Retrograde labeling of mouse spinal descending tracts by a recombinant adenovirus

The present study tested whether a gene-transfer based upon the retrograde axonal transport of the lacZ adenovirus is effective in the spinal descending tracts of the adult mouse. A small volume of a replication-defective recombinant adenovirus encoding E. coli beta-galactosidase was injected into the upper lumbar cord, and, seven days later, the mice were transcardially perfused by a fixative solution. X-gal staining of coronal or sagittal sections of the spinal cord and the brain revealed that many sites of origin for rubrospinal, vestibulospinal, and reticulospinal tracts were retrogradely labeled, whereas few of the corticospinal tract neurons were retrogradely labeled. Ependymal cells surrounding the central canal of the spinal cord, which were located far from the injection site, showed a high expression of beta-galactosidase activity. Motoneurons around the injection site were strongly stained by X-gal staining, and their axons in the ventral root were anterogradely labeled. Afferent fibers in the dorsal root were labeled by the transganglionic transport of beta-galactosidase. To examine the efficacy of the uptake and retrograde transport of HRP and adenovirus, we injected a mixed solution of 10% HRP and recombinant adenovirus. The number of HRP-labeled corticospinal neurons overwhelmed the number of X-gal stained ones, while the numbers of HRP-labeled rubrospinal and subcoeruleus-spinal neurons were smaller in comparison with the numbers of beta-galactosidase-positive counterparts. The present study revealed that the origins for the spinal descending tracts except for corticospinal neurons could be efficiently gene-transferred by the retrograde infection of a recombinant adenovirus. Such a difference in efficacy of retrograde infection among the spinal descending tracts is practically important when an adenovirus-mediated gene transfer is designed to treat certain neurological diseases affecting the spinal descending tracts.     

Identification of cembratriene-4,6-diol as antitumor-promoting agent from cigarette smoke condensate

Cigarette smoke condensate (CSC) was separated into severalfractions and each was tested for an inhibitory effect on theearly antigen (EA) of Epstein-Barr virus (EBV) which can beinduced by 12-0-tetradecanoylphorbol-13-acetate (TPA) in Rajicells. Two diastereoisomers of 2,7,11-cembratriene-4,6-diol(- and ß-CBT) were isolated from the neutral fractionsof CSC and these showed potent inhibitory effects on the inductionof EBV-EA by TPA. The doses of - and ß-CBT requiredfor 50% inhibition of EBV-EA induction by TPA were 7.7 and 6.7µg/ml, respectively, which are comparable with those ofretinoic acid, a potent inhibitor of induction of epideral ornithinedecarboxylase (ODC) activity and tumor promotion by TPA in mice.Application of - and ß-CBT to mouse skin prior totreatment with TPA inhibited TPA-induced ODC activity. The degreeof inhibition was dependent on the dose and application of 16.5µmol/mouse of - and ß-CBT resulted in a 50 and40% reduction, respectively, of the maximum of the ODC activityinduced as a result of treatment with TPA. In initiation-promotionexperiments, -CBT markedly inhibited the promoting effect ofTPA on skin tumor formation in mice which were initiated with7,12-dimethylbenz[a]anthracene, but ß-CBT was foundto be less effective. Application of 3.3 µmol of -CBT40 min prior to treatment with TPA (1 µg) resulted ina 53% reduction in the number of papillomas per mouse. Our presentdata suggest that EBV-EA inhibition assay using Raji cells iseffective for the first screening of inhibitors of tumor promotion,and provide evidence that CSC contains antitumor-promoting agentsin addition to carcinogenic and tumor-promoting agents alreadyreported.     

Combined treatment of pelvic exenterative surgery and intra-operative pelvic hyperthermochemotherapy for locally advanced rectosigmoid cancer: Report of a case

A huge rectosigmoidal cancer which extended into the urinary bladder in a 64-year-old man is herein described. The tumor occupied the pelvic and lower abdominal cavities, while the rectosigmoid was totally obstructed. No hepatic or pulmonary metastasis was evident. The ventral and flank sides of the peritoneum in the right lower abdomen, right common iliac vessels, bilateral ureters, terminal ileum, cecum, ascending colon, and urinary bladder were all directly invaded by the tumor, but the aorta, sacrum, and lower rectum were free of cancer. Consequently, an anterior pelvic exenteration was carried out along with an ileal conduit and a right hemicolectomy. Immediately after the exenteration, intra-pelvic hyperthermochemotherapy was performed using a 46–47°C perfusate containing 40 g/ml of mitomycin C (MMC) and 200 g/ml of cisplatin (CDDP), for 90 min, in an attempt to prevent any further local recurrence. A right hemicolectomy and a permanent colostomy were done simultaneously with the hyperthermia treatment. After an uneventful postoperative course, the patient was prescribed adjuvant chemotherapy, i.e., two administrations of 17 mg/m² and 21 mg/m² of MMC, and ten doses of 710 mg/m² of 5-fluorouracil (5-FU) followed by five doses of 535 mg/m² of 5-FU. At the time of this writing, the patient is still alive without recurrence at 21 months after surgery.     

Primary cerebral ganglioneurocytoma in an adult

A case of an unusual cerebral neuronal tumor in a 37-year-old woman is described. A clearly marginated tumor, which was found to occupy the septum pellucidum, genu of the corpus callosum, and right frontal lobe, was composed of ganglionic and small round cells. These two populations of neoplastic cells were both interpreted as being in the advanced stages of neuronal maturation, and the authors thus designated this tumor as a "ganglioneurocytoma." Related nosologic problems on central neuronal tumors and their possible histogenesis are also discussed.     

Endosonography during endoscopic mucosal resection to enhance its safety

BACKGROUND: We have performed endoscopic mucosal resection of the esophagus (172 cases), stomach (102 cases), and colon (28 cases) using a transparent plastic cap. Because the lesion-bearing mucosa is suctioned up inside the cap under endoscopic suction, the mucosa should be dissected sufficiently from the proper muscle layer to prevent perforation. METHODS: To avert the risk of perforation, we introduced endosonographic assessment of submucosal dissection (47 cases). In all cases, just keeping the ultrasonic probe on the surface of the mucosa allowed us to evaluate whether the mucosal lesion was lifted up sufficiently from the proper muscle layer after local saline injection. RESULTS: It was possible to confirm that the muscle layer was kept outside the strangulating snare by the same procedure (32 of 37 cases, 86.5%). CONCLUSIONS: We experienced five muscular resections in cases without the ultrasonic probe and no muscular resection with the ultrasonic probe. Thus we recommend endosonographic assessment during endoscopic mucosal resection to enhance its safety.     

Reductive metabolism In vivo of trans-4-phenyl-3-buten-2-one in rats and dogs.

The reductive metabolism in vivo of a flavoring additive, trans-4-phenyl-3-buten-2-one (PBO; trans-methyl styryl ketone) was investigated in rats and dogs. In both species, the double bond-reduced product, 4-phenyl-2-butanone (PBA), was detected by HPLC as the predominant species in blood after i.v. administration of PBO. PBA detected in rat blood was identified by comparison to the authentic sample. In contrast, the carbonyl-reduced product, trans-4-phenyl-3-buten-2-ol (PBOL) was also detected as a minor metabolite of PBO in both species. The area under the curve of PBOL in rat blood was only 3% of that of PBA. PBO was mutagenic in the Ames test using Salmonella typhimurium TA 100 when S-9 mix was added, but PBA and PBOL were not. It appears that PBO is mainly metabolized to PBA in vivo in rats and dogs as a detoxification pathway.     

More than 10 years of follow-up of two patients after total femur replacement for malignant bone tumor

One patient with osteosarcoma and one with Ewing’s sarcoma of the femur were in 1987 and 1988 treated with prosthetic replacement of the femur and chemotherapy. There has been no loosening of the prostheses and no recurrence of the tumor. The patients have maintained 60% and 63% limb function scores evaluated by ISOLS criteria.

---

Résumé  Deux patients, l’un avec un ostéosarcome, l’autre avec un sarcome d’EWING, furent opérés en 1987–1988 avec remplacement prothétique du fémur, associéà une chimiothérapie. Ces patients ont été suivis sans qu’il soit noté de récidive. Il n’y a pas de descellement, ni de luxation de la prothèse. Un score fonctionnel évalué selon les critères de l’ISOLS, montre une conservation de 60% et 63% de la fonction du membre inférieur.

---

---

Accepted: 17 March 2000     

Facilitation of ipsilateral motor pathways during recovery from hemiplegia in two adolescent patients.

In two hemiplegic patients with acquired cerebral lesions, transcranial magnetic stimulation (TMS) was carried out to examine the contribution of the ipsilateral motor pathways to recovery from hemiplegia. A 13-year-old girl (patient 1) had acute hemiplegia due to a rupture of an arteriovenous malformation, and a 13-year-old boy (patient 2) had subacute hemiplegia due to a brain tumour. They showed complete upper limb palsy but recovered after therapy; patient 1 had slightly disabled motor function of the arm, and patient 2 recovered completely. Motor evoked potentials (MEPs) were recorded from the biceps brachii muscles on both sides. The MEPs of the paretic biceps were only elicited by TMS of the intact hemisphere at the beginning of recovery from hemiplegia, but not by TMS of the affected hemisphere. The MEP amplitudes increased and cortical representation areas for the paretic biceps by TMS were enlarged temporarily during recovery. They regressed in patient 1 and MEPs were not evoked at all in patient 2 after recovery. Conversely, MEPs were obtained by TMS of the affected hemisphere after recovery in both patients. These data indicate that ipsilateral motor pathways play a role in recovery from hemiplegia, especially at the beginning, and become inactivated when the contralateral motor pathways recover.