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Biomedical subjects

J Lee

Publications and source records attributed to J Lee.

At least 523 records · Page 29Linked to original sources
PubMed2000

Alteration of tumour response to radiation by interleukin-2 gene transfer.

We have previously shown that BALB/c-derived EMT6 mammary tumours transfected with interleukin (IL)-2 have decreased hypoxia compared to parental tumours, due to increased vascularization. Since hypoxia is a critical factor in the response of tumours to radiation treatment, we compared the radiation response of IL-2-transfected tumours to that of parental EMT6 tumours. Because the IL-2 tumours have an altered host cell composition, which could affect the interpretation of radiation sensitivity as measured by clonogenic cells, we employed flow cytometric analysis to determine the proportion of tumour cells vs host cells in each tumour type. Using this approach, we were able to correct the plating efficiency based on the number of actual tumour cells derived from tumours, making the comparison of the two types of tumours possible. We also excluded the possibility that cytotoxic T-cells present in EMT6/IL-2 tumours could influence the outcome of the clonogenic cell survival assay, by demonstrating that the plating efficiency of cells derived from EMT6/IL-2 tumours remained unchanged after depletion of Thy-1+ cells. The in vivo radiation response results demonstrated that IL-2-transfected tumours were more sensitive to radiation than parental EMT6 tumours. The hypoxic fraction of the EMT6/IL-2 tumours growing in vivo was markedly decreased relative to parental EMT6 tumours thus the increased sensitivity results from the increased vascularity we have previously observed in these tumours. These results indicate the potential therapeutic benefit of combining radiation and immunotherapy in the treatment of tumours.

Animals↗
PubMed2000

Preplanned correction of enophthalmos using diced cartilage grafts.

A simple technique for correcting post-traumatic enophthalmos is presented. Autogenous costal cartilage was chopped into small pieces and used to fill up the medial orbital wall defect in five patients. The measured degrees of enophthalmos ranged from 2 to 4 mm, and 3-5. 5 ml of filler material was introduced into the periorbital space. A conservative approach via upper and lower eyelid incisions was used. It was found that 1.37-1.5 ml of graft material results in 1 mm advancement of globe position. This correlation appears to be a useful treatment guideline for medial orbital wall blow-out fractures. Transient diplopia developed in three cases, but settled within 4 months. There were no other major sequelae after the operation. The follow-up period ranged from 8 months to 3 years. The improved appearance and the stable results confirm the validity of this approach.

Adult↗
PubMed2000

Potentiating effect of obacunone from Dictamnus dasycarpus on cytotoxicity of microtuble inhibitors, vincristine, vinblastine and taxol.

The limonoid triterpene, obacunone, was found to enhance the cytotoxicity of vincristine against L1210 cells by approximately 10-fold. Further, it was found that the cytotoxicity of other microtubule inhibitors such as vinblastine and taxol in drug-sensitive KB-3-1 cells as well as in multidrug-resistant KB-V1 cells was enhanced greatly in the presence of obacunone. On the other hand, there was no remarkable potentiating effect of obacunone on the cytotoxicity of other antineoplastic drugs such as adriamycin, cisplatin or 5-fluorouracil. From these results, it is implied that the potentiating action of obacunone may be limited to microtubule inhibitors.

Animals↗
PubMed2000

Molecular alterations in hepatocyte transport mechanisms in acquired cholestatic liver disorders.

Recent advances in the molecular cloning of membrane transport systems that determine bile formation have facilitated studies of the molecular mechanisms of cholestatic liver disease. The present review summarizes what has been learned about the molecular alterations of these membrane transporters in hepatocytes and cholangiocytes in acquired cholestatic liver disorders. Much of this information has been obtained from the study of animal models of cholestasis and from more limited studies in clinical cholestatic liver diseases. Many of these responses may be interpreted as adaptations that serve to diminish cholestatic liver injury.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Blunt abdominal trauma resulting in Pneumatosis intestinalis in an infant.

We report a case of pnuematosis intestinalis in a 2-year-old boy after blunt abdominal trauma. In the setting of blunt trauma, the hypothesized mechanism of pneumatosis intestinalis is mechanical disruption of the intestinal mucosa with extravasation of luminal gas within the intestinal wall. Although the presence of intraluminal gas may imply intestinal necrosis and the need for an invasive procedure, this case report suggests that management without surgery can lead to successful outcome in selected cases.

Abdominal Injuries↗
PubMed2000

Computational studies of essential dynamics of Pseudomonas cepacia lipase.

In order to investigate the interfacial activation of a lipase from Pseudomonas cepacia (PcL), molecular dynamics (MD) simulations and essential dynamics (ED) analysis were performed in different solvent environments: vacuum and explicit water solvents. Starting from the active (open) structure of PcL, the essential dynamics analysis of the simulations revealed large correlated motions, which may be responsible for the activation of the enzyme. Fluctuations in the U1 (active-site lid) and U2 domains are found to be important in the activation of PcL. In contrast, the catalytic triad exhibits very little displacement. These results are consistent with the previous X-ray structural determination. A combined analysis of the trajectories showed some differences for the simulations in different solvent environments. It was found that the region around the helix alpha5 showed larger displacements in the water simulations. It can be concluded that the open structure of PcL becomes unstable in water solvents, leading to the closing of the so-called 'lid' region. The simulations and ED analysis on the closed structure of PgL provided additional information concerning the structural changes involved in the activation of the lipases. It was found that structural changes for PcL and PgL, which are responsible for the essential motions of the protein, showed contrasting behavior in the different solvent environments.

Binding Sites↗
PubMed2000

Is hands-on experience more effective than didactic workshops in postgraduate cancer pain education?

BACKGROUND: This study examined the nurse outcomes of a cancer pain education program for nurses of patients from 11 different ethnic groups. METHODS: Four hundred ninety six home, hospital, and hospice nurses participated in a one-day workshop or two half-day workshops on cancer pain assessment and management. Of these, 116 were randomized to participate in a bedside-precepted visit with an oncology nurse specialist with pain specialization and a focus group to discuss attitudinal issues. Eighty-six nurses served as controls. Pre-, post- and one-year follow-up tests were administered. RESULTS: Attitudes, knowledge, and application skills significantly improved for workshop-only and enriched-model nurses relative to controls. CONCLUSION: For postgraduate nurses, daylong cancer pain education workshops were, in the group studied, as effective as hands-on experience in improving cancer pain knowledge and changing attitudes. Both the workshop-only and the enriched-model nurses relative to controls had significantly improved knowledge and changed attitudes towards optimal pain management.

Adult↗
PubMed2000

Increased expression and shuttling of aquaporin-2 water channels in the kidney in DOCA-salt hypertensive rats.

An altered role of AQP2 water channels in DOCA-salt hypertension was investigated. DOCA-salt hypertension was induced in rats. Control groups were either treated with DOCA alone or subjected to a high-salt intake without DOCA. Four weeks after inducing the hypertension, AQP2 expression and shuttling were determined in the kidney. Adenylate cyclase activity was also determined to examine the upstream affecting the AQP2 system. The AVP-evoked cAMP generation in the cortex and outer medulla was augmented following the treatment with DOCA either alone or combined with high-salt intake. Accordingly, the expression and shuttling of AQP2 proteins were increased in the cortex and outer medulla. These findings suggest that DOCA enhances cAMP generation and expression/shuttling of AQP2 water channels in the kidney, which may be causally related with the development of hypertension.

Adenylyl Cyclases↗
PubMed2000

Candiduria: a randomized, double-blind study of treatment with fluconazole and placebo. The National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group.

Management of candiduria is limited by the lack of information about its natural history and lack of data from controlled studies on the efficacy of treating it with antimycotic agents. We compared fungal eradication rates among 316 consecutive candiduric (asymptomatic or minimally symptomatic) hospitalized patients treated with fluconazole (200 mg) or placebo daily for 14 days. In an intent-to-treat analysis, candiduria cleared by day 14 in 79 (50%) of 159 receiving fluconazole and 46 (29%) of 157 receiving placebo (P<.001), with higher eradication rates among patients completing 14 days of therapy (P<.0001), including 33 (52%) of 64 catheterized and 42 (78%) of 54 noncatheterized patients. Pretreatment serum creatinine levels were inversely related to candiduria eradication. Fluconazole initially produced high eradication rates, but cultures at 2 weeks revealed similar candiduria rates among treated and untreated patients. Oral fluconazole was safe and effective for short-term eradication of candiduria, especially following catheter removal. Long-term eradication rates were disappointing and not associated with clinical benefit.

Aged↗
PubMed2000

Distinct and redundant functions of mu1 medium chains of the AP-1 clathrin-associated protein complex in the nematode Caenorhabditis elegans.

In the nematode Caenorhabditis elegans, there exist two micro1 medium chains of the AP-1 clathrin-associated protein complex. Mutations of unc-101, the gene that encodes one of the micro1 chains, cause pleiotropic effects (). In this report, we identified and analyzed the second mu1 chain gene, apm-1. Unlike the mammalian homologs, the two medium chains are expressed ubiquitously throughout development. RNA interference (RNAi) experiments with apm-1 showed that apm-1 and unc-101 were redundant in embryogenesis and in vulval development. Consistent with this, a hybrid protein containing APM-1, when overexpressed, rescued the phenotype of an unc-101 mutant. However, single disruptions of apm-1 or unc-101 have distinct phenotypes, indicating that the two medium chains may have distinct functions. RNAi of any one of the small or large chains of AP-1 complex (sigma1, beta1, or gamma) showed a phenotype identical to that caused by the simultaneous disruption of unc-101 and apm-1, but not that by single disruption of either gene. This suggests that the two medium chains may share large and small chains in the AP-1 complexes. Thus, apm-1 and unc-101 encode two highly related micro1 chains that share redundant and distinct functions within AP-1 clathrin-associated protein complexes of the same tissue.

Adaptor Protein Complex 1↗
PubMed2000

Involvement of progesterone in gonadotrophin-induced pituitary adenylate cyclase-activating polypeptide gene expression in pre-ovulatory follicles of rat ovary.

The present study was designed to determine whether progesterone might have a role in gonadotrophin-induced pituitary adenylate cyclase-activating polypeptide (Pacap) gene expression in rat ovary. Northern blot analysis revealed that treatment of pregnant mare's serum gonadotrophin (PMSG)-primed immature rats with the progestin antagonist RU486 or an inhibitor of 3beta-hydroxysteroid dehydrogenase epostane, 1 h before HCG, resulted in a dose-dependent inhibition of the HCG-induced Pacap gene expression. In-situ hybridization demonstrated that the number of pre-ovulatory follicles expressing Pacap mRNA in their granulosa cells was greatly reduced in ovaries treated with RU486. Moreover, the suppressive effect of RU486 or epostane on the LH-induced Pacap gene expression in cultured pre-ovulatory follicles was reversed by co-treatment with the synthetic progestin R5020. We further cloned the 5'-flanking region of the rat Pacap gene and identified the presence of a consensus progesterone receptor element. When luciferase fusion genes containing Pacap gene promoter were transiently transfected into granulosa cells of pre-ovulatory follicles, luciferase activity was markedly stimulated by LH. Treatment with RU486 or epostane resulted in partial suppression of LH-stimulated PACAP promoter activity. Taken together, these results indicate that progesterone, acting through progesterone receptors, plays a role in gonadotrophin induction of Pacap gene expression in granulosa cells of pre-ovulatory follicles, and thereby may be involved in the process of ovulation.

Androstenols↗
PubMed2000

Spindle formation and dynamics of gamma-tubulin and nuclear mitotic apparatus protein distribution during meiosis in pig and mouse oocytes.

This work focuses on the assembly and transformation of the spindle during the progression through the meiotic cell cycle. For this purpose, immunofluorescent confocal microscopy was used in comparative studies to determine the spatial distribution of alpha- and gamma-tubulin and nuclear mitotic apparatus protein (NuMA) from late G2 to the end of M phase in both meiosis and mitosis. In pig endothelial cells, consistent with previous reports, gamma-tubulin was localized at the centrosomes in both interphase and M phase, and NuMA was localized in the interphase nucleus and at mitotic spindle poles. During meiotic progression in pig oocytes, gamma-tubulin and NuMA were initially detected in a uniform distribution across the nucleus. In early diakinesis and just before germinal vesicle breakdown, microtubules were first detected around the periphery of the germinal vesicle and cell cortex. At late diakinesis, a mass of multi-arrayed microtubules was formed around chromosomes. In parallel, NuMA localization changed from an amorphous to a highly aggregated form in the vicinity of the chromosomes, but gamma-tubulin localization remained in an amorphous form surrounding the chromosomes. Then the NuMA foci moved away from the condensed chromosomes and aligned at both poles of a barrel-shaped metaphase I spindle while gamma-tubulin was localized along the spindle microtubules, suggesting that pig meiotic spindle poles are formed by the bundling of microtubules at the minus ends by NuMA. Interestingly, in mouse oocytes, the meiotic spindle pole was composed of several gamma-tubulin foci rather than NuMA. Further, nocodazole, an inhibitor of microtubule polymerization, induced disappearance of the pole staining of NuMA in pig metaphase II oocytes, whereas the mouse meiotic spindle pole has been reported to be resistant to the treatment. These results suggest that the nature of the meiotic spindle differs between species. The axis of the pig meiotic spindle rotated from a perpendicular to a parallel position relative to the cell surface during telophase I. Further, in contrast to the stable localization of NuMA and gamma-tubulin at the spindle poles in mitosis, NuMA and gamma-tubulin became relocalized to the spindle midzone during anaphase I and telophase I in pig oocytes. We postulate that in the centrosome-free meiotic spindle, NuMA aggregates the spindle microtubules at the midzone during anaphase and telophase and that the polarity of meiotic spindle microtubules might become inverted during spindle elongation.

Animals↗
PubMed2000

Production of male cloned mice from fresh, cultured, and cryopreserved immature Sertoli cells.

Although it is generally accepted that relatively high efficiencies of somatic cell cloning in mammals can be achieved by using donor cells from the female reproductive system (e.g., cumulus/granulosa, oviduct, and mammary gland cells), there is little information on the possibility of using male-specific somatic cells as donor cells. In this study we injected the nucleus of immature mouse Sertoli cells isolated from the testes of newborn (Days 3-10) males into enucleated mature oocytes in order to examine the ability of their nuclei to support embryonic development. After activation of the oocytes that had received the freshly recovered immature Sertoli cells, some developed into the morula/blastocyst stage, depending on the age of the donor cells (22.0-37.4%). When transferred into pseudopregnant females, 7 (3.3%, 7 of 215) developed into normal pups at term. Nuclear transfer of immature Sertoli cells after 1 wk in culture also produced normal pups after embryo transfer (3.1%, 2 of 65). Even after cryopreservation in a conventional cryoprotectant solution, their ability as donor cells was maintained, as demonstrated by the birth of cloned young (6.7%, 7 of 105). Immature Sertoli cells transfected with green fluorescent protein gene also supported embryo development into morulae/blastocysts, which showed specific fluorescence. This study demonstrates that immature Sertoli cells, male-specific somatic cells, are potential donors for somatic cell cloning.

Animals↗
PubMed2000

Dichotomy between Tc-99m MDP bone scan and fluorine-18 fluorodeoxyglucose coincidence detection positron emission tomography in patients with non-Hodgkin's lymphoma.

The authors report two cases of non-Hodgkin's lymphoma that were evaluated not only by conventional staging work-up but also additional Tc-99m MDP bone scans and fluorine-18 fluorodeoxyglucose (F-18 FDG) coincidence detection (CoDe) positron emission tomographic (PET) imaging. There were discordant results between the Tc-99m MDP bone scans and F-18 FDG CoDe PET. In the first case, the bone marrow biopsy was positive, and F-18 FDG CoDe PET was consistent with a malignancy, but the findings of the Tc-99m MDP bone scintiscan were negative. In the second case, the bone marrow biopsy was negative, but F-18 FDG CoDe PET revealed focal skeletal involvement, which improved markedly on the follow-up study after chemotherapy. If skeletal involvement has a focal distribution and is confined to the marrow cavity, both bone marrow biopsy and bone scintigraphy can be falsely negative. In this situation, F-18 FDG PET is useful and revealing.

Adult↗
PubMed2000

Prospective, randomized, double-blind study comparing single-agent antibiotic therapy, ciprofloxacin, to combination antibiotic therapy in open fracture wounds.

OBJECTIVE: The purpose of this study was to compare the efficacy of a single agent, ciprofloxacin, with that of combination antibiotic therapy consisting of cefamandole and gentamicin in all types of open fracture wounds. STUDY DESIGN: A prospective double-blind randomized clinical trial. SETTING: A Level 1 trauma center. PATIENTS: One hundred ninety-five consecutive patients with 203 open fractures were enrolled over a twenty-month period. Twenty-nine fractures from low-velocity gunshot wounds were excluded, and three other patients were excluded because of protocol violations. Our final number of patients were 163, with 171 open fractures. MAIN OUTCOME MEASUREMENT: The infection rates for Type I and Type II open fractures for both antibiotic groups were calculated. The infection rate of Type III open fractures for both antibiotic groups was also calculated. Chi-square analysis with Yates correction was used to assess statistical significance of two treatment groups. RESULTS: The infection rate for Types I and II open fractures in the ciprofloxacin group was 5.8 percent and 6 percent for the cefamandole/gentamicin group (p = 1.000). The infection rate for Type III open fractures for the ciprofloxacin group was 31 percent (8 of 26) versus 7.7 percent (2 of 26) for the cefamandole/gentamicin group (p = 0.079). There were no statistically significant differences in infection rate between the group treated with ciprofloxacin and that treated with cefamandole/gentamicin for Types I and II open fracture wounds. However, there appeared to be a high failure rate for the ciprofloxacin Type III open fracture group, with patients being 5.33 times more likely to become infected than those in the combination therapy group. Although this difference was not statistically significant, possibly because of the small sample size, there was a definite trend toward statistical significance. CONCLUSION: Single-agent antibiotic therapy with ciprofloxacin is effective in treatment of Type I and Type II open fracture wounds. However, on the basis of our results, we cannot recommend ciprofloxacin alone for Type III wounds. Possibly one can use fluoroquinolones in combination therapy, specifically as an alternate to an aminoglycoside.

Adult↗
PubMed2000

Activity and immobilization after eccentric exercise: I. Recovery of muscle function.

PURPOSE: The purpose of the present study was to determine whether activity would affect the recovery of muscle function after high-force eccentric exercise of the elbow flexors. METHODS: Twenty-six male volunteers were randomly assigned to one of three groups for a 4-d treatment period: immobilization (N = 9), control (N = 8), and light exercise (N = 9). Relaxed arm angle (RANG), flexed arm angle (FANG), maximal isometric force (MIF), and perceived muscle soreness (SOR) were obtained for 3 consecutive days pre-exercise (baseline), immediately post-exercise, and for 8 consecutive days after the 4-d treatment period (recovery). During the treatment period, the immobilization group had their arm placed in a cast and supported in a sling at 90 degrees. The control group had no restriction of their arm activity. The light exercise group performed a daily exercise regimen of 50 biceps curls with a 5-lb dumbbell. RESULTS: All subjects showed a prolonged decrease in RANG, increase in FANG, loss in MIF, and increase in SOR in the days after eccentric exercise. During recovery, there was no significant interaction observed among groups over time in RANG (P > 0.05) or FANG (P > 0.05), but there was a significant interaction observed among groups over time in both MIF (P < 0.01) and SOR (P < 0.01). Recovery of MIF was facilitated by light exercise and immobilization, whereas recovery from SOR was facilitated by light exercise and delayed by immobilization. CONCLUSIONS: The recovery of MIF in both the light exercise and immobilization groups suggests that more than one mechanism may be involved in the recovery of isometric force after eccentric exercise.

Adult↗