MR detection of cytoplasmic fat in clear cell renal cell carcinoma utilizing chemical shift gradient-echo imaging

We attempted to determine whether cytoplasmic fat in clear cell renal cell carcinoma (RCC) can be identified by chemical shift gradient-echo magnetic resonance imaging (CSI). CSI was performed for 22 clear cell RCCs and 30 other renal tumors (including 16 non-clear cell RCCs), all of which were surgically proven. Signal reduction in out-of-phase images of these tumors was retrospectively evaluated and compared. The signal loss ratio (SLR) was defined and calculated. Fat staining of specimens from 16 tumors was performed and correlated with SLR. SLR was significantly higher in clear cell RCCs than in non-clear cell RCCs (P < 0.001). There was a significant correlation between degree of fat staining positivity of the specimens and SLR (P < 0.01). When signal reduction in out-of-phase images suggested the diagnosis of clear cell RCC, correct diagnosis of this entity was made in resected renal tumors with sensitivity, specificity, and accuracy of 82%, 90%, and 87%, respectively. CSI can demonstrate cytoplasmic fat in clear cell RCCs, which helps to differentiate this entity from other RCCs.     

Long-term immunological study on postoperative adjuvant treatment with interferon-gamma in patients with renal cell carcinoma who underwent nephrectomy

Previously, we reported the short-term immunological effects of postoperative adjuvant interferon-gamma (IFN-gamma) administration to renal cell carcinoma patients as determined by three-color flow cytometry. We now report the results of a long-term study on a larger number of subjects. Thirty-three patients with renal cell carcinoma received a prophylactic intramuscular injection of IFN-gamma (300 x 10(4) units per week) after nephrectomy. We evaluated immunological changes by measuring peripheral blood lymphocyte subsets including activated cytotoxic T lymphocytes (ACTL), cytotoxic T lymphocytes (CTL), activated suppressor T lymphocytes (ASTL), helper T lymphocytes (HTL), activated suppressor-inducer T lymphocytes (AITL), and suppressor-inducer T lymphocytes (SITL). We also estimated the natural killer (NK) activity by a cytolytic test. All 33 patients were examined for at least 12 months after the start of IFN-gamma injection, and 18 patients were examined for 30 months including the 6-month period following discontinuation of IFN-gamma injection. We found significant enhancement of the ACTL subset from the second week to the sixth month after the start of IFN-gamma injection. On the other hand, we found a significant decrease in the percentage of the HTL and SITL subsets for a long time after the start of injection. NK activity significantly increased throughout the period of administration, and it continued to increase for six months after discontinuation of IFN-gamma injection.     

Dopamine D3 agonists into the substantia nigra aggravate cataplexy but do not modify sleep

We have recently demonstrated that local perfusion of dopaminergic D2/D3 agonists into the ventral tegmental area (VTA) significantly aggravates cataplexy and increases sleep in narcoleptic Dobermans. We further assessed the roles of the mesostriatal dopaminergic system and found that local perfusion of quinpirole and 7-OH-DPAT into the substantia nigra (SN) significantly aggravated cataplexy, while perfusion of a D2/D3 antagonist significantly reduced cataplexy. Neither a D1 agonist nor a D1 antagonist modified cataplexy. SN perfusion of quinpirole did not significantly modify sleep, while VTA perfusion significantly increased the drowsy state. Although autoregulation of the VTA and SN dopaminergic neurons are involved in the regulation of cataplexy, both structures have distinct roles for the regulation of sleep.     

CAG repeat length in the androgen receptor gene is enhanced in patients with idiopathic azoospermia

Objectives. To determine whether the number of CAG repeats in the androgen receptor gene is enhanced in patients with idiopathic azoospermia.Methods. Using the polymerase chain reaction, the number of CAG repeats was assayed in 41 patients with idiopathic azoospermia and in 48 normozoospermic fertile men.Results. In the control group, the CAG repeat length ranged from 17 to 30 (mean 23.9 ± 2.9); in the azoospermic group, the CAG repeat length ranged from 20 to 34 (mean 26.5 ± 3.5). The difference between the two groups was statistically significant (P = 0.0013). None of the men in the control group had a CAG repeat length greater than 31; four of the azoospermic men had 34 CAG repeats.Conclusions. Results suggest that an increase in the number of CAG repeats in the androgen receptor gene to 31 or greater may be associated with the etiology of at least some cases of idiopathic azoospermia.     

Ultracompact, completely implantable permanent use electromechanical ventricular assist device and total artificial heart

An ultracompact, completely implantable permanent use electromechanical ventricular assist device (VAD) and total artificial heart (TAH) intended for 50-60 kg size patients have been developed. The TAH and VAD share a miniature electromechanical actuator that comprises a DC brushless motor and a planetary roller screw. The rotational force of the motor is converted into the rectilinear force of the roller screw to actuate the blood pump. The TAH is a one piece design with left and right pusher plate type blood pumps sandwiching an electromechanical actuator. The VAD is one half of the TAH with the same actuator but a different pump housing and a backplate. The blood contacting surfaces, including those of the flexing diaphragm and pump housing, of both the VAD and TAH were made of biocompatible polyurethane. The diameter, thickness, volume, and weight of the VAD are 90 mm, 56 mm, 285 cc, and 380 g, respectively, while those of the TAH are 90 mm, 73 mm, 400 cc, and 440 g, respectively. The design stroke volume of both the VAD and TAH is 60 cc with the stroke length being 12 mm. The stroke length and motor speed are controlled solely based on the commutation signals of the motor. An in vitro study revealed that a maximum pump flow of 7.5 L/min can be obtained with a pump rate of 140 bpm against a mean afterload of 100 mm Hg. The power requirement ranged from 4 to 6 W to deliver a 4-5 L/min flow against a 100 mm Hg afterload with the electrical-to-hydraulic efficiency being 19-20%. Our VAD and TAH are the smallest of the currently available devices and suitable for bridge to transplant application as well as for permanent circulatory support of 50-60 kg size patients.     

Fat and dietary fiber intake and colon cancer mortality: a chronological comparison between Japan and the United States

To estimate the role of dietary fiber (DF) and fat in the striking growth of colon cancer mortality in Japan after World War II, we analyzed relations between the above variables in comparison with those in the United States. In the United States, fat intake grew by only one-third over the past 70 years (from 124 g in 1909-1913 to 166 g in 1984), whereas colon cancer mortality increased fourfold (from 5 to 20 per 100,000). In Japan, although fat intake roughly doubled during the 40 years after World War II (from 20 to 38 g), colon cancer mortality grew 5.5-fold (from 2 to 11 per 100,000). It is difficult to give a consistent explanation for the growth patterns of colon cancer mortality in both countries on the basis of fat consumption as a cancer promoter. In the United States, DF intake continuously dwindled at a level always less than in Japan throughout this century. DF intake in Japan also declined rather steadily, except for war time, over the past 80 years. However, with regard to the growth pattern of colon cancer mortality, it began rising steeply around the period when the daily DF intake diminished below 20 g, suggesting the presence of a threshold level in this neighborhood in preventing the development of colon cancer.     

Knowledge, risk perception of AIDS and reported sexual behaviour among students in secondary schools and colleges in Tanzania.

A questionnaire survey was carried out among 1041 students in secondary schools and colleges in Dar-es-Salaam, Tanzania to evaluate the relationship between HIV-risky sexual behaviour and anti-condom bias, as well as with AIDS-related information, knowledge, perceptions and attitudes. Self-reportedly, 54% of students (75% of the boys and 40% of the girls) were sexually active, 39% had a regular sexual partner and 13% had multiple partners in the previous year. The condom use rate was higher than previous reports. However, 30% of sexually active respondents did not always use condoms (Risk-1 behaviour) and 35% of those with multiple partners in the previous year did not always use condoms (Risk-2 behaviour). Multiple logistic regression analyses indicated that 'sex partner hates condom' had association with both Risk-1 behaviour (OR 2.47; 95% CI 1.58-3.85) and Risk-2 behaviour (OR 2.47; 95% CI 1.10-5.48). 'Use of condom prevents HIV infection' also had association with both Risk-1 behaviour (OR 2.09; 95% CI 1.19-3.67) and Risk-2 behaviour (OR 3.73; 95% CI 1.28-11.03). Students engaging in risky behaviour were aware of the risk, even though they failed to change their behaviour. Reasons for the AIDS epidemic among Tanzanian students and the importance of more effective AIDS education are also discussed.     

Retinal ischemia-reperfusion injury attenuated by blocking of adhesion molecules of vascular endothelium

PURPOSE: To evaluate quantitatively the effects of blocking of adhesion molecules (P-selectin or intercellular adhesion molecule-1 [ICAM-1]) on leukocyte dynamics in the retinal microcirculation in vivo during ischemia-reperfusion injury and the therapeutic efficacy of the blocking of adhesion molecules on retinal ischemia-reperfusion injury. METHODS: Retinal ischemia was induced for 60 minutes in anesthetized pigmented rats by temporary ligation of the optic nerve. P-selectin or ICAM-1 monoclonal antibody (mAb) was administered at 5 minutes before reperfusion. At 4, 12, and 24 hours after onset of reperfusion, leukocyte behavior in the retinal microcirculation was evaluated in vivo with acridine orange digital fluorography. After 7 or 14 days of reperfusion, retinal damage was evaluated histologically. RESULTS: P-selectin mAb significantly inhibited leukocyte rolling along the major retinal veins after reperfusion. Subsequently, the number of accumulated leukocytes decreased in the P-selectin-inhibited rats. ICAM-1 mAb also inhibited leukocyte accumulation during the reperfusion period in a more substantial manner than P-selectin mAb. Histologic examination demonstrated the protective effect of the blocking of P-selectin or ICAM-1. In accordance with a reduction in leukocyte accumulation, the protective effect of mAb on retinal ischemia-reperfusion injury was more substantial in ICAM-1-inhibited rats. CONCLUSIONS: The present study demonstrates the inhibitory effect of P-selectin and ICAM-1 mAb on leukocyte accumulation and subsequent tissue injury during retinal ischemia-reperfusion injury.     

Effect of focal X-ray irradiation on experimental choroidal neovascularization.

PURPOSE: Radiation therapy has been used to treat choroidal neovascularization (CNV) in patients with age-related macular degeneration. The in vivo effect of applying focal x-ray irradiation to the eye of rabbits with experimental CNV was investigated. METHODS: CNV was induced in the rabbit eyes by subretinal implantation of gelatin hydrogel microspheres impregnated with basic fibroblast growth factor. Three weeks after implantation, 17 of 34 eyes with CNV lesions accompanied by fluorescein leakage were irradiated with a single dose of 20 Gy; the other 17 eyes were not irradiated and served as the controls. The eyes were examined before irradiation and 1, 2, and 4 weeks after irradiation, by indirect ophthalmoscopy and fluorescein angiography. The degree of a decreasing amount of fluorescein leakage from the CNV lesions after irradiation was graded using a computerized image analysis system and was compared in the irradiated and nonirradiated eyes. These eyes were also examined histologically and immunohistochemically. RESULTS: Fluorescein leakage from the CNV lesions had significantly decreased in the eyes irradiated with 20 Gy compared with the control eyes, throughout the study period (P < 0.05). Histologic and immunohistochemical studies at 4 weeks after irradiation demonstrated that the degree of vascular formation and the number of vascular endothelial cells in the subretinal membrane of the irradiated eyes were less than those of the control eyes. CONCLUSIONS: Focal x-ray irradiation at the ocular region effectively reduced experimental CNV activity. These results support the possibility that radiation therapy may be beneficial in treating CNV.     

17 Beta-estradiol increases VEGF receptor-2 and promotes DNA synthesis in retinal microvascular endothelial cells.

PURPOSE: Estrogen is known to promote angiogenesis in gonads. The presence of estrogen receptors in the vascular endothelium of organs other than gonads has been reported. The goal of this study was to determine whether estrogen promotes the proliferation of retinal microvascular endothelial cells and to explore the mechanism of it. METHODS: DNA was quantitated using primary cultures of bovine retinal endothelial cells that were incubated with different doses of 17 beta-estradiol (E2), VEGF, or both. The changes in expression level of VEGF and VEGF receptor-2 (VEGFR2) were measured using northern blot analysis after treatment with E2. The presence of estrogen receptors in the endothelial cells was studied by immunohistochemistry and western blot analysis. RESULTS: 17 Beta-estradiol (E2) increased the DNA level in bovine retinal capillary endothelial cells (BRECs) by 177% at 1 nM (P < 0.05) and 150% at 10 nM (P < 0.05) by comparison with unstimulated BREC. One hundred nanomole tamoxifen completely blocked the E2-induced DNA synthesis in BRECs. Ten nanomole E2 augmented vascular endothelial growth factor (VEGF)-induced DNA synthesis in BRECs significantly (160%, P < 0.01). Ten nanomole E2 also increased VEGF mRNA expression, which peaked after 24 hours (6.7 times, P < 0.05), and VEGF receptor-2 (VEGFR2) mRNA expression, which peaked after 9 hours (2.4 times, P < 0.05). The mRNA expression level of VEGFR2 peaked with 10 nM E2 (P < 0.05) and that of VEGF reached maximum with 1 nM E2 (15 times, P < 0.001). VEGFR2 and VEGF proteins increased in parallel with their mRNA levels. Immunocytochemistry showed estrogen receptor expression in BRECs, and western blot analysis indicated the presence of a 67-kDa protein that was compatible with the estrogen receptor. CONCLUSIONS: These findings suggest that E2 may stimulate BREC growth by the receptor-mediated pathway and that E2 may augment the VEGF-dependent angiogenesis partly through the upregulation of VEGFR2.