Inhibition of intimal hyperplasia after vein grafting by in vivo transfer of human senescent cell-derived inhibitor-1 gene

OBJECTIVE: To define the distribution and determinants of cardiovascular disease events among participants undergoing long-term antihypertensive therapy, and to stratify them into risk groups on the basis of pretreatment clinical profiles. DESIGN: A prospective cohort study of participants in a worksite-based antihypertensive treatment program in New York city (1973-1994). PATIENTS: We studied 8690 systematically treated patients who had at least 6 months of follow-up (average of 5.7 years) and, at entry, had had a systolic blood pressure of > or = 160 mmHg or a diastolic blood pressure of > or = 95 mmHg (after 1992 > or = 140/90 mmHg), or had been being administered antihypertensive medication. MAIN OUTCOME MEASURES: Blood pressure and incidence of morbid and mortal cardiovascular events. RESULTS: Blood pressure control (to 140 +/- 3/87 +/- 7 mmHg) was achieved by the first year and maintained through 18 years of therapy. In nearly 50,000 person-years of follow-up, there were 468 cardiovascular disease events [myocardial infarction including revascularization (282), strokes (93), congestive heart failure (30) and other cardiovascular deaths (63)]. Deaths from cardiovascular disease events accounted for 68% of all deaths. Myocardial infarction was most common throughout, but congestive heart failure incidence surpassed stroke incidence after 10 years. A scheme for risk stratification was constructed after analysis of the independent association of baseline factors and incident cardiovascular events. Upon the basis of ease of ascertainment and their demonstrated associations with occurrence of cardiovascular disease during treatment, we selected five pretreatment factors (history of heart attack, stroke, diabetes, age > or = 55 years and pulse pressure > or = 60 mmHg) to stratify patients into four groups. Those with no risk factor had a low risk (n=2999), those with one had a moderate risk (3042), those with two had a high risk (2237), and those with three or more had a very high risk (412). Overall, the unadjusted rates of incidence of cardiovascular disease events per 1000 person-years for patients in very high and low risk groups differed by factors of six and 14 for men and women, respectively. CONCLUSION: These results demonstrate that long-term control of blood pressure can be achieved in a general population. Nevertheless, cardiovascular disease events still accounted for most morbidity and mortality among these 'recovered' hypertensive patients. At entry, on the basis of readily identifiable characteristics, it was possible to stratify patients according to likelihood of subsequent events occurring despite control of blood pressure. This scheme could provide the basis for targeting more aggressive therapy where the potential for further cardioprotection is greatest.     

The characterization of low energy molecular hydrogen ion—induced defects in synthetic diamond by optical absorption

The results of optical absorption analysis of the synthetic diamonds(type Ib) which were implanted with 40 keV molecular hydrogen ions at doses of 10^15-10^17H/cm^2(at 100K),showed that the increase of optical density(OD) of modified layer(-140nm) in UV-VIS region was dependent upon the damage level caused by ion implantation process.The range of relative optical band gap(Er.opt) around 2.0eV suggested that an amorphous carbon network structure like a-C film,which probably contains some localized subtetrabedral-coordinated clusters embedded in the fourflod(sp^3) sites.was tentatively found in this layer,basing on the optical gap of carbon materials.The evolution of Er,opt with ion fluence indicated that no more hydrogenated carbon compositions were produced in as -implanted samples,while the increase of Er,opt with annealing temperature was very similar to that of hydrogen content dependence of Eopt in hydrogenately amorphous carbon(a-C:H):In addition the optical inhomogeneity of type Ib diamond has been revealed by a 2-dimension topograph in transmission mode at λ=430nm。     

A highly repetitive sequence isolated from genomic DNA of the medaka (Oryzias latipes)

In order to investigate the relationship between various temporomandibular joint (TMJ) pain levels and the detection of high signal intensity (joint effusion) on T2 weighted magnetic resonance imaging (MRI), 19 consecutive patients who complained of unilateral painful TMJ hypomobility (closed locking) were involved in this study. All patients were clinically examined in a routine manner, and all patients rated their pain levels by a visual analogue scale and eight pain questionnaire prior MRI study. T1 and T2 weighted MRI was taken in sagittal section at unilateral affected joint side. The presence or absence of a high signal intensity spot within the TMJ compartment were judged by three examiners. The high signal intensity was detected in 10 joints, but not in 9 joints. In between these two groups, the pain ratio was calculated and compared. The data showed that there was no significant statistical correlation between pain levels and the presence of high signals. This study disclosed that the MRI detection of high signal intensity in the closed locking TMJ did not directly relate to the presence of TMJ pain nor the increased pain level. These indicate the need of further larger studies.     

Immunochemical and biochemical identification of the rice seed protein encoded by cDNA clone A3-12

Previously isolated cDNA clone A3-12 that was expressed in E. coli as the fusion protein with Trp E showed immunoreactivity with the mouse antibody raised against isolated alpha-globulin from rice seed. The N-terminal amino acid sequences determined for the purified alpha-globulin and its tryptic peptides were identical with the deduced amino acid sequence reported, except for two residues at the protein N terminus. An error in the reported sequence was confirmed by re-sequencing the cDNA, the nucleotide sequence for the two N-terminal residues being shown to be CAGCTG and not CACGTG. Thus, the protein encoded by cDNA clone A3-12 was identified to be the major rice seed globulin, alpha-globulin, with an apparent molecular mass of 26kDa.     

Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration

In this study the potential of intraperitoneal (i.p.) and intravenous (i.v.) administration of chimeric iodine-131-labelled MOv18 IgG for radioimmunotherapy was determined. The dosimetry associated with both routes of administration of cMOv18 IgG was studied in patients. Eight patients suspected of having ovarian carcinoma received 150 MBq 131I-cMOv18 IgG i.p. Blood and urine were collected and serial gamma camera images were acquired. Another group of four patients received 7.5 MBq 131I-cMOv18 IgG i.v. For all patients, tissue biopsies were obtained at surgery. Activity in the blood after i.p. administration was described by a bi-exponential curve with a mean uptake and elimination half-life of 6.9+/-3.2 h and 160+/-45 h, respectively. For i.v. infusion the mean half-life for the elimination phase was 103+/-12 h. Cumulative excretion in the urine was 17%+/-3% ID and 21%+/-7% ID in 96 h for i.p. and i.v. administration, respectively. Scintigraphic images after i.p. administration showed accumulation in ovarian cancer lesions, while all other tissues showed decreasing activity with time. Tumour uptake determined in the ovarian cancer tissue specimens ranged from 3.4% to 12.3% ID/kg for i.p. administration and from 3.6% to 5.4% ID/kg for i.v. administration. Dosimetric analysis of the data indicated that 1.7-4.3 mGy/MBq and 1.7-2.2 mGy/MBq can be guided to solid or ascites cells after i.p. and i.v. administration, respectively. Assuming that an absorbed dose to the bone marrow of 2 Gy will be dose limiting, a total activity of 4.1 GBq 131I-cMOv18 IgG can be administered safely via the i.p. route and 3.5 GBq via the i.v. route. At this maximal tolerated dose, a maximum absorbed dose to 1-g tumours in the peritoneal cavity of 18 and 8 Gy can be reached after i.p. and i.v. administration, respectively. For the i. p. route of administration, dose estimates for the tumour are even higher when the electron dose of the peritoneal activity is also taken into account: total doses to the tumour of 30 Gy and 22 Gy will be absorbed at the tumour surface and at 0.2 mm depth, respectively. In conclusion, therapeutic tumour doses can be achieved with 131I-cMOv18 IgG in patients with intraperitoneal ovarian cancer lesions with no normal organ toxicity. The i.p. route of administration seems to be preferable to i.v. administration.     

Assessment of the role of the renin-angiotensin system in cardiac contractility utilizing the renin inhibitor remikiren

1. The role of the renin-angiotensin system in the regulation of myocardial contractility is still debated. In order to investigate whether renin inhibition affects myocardial contractility and whether this action depends on intracardiac rather than circulating angiotensin II, the regional myocardial effects of systemic (i.v.) and intracoronary (i.c.) infusions of the renin inhibitor remikiren, were compared and related to the effects on systemic haemodynamics and circulating angiotensin II in open-chest anaesthetized pigs (25-30 kg). The specificity of the remikiren-induced effects was tested (1) by studying its i.c. effects after administration of the AT1-receptor antagonist L-158,809 and (2) by measuring its effects on contractile force of porcine isolated cardiac trabeculae. 2. Consecutive 10 min i.v. infusions of remikiren were given at 2, 5, 10 and 20 mg min-1. Mean arterial pressure (MAP), cardiac output (CO), heart rate (HR), systemic vascular resistance (SVR), myocardial oxygen consumption (MVO2) and left ventricular (LV) dP/dtmax were not affected by remikiren at 2 and 5 mg min-1, and were lowered at higher doses. At the highest dose, MAP decreased by 48%, CO by 13%, HR by 14%, SVR by 40%, MVO2 by 28% and LV dp/dtmax by 52% (mean values; P < 0.05 for difference from baseline, n = 5). The decrease in MVO2 was accompanied by a decrease in myocardial work (MAP x CO), but the larger decline in work (55% vs. 28%; P < 0.05) implies a reduced myocardial efficiency ((MAP x CO)/MVO2). 3. Consecutive 10 min i.c. infusions of remikiren were given at 0.2, 0.5, 1, 2, 5 and 10 mg min-1. MAP, CO, MVO2 and LV dP/dtmax were not affected by remikiren at 0.2, 0.5 and 1 mg min-1, and were reduced at higher doses. At the highest dose, MAP decreased by 31%, CO by 26%, MVO2 by 46% and LV dP/dtmax by 43% (mean values; P < 0.05 for difference from baseline, n = 6). HR and SVR did not change at any dose. 4. Thirty minutes after a 10 min i.v. infusion of the AT1 receptor antagonist, L-158,809 at 1 mg min-1, consecutive 10 min i.c. infusions (n = 5) of remikiren at 2, 5 and 10 mg min-1 no longer affected CO and MVO2, and decreased LV dP/dtmax by maximally 27% (P < 0.05) and MAP by 14% (P < 0.05), which was less than without AT1-receptor blockade (P < 0.05). HR and SVR remained unaffected. 5. Plasma renin activity and angiotensin I and II were reduced to levels at or below the detection limit at doses of remikiren that were not high enough to affect systemic haemodynamics or regional myocardial function, both after i.v. and i.c. infusion. 6. Remikiren (10(-10) to 10(-4) M) did not affect contractile force of porcine isolated cardiac trabeculae precontracted with noradrenaline. In trabeculae that were not precontracted no decrease in baseline contractility was observed with remikiren in concentrations up to 10(-5) M, whereas at 10(-4) M baseline contractility decreased by 19% (P < 0.05). 7. Results show that with remikiren i.v., at the doses we used, blood pressure was lowered primarily by vasodilation and with remikiren i.c. by cardiac depression. The blood levels of remikiren required for its vasodilator action are lower than the levels affecting cardiac contractile function. A decrease in circulating angiotensin II does not appear to be the sole explanation for these haemodynamic responses. Data support the contention that myocardial contractility is increased by renin-dependent angiotensin II formation in the heart.     

Depression among cancer patients

OBJECTIVE: To identify important causes of premature mortality among Aboriginal adults in the Northern Territory (NT), 1979-1991. METHODS: All deaths of NT Aboriginal residents aged 15-64 years which occurred in the NT between 1979 and 1991 and which were recorded by the Registry of Births, Deaths and Marriages were included. Standardised mortality ratios (SMRs) were used to compare the number of deaths observed among Aboriginals in the NT to those expected, based on overall Australian rates. Years of potential life lost before age 65 (YPLL65) were estimated for specific causes of death. RESULTS: Aboriginal women (overall SMR, 5.5) and Aboriginal men (SMR, 4.7) experienced a high burden of excess mortality from almost every cause of death. This excess increased over time, especially for Aboriginal women. Among Aboriginal men, the most important causes of premature death were motor vehicle accidents (11% of excess deaths and 17% of YPLL65), ischaemic heart disease (10% of excess deaths and 10% of YPLL65), pneumonia and influenza (8% of excess deaths and 6% of YPLL65), and homicide (7% of excess deaths and 8% of YPLL65). For Aboriginal women, the most important causes included homicide (7% of excess deaths and 11% of YPLL65), chronic obstructive pulmonary disease (10% of excess deaths and 5% of YPLL65), rheumatic heart disease (7% of excess deaths and 8% of YPLL65), and ischaemic heart disease (6% of excess deaths and 5% of YPLL65). CONCLUSIONS: The wide variety of causes of excess mortality will require an equally wide variety of solutions, both medical and non-medical, and a long term commitment will be necessary to achieve reductions in premature mortality among NT Aboriginal adults.