Inhibition of angiogenesis by vitamin D3 analogues.

The effects of vitamin D3 and two analogues on embryonic angiogenesis were studied in 4.5-day-old chick embryo chorioallantoic membranes. The active metabolite of vitamin D3, 1 alpha,25-dihydroxyvitamin D3, and a synthetic vitamin D3 analogue, 22-oxa-1 alpha,25-dihydroxyvitamin D3, inhibited angiogenesis in a dose-dependent manner, the inhibition occurring in the picomolar range. In contrast, vitamin D3 was not effective. The results suggest that these two vitamin D3 analogues might be promising anti-angiogenic agents for controlling the angiogenesis which occurs in several pathological conditions, including tumor development.     

A case of Klinefelter's syndrome with bilateral absence of the vas deferens

A 33-year-old male presented to the Chiba University Hospital with the main complaint of right flank pain. Bilateral vas deferens were not palpable. Hormonal examination revealed hypergonadotropic hypogonadism and cytogenetic studies a 47,XXY karyotype. The significance of the association of this karyotype with the absence of vas deferens is discussed.     

Intraparenchymal blood-fluid levels in traumatic intracerebral haematomas

Summary Blood-fluid levels within the cerebral parenchyma are observed more frequently on CT and MRI in traumatic intracerebral haematomas than in those of other aetiologies. The intraparenchymal blood-fluid interface can be formed without a fluid cavity. It is suggested that the blood-fluid levels represent layering of red blood cells within areas of contusion necrosis as well as extensive contusion oedema. The more extensive the damage to brain tissue, the more often blood-fluid levels formed. A poorer outcome can be therefore predicted when an intraparenchymal blood-fluid interface is seen.     

Clinicopathologic Study of Angiogenesis in Japanese Patients with Breast Cancer

p = 0.0007) and tumor necrosis (TN) (HMC: p = 0.0050). Univariate analysis showed that AMC or HMC was a statistically significant predictor of overall survival in all patients ( p = 0.0086 and p = 0.0307, respectively). Multivariate analysis showed that AMC was an independent predictor of node status when we fitted a model with node status, BVI, and either AMC or HMC; but HMC was not independent. However, when we fitted a model including all 11 of the other indicators and AMC or HMC, the node status, HG, and LI were independent predictors, but AMC and HMC were not. Although AMC was a better method than HMC for evaluating angiogenesis, we cannot confirm angiogenesis as a significant independent prognostic factor associated with long-term survival in Japanese breast cancer patients.     

Distribution characteristics of immunosuppressants FK506 and cyclosporin A in the blood compartment

Using two representative immunosuppressants, FK506 (FK) and cyclosporin A (CyA), of which the mechanism of pharmacological action is the same although there is a great difference in the pharmacological intensity, the distribution characteristics were studied in both in vivo and in vitro experiments using rat, dog, and human blood. Blood samples were fractionated by means of sedimentation in Ficoll-Paque®, and the drug contents in the diluted plasma fraction, erythrocyte fraction, and lymphocyte fraction were measured by an HPLC method. FK distributes to the lymphocyte fraction to a level about three times greater than that of CyA, while CyA distributes to the erythrocyte fraction to a level ten times that of FK. The distribution pattern of these fractions was independent of the drug concentration and species after correcting the drug concentration in each fraction with the blood drug concentration. The uptakes of FK and CyA in the isolated lymphocytes obtained from the rat spleen and human peripheral blood were also studied. The amount of FK taken up by the spleen lymphocytes is five times greater than that of CyA. In the case of the uptake study using human peripheral blood lymphocytes, the concentration of FK in the lymphocyte is 100-fold higher than that of CyA. This difference in the lymphocyte level between the two immunosuppressants is thought to be one of the reasons why FK is more potent than CyA, a difference of about 100-fold in the in vitro pharmacological study and about tenfold in the in vivo organ transplantation experiments.     

Prediction of outcome of prolonged coma caused by brain damage

Thirty-one prolonged coma patients, who continued in a comatose state for at least 2 months, were classified electrophysiologically employing EEG, a compressed spectral array of continuous EEG frequency analysis, BSR, SEP and SSEP. The prognoses of long-term follow-up (at least 8 months) in these patients were compared with the results of such electrophysiological analysis and with the neurological gradings of the prolonged coma patients. In the continuous EEG frequency analysis, 22 cases were classified as having a changeable spectrogram, nine cases as having a slow monotonous spectrogram, and no cases as having a borderline spectrogram. We also classified the changeable spectrograms into the following three patterns: no desynchronization, slight desynchronization, and desynchronization. The nine cases with a slow monotonous spectrogram revealed severe damage of the brain stem and cerebral function with multimodality evoked potentials, and most of these cases could not survive without assisted respiration. The 22 cases with a changeable spectrogram had mild damage of the brain stem and cerebral function with multimodality evoked potentials, and these cases were identical with a persistent vegetative state. Three of the cases showed a changeable spectrogram that revealed a desynchronization pattern, normal BSR and normal N20 of SEP and SSEP, recovered spontaneously from the persistent vegetative state within 6 months after electrophysiological evaluation. We conclude that not only a neurological but also an electrophysiological classification is necessary to evaluate the brain function and prognosis of prolonged coma.     

Diffuse prolonged depression of cerebral oxidative metabolism following concussive brain injury in the rat: a cytochrome oxidase histochemistry study.

Utilizing a lateral fluid percussion injury as a model of cerebral concussion, rats were studied histochemically measuring the degree of cytochrome oxidase activity present within different structures at different times following injury. After concussion, the cerebral cortex ipsilateral to the site of injury exhibited a diffuse decrease in its level of chromotome oxidase (CO) activity beginning at as soon as one day and lasting for up to 10 days after the insult. The ipsilateral dorsal hippocampus also exhibited an injury-induced decrease in CO activity, however, it was not as severe as in the cortex. These results indicate that oxidative metabolism is depressed primarily within the cerebral cortex and hippocampus for several days following a cerebral concussion. We propose that this period of metabolic depression may delineate a period of time during which the injured brain is unable to function normally and thus would be vulnerable to a second insult.     

Clinical analysis of ureteral tumours with or without renal pelvic neoplasms

Twelve patients with ureteral tumours with or without ipsilateral renal pelvic neoplasms were retrospectively analysed. Haematuria was the most common symptom. Location of all tumours was preoperatively detected by conventional diagnostic methods, such as intravenous or retrograde pyelography, washing cytology of the upper urinary tract, computed tomography, echogram and abdominal aortography. Cumulative proportion survivals of 1, 3 and 5 years were 81.9%, 68.2% and 45.5%, respectively. Patients with high Karnovsky rating survived longer (p<0.05) than those with low rating. Patients with low-stage tumours (T₁, T₂) showed longer survival rate (p<0.001) than those with high-stage tumours (T₃, T₄). Vascular invasion of tumour cells was present in removed specimens in 4 out of 7 patients who died or are alive with cancer, but none in those who survived without disease. Good therapeutic response could not be achieved unless surgery was performed.     

Effects of calcium in continuous cardioplegia on myocardial protection

The effects of calcium (Ca) on a hyperkalemic cardioplegic solution for continuous cardioplegia were examined in an isolated perfused working rat heart model. The coronary arteries were perfused with a modified Krebs-Henseleit bicarbonate buffer (K-H) solution, containing various concentrations of Ca(0.1, 0.6, 1.2, and 2.5 mmol/l) and a high concentration of potassium (20 mmol/l), for 180 min, after which cardiac arrest was induced at 37°C for 180 min. Cardiac function and creatine kinase (CK) were measured. In the control group, K-H solution was infused in place of the cardioplegic solution, and cardiac arrest was not induced. No significant differences were observed between the groups infused with the K-H solution containing Ca concentrations of 0.6, 1.2, and 2.5 mmol/l in the percent recovery of aortic flow (82.1±2.9%, 80.6±2.0%, and 71.5±3.7% (mean±SEM) respectively) or in the recovery of other indices of cardiac function, or in CK leakage. There were also no significant differences in the recovery of cardiac function and CK leakage between these groups and the control group. In the Ca 0.1 mmol/l group, however, the characteristic Ca paradox was observed. These findings suggest that if the Ca concentration in a cardioplegic solution is higher than 0.6 mmol/l during continuous cardioplegia, excellent cardioprotective effects will be achieved.