The three isoforms of TGF-beta had similar mitogenic potentials, as assessed by thymidine incorporation (half-maximal effective concentration approximately 2 ng/ml). However, combined exposure to EGF and TGF-beta yielded an isoform-dependent attenuation of EGF-induced mitogenesis. Combinations of 20 ng/ml EGF and 2 ng TGF-beta 1, TGF-beta 2, or TGF-beta 3 resulted in thymidine incorporation values 0.76, 0.74, and 0.86 times that of EGF alone, respectively; attenuation of EGF mitogenicity, interactions between EGF and TGF-beta isoforms, and differences between isoforms were all statistically significant by analysis of variance. Treatment with TGF-beta isoforms significantly reduced EGF-induced receptor angiotensin II substrate phosphorylation. TGF-beta isoform-specific signaling also significantly attenuated EGF-induced phosphorylation of the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase 2. These results suggest that isoform-specific TGF-beta signaling modulates the EGF signal transduction pathway upstream of MAP kinase.
Animals↗
Modulation of MHC isoforms in functionally overloaded and exercised rat plantaris fibers.
The effects of 1 and 10 wk of functional overload (FO) of the rat plantaris with (FOTr) and without daily endurance treadmill training on its myosin heavy chain (MHC) composition were studied. After 1 and 10 wk of FO, plantaris mass was 22 and 56% greater in FO and 37 and 94% greater, respectively, in FOTr rats compared with age-matched controls. At 1 wk, pure type I and pure type IIa MHC fibers were hypertrophied in FO (39 and 44%) and FOTr (70 and 87%) rats. By 10 wk all fiber types comprising >5% of the fibers sampled showed a hypertrophic response in both FO groups. One week of FO increased the percentage of hybrid (containing both type I and type IIa MHC) fibers and of fibers containing embryonic MHC. By 10 wk, the percentage of pure type I MHC fibers was approximately 40% in both FO groups compared with 15% in controls, and the percentage of fibers containing embryonic MHC was similar to that in controls. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses showed an increase in type I MHC and a decrease in type IIb MHC in both FO groups at 10 wk, whereas little change was observed at 1 wk. These data are consistent with hypertrophy and transformation from faster to slower MHC isoforms in chronically overloaded muscles. The additional overload imposed by daily endurance treadmill training employed in this study (1.6 km/day; 10% incline) results in a larger hypertrophic response but appears to have a minimal effect on the MHC adaptations.
Animals↗
Benign prostatic hyperplasia: diagnosis and treatment guideline.
OBJECTIVE: To critique the US Department of Health and Human Services Public Health Service, Agency for Health Care Policy and Research, Clinical Practice Guideline on Benign Prostatic Hyperplasia: Diagnosis and Treatment; and to provide an update on management and treatment of benign prostatic hyperplasia (BPH) since the Guideline was published. DATA SOURCES: A review of the published medical literature in MEDLINE from 1994 to April 1996, limited in focus to drug treatment of BPH, English language, and human subjects, was performed. STUDY SELECTION: Controlled clinical studies of drug treatment for symptomatic BPH that used objective parameters (e.g., urinary flow rate, prostatic volume, voiding symptom scores) were evaluated. A single reviewer assessed each study. DATA EXTRACTION: Study methods, inclusion and exclusion criteria, and treatment outcomes were assessed for all studies. Independent extraction was performed by a single observer. DATA SYNTHESIS: Management of BPH is directed at ameliorating voiding symptoms. For moderate or severe BPH, medical or surgical therapy should be offered to the majority of patients. Medical therapy options include alpha-adrenergic antagonists and finasteride. The former offer the advantage of a more prompt onset of action (within weeks) when compared with finasteride. Finasteride produces a lower response rate and smaller improvement in voiding symptoms. Combination therapy of terazosin and finasteride has not been proven to be more effective than terazosin monotherapy. CONCLUSIONS: When medical therapy is indicated for moderate or severe BPH, alpha-adrenergic antagonists exhibit a faster onset of action and produce greater improvement of voiding symptoms than does finasteride.
Humans↗
Minimal cardiac effects in asymptomatic athyreotic patients chronically treated with thyrotropin-suppressive doses of L-thyroxine.
Biondi, Fazio, and colleagues recently reported that long term T4 treatment to suppress serum TSH markedly affects cardiac function. T4-treated patients had more symptoms [12.2 +/- 3.9 (+/-SD) vs. 4.2 +/- 2.3 by quantitative questionnaire], higher mean heart rate, increased incidence of atrial extrasystoles, increased interventricular septal thickness and left ventricular mass index (LVMi), and significant diastolic dysfunction. The severity of cardiac abnormalities was highly correlated with scores of a rating scale used for assessing symptoms of thyrotoxicosis. We have duplicated their studies in 17 athyreotic patients (mean age, 45 +/- 10 yr; range, 27-63 yr) without heart disease or hypertension whose dose of T4 was titrated to suppress serum TSH to less than 0.01 microU/mL. The mean duration of T4 treatment was 9.2 +/- 5.4 yr. Controls were healthy volunteers matched for sex and age (+/-3 yr). The mean T4 dose was 2.8 +/- 0.9 micrograms/kg (0.192 +/- 0.058 mg/day). By questionnaire, patients had minimal symptoms, although their symptom score was significantly greater than the control value (4 +/- 3 vs. 2 +/- 1; P < 0.05; maximum score, 36). No differences in mean heart rate or in atrial or ventricular extrasystoles were noted. In patients, indexes of systolic and diastolic function and interventricular septal thickness were similar to control values. The mean LVMi was normal in both groups. However, the mean LVMi in patients (117 +/- 35 g/m2) was higher than that in controls (92 +/- 31; P < 0.05). In conclusion, patients were minimally affected by TSH-suppressive doses of T4. They had few symptoms and no increase in extrasystoles or basal heart rate. Based on current knowledge, the increase in LVMi observed in patients without associated significant systolic or diastolic abnormalities does not have clinical or prognostic importance. Therefore, in the absence of symptoms of thyrotoxicosis, patients treated with TSH-suppressive doses of L-T4 may be followed clinically without specific cardiac laboratory studies.
Adult↗
Granddaughters' accounts of the influence of parental mediation on relational closeness with maternal grandmothers.
This study explores granddaughters' reports of the nature and impact of parental mediation on the development of their feelings of closeness toward their maternal grandmothers. Results from close-ended questions assessing granddaughters' perceptions of parental mediation and relational closeness indicated that closeness was predicted by mediation involving: visits alone with grandmothers, the absence of criticism of grandmothers, communication indicating the grandmothers were important persons, and less influence on conversations or activities. Qualitative analysis of granddaughters' accounts of the influence of parents illustrated what they perceived to be important issues in mediation. Additionally, accounts revealed the role of other family members in the relationship mediation process.
Adolescent↗
Chest teleradiology in a teaching hospital emergency practice.
OBJECTIVE: New standards for hospital accreditation and health care reimbursement may require that faculty subspecialists be more available after regular working hours to supervise residents in academic radiology departments. We designed a receiver operating characteristic study to determine whether a thoracic radiologist who evaluated computed radiography (CR) images of the chest at a home-based teleradiology workstation could add significant value to a junior resident's interpretations of films within the hospital for acutely ill patients. SUBJECTS AND METHODS: Using a hybrid cassette, we obtained analog chest films and CR images simultaneously for each of 252 acutely ill patients in the emergency department and in an intensive care unit. Interpretations of the analog films by three first-year residents were analyzed for 11 parameters deemed critical for patient management. Likewise, CR images of the same chest studies were viewed on a home teleradiology workstation by a faculty thoracic radiologist who analyzed the images for these 11 interpretive parameters. All interpretations by radiology residents and by the home-based thoracic radiologist were then compared with the interpretations of a consensus panel consisting of another thoracic radiologist and a full-time emergency department radiologist. RESULTS: Analysis of the pooled results from the three junior residents as a group failed to show significant differences between their interpretations of chest films and the interpretations of CR images by a thoracic radiologist at a home workstation. However, we observed significant differences for several image interpretation parameters between individual residents and the home-based radiology subspecialist. CONCLUSION: The data confirm that significant value can be added to the interpretations of chest films by individual junior residents when a home-based thoracic radiologist uses teleradiology to provide expert interpretations. Accordingly, it is reasonable to infer that on-line supervision by faculty subspecialists via teleradiology could be used to complement the scheduled visits that are being made now by individual faculty members of our institution to interpret films periodically with a radiology resident during overnight and weekend periods.
Emergency Service, Hospital↗
Long-term outcome of high-dose cytarabine-based consolidation chemotherapy for older patients with acute myelogenous leukemia.
Despite reports of improved response and leukemia-free survival for adults with acute myelogenous leukemia, advanced age remains a significant adverse prognostic factor for both response to induction therapy and prolonged leukemia-free survival. In addition to a high incidence of treatment-related complications, older patients may have other disease characteristics which predict for brief remission duration despite intensive consolidation chemotherapy. We analyzed the long-term results of high-dose cytarabine-anthracycline consolidation chemotherapy in older patients and examined the effect of major prognostic factors including a history of myelodysplasia, increased age, and cytogenetics. One hundred and ten patients age > or = 60 with newly diagnosed acute myelogenous leukemia were enrolled on three sequential studies conducted from 1982 to 1996. Fifty-six patients (51%) achieved a complete remission and were eligible for high-dose cytarabine-based consolidation chemotherapy administered in two to three courses. After a median follow-up of surviving patients for seventeen months, twelve patients remain alive with eleven in continued remission. Median remission duration for all eligible patients is nine months and the actuarial leukemia-free survival is 14 +/- 10%. Toxicity of consolidation therapy included treatment-related death in six patients and serious neurotoxicity in five. When compared to younger patients, patients over age 60 sustained a much higher risk of relapse despite successfully completing intensive consolidation therapy, regardless of whether other adverse prognostic features were present. Advanced age in acute myelogenous leukemia is associated with a significantly higher risk of relapse unmodified by the presence or absence of other adverse disease characteristics. Although older patients tolerated intensive therapy designed to address the high risk of relapse, there was no apparent benefit of high-dose cytarabine consolidation alone as post-remission treatment for acute myelogenous leukemia in this population.
Aged↗
Skin ulcer and immunoblot patterns by inoculation sites in BALB/c mice infected with Leishmania major.
The skin ulcer in Leishmania major infection is known to be variable according to the inoculation sites even in a susceptible host. The present study traced the immunoblot patterns by the site of inoculation and duration of infection in BALB/c mice. L. major were subcutaneously inoculated on the nose, footpad, and back of the mice, in a dose of 3 x 10(6) promastigotes. Sera of the mice were collected every 10 days after inoculation. SDS-PAGE separated soluble protein bands of the promastigotes and immunoblot was carried out with the infection sera. The skin ulcer first appeared on the nose at 15 days, and on the footpad at 17 days after inoculation. The ulcer on the back appeared after 90 days. In the mice with ulcer on the nose or footpad, serum IgG antibody reacted to 202, 139, 98, 83, 81, 67 65, 62, 59, 54, 52, 42, 26 and 23 kDa bands at 20 days after inoculation. In mice inoculated on the back, however, the immunoblot showed visible reactions with 202, 83, 81, 74, 67, 65, 62, 59, 54, 52, 20 and 17 kDa bands at 90 days after inoculation. The present result showed that the antigenic protein bands of L. major promastigotes were differed by the inoculation site and duration of infection. Since the skin ulcer and the serum antibodies to antigenic bands between 67-52 kDa appeared simultaneously, it is suggested that the serum IgG antibodies may play a role in formation of the skin ulcer in BALB/c mice.
Animals↗
Immunoblot patterns of clonorchiasis.
Clonorchis sinensis is a liver fluke which is the most prevalent helminth of humans in Korea. The better diagnostic measure of clonorchiasis is required for its nationwide control program. The present study observed antigenic bands of C. sinensis and reacting immunoglobulins in serum of infected residents. Adult C. sinensis were recovered from experimentally infected rabbits and soluble crude extract of the worms was used as the antigen after supplementation of E-64, a cysteine proteinase inhibitor. SDS-PAGE of the crude antigen resolved more than 20 protein bands between 200 and 14 kDa. The sera of infected humans collected at an endemic village showed specific IgG and IgE antibodies but little IgM and IgA antibodies. The protein bands of 94, 80, 72, 68, 52, 47, 43, 37, 34, and 28-25 kDa strongly reacted with serum Ig(GMA) or IgG antibody and 64, 62, 52, 47, 44, 34, 28, and 26 kDa bands reacted with serum IgE antibody. However, the 94, 80, 72, 68, 64, 62, 52, 47, and 40 kDa bands of C. sinensis antigen were found non-specific. The protein bands of 43, 34, and 28-25 kDa of C. sinesis are primary target molecules of further analysis.
Animals↗
Why do some women participate in the labor force while others stay at home?
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Asia↗
Alkylation specificity for a series of distamycin analogues that tether chlorambucil.
The sequence specificity of alkylation for a series of pyrrole- and imidazole-containing analogues of distamycin that tether the nitrogen mustard chlorambucil (CHL) was determined using modified sequencing techniques. Examination of the sequence specificity of alkylation for the imidazole-CHL conjugates using a Taq polymerase stop assay revealed that although the doses required to produce similar amounts of damage were at least 10-fold lower, the sequence specificity of alkylation was essentially identical to that seen for CHL. The guanine-N7 alkylation pattern, which consisted of guanines within runs of guanines, was confirmed using a piperidine cleavage assay. The pyrrole-CHL conjugates also produced a similar pattern of alkylation to that seen for CHL, but one exception was a unique site strongly alkylated only by the di- and tripyrrole-CHL conjugates. The unique lesions, at AG for the dipyrrole-CHL conjugate and G for the tripyrrole-CHL conjugate in the sequence 5'-GAAGAT, were confirmed as minor groove adenine- and guanine-N3 lesions using a thermal cleavage assay.
Alkylation↗
A multicenter study of recombinant factor VIII (Recombinate) in previously treated patients with hemophilia A. The Recombinate Previously Treated Patient Study Group.
A prospective, open-label multicenter investigation has been conducted to compare pharmacokinetic parameters of recombinant DNA-derived FVIII (rFVIII) and plasma-derived FVIII concentrate (pdFVIII) and to assess safety and efficacy of long-term home-treatment with rFVIII for subjects with hemophilia A. Following comparative in vivo pharmacokinetic studies, 69 patients with severe (n = 67) or moderate (n = 2) hemophilia A commenced a program of home treatment using rFVIII exclusively for prophylaxis and treatment of all bleeding episodes for a period of 1.0 to 5.7 years (median 3.7 years). The mean in vivo half-lives of rFVIII and pdFVIII were both 14.7 h. In vivo incremental recoveries at baseline were 2.40%/IU/kg and 2.47%/IU/kg, respectively (p = 0.59). The response to home treatment with rFVIII was categorized as good or excellent in 3,195 (91.2%) of 3,481 evaluated bleeding episodes. Thirteen patients received rFVIII for prophylaxis for twenty-four surgical procedures. In all cases, hemostasis was excellent. Adverse reactions were observed in only 13 of 13,591 (0.096%) infusions of rFVIII: none was serious. No patient developed an inhibitor to rFVIII.
Adolescent↗
[A randomized comparative study of surgical adjuvant chemotherapy using 5-fluorouracil and dl-leucovorin with CDDP 5-FU and dl-leucovorin for colorectal cancer].
A randomized comparative study of surgical adjuvant chemotherapy using dl-leucovorin (dl-LV) and 5-fluorouracil (5-FU) (FL-therapy) with CDDP, 5-FU, and dl-LV (PFL-therapy) was conducted. The following were the administration schedules: Arm A was 13 mg/m2 of CDDP, 300 mg/m2 of 5-FU, and 30 mg/body of dl-LV for 5 consecutive days and arm B was 300 mg/m2 of 5-FU and 30 mg/body of dl-LV for 5 consecutive days. Both regimens were followed by biweekly administration of the same dose of dl-LV and 5-FU in outpatients. Arm A was started at the 26th postoperative day and arm B at the 21st day on average. Some 26 cases composed of 11 cases of arm A and 15 cases of arm B completed the administration schedules. Only one case in arm A was complicated by local recurrence around 35 months after operation. Major toxicities were anorexia and neutropenia. Both toxicities were seen more in arm A than in arm B, showing complete recovery in all cases. These data suggest that PFL-therapy and FL-therapy seem to be possible and promising surgical adjuvant therapies for advanced colorectal carcinoma.
Adenocarcinoma↗
Problem-based learning at the University of Southern California School of Dentistry.
Responding to the recent Institute of Medicine report on dental education, the Center for Craniofacial Molecular Biology (CCMB) of the University of Southern California School of Dentistry has developed a parallel track program in dental education leading to the D.D.S. degree. This program was proposed in May of 1995, and the first class of twelve students was admitted in September of that year. Currently two classes are enrolled and plans to admit a further twelve students (Class of 2001) are in place. The educational strategy for this program is totally problem-based. Students work in groups of six with a faculty facilitator, not necessarily a content expert. Facilitators are largely drawn from the multidisciplinary pool of research faculty at the center. All learning is mediated through biomedical and biodental problem cases. No formal lectures or classes are scheduled. The learning of clinical dental skills is promoted through focussed dental patient simulations in which students review clinical charts, radiographs, medical reports and then explore identified, hands-on learning needs using patient simulators in a clinical context. Early patient exposure is obtained through dental office visits and other special patient clinics. Initial experience with this program suggests that the problem-based learning (PBL) students learn as well (if not better) than their traditional program peers and develop excellent group and cognitive analytical skills. The absence of a pool of dentally related biomedical cases suitable for a PBL program has necessitated the use of innovative approaches to their development and presentation. It is believed that this educational approach will produce dental clinicians equipped with the self-motivated, life-long learning skills required in the ever-changing world of bio-dental sciences in the twenty-first century.
California↗
Plinth padding and measures of posteroanterior lumbar stiffness.
OBJECTIVE: To investigate whether measurement of posteroanterior (PA) lumbar stiffness is affected by the presence of padding on the testing plinth. DESIGN: Within a repeated-measures design, measurements were made of lumbar PA stiffness in subjects without low back pain on both a rigid and a padded plinth surface. SUBJECTS: Nineteen subjects with no history of any low back pain requiring treatment over the preceding 12 months participated in this study. METHODS: PA stiffness was measured at L3 on two occasions under two different conditions. The first condition involved measurement of lumbar stiffness on a rigid plinth surface; the second involved measurement on a padded plinth surface. A reliable mechanical device was used to obtain the PA stiffness measures. RESULTS: Mean lumbar PA stiffness values obtained when testing on a padded plinth were 2.86 N/mm less than those values obtained when testing the same lumbar spines on a rigid plinth. A paired t test showed a significant difference between the PA stiffness measures at L3 obtained on the padded plinth and those obtained on the rigid plinth (t = 6.66, df = 18, p < or = .0001). CONCLUSIONS: These findings suggest that to improve the reliability of lumbar PA stiffness assessment, testing should be performed under the same plinth surface conditions.
Adult↗
Synthesis, DNA binding, cytotoxicity and sequence specificity of a series of imidazole-containing analogs of the benzoic acid mustard distamycin derivative tallimustine containing an alkylating group at the C-terminus.
In an attempt to produce additional alkylation and crosslinking in the minor groove of DNA, imidazole-containing analogs of distamycin were synthesized with benzoic acid mustard (BAM) and methoxyaziridinyl moieties present at the N- and C-termini, respectively. Analogs 1a-c differed in the number of methylene units (2-4 respectively) between the C-terminal carbonyl group and the methoxyaziridinyl moiety. DNA binding affinity to several polynucleotides decreased with increasing linker length, whereas DNA interstrand crosslinking ability, as measured by a plasmid gel based assay, increased. The in vitro cytotoxicity in human chronic myeloid leukemia K562 cells and the panel of human tumor cell lines at the National Cancer Institute decreased with increasing number of methylene units, and no increase in cytotoxicity was observed over compound AR-1-122 which did not contain the methoxyaziridinyl moiety. 1a-c had the same sequence selectivity of alkylation as AR-1-122, showing alkylation only at 5'-TTTTGPu sequences. The relative binding to these sequences decreased with increasing number of methylene units. The addition of a methoxyaziridinyl moiety in this group of imidazole and BAM-containing compounds can, therefore, increase crosslinking ability to naked DNA but this does not result in an increase in cytotoxicity. In contrast the cytotoxicity was related to their ability to produce sequence specific alkylation at 5'-TTTTGPu sequences.
Alkylating Agents↗
[Combination hepatic intra-arterial 5-fluorouracil and CDDP administration with oral regimen in patients with colorectal cancer metastasis to the liver].
We investigated therapeutic effectiveness and side effects of a combination weekly high-dose 5-FU plus one shot CDDP HAI (WHF + CDDP method) with oral regimen in patients with colorectal cancer metastasis to the liver. All 24 patients enrolled in this study showed 54% efficacy whereas patients combined HAI with oral regimen over one week obtained 83% efficacy for multiple liver metastasis. They showed good quality of the life during combination chemotherapy without any symptoms of metastatic lesions. The WHF + CDDP method combined with oral regimen is a promising treatment for colorectal cancer metastasis to the liver as well as extrahepatic distant organs, and this protocol may be satisfactorily accepted by most colorectal cancer laden patients because of negligible side effects.
Administration, Oral↗