The effects of UVB and arsenic and their interaction on beta2-adrenergic receptors in cultured keratinocytes.
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Biomedical subjects
Publications and source records attributed to H R Chang.
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We evaulated the effectiveness and adverse effects of deep sclerectomy with collagen implant (DSCI), which is a kind of nonpenetrating filtering surgery. In this retrospective study, DSCI was performed in 15 eyes of 11 glaucoma patients. An trabeculo-Descemet's membrane (TDM) window is created by a deep sclerokeratectomy, and the collagen implant is placed in the sclera bed under a superficial flap (deep sclerectomy with collagen implant). In 3 of 15 eyes the DSCI was intraoperatively converted to conventional filtering surgery for a large perforation of the TDM. These eyes were not included in the results of the surgical outcomes. The mean age of the patients was 50.3 +/- 14.4 years, and the mean follow-up period was 11.1 +/- 5.9 months. A diagnosis of chronic open angle glaucoma was made in 7 eyes and a diagnosis of secondary glaucoma in 5 eyes. The mean preoperative IOP was 25.8 +/- 11.9 mmHg, the immediate postoperative IOP was 6.4 +/- 2.9 mmHg, and at the final follow-up, the IOP was 11.9 +/- 2.5 mmHg. The IOP in 5 eyes was under 6 mmHg temporarily. However, there was no serious complication such as shallow anterior chamber. DSCI is considered to be a good surgical procedure that has similar surgical outcomes to a conventional trabeculectomy without serious complications.
Behavioral and memory impairment resulting from lead exposure is well known but the mechanism is not. We utilized the brain of lead exposed rats to investigate this problem. In an effort to elucidate the mechanism responsible for this alteration we examined blood and brain lead levels, brain beta-adrenoceptor density and cyclic AMP production in lead exposed rats. Wistar rats used in these trials were divided into six groups of ten animals each. Five groups were given drinking water containing 0.05, 0.1, 0.5, 1 and 2% lead acetate for a period of 60 days. One group (control group, 0% lead acetate) was given pure water. Application of a trend test indicated that both blood and brain lead levels increased significantly from group 0% to group 2% (group 0% <group 0.05% <group 0.1% <group 0. 5%<group 1%<group 2%), but that brain beta-adrenoceptor density and cyclic AMP levels stimulated by isoproterenol decreased (group 2%<group 1%<group 0.5%<group 0.1%<group 0.05%<group 0%). Kd did not vary among the six groups and this indicated that the affinity of the remaining beta-adrenoceptors for [125I]iodocyanopindolol was not changed. Linear regression analysis showed that beta-adrenoceptor density and stimulated cyclic AMP level in brain was found to be negatively correlated with brain lead level (P<0.001). The results show lead exposure that may be the result of an alteration of beta-adrenergic receptor and adenylate cyclase activity in brain.
Lead exposure is considered to be a risk factor of cardiovascular disease. To investigate the relationship between lead and cardiovascular disease/hypertension in lead exposure, beta-adrenergic system is explored in this study. We address three topics in this study: (a) the relationship between beta-adrenergic receptor and lead level in heart, aorta, and kidney of lead-exposed rats; (b) the relationship between beta-adrenergic receptor in heart, aorta, kidney, and blood pressure in lead-exposed rats; and (c) the change of cyclic AMP level in heart, aorta, and kidney of rats with different lead levels. Wistar rats were chronically fed with 2, 1, 0. 5, 0.1, 0.05, and 0.01% lead acetate and water for 2 months. Plasma catecholamine level was measured by high-performance liquid chromatography. Radioligand binding assay was measured by a method that fulfilled strict criteria of beta-adrenoceptor using the ligand [(125)I]iodocyanopindolol. Cyclic AMP (cAMP) level was determined by radioimmunoassay. The levels of lead were determined by electrothermal atomic absorption spectrometry. The results showed that increased plasma norepinephrine level, decreased aorta beta-adrenergic receptor and cAMP, and increased kidney beta-adrenergic receptor and cAMP contributed to the elevation of blood pressure in lead-induced hypertension. The decrement of beta-adrenoceptor and cAMP in heart resulted in decreased contractility in heart.
BACKGROUND: The optimal management of ductal carcinoma in situ (DCIS) remains controversial. Investigators have focused on identifying patients who are eligible for treatment by excision alone. A retrospective analysis of patients with DCIS treated by various modalities was conducted to compare outcomes and determine factors significant for local recurrence (LR). METHODS: Between 1985-1992, 88 consecutive diagnoses of DCIS were identified in 85 patients. Seventy-four percent were detected mammographically. The most common histologic subtypes were comedo (54%) and cribriform (23%). Tumor sizes were < 2.5 cm (49%), > 2.5-5 cm (26%), > 5 cm (23%), and unknown (2%). Final resection margins were tumor free (75%), close/positive (23%), and unknown (2%). Treatment methods included mastectomy (30%), localized surgery and radiation therapy (LSR) (43%), or wide localized surgery alone (LS) (27%). Radiation therapy (RT) was comprised of 50 grays to the breast, and 53% of treated patients received local "boost" irradiation. RESULTS: The median follow up was 8.3 years. The overall recurrence rate was 13. 6%, whereas the median time to LR was 27.8 months. Recurrence rates according to treatment modality were: LS: 25%; LSR: 13%; and mastectomy: 4%. However, if surgical margins were tumor free, LSR had a LR rate of 3.4%. After RT, no LR occurred prior to 15 months, and 4 of 5 tumors were noninvasive. Nine patients treated by excision alone conformed to the criteria of Lagios et al. criteria and LR occurred in three of nine tumors. Of the factors analyzed, margin status was found to be the best predictor for LR (P = 0.05). CONCLUSIONS: If surgical margins are tumor free, the LSR regimen is equivalent to mastectomy for local tumor control. Annual mammograms may be adequate for the follow-up of patients with irradiated breasts, but biannual studies still are recommended for patients treated with excision alone.
It has been proposed that two types of vitiligo exist from the physiological and clinical points of view. Nonsegmental-type vitiligo is associated with autoimmune diseases while segmental-type vitiligo results from the dysfunction of sympathetic nerves in the affected area. Using laser Doppler flowmetry and iontophoresis for cutaneous microcirculatory assessments, we evaluated these two types of vitiligo in regard to their physiological changes. Ten patients with facial stable stage segmental-type vitiligo and ten stable nonsegmental-type vitiligo patients were selected for this study. Our results revealed that a nearly threefold increase in cutaneous blood flow was noticed in segmental-type vitiligo as compared to contralateral normal skin. In contrast, a 1.4-1.5 times difference was found among nonsegmental-type vitiligo, lesion side clinically normal skin and contralateral normal skin. There was a significant increase in cutaneous alpha- and beta-adrenoceptor response in segmental-type vitiligo lesions. However, no change in plasma catecholamines or adrenoceptor densities on blood cells was noticed. Our findings suggest that a dysfunction of the sympathetic nerves exists in the affected skin and plays a role in the pathogenesis of segmental-type vitiligo.
It has been speculated that impaired salivary flow is common in patients with end-stage renal disease (ESRD) requiring hemodialysis (HD). The aim of this study is to investigate the relation between oral manifestations and salivary function in patients with ESRD undergoing HD. Salivary function was measured by quantitative salivary scintigraphy in 60 patients with ESRD undergoing HD, as well as in 36 age- and sex-matched healthy controls for comparison. The 60 patients with ESRD undergoing HD were separated into two subgroups: group 1, 30 patients with oral manifestations, and group 2, 30 patients without oral manifestations. After an intravenous injection of 5 mCi of technetium 99m pertechnetate, sequential images at 1 minute per frame were acquired for 30 minutes. The 1- and 15-minute uptake ratios were calculated as the tracer uptakes in the four major salivary glands over the background regions of interest. Saliva excretion was stimulated by one 200-mg tablet of ascorbic acid administered orally 15 minutes post-tracer injection, then the maximal excretion ratios of the four major salivary glands were calculated. Our results show significantly poorer salivary function in patients with ESRD with oral manifestations compared with patients with ESRD without oral manifestations and healthy controls by means of objective and quantitative salivary scintigraphy.
The purpose of this study is to evaluate the clinical usefulness of a newly developed biomicroscopic vitreous observation system. Vitreous observation was performed in 300 eyes with age- or disease-related vitreous changes using a 3 CCD video camera mounted on a slit-lamp biomicroscope and connected to a personal computer for real-time observation and especially for the capture and archiving of images. Various types of fundus lenses were used to scan the vitreous status systemically from the posterior pole to the vitreous base. This system allowed us to obtain and immediately review the images of the vitreoretinal relationship. The image quality was sufficient for clinical evaluation of the vitreous status. We were able to identify some variations of posterior vitreous detachments and clarify the changes of the vitreoretinal interface in the study eyes. This system is very useful for the dynamic observation and documentation of vitreous images in order to determine the role of vitreous in many vitreoretinal disorders. Furthermore it is more convenient and affordable than previous methods.
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BACKGROUND: Compared with invasive ductal carcinoma, invasive lobular carcinoma of the breast is considered by many to be a more indistinct and multicentric form of cancer that is detected later and is treated less optimally by breast-preservation techniques. This study analyzed the presentation, treatment trends, and survival rates of women who had invasive lobular and ductal breast carcinoma. The objective was to determine the utility of breast-preservation therapy for invasive lobular carcinoma by analysis of historic data on tumor features and survival. STUDY DESIGN: Data on 291,273 women diagnosed with invasive carcinoma between 1985 and 1993 were obtained from the National Cancer Data Base. Analysis included the patient's age at diagnosis; tumor histology, anatomic site, diameter, grade, and stage; treatment; and disease status 5 years after diagnosis. RESULTS: The mean patient age at diagnosis was 61.0 years for invasive ductal carcinoma, 63.0 years for invasive lobular carcinoma, and 60.6 years for tumors with combined histology. The anatomic location, tumor diameter, and tumor grade were similar for each histotype. Breast-preservation therapy was less frequent for invasive lobular carcinoma. The 5-year overall survival and local disease-free survival rates for women treated with breast preservation were similar for invasive ductal carcinoma (84% overall survival; 97% disease-free survival) and invasive lobular carcinoma (87% overall survival; 98% disease-free survival). CONCLUSIONS: Invasive lobular carcinoma presents with a similar age distribution, anatomic subsite, diameter, and grade as invasive ductal carcinoma. Breast preservation is selected less commonly for women who have invasive lobular carcinoma, but this choice of therapy does not compromise the disease-free or overall survival status of this group of patients.
BACKGROUND: Routine axillary dissection in patients with invasive small breast cancer remains controversial. We previously reported a model for predicting nodal involvement in patients with T1a or T1b breast cancer that may guide the practice of selective nodal dissection. The objective of this study was to determine whether the prognosticators that predict nodal metastases also predict survival. STUDY DESIGN: This study is a retrospective review of 2,153 women with small invasive breast cancer (< or = 1 cm) diagnosed between January 1984 and December 1995. Cases were identified from a statewide tumor registry, the Hospital Association of Rhode Island, and the tumor registry at Baystate Medical Center in Massachusetts. The impact on survival of patient age (< or = 40 versus > 40 years), nodal status (positive versus negative), tumor size (T1a versus T1b), and tumor grade (1 versus 2 or 3) were analyzed. Breast cancer-specific survival (BCSS) was analyzed using the Kaplan-Meier method and the proportional hazards regression method. RESULTS: There were 388 patients with tumors 0.5 cm or less (T1a) and 1,765 with tumors 0.6-1.0 cm (T1b). Nodal status was known in 68% of cases (1,461 of 2,153), and tumor grade was recorded in 42% of cases (902 of 2,153). In univariate analysis, age, grade, and nodal status were significant in their association with BCSS. Tumor size did not influence BCSS among patients with small invasive tumors. Women older than 40 years had superior survival compared with younger women (93% versus 78% at 5 years; p = 0.01). Similarly, women with low grade (1) tumors did better than those with higher grade (2 or 3) tumors (98% versus 88% at 5 years; p = 0.03). The 5-year BCSS was 96% versus 78% for node-negative versus node-positive disease, and the 10-year BCSS was 91% versus 62% (p = 0.001). In the multivariate analysis, age and nodal status remained firmly associated with survival, although grade lost its significance. CONCLUSIONS: Small tumor size does not affect survival. Although risk profiles for nodal involvement can be constructed to help guide the practice of selective axillary lymphadenectomy in patients with small invasive breast cancers, these factors cannot serve as a surrogate to nodal status in establishing patient prognosis. Nodal status remains the most powerful determinant of survival in breast cancer patients, even those with very small tumors.
Injection of 10 cysts of Toxoplasma gondii (Me49 strain) into Swiss Webster mice results in 1) an acute phase of infection lasting for 2-3 wk, characterized by weight loss, and 2) a chronic phase in which surviving mice show either partial weight recovery (Gainers) or persistent, although stable, cachexia (Nongainers). In response to a second immunological stimulation with lipopolysaccharide (LPS) in the chronic phase of the infection, it is shown that 1) the increase in energy expenditure was more prolonged in both groups of infected mice than in controls, 2) the intensity and duration of hypophagia were also differently affected with Nongainers > Gainers > controls, and 3) the infected mice had higher serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-10 and a lower ratio of IL-10 to TNF-alpha than controls. In contrast, serum IL-4 increased to the same level in all three groups. Evaluation of the permeability of the blood-brain barrier by intravenous injection of Evans blue revealed a marked staining in the brain of only the infected Nongainers. Taken together, these results indicate that, in mice with chronic toxoplasmosis, a second nonspecific challenge (with LPS) exacerbates the hypophagic and hypermetabolic states, the latter being associated with hyperresponsiveness in TNF-alpha and IL-10 production. Furthermore, the greater exacerbation of the hypophagic state in mice showing persistent cachexia may be due to a preexisting higher permeability of the blood-brain barrier, which would allow a greater access of plasma-borne cytokines and/or other neuroimmunologically active substances to the central nervous system.
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The effect of lead on cardiac beta-adrenoceptors was studied. Wistar rats used in these trials were divided into seven groups of ten animals each (A-G). Of these, groups B was given drinking water containing 0.01% lead acetate, group C 0.05%, group D 0.1%, group E 0.5%, group F 1% and group G 2% for a period of 60 days. Group A was given pure water. A radioligand-binding assay fulfilling strict criteria of receptor affinity and density was used to quantify cardiac beta-adrenoceptors. Application of a trend test indicated that both blood and heart lead levels increased significantly from group A to group G (A < G), but that beta-adrenoceptor density decreased (G < A), whereas Kd did not vary among the seven groups. Linear regression analysis showed that decrease of cardiac beta-adrenergic receptor density was closely related to elevation of blood and heart lead levels. The results show that lead exposure results in a reduction of cardiac beta-adrenoceptor density.
OBJECTIVE: To establish a model based on risk factor analysis to guide selective axillary lymph node dissection in patients with T1a and T1b breast cancers. DESIGN: Retrospective review to determine histopathologic features and patient demographic profiles that may influence the incidence of nodal metastases. SETTING: Primary care and referral centers in Rhode Island and Massachusetts. PATIENTS: Women with invasive breast cancers with nodal status reported to the statewide tumor registry, the Hospital Association of Rhode Island, and the tumor registry at Baystate Medical Center, Springfield, Mass, between January 1984 and December 1995. There were 12030 patients with breast cancer reported; 2185 (18%) of these had tumors 1 cm or less in diameter. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Axillary node metastases. RESULTS: The nodal status of 377 patients with T1a tumors and 1808 patients with T1b tumors was studied. Seventy-five percent had axillary dissections, and 16% were found to have nodal metastases. Thirty-one percent (29/93) of patients younger than 40 years had positive nodes compared with 15% (241/1546) of older patients (P = .001). The T1a tumors had fewer metastases than the T1b tumors did (11% vs 17%; P = .02). Nuclear grade was available in 49% of cases. Nuclear grades 2 and 3 were associated with nodal involvement twice as often as grade 1 tumors were (P = .002). Patients with no poor prognostic factors had a 7% or less chance of nodal involvement, while patients with all 3 poor prognostic indicators had a 33.5% chance of nodal involvement. CONCLUSIONS: Selective nodal dissection may be possible through risk factor analysis. Prospective registration of complete histopathologic information will allow more comprehensive analysis and may further enhance the selective treatment of patients with minimally invasive breast cancer.
Beta-adrenergic receptor-mediated relaxation of blood vessels declines in lead induced hypertension although the mechanism is unknown. We have utilized the aorta of lead hypertensive rats to investigate this problem. In an effort to elucidate the mechanism responsible for this alteration we examined plasma catecholamine levels, vascular beta-adrenergic receptor density, and cyclic adenosine monophosphate (cAMP) production in lead hypertensive rats. The density of beta-adrenergic receptors was 41% lower in the blood vessels of lead hypertensive rats compared with control rats. The corresponding apparent Kd values were not significantly different between two groups. The plasma catecholamine level was significantly higher in lead hypertensive rats compared with controls (P < 0.001). Stimulation of the vascular beta-adrenoceptor resulted in significantly lower levels of cAMP in lead hypertensive rats compared with controls (P < 0.001). The present results suggest that there is reduced beta-adrenoceptor density and diminished cAMP accumulation in blood vessels from lead hypertensive rats. Plasma catecholamine may play a role in the diminished beta-adrenoceptor and responsiveness to cAMP-mediated vascular relaxation in lead exposure.
While mammography screening among women aged 50 years or older has proven to reduce breast cancer mortality, screening in younger women has been repeatedly scrutinized. To test the effect of screening among younger women, we examined 84 consecutive patients aged 40-49 at the time of breast cancer diagnosis: 27 (32.1%) were diagnosed solely by mammography, and 57 (67.9%) had a palpable mass. The mean tumor sizes were 1.3 cm and 3.6 cm for the two groups respectively. While 68.8% nonpalpable invasive tumors were classified as Stage I cancer, only 34% of patients with palpable breast cancer had Stage I disease. None of the patients with nonpalpable breast cancer had disease beyond Stage II. In contrast, 28.3% of the patients with palpable invasive breast cancer presented with advanced disease. In addition, 6.3% versus 41.5% of patients with nonpalpable and palpable breast cancer respectively had nodal metastases. The five-year survival rates for the two groups were 100% and 73% respectively, favoring breast cancer detected mammographically. Screening of women aged 40-49 also resulted in more breast-conserving surgery and less chemotherapy. We conclude that screening in this age group should be continued, although individual assessment is needed.
The 16S rRNA gene sequences of Salmonella typhi and Salmonella typhimurium were amplified by PCR, cloned, and sequenced. These sequences were analyzed by comparison with reference organisms from the family Enterobacteriaceae. Both S. typhi and S. typhimurium belong to the gamma subdivision of the class Proteobacteria.