Expression of androgen receptor through androgen-converting enzymes is associated with biological aggressiveness in prostate cancer.

AIMS: The association between the expression of androgen receptor (AR) or androgen-converting enzymes and malignant potential in prostate cancer (PCa) was examined. METHODS: PCa specimens from 44 cases of stage II, 10 cases of stage III, four cases of stage IV and two recurrent cases were semi-quantitatively studied with immunohistochemistry for AR and androgen-converting enzymes. RESULTS: The expression scores for AR, 5alpha-reductase type 1 (SRD5A1), 5alpha-reductase type 2 (SRD5A2), and aldo-keto reductase family 1 member C3 (AKR1C3) in the metastatic lesion of stage IV or recurrent cancer (n = 6) were 284.2 (30.1), 300 (0.0), 279.2 (51) and 254.2 (74.9), respectively; these scores were significantly higher than the respective scores of 121.8 (82.1), 135.1 (59.7), 167.0 (66.4) and 150.5 (62.8) for stage II and III cancer (n = 54) (p<0.001, p<0.001, p = 0.002 and p = 0.018, respectively). The expression scores for AR and SRD5A1 in stage II and III cancer with Gleason score 7 (n = 19) were 128.7 (72.3) and 150.5 (52.9); these were significantly higher than the scores of 78.8 (67.2) and 100.0 (39.6), respectively, for cancers with a Gleason score of < or =6 (n = 20) (p = 0.032 and p = 0.002, respectively). The expression scores for AR, SRD5A1 and AKR1C3 in stage II and III cancer with primary Gleason pattern > or =4 (n = 21) were 158.1 (84.3), 158.3 (61.1) and 173.8 (64.8); these were significantly higher than the scores of 98.6 (72.8), 120.3 (54.7) and 135.6 (57.6), respectively, for cancers with primary Gleason pattern < or =3 (n = 33) (p = 0.011, p = 0.026 and p = 0.034, respectively). Within Gleason score 9 cancer, the expression scores for AR and SRD5A1 in the primary lesion of stage IV (n = 3) were 276.7 (5.8) and 283.3 (28.9); these scores were significantly higher than the scores of 182.1 (86.0) and 140.0 (56.6), respectively, for stage II and III cancer (n = 7) (p = 0.027 and p = 0.001, respectively). CONCLUSIONS: Both AR and androgen-converting enzymes were upregulated in high-grade or advanced PCa.

Spinally-mediated behavioural responses evoked by intrathecal high-dose morphine: possible involvement of substance P in the mouse spinal cord.

Intrathecal (i.t.) administration of morphine in the spinal subarachnoid space of mice produced a severe hindlimb scratching followed by biting and licking. The onset of the scratching behaviour was observed 60-70 s after i.t. injection of morphine (60 and 90 nmol), and had a duration of 3-4 min. The morphine-induced behaviour was increased additively by i.t. co-administration of substance P (SP). This characteristic behavioural response was inhibited dose-dependently by i.t. co-administration of the tachykinin NK-1 receptor antagonists, sendide and CP-96,345. Significant antagonistic effects of SP (1-7), a putative antagonist for NK-1 receptors and [D-Phe7, D-His9]SP (6-11), a selective antagonist for SP receptors, were observed against the morphine-induced behaviour. Pretreatment with i.t. SP antiserum and i.t. capsaicin resulted in reduction of the response to morphine. I.t. administration of somatostatin (SOM) antiserum, cysteamine, a relatively selective depletor of SOM and cyclo-SOM, a SOM receptor antagonist, produced no inhibitory effect on the morphine-induced behaviour. These results demonstrate that a spinal system of neurones containing SP may be involved in elicitation of the behavioural episode following i.t. injection of morphine in mice.

[A case of pseudoxanthoma elasticum associated with asymptomatic multiple cerebral infarction, hypothyroidism, glucose tolerance abnormality and multiple congenital anomalies].

We report a case of pseudoxanthoma elasticum (PXE) associated with asymptomatic multiple cerebral infarction on magnetic resonance imaging (MRI), endocrinological abnormalities and multiple congenital physical anomalies. A 40-year-old woman suddenly developed paresthesia in the right half of the body. Physical examination demonstrated loosening of the skin and yellowish papules in the neck and axilla, retinal angioid streaks, cardiac mitral regurgitation, congenital aplasia of the uterus and vagina, and congenital abduction palsy of the right eye. The biopsy of the papules in the neck showed typical features of PXE. Laboratory tests revealed positive antibodies to thyroglobulin and microsome, high TSH level with normal free T3 and T4, and impaired glucose tolerance. The laboratory data and the findings of ultrasonic examination on the thyroid suggested presence of Hashimoto's disease. MRI of the brain demonstrated multiple cerebral infarcts through they were asymptomatic. MRI failed to clarify the lesion responsible for the hemiparesthesia. Carotid arteriography showed slight stenosis with ulceration near the origin of the right internal carotid artery, and severe stenosis of the horizontal portion of the right middle cerebral artery. MRI study of the brain is recommended in PXE patients since the complication of brain pathology worsens the prognosis of the disease.