SALVAGE THERAPY IN PATIENTS WITH UNRESECTABLE HILAR CHOLANGIOCARCINOMA

We describe our methods and outcomes of multidisciplinary treatments in patients with unresectable hilar cholangiocarcinoma. Fifty‐seven patients with a known outcome were enrolled. Thirty‐four of 57 patients were treated and evaluated by salvage therapy. For salvage therapy, we used internal and external radiotherapy, photodynamic therapy, YAG laser therapy and microwave coagulation therapy. The median survival time was 548 days for the group receiving salvage therapy and 198 days for the group not receiving this treatment. In conclusion, although no randomization of the patients was performed in this retrospective study, our present data provide convincing evidence that salvage therapy is a useful therapeutic approach for unresectable hilar cholangiocarcinomas.     

Expression of measles virus nucleocapsid protein in osteoclasts induces Paget's disease-like bone lesions in mice.

We targeted the MVNP gene to the OCL lineage in transgenic mice. These mice developed abnormal OCLs and bone lesions similar to those found in Paget's patients. These results show that persistent expression of MVNP in OCLs can induce pagetic-like bone lesions in vivo. INTRODUCTION: Paget's disease (PD) of bone is the second most common bone disease. Both genetic and viral factors have been implicated in its pathogenesis, but their exact roles in vivo are unclear. We previously reported that transfection of normal human osteoclast (OCL) precursors with the measles virus nucleocapsid (MVNP) or measles virus (MV) infection of bone marrow cells from transgenic mice expressing a MV receptor results in formation of pagetic-like OCLs. MATERIALS AND METHODS: Based on these in vitro studies, we determined if the MVNP gene from either an Edmonston-related strain of MV or a MVNP gene sequence derived from a patient with PD (P-MVNP), when targeted to cells in the OCL lineage of transgenic mice with the TRACP promoter (TRACP/MVNP mice), induced changes in bone similar to those found in PD. RESULTS: Bone marrow culture studies and histomorphometric analysis of bones from these mice showed that their OCLs displayed many of the features of pagetic OCLs and that they developed bone lesions that were similar to those in patients with PD. Furthermore, IL-6 seemed to be required for the development of the pagetic phenotype in OCLs from TRACP/MVNP mice. CONCLUSIONS: These results show that persistent expression of the MVNP gene in cells of the OCL lineage can induce pagetic-like bone lesions in vivo.     

Involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters in neonatal rat spinal cord.

1. The possible involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters was examined in the spinal cord of the neonatal rat. 2. The magnitude of substance P (SP)- or neurokinin A (NKA)-evoked depolarization of a lumbar ventral root in the isolated spinal cord preparation was increased by a mixture of peptidase inhibitors, consisting of actinonin (6 microM), arphamenine B (6 microM), bestatin (10 microM), captopril (10 microM) and thiorphan (0.3 microM). The mixture augmented the response to NKA more markedly than that to SP. 3. In the isolated spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow depolarization of the L3 ventral root was augmented by the mixture of peptidase inhibitors in the presence of naloxone (0.5 microM) but not in the presence of both naloxone and a tachykinin receptor antagonist, GR71251 (5 microM). 4. Application of capsaicin (0.5 microM) for 6 min to the spinal cord evoked an increase in the release of SP from the spinal cord. The amount of SP released was significantly augmented by the mixture of peptidase inhibitors. 5. Synaptic membrane fractions were prepared from neonatal rat spinal cords. These fractions showed degrading activities for SP and NKA and the activities were inhibited by the mixture of peptidase inhibitors. The degrading activity for NKA was higher than that for SP and the inhibitory effect of the mixture for NKA was more marked than that for SP. Although some other fractions obtained from homogenates of spinal cords showed higher degrading activities for SP, these activities were insensitive to the mixture of peptidase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)     

The excitatory and inhibitory modulation of primary afferent fibre-evoked responses of ventral roots in the neonatal rat spinal cord exerted by nitric oxide.

1. We investigated the role of nitric oxide (NO) in modulating spinal synaptic responses evoked by electrical and noxious sensory stimuli in the neonatal rat spinal cord in vitro. 2. Potentials were recorded extracellularly from a ventral root (L3-L5) of the isolated spinal cord preparation or spinal cord-saphenous nerve-skin preparation of 0- to 2-day-old rats. Spinal reflexes were elicited by electrical stimulation of the ipsilateral dorsal root or by noxious skin stimulation. 3. In the spinal cord preparation, single shock stimulation of a dorsal root at C-fibre strength induced mono-synaptic reflex followed by a slow depolarizing response lasting about 30 s (slow ventral root potential; slow VRP) in the ipsilateral ventral root of the same segment. Bath-application of NO gas-containing medium (10(-4)- 10(-2) dilution of saturated medium) and NO donors, 1-hydroxy-2-oxo-3-(N-ethyl-2-aminoethyl)-3-ethyl-1-triazene (NOC12, 3-300 microM), S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 3-300 microM) and S-nitroso-L-glutathione (GSNO, 3-300 microM), produced an inhibition of the slow VRP and a depolarization of ventral roots. Another NO donor, 3-morpholinosydononimine (SIN-1, 30-300 microM), also depressed the slow VRP but did not depolarize ventral roots. These agents did not affect the mono-synaptic reflex. 4. In the spinal cord-saphenous nerve-skin preparation, application of capsaicin (0.1-0.2 microM) to skin evoked a slow depolarizing response of the L3 ventral root. This slow VRP was depressed by NOC12 (10-300 microM) and SIN-1 (100-300 microM). When the concentration of NOC12 was increased to 1 mM, spontaneous synaptic activities were augmented and the depressant effect of NOC12 on the slow VRP became less pronounced. 5. A NO-scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide( carboxy- PTIO, 100-300 microM) prevented the depressant effect on the dorsal root-evoked slow VRP and ventral root depolarizing effects of NO donors. Carboxy-PTIO increased spontaneous synaptic activities and markedly potentiated the slow VRP. A NO synthase (NOS) inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 0.03-1 microM), but not D-NAME (0.03-1 microM), also markedly potentiated the slow VRP and this effect was reversed by L-arginine (300 microM). 6. 8-Bromo-cyclic guanosine 3': 5'-monophosphate (8-Br-cyclic GMP, 100-300 microM) produced both an inhibition of the slow VRP and a depolarization of ventral roots. A cyclic GMP-dependent protein kinase inhibitor, KT5823 (0.3 microM), partly inhibited the depressant effects of NO donors and 8-Br-cyclic GMP on the dorsal root-evoked slow VRP. In contrast, KT5823 did not inhibit the depolarizing effects of NO donors. 7. Perfusion of the spinal cord with medium containing tetrodotoxin (0.3 microM) and/or low Ca2+ (0.1 mM)-high Mg2+ (10 mM) markedly potentiated the depolarizing effect of NO donors. The SNAP-evoked depolarization in the tetrodotoxin-containing low Ca(2+)-high Mg2+ medium was significantly inhibited by excitatory amino acid receptor antagonists D-(-)-2-amino-5-phosphonovaleric acid (30 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM). 8. The present study suggests that inhibitory and excitatory mechanisms meditated by the NO-cyclic GMP cascade are involved in the primary afferent fibre-evoked nociceptive transmission in the neonatal rat spinal cord. The inhibitory mechanism, but not the excitatory mechanism, appears to be partly mediated by cyclic GMP-dependent protein kinase. It is also suggested that Ca(2+)-independent release of excitatory amino acid neurotransmitters contributes to the depolarizing response to NO of ventral roots.     

Some chemical and serological properties of perchloric acid-soluble glycoproteins separated from ascitic fluid of a patient with metastatic omentum tumor from ovarian cancer

One mol perchloric acid-soluble fraction (PASF) obtained from ascitic fluid of a patient (blood group B) with metastatic omentum tumor from ovarian cancer was a glycoprotein fraction containing 35.4% carbohydrate and exhibited A, B and Thomsen-Friedenreich (T) activities. This fraction was separated into three fractions, Frs. 1-3, by a gel filtration with Bio-Gel A-1.5 m column. Among these fractions, Fr. 1 which was obtained in a 5.5% yield to PASF, was a glycoprotein fraction with a high molecular weight, 23.3% carbohydrate and A, B and T activities. Other minor fraction, Fr. 2, and the major fraction, Fr. 3, contained 43.2% and 43.9% carbohydrate, but did not show A, B and T activities, respectively.     

CT and MR findings in diastematomyelia, with embryogenetic consideration.

Diastemstomyelia is an extremely rare disorder that is seldom found among the Japanese. This paper presents two Japanese patients, a newborn male and a newborn female, with diastematomyelia. CT demonstrated bony spurs more clearly than plain film, and magnetic resonance images indicated split cords and associated anomalies. Although the embryogenesis of diastematomyelia has not been clearly elucidated, the coincidence of levels of associated anomalies and diastematomyelia in our cases and in the literature supports Bremer's embryogenetic explanation of persistent accessory neurenteric canal.