Solid-phase synthesis of 2,3,5-trisubstituted 4H-imidazolones.
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Biomedical subjects
Publications and source records attributed to Y Yu.
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Laminated tears of the rotator cuff are often lined by a cellular layer that has an appearance suggestive of synovium. This study demonstrates, by histologic and immunohistochemical means, that the lining cells are synovial. It remains unclear whether these cells arise by synovial extension from the joint or bursa, or by metaplasia in the presence of synovial fluid, and this has implications for surgical repair of laminated cuff defects. We suggest that these defects be curetted, to remove at least some of this synovial lining, before suture repair.
PURPOSE: The purpose of this report is to describe the design and construction of an 8 T/80 cm whole-body MRI system operating at 340 MHz. METHOD: The 8 T/80 cm magnet was constructed from 414 km of niobium titanium superconducting wire. The winding of this wire on four aluminum formers resulted in a total inductance of 4,155 H. Gradient subsystems included either a body gradient or a head gradient along with a removable shim insert. The magnet and gradient subsystems were interfaced to two spectrometers. These provided the control of the gradient amplifiers and the two sets of four RF power amplifiers. The latter provide in excess of 8 kW of RF power from 10 to 140 MHz and 10 kW of RF power from 245 to 345 MHz. A dedicated computer-controlled patient table was designed and assembled. The entire system is located in a clinical setting, facilitating patient-based studies. RESULTS: The 8 T/80 cm magnet was energized without complication and achieved persistent operation using 198.9 A of current, thereby storing 81.5 MJ of magnetic energy. Exceptional performance was observed for nearly all components both in isolation and when combined within the complete system. CONCLUSION: An 8 T/80 cm MRI system has been assembled. The magnet subsystem is extremely stable and is characterized by good homogeneity and acceptable boil-off rates.
The presence of magnetic susceptibility can lead to substantial geometric distortions when imaging the human head at 8 T. These are particularly significant in gradient echo images where susceptibility often results in a noticeable loss of MR signal in the temporal lobe, the frontal lobe, and the paranasal sinus regions. In this work, anterior coronal gradient and spin echo images were acquired from the frontal lobe and sinus regions. The spin echo was shown to significantly overcome the loss of signal observed in the corresponding gradient echo images, resulting in data of greatly increased quality. In conclusion, whereas susceptibility artifacts are significant in ultra high field MRI, they can be largely surmounted by using spin echo techniques, as had been previously demonstrated in studies at lower field strength.
PURPOSE: The purpose of this work was to describe the human leptomeningeal and cortical vascular anatomy as seen at high resolution on an 8 T UHFMRI system. METHOD: With a 1024 x 1024 matrix, axial gradient echo images of the cerebral cortex were acquired on a human volunteer at 8 T with TR 500 ms, TE 16 ms, flip angle 22.5 degrees, bandwidth 53 kHz, and slice thickness 2.84 mm. The same subject was evaluated at 1.5 T using similar parameters. The images were then reviewed in detail and compared with known cortical and leptomeningeal vascular anatomy. RESULTS: Two hundred forty micron in-plane resolution images of the human brain were acquired at 8 T without evident artifact from susceptibility distortions, RF penetration, or dielectric resonances. The CSF, gray matter, and white matter structures were well discerned. The microscopic leptomeningeal vascular anatomy was well visualized, and the course of small perforating cortical vessels could be followed from the cortical surface to the white matter junction. CONCLUSION: Initial 8 T images of the brain demonstrate detailed leptomeningeal and cortical vascular anatomy.
Dictyostelium discoideum has a well characterized life cycle where unicellular growth and multicellular development are separated events. Development is dependent upon signal transduction mediated by cell surface, cAMP receptor/G protein linkages. Secreted cAMP acts extracellularly as a primary signal and chemoattractant. There are 4 genes for the distinct cAMP receptor subtypes, CAR1, CAR2, CAR3 and CAR4. These subtypes are expressed with temporally and spatially specific patterns and cells carrying null mutations for each gene have distinct developmental phenotypes. These results indicate an essential role for cAMP signalling throughout Dictyostelium development to regulate such diverse pathways as cell motility, aggregation (multicellularity), cytodifferentiation, pattern formation and cell type-specific gene expression.
This study compared barnidipine, a calcium-channel blocker, and benazepril, an angiotensin-converting enzyme inhibitor, in 85 Chinese patients with renal parenchymal hypertension (diastolic blood pressure range 95 - 110 mmHg). Patients were randomly assigned to receive either 10 mg barnidipine or 10 mg benazepril orally daily for 4 weeks. In patients with diastolic blood pressure > 90 mmHg after 2 weeks of treatment, the dose of barnidipine or benazepril was increased by 5 or 10 mg, respectively. Both the barnidipine-treated group (n = 43) and the benazepril-treated group (n = 42) showed significant mean reductions from baseline in sitting systolic and diastolic blood pressures. The decrease in diastolic blood pressure with benazepril was significantly greater than with barnidipine treatment. Sitting heart rate was not changed by either drug. There was no significant difference in adverse events between the two groups. Barnidipine is similar to benazepril for the treatment of renal parenchymal hypertension.
Our previous study demonstrated that the CYP2C9*3 gene variant was significantly associated with elevated plasma irbesartan concentration and blood pressure decline, assessed by a 4-week follow-up and revisit following daily administration of irbesartan. We conducted a further analysis to examine the acute effects of the CYP2C9 polymorphism on plasma concentration and blood pressure through remeasurement 6 h after administration of irbesartan. We used an extreme-sampling approach by selecting individuals from the top and bottom deciles of blood pressure response residuals to irbesartan from the previous study population in Anhui, Taihu, and Dongzhi Counties, in China. A total of 196 subjects were available for the analysis. Pre- and posttreatment systolic and diastolic blood pressures (SBP and DBP), and venous blood samples (0.5, 2, and 6 h following the first treatment) were collected from each individual. Plasma irbesartan concentrations were determined by a standard HPLC/fluorescence method. The observed frequencies were 97.7% for CYP2C9*1 (Ile359) and 2.3% for CYP2C9*3 (Leu359). Subjects with the CYP2C9*1/CYP2C9*3 genotype had significantly higher plasma irbesartan concentrations when compared with those with the CYP2C9*1/CYP2C9*1 genotype (beta +/- SE = 81 +/- 36) and greater DBP response (beta +/- SE = 5.6 +/- 2.5 mmHg) at the 6-h time point after adjusting for important confounders. Our finding suggests that the CYP2C9*3 gene variant significantly alters the plasma concentration and acute DBP response at the 6-h point following irbesartan treatment in Chinese hypertensive patients.
The influence of electroacupuncture (EA), a traditional Chinese medical treatment, on type II collagen-induced arthritis (CIA) was examined in DBA/IJ mice in vivo. Mice were immunized intradermally twice at a 3-week interval with bovine type II collagen (C II). EA stimulation, begun on day 21 simultaneously with the second immunization, was applied at the acupoint equivalent to GV4 three times a week for 3 weeks. The results showed that EA delayed the onset, attenuated the severity of arthritis, and reduced the anti-collagen antibody level. Furthermore, we investigated the impact of EA on the productions of endogenous interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE2), and the levels of IL-1 beta mRNA in splenocytes and synovial tissues from C II immunized mice on day 45 and cyclooxygenase-2 (COX-2) mRNA in lipopolysaccharide (LPS)-stimulated macrophages of normal mice by using reverse transcriptase-polymerase chain reaction (RT-PCR). EA stimulation significantly inhibited the concentrations of splenic endogenous IL-1 beta and serum PGE2. The expression of IL-1 beta mRNA in spleen cells was obviously down-regulated and that in synovial tissues was modestly affected by EA. COX-2 mRNA was highly expressed in cultured peritoneal macrophages when stimulated with LPS. Previous treatment with EA also reduced LPS-stimulated induction of COX-2 mRNA. These data suggest that EA has an inhibitory effect on murine CIA, and the partial mechanism of its therapeutic result may be attributed to inhibiting the productions of IL-1 beta and PGE2 by suppressing the IL-beta and COX-2 gene activations.
The relationship between human papillomavirus (HPV) infection and breast cancer is controversial. In this study, paraffin-embedded tissue blocks prepared from 72 patients with benign, premalignant or malignant mammary lesions were randomly collected from the Shanghai region of China and Tokushima in Japan. DNA specimens extracted from all tissues were amplified by the polymerase chain reaction (PCR) using HPV16, 18 and 33 primers. Southern blot hybridization showed 19 cases to be positive for HPV33 DNA: The positive rate for HPV33 DNA in Chinese (41.7%) was significantly higher than in Japanese (11.1%) (P < 0.01): The positive rate for HPV33 DNA in invasive ductal carcinoma (34.1%) was higher than in benign or borderline mammary lesions (5%) (P < 0.02). There were no statistically significant difference among the relationship of the nuclear grade of breast cancers with HPV33 DNA-positivity. This is the first report of a positive correlation between HPV33 DNA and breast lesions in Chinese and Japanese populations. These results suggest that the infection by HPV33, but not HPV 16 or HPV 18, may be involved in breast hyperplastic lesions, especially breast cancer, in humans.
This paper reports a 15-year follow-up study of 12,693 persons in Linxian, China, who were originally screened by esophageal balloon cytology in 1974. The purpose of the study was to evaluate the ability of esophageal balloon cytology to identify individuals at increased risk for developing esophageal cancer. Age, sex and cytologic diagnoses were obtained from the original 1974 records, and information on vital status, cancer experience and potential confounding risk factors was collected from interviews and medical abstracts in 1989. A total of 1,162 incident cases of esophageal cancer and 993 deaths due to esophageal cancer were identified and used in this analysis. The follow-up study showed that the risk of esophageal cancer incidence and mortality increased in parallel with the presumed severity of the 1974 Chinese cytologic diagnoses. After adjusting for potential confounding factors, the relative risks (and 95% confidence intervals) for esophageal cancer incidence, by cytologic diagnosis, were: normal, 1.00; esophagitis, 1.52 (1.07-2.14); hyperplasia, 1.17 (1.02-1.33); dysplasia 1, 1.53 (1.10-2.14); dysplasia 2, 1.89 (1.47-2.41); and suspicious for cancer, 5.77 (3.79-8.80). These results suggest that esophageal balloon cytology, as performed and interpreted in Linxian in 1974, successfully identified individuals at increased risk for esophageal cancer.
Ovarian tumor markers CA125 and CA130 are here investigated in the search for harbingers of an elevated cancer risk or pre-cancer. A circadian rhythm of large amplitude is demonstrated for salivary CA125 and CA130 of a clinically healthy 28-year-old woman (AP). The circadian rhythms of both markers found in AP have a pattern similar to that of a patient (EH) with a müllerian cancer involving the ovary, with high values in the early morning and low values in the afternoon. Whereas acrophases occur approximately at the same circadian stage in both AP and EH, the MESOR and circadian amplitude are higher in EH as compared to AP. The circadian rhythm of salivary CA130 of AP is similar to that of other clinically healthy women. CA130 concentrations are lower than CA125 concentrations in unstimulated saliva (before rinsing of the mouth) in this clinically healthy woman (AP), and in other women studied herein. This difference between CA130 and CA125 concentrations is observed irrespective of circadian stage and irrespective of the concentration range of CA125 at the outset. After rinsing of the mouth, a statistically significant decrease in both CA130 and CA125 concentration is observed in AP and in another healty woman (GC) who collected saliva both before and after rinsing of the mouth.
Several rhythmic components were previously mapped for salivary and/or urinary CA125 and CA130. On the background of such reference standards, OVX1 and M-CSF were assayed on 242 urine samples and 160 saliva samples provided by a 71-year-old patient with a Müllerian/ovarian adenocarcinoma. Serum OVX1 correlates with serum CA125 (P = 0.002); when circulating CA125 concentrations decreased (from 122 to 14 U/ml), the urinary excretion rate of OVX1 decreased (P = 0.005), whereas the urinary excretion rate of CA125 increased (P < 0.001). Salivary OVX1 and urinary M-CSF show ultradian variations (with a frequency of one cycle in 14-17 hours), which could be utilized to guide treatment timing targeted first to optimize treatment efficacy and as a second consideration to minimize treatment toxicity.
Studies in epithelial cancer, including colorectal cancer, suggest that c-erbB-2 may be an important gene in metastatic disease. The expression of c-erbB-2 mRNA and c-neu were assessed in 25 human non-metastasising colorectal cancers and 34 primary metastasising colorectal cancer and their liver metastasis by in situ hybridisation and immunohistochemistry respectively. The metastasising colorectal cancers and their liver metastases expressed c-erbB-2 mRNA (76%, 70%) and c-neu (70%, 68%) at significantly higher levels than the nonmetastasising tumours (28% and 36% respectively chi-squared: p < 0.003 and p < 0.04). Moreover, c-erbB-2 mRNA predicted the development of liver metastases in tumours that had not metastasised to lymph nodes (p = 0.002). This gene may play an important role in the development of metastasis in colorectal cancer and its mRNA expression may have important implications for deciding which patients with lymph node negative disease require chemotherapy.
We have previously shown that c-erbB-2 oncoprotein encoded by the erbB-2 gene is overexpressed in human colorectal cancers that metastasis compared to those that are cured by surgery. To determine whether c-erbB-2 is also differentially expressed in vivo in metastasising and non-metastasising tumours, we developed models of colorectal cancer growth in nude mice. Human colon cancer cell lines, HCT116, KM12SM, LIM1215 and SW480, were injected into the caecum after characterising their morphology, doubling time, DNA flow-cytometry and expression of c-erbB-2. Six weeks later, xenografted tissues were fixed for histological analysis and detection of c-erbB-2 by immunohistochemistry, 78% (21/27) of mice developed caecal cancers. The caecal tumours derived from HCT116, KM12SM or LIM1215 were highly metastatic; 67 to 100% of them had liver metastases and lymph node involvement and 33 to 75% had lung tumours. Most of the tumours were c-erbB-2-positive. In contrast SW480 caecal tumours had only 33% lymph node involvement, but not liver or lung metastases. Only one SW480 caecal tumour and one lymph node metastasis expressed c-erbB-2. C-erB-2 was more frequently expressed in xenografted tissues in colon cancer primaries and secondaries of the highly metastatic cells (HCT116, KM12SM and LIM1215) compared to the cells (SW480) giving predominantly local growth. Our results suggest that c-erbB-2 gene may play an important role in the development of metastasis from colorectal cancer.
The influence of moxibustion, a traditional Chinese medical treatment; on type II collagen-induced arthritis (CIA) was examined in DBA/1J mice in vivo. Mice were immunized intradermally twice at 3-week intervals with bovine type II collagen (C II). The main incidence of arthritis started around day 30 and lasted to day 60 after the first immunization. Moxibustion, using three different regimens, was applied at the acupoint equivalent to GV4 every other day. Moxibustion, from day 0 to day 30 after the first immunization, suppressed the onset and development of arthritis, as well as anti-collagen antibody level. Treatment with moxibustion, from the day 31 to day 60, also resulted in a significant inhibition of progression of arthritis and production of anti-C II antibody. Furtherfore we examined the influence of moxibustion on the established arthritis. Moxibustion given from day 61 to day 120, mildly but significantly decreased the anti-C II antibody level in diseased mice, while the bone erosion and joint destruction were not affected. These results indicate that moxibustion could prevent the incidence and attenuates the development of murine CIA.
The present study was designed to investigate the antipyretic action of peripheral stimulation with electroacupuncture (EA) in SD rats. EA stimulation was applied for 30 min to the peripheral muscle where the equivalent Quchi (LI11) acupoint is located. We first examined the effects of EA stimulation on fever induced by either lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta) or prostaglandin E2 (PGE2). Intraperitoneal injection of LPS at a dose of 100 micrograms/kg caused a high rectal temperature, which was suppressed by EA stimulation. EA stimulation also inhibited the development of fever induced by IL-1 beta injection either intravenously or into the preoptic area (POA). The rats that received administration of PGE2 into POA developed rapid and high fevers, which were attenuated by EA stimulation. In the second part of the experiment, we investigated the levels of cytokines and PGE2 during the development of fever. The concentrations of IL-6 and PGE2 but not IL-1 beta, in brain and serum were increased by intraperitoneal injection of 100 micrograms/kg LPS. EA stimulation reduced PGE2 levels in both brain and serum in LPS-injected rats, but failed to change the levels of IL-6. Intravenous injection of IL-1 beta produced high brain and serum PGE2 levels, which were also significantly suppressed by EA stimulation. The results suggest that EA stimulation possesses an antipyretic effect through the inhibition of the action of PGE2 in rats.