Clinical study of penile cancer]

Recent progress in molecular biology suggests a certain relationship between penile cancer and human papilloma virus infection. However, the treatment for penile cancer has not been established since each institute has experienced only a small number of patients. We analyzed the result of our treatment for 14 penile cancer patients during past twenty years. Ten of the 14 patients were initially treated for the primary lesion with a combination of peplomycin (PEP) or bleomycin (BLM) and radiation therapy. Of these, 9 were found not to have residual viable cancer cells in their primary lesions. No local recurrence was found in all 7 patients in whom the penis was preserved. This result suggests that combination of PEP (BLM) and radiation preserves the penis without increasing the risk of local recurrence. Penile cancer-related death did not occur in patients without lymph node metastasis. However, this cancer death did occur in 4 out of 7 patients with lymph node metastasis, suggesting that metastasis is one of the important prognostic factors. PEP (BLM) and radiation therapy with or without regional lymph node dissection did not improve the prognosis of patients with advanced penile carcinoma, such as with pN2, pN3 or distant metastasis. More effective management may be necessary for these patients.     

A composite nasolabial flap for an entire ala reconstruction.

BACKGROUND: It is difficult to reconstruct an entire alar defect. We report a case of an entire alar reconstruction carried out in two stages with a composite nasolabial flap lined with retroauricular skin and supported with the attached conchal cartilage. OBJECTIVE: A composite nasolabial flap was applied for reconstruction of entire alar defect in this patient. METHODS: The lining skin for the flap was obtained from retroauricular region acceptable to the patient, and the conchal cartilage was used simultaneously for support and as the attachment for the lining skin. The flap was then replaced and secured. Half a year later, the flap was flipped and transferred to the alar defect as a second step. RESULTS: The final shape and texture were satisfactory. All procedures were performed under local anesthesia. CONCLUSION: Our design of composite flap has been successfully utilized to repair an entire alar defect with cosmetically and functionally good results, minimizing the donor area and the resulting operation scars. This composite nasolabial flap is thought to be the best choice of a flap for an entire alar defect reconstruction.     

Reversal of multidrug resistance by new dihydropyridines with lower calcium antagonistic activity

Summary BS compounds, a series of new dihydropyridines, successfully overcame multidrug resistance in P388/ADR cells in vitro. These agents synergistically potentiated the cytotoxicity of Adriamycin to P388/ADR cells at a concentration of 1–2 M, whereas they showed hardly any synergistic effect in the parental cell line (P388/S) at the same concentration. They inhibited the active drug efflux in P388/ADR cells as well as the binding of [G-³H]-vinblastine to membrane vesicles from P388/ADR, which was increased in resistant P388 cells as compared with parental cells. Besides, unlike the activity of clinically used calcium antagonists, the calcium antagonistic activity associated with BS compounds was very weak: their arterial relaxation activity was <21% of that of verapamil. These data suggest that BS compounds specifically overcome multidrug resistance without the serious hypotensive side effects that accompany the use of verapamil orother calcium antagonists.     

Antiarrhythmic effect and its underlying ionic mechanism of 17beta-estradiol in cardiac myocytes.

1. The effects of oestrogens on action potential and membrane currents were examined in single guinea-pig atrial myocytes. 2. 17Beta-estradiol (3-10 microM) shortened the action potential duration without significant changes in the resting membrane potential. E-4031 (1 microM) markedly prolonged the action potential duration and induced early afterdepolarization, and 17beta-estradiol (10 microM) abolished it. 3. When cells were perfused in isoproterenol-containing solution, action potentials due to abnormal automaticity caused by membrane depolarization developed, and were also inhibited by 17beta-estradiol. 4. Under voltage clamp conditions, the voltage-dependent Ca2+ currents consisted of both T-(I(Ca,T)) and L-type (I(Ca,L)). 17Beta-estradiol reduced I(Ca,L) concentration-dependently, while it (10 microM) suppressed I(Ca,T) only by approximately 10%. 17Beta-estradiol did not affect time courses of I(Ca,L) inactivation, but it shifted the steady-state inactivation curve to more negative potentials. 5. 17Beta-estradiol (10 microM) did not affect the time-dependent K+ current (I(K)), referred to as I(Kr) and I(Ks) and inwardly rectifying K+ current. However, 17beta-estradiol (30 microM) or diethylstilbestrol (10 microM) inhibited K+ currents. 6. DES and ethinylestradiol (EES) also suppressed I(Ca,L), but testosterone and progesterone failed to inhibit I(Ca,L) The potency of the inhibitory effect on I(Ca,L) was DES> EES> 17beta-estradiol. 7. 17Beta-estradiol and DES also inhibited the cyclic AMP-enhanced I(Ca,L), but cyclic GMP in the pipette or pretreatment of L-NAME could not block the effects of oestrogen on I(Ca,L). 8 These results suggest that oestrogen specifically has antiarrhythmic effects, possibly by acting the L-type Ca2+ channels. The antiarrhythmic effects of oestrogens may contribute to the cardioprotective actions of oestrogens.     

Structural changes in gonadotropin-producing cells of male frogs, Rana nigromaculata, in the process of sexual maturation

Changes in the number, size, and structure of gonadotropin-producing cells, called basophil type 2 cells, were evaluated by light and electron microscopy throughout the process of sexual maturation in second-year male frogs, Rana nigromaculata. Hyperfunctional conditions were recognized two times, in the middle of May, and in and after August. The former activation corresponded well with the start of spermatogenesis, and the latter accompanied the increasing activity of the interstitial cells. Whether or not the hormone secreted during these two periods was the same substance is discussed.     

Expression of junctional adhesion molecules on the human lymphatic endothelium

Human lymphatic vessels express several leukocyte adhesion molecules. The study here investigated the expression of three junctional adhesion molecules (JAM) which are a newly reported glycoprotein family of adhesion molecules on human lymphatic endothelium. In this study, JAM-1 and JAM-3 but not JAM-2 were detected in cultured human neonatal dermal lymphatic endothelial cells (LEC) at the gene and protein levels by microarray, RT-PCR, real-time PCR, and immunohistochemical analysis. The JAM-1 and JAM-3 expression was not altered in the TNF-alpha-treated LEC or in the untreated cells. In human tissue, the expression of JAM-1, and the expression of JAM-1, JAM-2, and JAM-3 were observed in collecting lymphatic vessels of uninflamed small intestine, and in initial lymphatics of inflamed tongue and uninflamed gingival tissue. It is thought that JAM-2 mRNA could be produced in mature vascular endothelium but not in cultured cells, and that human intestinal and oral lymphatic vessels usually express JAM-1, JAM-2, and JAM-3. There were initial lymphatics simultaneously expressing JAM-1, JAM-2, and JAM-3 in the mucosal connective tissue papillae of gingival tissue. The three JAM expressions on the lymphatic endothelium may contribute to both seal the cell-cell contact at interendothelial junctions and also allow lymphocytes to transmigrate into lymphatic vessels from tissue, independent of inflammatory cytokines.     

Emerging Roles for Lysophospholipid Mediators in Pregnancy

Recent progress in lipid research has unveiled new biologic roles for lysophospholipids as mediators of intercellular signaling. Lysophosphatidic acid (LPA) and sphingosine 1‐phosphate (S1P) are representative lysophospholipids. Accumulating evidence suggests that, acting as intercellular mediators, these and other lysophospholipids may play important roles in physiological and pathological situations. This review discusses the possible involvement of LPA and S1P in reproductive processes, with a focus on the regulatory mechanisms of pregnancy maintenance. As LPA promotes prostaglandin synthesis, mediators in the LPA pathway may also play a significant role in implantation and parturition. S1P signaling is thought to be essential in vascular formation within the uteroplacental unit and in fetomaternal immunologic interactions. Derangements in either one of these lysophospholipid signaling pathways could result in pregnancy complications that may include implantation failure, preeclampsia, and preterm labor.     

Clinical features and varieties of non-motor fluctuations in Parkinson's disease: A Japanese multicenter study

ObjectiveThis multicenter cross-sectional study aimed to investigate the clinical features and varieties of non-motor fluctuation in Parkinson's disease (PD).MethodsTo identify motor and non-motor fluctuation, we employed the wearing-off questionnaire of 19 symptoms (WOQ-19) in 464 PD patients. We compared the frequency of levodopa-related fluctuation as identified by the WOQ-19 with recognition by neurologists. We compared patients with both motor and non-motor fluctuations with those who only had motor fluctuations. Non-motor fluctuations were separated into psychiatric, autonomic, and sensory categories for further analysis.ResultsThe patients' average age was 70.8 ± 8.4 years (mean ± SD) and disease duration was 6.6 ± 5.0 years. The frequency of motor fluctuations was 69% and for non-motor fluctuation 40%. Fifty-three percent of patients with motor fluctuations also had non-motor fluctuations, whereas 93% of patients with non-motor fluctuations also had motor fluctuations. The WOQ-19 showed a sensitivity of 82% but a specificity of only 40%. The patients with both non-motor and motor fluctuations exhibited more severe motor symptoms, more non-motor symptoms and higher levodopa daily doses (p < 0.05). Patients had significantly higher fluctuation rates if they had psychiatric (49%) and sensory (45%) symptoms than patients with autonomic symptoms (32%, p < 0.01). Forty-eight percent of patients with non-motor fluctuations exhibited more than one type of non-motor fluctuation.ConclusionForty percent of PD patients presented with non-motor fluctuations, and almost half of these exhibited more than one type. Appropriate recognition of levodopa-related fluctuations, both motor and non-motor, can lead to treatment modifications in PD patients.