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Biomedical subjects

M Chun

Publications and source records attributed to M Chun.

At least 19 recordsLinked to original sources

Differences in stress and coping models of emotional distress among Korean, Korean-American and White-American caregivers.

This study compares path models of emotional distress among three groups of caregivers for elderly patients with dementia: 64 Koreans residing in Korea, and 53 Korean-Americans and 54 White-Americans living in the USA. The results support a common core model throughout the three groups: patient's disruptive behavior leads to caregiver burden, which then affects caregivers' depression and anxiety. Instrumental support was found to be an important factor for Korean caregivers and emotional support was important for Korean-Americans. Only Korean-American caregivers appraised all three patient's problems--patient's disruptive behaviors, memory problems, and depression as burdensome. These findings suggest that stress and coping processes in caregivers from different cultures involve a common core with important differences in the effects of the patient's problems and of social support.

Adaptation, Psychological↗

The addition of induction chemotherapy with etoposide, ifosfamide, and cisplatin failed to improve therapeutic outcome of concurrent chemoradiotherapy in patients with locally advanced non-small cell lung cancer -- single institution retrospective analysis.

Although chemoradiotherapy (CRT) is a standard treatment for unresectable locally advanced non-small cell lung cancer (NSCLC), the optimal sequencing remains to be determined. We retrospectively compared the treatment results of induction chemotherapy followed by concurrent CRT (induction group, 32 patients) with those of concurrent CRT alone (concurrent group, 41 patients) in unresectable stage IIIA/IIIB NSCLC patients. In induction group, 2 cycles of induction chemotherapy (etoposide/ifosfamide/cisplatin: 24 patients, others: 8 patients) were followed by concurrent CRT (60 Gy/30 fractions, 6 mg/m2 of cisplatin daily), while the same concurrent CRT was administered in concurrent group. Clinicopathologic characteristics including age, weight loss, histologic types, and clinical stage did not show significant differences between two groups except for a higher proportion of patients with ECOG performance status 2 in concurrent group (3% vs. 27%, p=0.015). Overall toxicity was generally acceptable with 1 treatment-related death from tracheoesophageal fistula in induction group. The response rates after concurrent CRT were 41% for induction group and 54% for concurrent group, which showed no significant difference (p=0.560). With median follow-up of 13 (1-92) months, there was a trend toward an advantage for concurrent group in median progression-free survival (6 months vs 8.3 months, p=0.067) and overall survival (12 months vs. 14.5 months, p=0.059). In multivariate analysis, only more than 10% weight loss within 6 months was significantly associated with poor survival (p=0.001). In conclusion, the addition of induction chemotherapy to concurrent CRT did not show any advantage over concurrent CRT alone in locally advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗

Concurrent chemoradiotherapy in patients with nasopharyngeal cancer: prognostic significance of low expression of bax.

A randomized trial has demonstrated that concurrent chemoradiotherapy (CRT) is superior to radiotherapy (RT) alone in locally advanced nasopharyngeal cancer (NPC). Our study comprise 35 patients with locally advanced NPC (stage I: 1, II: 12, III: 7, IV: 15) with 1 cycle of induction chemotherapy (5-fluorouracil 1,000 mg/m(2)/day and cisplatin 20 mg/m(2)/day, days 1- 4) followed by concurrent CRT starting on day 22. Concurrent CRT consisted of RT (70 Gy/35 fractions for 7 weeks) with cisplatin 20 mg/m(2)/day for 4 days on weeks 1, 4, 7 of RT. Complete response (CR) was achieved in 33 patients (94%). Four-year progression-free survival (PFS) and overall survival (OS) of all patients were 57% and 65%, respectively. In analysis of prognostic factors, low expression of bax was the most significant independent predictor of poor prognosis in both PFS (p=0.002) and OS (p=0.008). In conclusion, the outcome of patients treated with this combined therapeutical modality appears to be comparable with that of Intergroup 0099 trial with high CR rate. Low expression of bax was significantly associated with poor PFS and OS.

Adult↗

PYCNOGENOL chewing gum minimizes gingival bleeding and plaque formation.

PYCNOGENOL is an antioxidant phytochemical shown to have antiinflammatory activity in both the in vitro and in vivo models. This study compared the effects of chewing gums with and without PYCNOGENOL on gingival bleeding and plaque formation in 40 human subjects. In this double-blind study, subjects were assigned randomly to receive either control gums without PYCNOGENOL or experimental gums containng 5 mg PYCNOGENOL. Subjects used chewing gums for 14 days. Gingival bleeding and plaque scores were taken before and after the experiment. PYCNOGENOL chewing gums significantly reduced gingival bleeding, while no changes were noted in bleeding indexes in control subjects who used regular chewing gums. Subjects using regular control gums had significant increases of dental plaque accumulation during the two-week period. No increases in plaque accumulation were noted in subjects using PYCNOGENOL chewing gums. The data of this study suggest that the use of Pycnogenol chewing gums can minimize gingival bleeding and plaque accumulation.

Adult↗

Expression of neutrophil collagenase (matrix metalloproteinase-8) in human atheroma: a novel collagenolytic pathway suggested by transcriptional profiling.

BACKGROUND: Loss of interstitial collagen, particularly type I collagen, the major load-bearing molecule of atherosclerotic plaques, renders atheroma prone to rupture. Initiation of collagen breakdown requires interstitial collagenases, a matrix metalloproteinase (MMP) subfamily consisting of MMP-1, MMP-8, and MMP-13. Previous work demonstrated the overexpression of MMP-1 and MMP-13 in human atheroma. However, no study has yet evaluated the expression of MMP-8, known as "neutrophil collagenase," the enzyme that preferentially degrades type I collagen, because granulocytes do not localize in plaques. METHODS AND RESULTS: Transcriptional profiling and reverse transcription-polymerase chain reaction analysis revealed inducible expression of MMP-8 transcripts in CD40 ligand-stimulated mononuclear phagocytes. Western blot analysis demonstrated that 3 atheroma-associated cell types, namely, endothelial cells, smooth muscle cells, and mononuclear phagocytes, expressed MMP-8 in vitro upon stimulation with proinflammatory cytokines such as interleukin-1beta, tumor necrosis factor-alpha, or CD40 ligand. MMP-8 protein elaborated from these atheroma-associated cell types migrated as 2 immunoreactive bands, corresponding to the molecular weights of the zymogen and the active molecule. Extracts from atherosclerotic, but not nondiseased arterial tissue, contained similar immunoreactive bands. Moreover, all 3 cell types expressed MMP-8 mRNA and protein in human atheroma in situ. Notably, MMP-8 colocalized with cleaved but not intact type I collagen within the shoulder region of the plaque, a frequent site of rupture. CONCLUSIONS: These data point to MMP-8 as a previously unsuspected participant in collagen breakdown, an important determinant of the vulnerability of human atheroma.

Aorta↗

Tip60 and HDAC7 interact with the endothelin receptor a and may be involved in downstream signaling.

Endothelins exert their biological effects through G protein-coupled receptors. However, the precise mechanism of downstream signaling and trafficking of the receptors is largely unknown. Here we report that the histone acetyltransferase Tip60 and the histone deacetylase HDAC7 interact with one of the ET receptors, ETA, as determined by yeast two-hybrid analysis, glutathione S-transferase pull-down assays, and co-immunoprecipitation from transfected COS-7 cells. In the absence of ET-1, Tip60 and HDAC7 were localized mainly in the cell nucleus while ETA was predominantly confined to the plasma membrane. Stimulation with ET-1 resulted in the internalization of ETA to the perinuclear compartment and simultaneously in the efflux of Tip60 and HDAC7 from the nucleus to the same perinuclear compartment where each protein co-localized with the receptor. Upon co-transfection with ETA into COS-7 cells, Tip60 strongly increased ET-1-induced ERK1/2 phosphorylation, whereas HDAC7 had no significant effect. We thus suggest that protein acetylase and deacetylase interact with ETA in a ligand-dependent fashion and may participate in ET signal transduction.

Acetyltransferases↗

High dose rate interstitial brachytherapy in soft tissue sarcoma: technical aspects and results.

BACKGROUND: Radiation is essential for function preservation in the management of soft tissue sarcoma (STS). One of the advantages of brachytherapy is that it allows for specific localization of radiation dose to the tumor bed. We examined the results of our clinical experiences with immediate postoperative high dose rate (HDR) brachytherapy and external beam radiation treatment (EBRT) for STS. METHODS: A total of 17 patients (11 primary and six recurrent) between 1995 and 1999 were included in this review. The inclusion criteria for HDR and EBRT were as follows: (1) high-grade tumor, (2) low-grade tumor of > or = 10 cm, (3) recurrent tumor, (4) tumor abutting or invading critical structures and (5) positive margin. The catheters (six French) were placed parallel to the long axis of the tumor with a 1-1.5 cm spacing in between. If necessary, muscle or gel-foam was placed over the critical structures to maintain a minimum space of 0.5 cm from the catheters. On postoperative day 6, patients received HDR (2-3 Gy/fraction x6, twice daily). Three weeks later, patients received EBRT (total 36-60 Gy). The follow-up duration was between 13 and 60 months (median 31 months). RESULTS: There was no local failure within the radiation field in any of the patients. One patient required wound revision for delayed healing after brachytherapy. During EBRT, most patients experienced only mild erythema (grade 1 or 2 skin reaction). In long-term follow-up, there were no patients with neuropathy or significant fibrosis. CONCLUSIONS: Our results suggest that immediate postoperative HDR with a total dose of 12-18 Gy over 3 days is an effective treatment combined with EBRT in the management of STS.

Brachytherapy↗

Modified partial hyperfractionation in radiotherapy for bulky uterine cervical cancer: reduction of overall treatment time.

PURPOSE: The purpose of this study was to assess the feasibility and toxicity of modified fractionation of external beam radiation with the intention of reducing the overall treatment time (OT) by 1 week in cervical cancer. METHODS AND MATERIALS: Thirty-one patients (Group 1, n = 31) with bulky cervical cancer (>/= 4 cm with Stage II and III, >/= 5 cm with Stage IB2) were entered into the twice a day (b.i. d.) protocol (18 Gy/10 fx in 2 weeks followed by 18 Gy/12 fx, b.i.d. in 6 days, then midline block at 36 Gy with 45 Gy to the whole pelvis and 51-59 Gy to the parametrium). These patients underwent high-dose-rate brachytherapy with 4 Gy/fx x 7 to point A, biweekly. During the same period, patients with non-bulky tumors (Group 2, n = 31) received conventional treatment and similar brachytherapy. RESULTS: The OT of Group 1 was 7 weeks or less in 61.3%, 7.1-8 weeks in 29%, and more than 8 weeks in 9.7% (19.4%, 51.6%, and 29% in Group 2, respectively, p = 0.003). Incidences of acute complications and treatment breaks were similar in both groups. Late complication (rectal bleeding) occurred only in Group 1 (13%, 4/31), but was self-limited. Locoregional failures occurred within 2 years after completion of radiation therapy in both groups (16% and 13% in Group 1 and 2, respectively, with minimum and median follow-ups of 2 years and 34 months). CONCLUSION: Partial hyperfractionation on the third week of radiation permitted patients to finish their treatment with shorter OT without excessive acute complications and with acceptable grade 2 late rectal bleeding complications. This treatment scheme may be an effective method for the improvement of local control of bulky cervical cancer.

Adult↗

Immunohistochemical localization of phospholipase D1 in rat central nervous system.

Phospholipase D (PLD) is one of the intracellular signal transduction enzymes and plays an important role in a variety of cellular functions. We investigated the distribution of PLD isozyme, PLD1 in the rat brain and spinal cord using an immunological approach. Western blot analysis showed the presence of PLD1 protein in all tissues studied, with significantly higher levels in the brainstem and spinal cord, which was correlated with the results obtained from PLD activity assay. Prominent and specific signals of PLD1 were observed in many functionally diverse brain areas, including the olfactory bulb, medial septum-diagonal band complex, cerebral cortex, brainstem, cerebellum, and spinal cord. In the brainstem, the red nucleus, substantia nigra, interpeduncular nucleus, cranial motor nuclei (trigeminal motor, abducent, facial, and hypoglossal), sensory cranial nerve nuclei (spinal trigeminal, vestibular, and cochlear), as well as nuclei of the reticular formation, all showed intense immunoreactivity. Purkinje cells and deep cerebellar nuclei of the cerebellum were also labeled intensely. However, no significant labeling was found in the thalamus, epithalamus, and basal ganglia. Although many of the PLD1 immunoreactive cells were neurons, PLD1 was also expressed in glial cells such as presumed astrocytes and tanycytes. These findings suggest that PLD1 may play an important role in the central nervous system of the adult rat.

Animals↗

A rat model for radiation-induced proctitis.

Radiation proctitis is a frequent acute complication encountered with pelvic irradiation. This study was aimed at establishing the optimal radiation dose for radiation-induced proctitis in rats. Female Wistar rats were used. The rectal specimens were examined morphologically at 5th and 10th day following 10-30 Gy irradiation in single fraction. With increasing dose, mucosal damage became worse, and there was a prominent reaction after > or =15 Gy. We selected 17.5 Gy as an optimal dose for radiation proctitis and examined specimens at day 1-14 and at week 4, 6, 8, and 12 after 17.5 Gy. The rectal mucosa revealed characteristic histological changes with time. An edema in lamina propria started as early as 1-2 days after irradiation and progressed into acute inflammation. On day 7 and 8, regeneration was observed with or without ulcer. Four weeks later, all regeneration processes have been completed with end result of either fibrosis or normal appearing mucosa. This study showed that the radiation injury of the rectum in rat develops in dose-dependent manner as it has reported in previous studies and suggested that 17.5 Gy in single fraction is the optimum dose to evaluate the protective effect of various medications for radiation proctitis in face of the clinical situation.

Animals↗

The effect of external electron beam on neointima in rat carotid artery injury model.

PURPOSE: Endovascular irradiation with either a gamma or a beta source has shown to reduce neointimal proliferation. However, the effect of external-beam radiation on neointimal hyperplasia is controversial. The objective of this study was to determine the effect of external-beam irradiation with different doses on neointimal hyperplasia in the rat carotid artery injury model. METHODS AND MATERIALS: Twenty-seven Sprague-Dawley rats underwent endothelial denudation injury by 2F Fogarty balloons on carotid artery. Immediately after the injury, rats were irradiated externally using 6-MeV electrons. Rats were grouped according to the radiation doses, 0 Gy as controls (n = 5), 5 Gy (n = 5), 10 Gy (n = 5), 15 Gy (n = 6), and 20 Gy (n = 6). Then, rats were sacrificed after 2 weeks and the carotid arteries were perfusion-fixed in paraformaldehyde. External elastic lamina (EEL) area, lumen area, maximal intimal thickness (MIT), and intimal area (IA) of the injured segments were measured on the basis of histomorphometry. RESULTS: In EEL and lumen area, there was no statistically significant difference between the irradiated groups and the controls. In MIT and IA, low-dose radiation (5 Gy and 10 Gy) did not induce any significant reduction. High-dose radiation (15 Gy and 20 Gy), however, reduced MIT and IA significantly. CONCLUSION: External electron beam reduced the intimal area, and the inhibition of neointimal proliferation was dependent upon radiation doses. This study suggests that the minimal effective dose for the inhibition of neointimal hyperplasia following denudation injury in the rat carotid model is between 10 Gy and 15 Gy.

Animals↗

Double-labeling techniques demonstrate that rod bipolar cells are under GABAergic control in the inner plexiform layer of the rat retina.

The synaptic connectivity between rod bipolar cells and GABAergic neurons in the inner plexiform layer (IPL) of the rat retina was studied using two immunocytochemical markers. Rod bipolar cells were stained with an antibody specific for protein kinase C (PKC, alpha isoenzyme), and GABAergic neurons were stained with an antiserum specific for glutamic-acid decarboxylase (GAD). Some amacrine cells were also labeled with the anti-PKC antiserum. All PKC-labeled amacrine cells examined showed GABA immunoreactivity, indicating that PKC-labeled amacrine cells constitute a subpopulation of GABAergic amacrine cells in the rat retina. A total of 150 ribbon synapses established by rod bipolar cells were observed in the IPL. One member of the postsynaptic dyads was always an unlabeled AII amacrine cell process, and the other belonged to an amacrine-cell process showing GAD immunoreactivity. The majority (n=92) (61.3%) of these processes made reciprocal synapses back to the axon terminals of rod bipolar cells. In addition, 78 conventional synapses onto rod bipolar axons were observed, and among them 52 (66.7%) were GAD-immunoreactive. Thus GABA provides the major inhibitory input to rod bipolar cells.

Animals↗

Alzheimer's disease after remote head injury: an incidence study.

OBJECTIVE: To evaluate a history of remote head injury as a risk factor for subsequent dementia due to Alzheimer's disease. METHODS: 271 participants of a community based longitudinal study of aging in north Manhattan without evidence of significant cognitive impairment were interrogated for a history of head injury on two occasions at entry into the study. The examining physician sought a history of head injury with loss of conciousness. Independently, a risk factor interviewer inquired about a history of head injury with loss of consiousness or amnesia, the duration of any loss of consiousness, and the date of the head injury. Patients were followed up with standardised annual evaluations for up to five years to determine the first occurrence of dementia. RESULTS: Over the course of the study incident dementia due to probable or possible Alzheimer's disease was diagnosed in 39 patients. Cox proportional hazards modelling showed that a history of head injury with loss of consiousness reported to the physician was associated with earlier onset of dementia due to Alzheimer's disease (relative risk (RR) = 4.1, 95% confidence interval (95% CI) 1.3-12.7). head injury with loss of consiousness or amnesia reported to the risk factor interviewer was not significantly associated with earlier onset of Alzheimer's disease overall (RR 2.0, 95% CI 0.7-6.2), but those who reported loss of consiousness exceeding five minutes were at significantly increased risk (RR 11.2, 95% CI 2.3-59.8). Incident Alzheimer's disease was significantly associated with head injury which occurred within the preceding 30 years (RR 5.4, 95% CI 1.5-19.5). CONCLUSION: The results of this cohort study are consistent with the findings of several case-control studies suggesting that head injury may be a risk factor for Alzheimer's disease.

Age of Onset↗

Effect of age, ethnicity, and head injury on the association between APOE genotypes and Alzheimer's disease.

The association between apolipoprotein E (APOE)-epsilon 4 and Alzheimer's disease has been confirmed worldwide. We and others have observed a diminished association in the very old and among African-Americans compared to Caucasians and Hispanics in New York. In this review we describe a new method we developed to compare relative risks by APOE genotypes in an expanded cohort of cases and controls from three ethnic groups in a New York City community and discuss the association as between APOE epsilon 4 and Alzheimer's disease as modified by head injury. Compared to persons with APOE epsilon 3/epsilon 3 genotypes, relative risk (RR) for Alzheimer's disease associated with APOE epsilon 4 homozygosity was similar across ethnic groups (African-American RR = 3.3; 95% c.i. 1.6-6.8; Caucasian RR = 5.3; 1.6-16.0; Hispanic RR = 2.5; 1.1-5.8). The risk was also increased for APOE epsilon 4 heterozygous Caucasians (RR = 3.2; 1.8-5.8) and Hispanics (RR 1.5; 1.0-2.2) but not African-Americans (RR = 0.6; 0.4-0.9). Risk of AD was not significantly diminished for individuals in any group with APOE epsilon 2/epsilon 2 or -epsilon 2/epsilon 3 genotypes. A 10-fold increase in the risk of Alzheimer's disease was associated with both APOE epsilon 4 and a history of traumatic head injury, compared to a twofold increase in risk with APOE epsilon 4 alone. Head injury in the absence of an APOE epsilon 4 allele did not increase risk. These results imply that in Alzheimer's disease genotypic risk associated with APOE may be influenced by age, ethnicity, and certain environmental factors.

Black or African American↗

Identification, sequence, and expression of caveolin-2 defines a caveolin gene family.

Caveolin, a 21- to 24-kDa integral membrane protein, is a principal component of caveolae membranes. Caveolin interacts directly with heterotrimeric guanine nucleotide binding proteins (G proteins) and can functionally regulate their activity. Here, an approximately 20-kDa caveolin-related protein, caveolin-2, was identified through microsequencing of adipocyte-derived caveolin-enriched membranes; caveolin was retermed caveolin-1. Caveolins 1 and 2 are similar in most respects. mRNAs for both caveolin-1 and caveolin-2 are most abundantly expressed in white adipose tissue and are induced during adipocyte differentiation. Caveolin-2 colocalizes with caveolin-1, indicating that caveolin-2 also localizes to caveolae. However, caveolin-1 and caveolin-2 differ in their functional interactions with heterotrimeric G proteins, possibly explaining why caveolin-1 and -2 are coexpressed within a single cell.

3T3 Cells↗

Comparison of the kidney dose between supine and prone position for pelvic and periaortic irradiation.

We compared the doses received by the kidney in supine and prone positions for pelvic and periaortic irradiation. Kidney locations were verified by CT images taken with patients in the same position as during the treatment. Due to the shift of the kidney anteriorly during prone position, treatment in supine position delivered a much lower dose to most of the kidney than treatment in the prone position. Therefore, for periaortic irradiation treatment, the supine position should be considered to minimize the dose to the kidneys, even though the prone position with a belly board can reduce the dose to the small bowel.

Humans↗

Relative risk of Alzheimer disease and age-at-onset distributions, based on APOE genotypes among elderly African Americans, Caucasians, and Hispanics in New York City.

Apolipoprotein-E epsilon 4 (APOE-epsilon 4) has been consistently associated with Alzheimer disease (AD) and may be responsible for an earlier age at onset. We have previously reported a diminished association between APOE-epsilon 4 and AD in African Americans. Using a new method, which allows inclusion of censored information, we compared relative risks by APOE genotypes in an expanded collection of cases and controls from three ethnic groups in a New York community. The relative risk for AD associated with APOE-epsilon 4 homozygosity was increased in all ethnic groups (African American relative risk [RR]=3.0; 95% confidence interval [CI]=1.5-5.9; Caucasian RR=7.3, 95% CI=2.5-21.6; and Hispanic RR=2.5, 95% CI=1.1-5.7), compared with those with APOE-epsilon 3/epsilon 3 genotypes. The risk was also increased for APOE-epsilon 4 heterozygous Caucasians (RR=2.9, 95% CI=1.7-5.1) and Hispanics (RR=1.6, 95% CI=1.1-2.3), but not for African Americans (RR=0.6, 95% Ci=0.4-0.9). The age distribution of the proportion of Caucasians and Hispanics without AD was consistently lower for APOE-epsilon 4 homozygous and APOE-epsilon 4 heterozygous individuals than for those with other APOE genotypes. In African Americans this relationship was observed only in APOE-epsilon 4 homozygotes. These results confirm that APOE genotypes influence the RR of AD in Caucasians and Hispanics. Differences in risk among APOE-epsilon 4 heterozygote African Americans suggest that other genetic or environmental factors may modify the effect of APOE-epsilon 4 in some populations.

Age of Onset↗