Age-adjusted homicide rates by ZIP codes, Kansas City, Missouri, 1991-1995.
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Homicide↗
Biomedical subjects
J Cai
Publications and source records attributed to J Cai.
Interaction of clozapine and other antipsychotic drugs with human alpha 1-adrenergic receptor subtypes.
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Adrenergic alpha-Antagonists↗
[Diagnosis and treatment of early gastric cancer: an experience from 61 cases].
OBJECTIVE: To review the clinical signs of diagnostic significance and treatment of early gastric cancer. METHODS: Sixty-one gastric cancer patients were collected for this study. They were surgically treated and pathologically confirmed to be in the early stage of disease. The x-ray and gastroscopic findings of these patients were reviewed. RESULTS: Double-contrast barium meal examination was performed in 46 cases and 27 of them were diagnosed as gastric cancer with a detection rate of 58.7%. Superficial type of tumor was easily misdiagnosed as superficial gastritis and concave type of tumor misdiagnosed as benign gastric ulcer under x-ray imaging. All the patients were gastroscopically examined. With examiner's naked eyes, diagnosis of cancer was made in 27 cases (44.3%). Visual diagnosis was difficult when the tumor was small. Attention should be focused on the gastric incisura angularis, antrum and lesser curvature to perform site-directed biopsy. Final diagnosis depended on the pathological diagnosis of the biopsied materials. Pathologic diagnosis would be correct provided the biopsy material was taken from the proper site. It was correct in 58 of the 61 cases (95.1). Surgical treatment consisted of radical gastrectomy and D2 lymph node dissection. All but 2 were tumor free after surgical treatment. Prognosis was good in this series of early gastric cancer patients, 38 of them were alive over 5 years and 12 patients survived over 10 years. CONCLUSION: Careful x-ray and gastroscopic examinations of patients with epigastric symptoms are indicated not to miss any early case of gastric cancer.
Adult↗
[Analysis of MRI and CT manifestations of paranasal sinuses and orbitocranial disorders with secondary exophthalmos].
OBJECTIVE: To study the MRI and CT manifestations of paranasal sinuses and orbitocranial disorders with secondary exophthalmos. METHODS: MRI and CT scans of 51 patients were examined. RESULTS: MRI offers more information for evaluation of soft tissue lesions; the cavernous hemangioma and dermoid cyst were found to present rather characteristic images. Whereas in evaluation of lesions involving bony structures and calcifications, CT was superior to MRI. CONCLUSION: CT and MRI may evaluate the tumor location, extension into adjacent areas and are valuable in differential diagnosis of paranasal sinuses and orbitocranial disorder with secondary exophthalmos.
Adolescent↗
[Computer-assisted identification of fundus lesions and a study of its reliability].
This study aimed at the use of computer for identifying fundus lesions quickly and reliably. We adopted the 'area filling' method to program in Visula C++, used the program to mesure the retina cotton-wool patches in diabetics (15 eyes), and then calculated the coefficient of variation to evaluate its reproducibility. The results showed that the coefficient of variation of the measurements ranged from 3.22% to 9.46%. In conclusion, this method is convient, quick and reliable.
Algorithms↗
Molecular cloning and expression of human grap-2, a novel leukocyte-specific SH2- and SH3-containing adaptor-like protein that binds to gab-1.
The SH2- and SH3-containing adaptor molecules serve to recruit cytosolic signal-transducing molecules to the activated receptor tyrosine kinases. In this study, we report the molecular cloning of a novel adaptor-like protein, Grap-2 (Grb-2 related adaptor protein 2), using the multisubstrate docking protein Gab-1 as bait in the yeast two-hybrid system. Sequence analysis revealed that Grap-2 contains a SH3-SH2-SH3 structure that has a high degree of sequence homology to those of the Grb-2 and Grap adaptor molecules. However, unlike in Grap and Grb-2, the SH2 and the C-terminal SH3 domains of Grap-2 are separated by a 120-amino-acid glutamine-rich sequence that shows no apparent homology to any known molecule or structural motif. The C-terminal SH3 domain of Grap-2 alone is sufficient to bind to Gab-1. Furthermore, Northern blot analysis demonstrated that Grap-2 has two major transcripts of 1.4 and 4.0 kb that can only be detected in tissues rich in leukocytes and in two leukemia cell lines. This highly restricted pattern of expression suggests that Grap-2 may participate in leukocyte-specific protein tyrosine kinase signaling.
Adaptor Proteins, Signal Transducing↗
Human prostaglandin transporter gene (hPGT) is regulated by fluid mechanical stimuli in cultured endothelial cells and expressed in vascular endothelium in vivo.
BACKGROUND: biomechanical forces generated by blood flow within the cardiovascular system have been proposed as important modulators of regional endothelial phenotype and function. This process is thought to involve the regulation of vascular gene expression by physiological fluid mechanical stimuli such as fluid shear stresses. METHODS AND RESULTS: We demonstrate sustained upregulation of a recently identified gene encoding a human prostaglandin transporter (hPGT) in cultured human vascular endothelium exposed to a physiological fluid mechanical stimulus in vitro. This biomechanical induction is selective in that steady laminar shear stress is sufficient to upregulate the hPGT gene at the level of transcriptional activation, whereas a comparable level of turbulent shear stress (a nonphysiological stimulus) is not. Various biochemical stimuli, such as bacterial endotoxin and the inflammatory cytokines recombinant human interleukin 1beta cytokines (rhIL-1beta) and tumor necrosis factor-alpha (TNF-alpha), did not significantly induce hPGT. Using a specific antiserum to hPGT, we demonstrate endothelial expression within the arterial vasculature and the microcirculation of highly vascularized tissues such as the heart. CONCLUSIONS: Our results identify hPGT as an inducible gene in vascular endothelium and suggest that biomechanical stimuli generated by blood flow in vivo may be important determinants of hPGT expression. Furthermore, this demonstration of regulated endothelial expression of hPGT implicates this molecule in the regional metabolism of prostanoids within the cardiovascular system.
Antiporters↗
ATP hydrolysis catalyzed by human replication factor C requires participation of multiple subunits.
Human replication factor C (hRFC) is a five-subunit protein complex (p140, p40, p38, p37, and p36) that acts to catalytically load proliferating cell nuclear antigen onto DNA, where it recruits DNA polymerase delta or epsilon to the primer terminus at the expense of ATP, leading to processive DNA synthesis. We have previously shown that a subcomplex of hRFC consisting of three subunits (p40, p37, and p36) contained DNA-dependent ATPase activity. However, it is not clear which subunit(s) hydrolyzes ATP, as all five subunits include potential ATP binding sites. In this report, we introduced point mutations in the putative ATP-binding sequences of each hRFC subunit and examined the properties of the resulting mutant hRFC complex and the ATPase activity of the hRFC or the p40.p37.p36 complex. A mutation in any one of the ATP binding sites of the p36, p37, p40, or p140 subunits markedly reduced replication activity of the hRFC complex and the ATPase activity of the hRFC or the p40.p37.p36 complex. A mutation in the ATP binding site of the p38 subunit did not alter the replication activity of hRFC. These findings indicate that the replication activity of hRFC is dependent on efficient ATP hydrolysis contributed to by the action of four hRFC subunits.
Adenosine Triphosphate↗
Presence of activated ras correlates with increased cysteine proteinase activities in human colorectal carcinomas.
The metastatic potential of ras-transfected cells has been attributed in part to significant ras induction of proteinase expression. To determine whether primary cancers also demonstrate higher cysteine proteinase activities in the presence of activated ras genes or altered ras protein expression, we have analyzed 60 primary human colorectal carcinomas for ras gene or protein changes together with the expression of cathepsins B and L. Cancers containing K-ras mutations (47% of 60 carcinomas) demonstrated greater increases in cathepsin L activity than cancers without K-ras mutations (p = 0.029), with particularly significant correlations for earlier stage cancers (Dukes' A and B carcinomas, p = 0.006). Western blots used to characterize ras protein patterns in the same cancer/normal pairs have demonstrated that N-ras protein is more highly expressed in colon tissues than H- or K-ras proteins and that N-ras overexpression occurs in almost 70% of colorectal cancers, with or without a concurrent change in electrophoretic mobility of N-ras protein. Our current study has now shown that N-ras protein overexpression alone does not significantly induce cathepsin B or L activity levels in colon cancers. However, carcinomas demonstrating altered N-ras protein forms, in the absence of any K- or N-ras mutations, expressed significantly higher levels of cathepsin B and L activities compared with carcinomas with normal N-ras protein banding patterns. Our data suggest that colorectal carcinomas with either K-ras mutations or altered forms of N-ras protein may increase their tumorigenic potential via the induction of cathepsin L or B expression levels. Our results also confirm that ras oncogene up-regulation of cathepsin B and L activities, previously reported in cultured cells, is a frequent event in primary human colorectal carcinomas.
Blotting, Western↗
Mitochondrial control of apoptosis: the role of cytochrome c.
Mitochondrial cytochrome c (cyt c) has been found to have dual functions in controlling both cellular energetic metabolism and apoptosis. Through interaction with apoptotic protease activating factors (Apaf), cyt c can initiate the activation cascade of caspases once it is released into the cytosol. The loss of a component of the mitochondrial electron transport chain also triggers the generation of superoxide. Although cyt c can be released independent of the mitochondrial permeability transition (MPT), the accompanying cellular redox change can trigger the MPT. Since another apoptotic protease, AIF, is released by MPT, the two separate pathways provide redundancy that ensures effective execution of the cell death program. Anti-apoptotic Bcl-2 family proteins function as gatekeepers to prevent the release of both cyt c and AIF. In spite of their stabilization effect on the mitochondrial outer membrane, Bcl-2 proteins may also be involved in the direct binding of Apaf molecules as regulatory elements further downstream from the mitochondrial apoptotic signals.
Animals↗
Cloning and functional characterization of the 5'-flanking region of human methionine adenosyltransferase 2A gene.
Methionine adenosyltransferase (MAT) is a critical cellular enzyme which catalyzes the formation of S-adenosylmethionine, the principal methyl donor. In mammals, two different genes, MAT1A and MAT2A, encode for liver-specific and non-liver-specific MAT, respectively. We have cloned and characterized a 1.4-kb 5'-flanking region of the human MAT2A (GenBank Accession No. AF039088). Two major transcriptional start sites were identified by primer extension and S1 nuclease protection analysis; one was within 10 nucleotides downstream and the other was located at 158 nucleotides upstream from the consensus TATA box, respectively. The promoter is highly GC rich (75%) in the first 300 base pairs and contains several Sp-1 binding sites, a C/EBP, a HSF2, a STATx, a c-Myb, several v-Myb, and numerous GATA consensus binding sites. The human MAT2A promoter was able to efficiently drive luciferase expression in both Jurkat and 293 cells, but sequential deletion analysis of the promoter revealed that different regions of the promoter are important for cell-specific MAT2A expression.
Base Sequence↗
Superoxide in apoptosis. Mitochondrial generation triggered by cytochrome c loss.
Activation of apoptosis is associated with generation of reactive oxygen species. The present research shows that superoxide is produced by mitochondria isolated from apoptotic cells due to a switch from the normal 4-electron reduction of O2 to a 1-electron reduction when cytochrome c is released from mitochondria. Bcl-2, a protein that protects against apoptosis and blocks cytochrome c release, prevents superoxide production when it is overexpressed. The switch in electron transfer provides a mechanism for redox signaling that is concomitant with cytochrome c-dependent activation of caspases. The block of cytochrome c release provides a mechanism for the apparent antioxidant function of Bcl-2.
Apoptosis↗
Differential expression of methionine adenosyltransferase genes influences the rate of growth of human hepatocellular carcinoma cells.
Methionine adenosyltransferase (MAT) catalyzes the formation of S-adenosylmethionine (SAM), the principal methyl donor, and is essential to normal cell function. The two forms of MAT, liver specific and non-liver specific, are products of two genes, MAT1A and MAT2A, respectively. We have reported a switch from MAT1A to MAT2A gene expression in human liver cancer cells. In the current work, we examined whether the type of MAT expressed by the cell influences cell growth. HuH-7 cells were stably transfected with MAT1A and were subsequently treated with antisense oligonucleotides directed against MAT2A. MAT2A antisense treatment reduced the amount of MAT2A mRNA by 99% but had no effect on MAT1A mRNA. Cell growth and DNA synthesis rates were reduced by approximately 20-25% after transfection with MAT1A and by an additional 30-40% after MAT2A antisense treatment. SAM level and SAM:S-adenosylhomocysteine (SAH) ratio increased by 50-75% after MAT1A transfection and by an additional 60-80% after MAT2A antisense treatment. DNA methylation changed in parallel to changes in SAM level and SAM:SAH ratio. Supplementing untransfected HuH-7 cells with SAM in the culture medium increased SAM level, SAM:SAH ratio, and DNA methylation and decreased cell growth and DNA synthesis. In conclusion, cell growth is influenced by the type of MAT expressed. The mechanism likely involves changes in SAM:SAH ratio and DNA methylation.
Carcinoma, Hepatocellular↗
Body weight change and carotid artery wall thickness. The Atherosclerosis Risk in Communities (ARIC) Study.
The impact of weight change in adulthood on cardiovascular disease is controversial. This study examined the association of change in body weight, from young adulthood to middle age, with average carotid artery intimal-medial wall thickness by B-mode ultrasound measured in middle age. Participants were 13,282 men and women aged 45-64 years from the baseline examination of the Atherosclerosis Risk in Communities (ARIC) Study (1987-1989). Weight change was calculated as the difference between weight at the baseline examination and self-reported weight at age 25. White men gained a mean of 9.7 kg; black men, 10.1 kg; white women, 12.0 kg; and black women, 20.8 kg. Weight change was positively, albeit modestly, associated with intimal-medial thickness in black men and white men and in white women, but not in black women. Adjusted for age, examination center, smoking, education, sports activity level, height, and body mass index at age 25, the differences in intimal-medial thickness associated with a 10-kg increment in weight change were 0.016 (95% confidence interval 0.010 to 0.022) mm in white men, 0.008 (95% confidence interval 0.001 to 0.015) mm in black men, 0.013 (95% confidence interval 0.009 to 0.017) mm in white women, and 0.002 (95% confidence interval -0.002 to 0.006) mm in black women. These findings support the hypothesis that weight gain in adulthood promotes atherosclerotic changes in white men and women and in black men.
Arteriosclerosis↗
The effect of age on the association between body-mass index and mortality.
BACKGROUND: The effect of age on optimal body weight is controversial, and few studies have had adequate numbers of subjects to analyze mortality as a function of body-mass index across age groups. METHODS: We studied mortality over 12 years among white men and women who participated in the American Cancer Society's Cancer Prevention Study I (from 1960 through 1972). The 62,116 men and 262,019 women included in this analysis had never smoked cigarettes, had no history of heart disease, stroke, or cancer (other than skin cancer) at base line in 1959-1960, and had no history of recent unintentional weight loss. The date and cause of death for subjects who died were determined from death certificates. The associations between body-mass index (defined as the weight in kilograms divided by the square of the height in meters) and mortality were examined for six age groups in analyses in which we adjusted for age, educational level, physical activity, and alcohol consumption. RESULTS: Greater body-mass index was associated with higher mortality from all causes and from cardiovascular disease in men and women up to 75 years of age. However, the relative risk associated with greater body-mass index declined with age. For example, for mortality from cardiovascular disease, the relative risk associated with an increment of 1 in the body-mass index was 1.10 (95 percent confidence interval, 1.04 to 1.16) for 30-to-44-year-old men and 1.03 (95 percent confidence interval, 1.02 to 1.05) for 65-to-74-year-old men. For women, the corresponding relative risk estimates were 1.08 (95 percent confidence interval, 1.05 to 1.11) and 1.02 (95 percent confidence interval, 1.02 to 1.03). CONCLUSIONS: Excess body weight increases the risk of death from any cause and from cardiovascular disease in adults between 30 and 74 years of age. The relative risk associated with greater body weight is higher among younger subjects.
Adult↗
Effects of Tripterygium wilfordii hook F extracts on induction of cyclooxygenase 2 activity and prostaglandin E2 production.
OBJECTIVE: Extracts of the Chinese herbal remedy Tripterygium wilfordii Hook F (TWHF) have been reported to be effective in the treatment of patients with a variety of inflammatory and autoimmune diseases, but the mechanism of this therapeutic effect has not been completely delineated. The present study was designed to assess the effects of TWHF on the in vitro synthesis of prostaglandin E2 (PGE2) and on the expression of the cyclooxygenase isoforms, COX-1 and COX-2, in various human cell types. METHODS: Monocytes from human peripheral blood (HM), fibroblasts from rheumatoid arthritis synovial tissue (RASF), human neonatal foreskin fibroblasts (HFF), and the histiocytic cell line U937 were cultured for designated time periods with or without lipopolysaccharide (LPS), and in the presence or absence of varying concentrations of the following inhibitors: the methanol/chloroform (T2) extract of TWHF, the ethyl acetate (EA) extract of TWHF, a purified diterpenoid component of TWHF (triptolide), dexamethasone, and indomethacin. Culture supernatants were harvested for PGE2 content assays. Total RNA was extracted from the cells and analyzed for COX-1 and COX-2 messenger RNA (mRNA) expression using reverse transcriptase-polymerase chain reaction or Northern blotting. RESULTS: Both the T2 and EA extracts inhibited PGE2 synthesis in the LPS-stimulated HM, RASF, and HFF cells, which was reflected by a marked suppression in the levels of mRNA for COX-2. In contrast, neither extract inhibited PGE2 production in U937 cells that did not express COX-2. Triptolide also inhibited LPS-stimulated induction of COX-2 mRNA and synthesis of PGE2, at the same inhibitory concentration as seen with the EA extract. The effects of T2, EA, and triptolide paralleled the inhibitory action of dexamethasone. CONCLUSION: The data indicate that both the T2 and EA extracts of TWHF, as well as the triptolide component, inhibit PGE2 production in a variety of human cells by blocking the up-regulation of COX-2.
Acetates↗
Changes in glutathione homeostasis during liver regeneration in the rat.
We have shown previously that plating primary cultures of rat hepatocytes under low density, which stimulates hepatocytes to shift from the G0 to the G1 phase of the cell cycle, resulted in increased levels of glutathione (GSH) and cysteine, and increased activity of gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in GSH synthesis (Lu et al., Am. J. Physiol. 1992;263:C1181-C1189). In the current work we examined changes in GSH homeostasis after two-thirds partial hepatectomy (PH). Male Sprague-Dawley rats underwent two-thirds PH or sham operation. GSH, oxidized glutathione (GSSG), cysteine, GSH efflux, DNA synthesis, changes in GCS subunit messenger RNA (mRNA), and protein levels were measured 12 and 24 hours after PH. Both liver GSH and cysteine levels were doubled at 12 hours and remained elevated at 24 hours after PH. GSSG levels also increased, but the ratio of GSH to GSSG levels remained unchanged. The increase in GSH and cysteine levels preceded the increase in DNA synthesis. Sinusoidal GSH efflux was unchanged after two-thirds PH, but biliary GSH efflux decreased. However, total GSH efflux was minimally altered after two-thirds PH. The increase in GSH can be largely accounted for by the increase in both cysteine availability and the activity of GCS. The steady-state mRNA and protein levels of the GCS heavy subunit were increased at 12 hours after PH. The mRNA level of the GCS light subunit was unchanged. In summary, early in the course of liver regeneration the steady-state hepatic GSH levels double because of an increase in the biosynthesis of GSH.
Animals↗
Aerosol cyclosporine prevents acute allograft rejection in experimental lung transplantation.
BACKGROUND: The incidence of acute rejection and the morbidity of systemic cyclosporine (INN: cyclosporine) after lung transplantation is significant. Experimental evidence suggests that the allograft locally modulates the immune mechanisms of acute rejection. The purpose of this study was to determine whether aerosolized cyclosporine would prevent acute cellular rejection, achieve effective graft concentrations with low systemic drug delivery, and locally affect production of the inflammatory cytokines involved in acute rejection. METHODS: Unilateral orthotopic left lung transplantation was performed in 64 rats (ACI to Lewis), which were divided into eight groups (each group, n = 8): group A, no treatment; groups B to D, aerosol cyclosporine 1 to 3 mg/kg per day, respectively; group E to H, systemic cyclosporine 2, 5, 10, and 15 mg/kg per day, respectively. After the animals were killed on postoperative day 2, 4, or 6, the transplanted lung, native lung, spleen, and blood were collected. Histologic studies, high-pressure liquid chromatography for trough cyclosporine concentrations, and reverse-transcriptase polymerase chain reaction for cytokine gene expression were performed. RESULTS: Untreated animals showed grade 4 rejection by postoperative day 6. Aerosol cyclosporine prevented acute rejection in a dose-dependent fashion, with group D animals (3 mg/kg per day) showing minimal grade 1 changes. Among animals receiving systemic cyclosporine, only group H (15 mg/kg per day) controlled (grade 1) rejection. However, aerosol cyclosporine, at an 80% lower dose, achieved significantly lower concentrations of cyclosporine in the graft (12,349 vs 28,714 ng/mg, p = 0.002004) and blood (725 vs 3306 ng/ml, p = 0.000378). Group F (systemic 5 mg/kg per day) had higher cyclosporine concentrations in the blood than group D (p = 0.004572) and similar tissue concentrations (p = 0.115180), yet had grade 2 rejection. Reverse-transcriptase polymerase chain reaction demonstrated equivalent suppression of inducible nitric oxide synthase but a 20- to 25-fold higher expression of interleukin-6, interleukin-10, and interferon-gamma in group D versus group H recipient allografts. CONCLUSION: Local delivery of cyclosporine by aerosol inhalation dose-dependently prevented acute pulmonary allograft rejection. Effective graft levels and low systemic drug delivery required significantly lower doses than systemic therapy alone. The gene expression of proinflammatory cytokines involved in allograft rejection was suppressed by aerosol cyclosporine therapy.
Administration, Inhalation↗