Resistance to highly virulent mouse hepatitis virus acquired by mice after low-virulence infection: enhanced antiviral activity of macrophages.

As early as 1 to 2 days after intranasal inoculation with a mouse hepatitis virus of low virulence, MHV-S, susceptible DDD mice became fully resistant to a normally lethal challenge with a highly virulent MHV-2. The resistance of MHV-S-pretreated mice was correlated with significantly decreased MHV-2 multiplication in the liver, spleen, and brain. Infection with MHV-S did not induce a high level of interferon in DDD mice, and no neutralizing antibody against MHV-2 was detected in the sera of mice until day 6 of MHV-S infection. The multiplication of MHV-2 was suppressed in peritoneal cells (PC) in vivo and peritoneal adherent cells (PAC) in vitro of MHV-S-pretreated mice was compared with those of normal mice. This suppression of virus multiplication was demonstrated in PAC collected during days 1 to 3 of infection but not in PAC collected from day 5 on. PC from MHV-S-pretreated mice were also suppressive to MHV-2 growth in DK cells as compared with PC from normal mice. By treatment of MHV-S-pretreated mice with silica, suppression of virus growth in the liver was partially diminished. These findings suggest that increased suppression of MHV-2 growth in PAC (mostly macrophages) of MHV-S-pretreated mice is responsible for resistance.     

Single administration of 1-benzyl-1,2,3,4-tetrahydroisoquinoline increases the extracellular concentration of dopamine in rat striatum

We performed a combined neurochemical and behavioral study to determine the effects of 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1-BnTIQ) on the extracellular dopamine concentrations in the striatum. Single dose administration of 1-BnTIQ (20, 40, and 80 mg/kg i.p.) increased striatal dopamine extracellular levels in a dose-dependent manner when an in vivo microdialysis technique was used to assess dopamine levels in the striatum of rats. Enhancement of striatal dopamine levels by systemic administration of a single dose of 1-BnTIQ was suppressed by perfusion of tetrodotoxin and a calcium ion-free solution into the striatum. This 1-BnTIQ-induced increase in extracellular dopamine concentration was also inhibited by pre-treatment with a dopamine uptake inhibitor, GBR12909 (1-(2-[bis(4-Fluorophenyl)-4-(3-phenylpropyl)piperazine dihydrochloride). Local application of 1-BnTIQ into the striatum via a dialysis probe failed to enhance the extracellular concentration of dopamine. However, microinjection of 1-BnTIQ into the substantia nigra pars compacta increased the extracellular dopamine levels in the striatum. Locomotor activity was increased by systemic administration of a single dose of 1-BnTIQ in a dose-dependent manner. This 1-BnTIQ-induced locomotor activity was attenuated by pre-treatment with SCH23390 (R(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochlodride) and raclopride, D₁ and D₂ dopaminergic receptor antagonists, respectively. Moreover, 1-BnTIQ induced ipsilateral rotational behavior in 6-hydroxydopamine–lesioned rats. These results suggest that systemic administration of a single dose of 1-BnTIQ increases striatal extracellular dopamine concentration through activation of dopaminergic nigra striatal neurons via the dopamine transporter.     

A case of ossified yellow ligaments (ossified ligamenta flava) of the thoraco-lumbar region and magnetic resonance imaging

A Case of ossified yellow ligaments in thoraco-lumbar region is reported. A 47-year-old-male complained low back pain with suddenness in August, 1984. One month later, he noticed dyesthesia on his right lower extremity and gait disturbance. These symptoms progressed slowly. In June, 1985, he admitted to The Jikei University Hospital. On neurological examinations, he was noticed an intermittent claudication, spastic paraparesis and stocking type sensory loss in his lower extremities. Plain lumbar X-ray films showed ossified yellow ligaments (OYL) in the posterior half of the spinal canal from the level of 10th thoracic to second lumbar vertebrae. Magnetic resonance imaging disclosed marked indentations of the spinal cord at the same level. The wide laminectomy was carried out and OYL were removed totally in gentle manner. Postoperative course was uneventful. His sensory disorders improved remarkably and he gained good muscle strength in his lower extremities, but a considerable spasticity remained still. OYL is closely related to the developmental canal stenosis, the spondylosis and the other degenerative disorders such as ossification of posterior longitudinal ligaments. This allows more complicated neurological signs and symptoms in the case of OYL. When OYL is suggested, it is recommended to performed whole spinal radiological survey. The surgical consideration should be done. From this point of view, MRI would be a most useful weapon.     

Evaluation of cardiotoxicity in new anthracycline analog ME 2303. ME 2303 Study Group

ME 2303 is a new anthracycline analog which differs from adriamycin in the sugar moiety. ME 2303 displays a higher antitumor activity against L 1210 and P 388 Leukemia than adriamycin. To evaluate the cardiotoxicity of ME 2303, ECG tracings (21 patients) and Holter ECGs (9 patients) were recorded before and after the administration of ME 2303 for various malignancies (mean dose 123.8 mg/m2), and some of the electrocardiographic parameters were analyzed. Control ECGs were normal in 17 patients, in 4 patients minor ECG findings like sinus tachycardia (2 patients), low voltage (1 patient) and flattening of the T wave (1 patient) were observed. After treatment, no relevant ECG changes were observed except one case who showed a flat T in pretreatment ECG. In this patient developed ST-T changes were seen after treatment. The basic rhythm was sinus rhythm in all of the cases, and the heart rate showed no significant changes. ME 2303 had no effects on the specialized conduction system. With regard to arrhythmia, no increase in number and severity was observed. In Holter ECG no development of ST-T changes was seen after treatment.     

Clinical Study of Renal Cell Carcinoma with Brain Metastasis

Background:
The clinical outcome of patients with renal cell carcinoma with brain metastasis was analyzed.
Methods:
Nine patients (median age, 60 years) with primary renal cell carcinoma and distant metastasis, including brain metastasis, were treated. The median time to the development of brain metastasis was 15 months after the initial visit. Patients with poor performance status or progressive disease were treated with interferon or conservative therapy alone. Patients with good performance status and other well-controlled metastatic foci were treated either with radiotherapy, or by tumorectomy of brain metastasis, or both. The median follow-up was 26 months after the initial visit.
Results: The 1-year, cause-specific survival rate was 17%. Of the 5 patients treated with α-interferon alone, all died of disease after the treatments, without improvement of performance status, 1 to 4 months after the diagnosis of brain metastasis. Two of 4 patients who underwent radiotherapy were treated with a combination of γ-knife and tumorectomy of brain metastasis. They remained alive 10 and 22 months after diagnosis of brain metastasis. The 2 patients who underwent the combination treatment of γ-knife and tumorectomy showed improvement of their performance status after these treatments for brain metastasis.
Conclusion:
Brain metastasis is an unfavorable prognostic factor in renal cell carcinoma. Although a larger number of patients would be necessary to demonstrate the definitive effects of γ-knife treatment, our results suggest that the combination of γ-knife and tumorectomy of brain metastases may be recommended for selected patients with good performance status and other well-controlled metastatic foci.     

Subrenal capsule assay as a chemosensitivity test (V)--Experimental chemotherapy of cyclosporin A-treated mice and nude mice

We studied fundamentally subrenal capsule assay, using human tumor specimens (breast, gastric and colon cancers) serially transplanted in nude mice. Mitomycin C, 5-fluorouracil, adriamycin, cisplatinum or cyclophosphamide was injected into immunocompetent CDF1 mice treated with cyclosporin A (CsA) after tumor implantation. On day 6 and day 9 after inoculation, the chemosensitivity profiles of tumor xenografts were similar in CsA-treated mice and nude mice, macroscopically and microscopically. It is suggested that CsA-treated mice were an appropriate model as hosts for chemosensitivity testing. When we examine chemosensitivity effect macroscopically, a method of comparing chemotherapy groups with control groups; i.e. inhibition rate by measurement of tumor volume, was induced, in addition to the tumor size measurement. High toxicity due to cancer chemotherapeutic agents was found in CsA-treated mice, so that careful examination on treatment schedules with CsA and chemotherapeutic agents will be required.     

Malfunction of gene expression as a possible cause of delayed neuronal death

To clarify a possible cause of delayed neuronal death, synthesis of protein and ribonucleic acid (RNA) following transient forebrain ischemia was evaluated autoradiographically. Mongolian gerbils were subjected to transient forebrain ischemia for 5 minutes by occluding bilateral common carotid arteries. They were used for autoradiographic study at 1, 2, and 5 days after ischemia. Tracer dose of 14C-valine or 14C-uridine was injected intravenously, and animals were sacrificed 45 minutes thereafter. Brains were frozen and thin sliced for macroautoradiography. After the first autoradiogram was obtained, tissue sections were incubated in cold 5% trichloroacetic acid for 1 hour, dried and again used for autoradiogram. With this preparation we could differentiate the tracer incorporated into protein or RNA fraction from the total tissue radioactivity. In the different set of animals, microautoradiograms of 3H-valine and 3H-uridine was obtained to detect subcellular distribution of synthesized protein or RNA. At 1 day after ischemia, protein synthesis in the CA 1 region of the hippocampus was reduced by 57% of the sham control, but RNA synthesis was not reduced quantitatively. Microautoradiogram of 3H-uridine however, indicated that silver grains in the cytoplasms of the CA 1 pyramidal cells were much reduced as compared to sham controls, though the amount of silver grains in the nucleus was the same as sham controls. Therefore, synthesized RNA in the nucleus was not transported to the cytoplasm. At 2 days after ischemia, protein and RNA synthesis was preserved to the same level as sham controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mass screening for uterine cancer during the last 10 years--its present situation and problems

In Omagari city and five towns, 37,793 women were subjected to mass screening of uterine carcinoma from 1979 to 1988. The detection rate of uterine carcinoma was 0.058%. Initial screening rate was 41% 10 years ago, but in 1988, it was decreased to 18%. The peak age of the mass screening was 50-54 years old, but the carcinoma and dysplasia high degree were detected mostly in patients aged 60 years old or more. And the constitution of the age of mass screening in this study was inadequate for the screening of endometrial carcinoma. It is important to emphasize that older women (aged 60 or above) and nullipara should be encouraged to actively participate in the screening of cervical and endometrial carcinoma.