Augmented production of granulocyte-macrophage colony-stimulating factor and alpha/beta interferon in mice inoculated with heat-killed Corynebacterium liquefaciens.

We demonstrated that heat-killed Corynebacterium liquefaciens bacteria, as a known potent host immune activity modulator, stimulate spleen cells to produce granulocyte-macrophage (GM) colony-stimulating factor (CSF) and another CSF with similar activity, as well as alpha/beta interferon, when injected intravenously into mice. Alpha/beta interferon was shown to be produced by C. liquefaciens-activated plastic-G-10 column-adherent cells (A cells) in a thymus-independent manner. In contrast, augmented production of GM-CSF required the action of C. liquefaciens-activated T lymphocytes that collaborated with normal A cells. Non-T spleen cells from C. liquefaciens-stimulated athymic mice, however, produced an alternative CSF that partially replaced GM-CSF. Correspondingly, the numbers of GM-producing CFU developing in cultures of spleen cells from C. liquefaciens-treated euthymic or athymic mice were 10 to 30 times higher than those in cultures of spleen cells from untreated mice. These results suggest that gram-positive rods such as C. liquefaciens activate T and A cells for production of multiple cytokines and that potential cooperative actions of these cytokines underlie the known immunomodulatory action of coryneforms.     

Intrathecal administration of N-methyl-D-aspartate receptor antagonist reduces the minimum alveolar anaesthetic concentration of isoflurane in rats

We have studied the effect of intrathecal administration of N-methyl-D- aspartate (NMDA) receptor antagonists on the minimum alveolar anaesthetic concentration (MAC) of isoflurane in rats. In Wistar rats fitted with indwelling intrathecal catheters, we determined the MAC of isoflurane after administration of a competitive NMDA receptor antagonist, APV (0.01, 0.1, 1.0, 10, 30 micrograms), a non-competitive NMDA receptor antagonist, MK801 (0.1, 1.0, 10, 30 micrograms). NMDA (0.01, 0.1, 1.0, 10, 30 micrograms) and saline. APV at all doses except 0.01 micrograms decreased MAC by 17.1-32% (P < 0.001 and P < 0.0001). Although MK801 at 10 and 30 micrograms reduced MAC by 24.3-31.7% (P < 0.001 and P < 0.0001), lower doses did not affect MAC. Intrathecal administration of NMDA reversed these decreases in MAC, but not to control values with APV 10 and 30 micrograms and MK801 30 micrograms. We suspect that NMDA and NMDA receptor antagonists play important roles in the spinal cord in determining the MAC of isoflurane.      

Long-term follow-up results of 175 patients with malignant glioma: Importance of radical tumour resection and postoperative adjuvant therapy with interferon,ACNU and radiation

Summary We analysed long-term follow-up results of 175 patients with malignant glioma (110 glioblastoma and 65 anaplastic astrocytoma) treated under five different regimes during the past two decades. The factors of age (less than 40), histology (anaplastic astrocytoma) and type of adjuvant therapy (radiation and chemotherapy) contributed to long survival. The other important factor was the response to adjuvant therapy.Cases of gross total removal or complete response (CR) of a residual tumour to an adjuvant therapy showed a better prognosis. The three and five year survival rate was 42% and 24%, respectively. The highest CR ratio (23%) was seen in patients treated by intravenous injection of interferon and ACNU in addition to radiotherapy (IAR therapy).     

Surgical treatment of myasthenia gravis associated with Graves's disease]

During past 30 years, we experienced 253 patients who underwent surgery for myasthenia gravis. Among these patients, 9 were associated with Graves' disease. No patients had thymoma. Five patients underwent thymectomy after they had become euthyroid by medical treatment, though four patients required subtotal thyroidectomy before thymectomy. One patient developed myasthenic crisis following thyroidectomy and was treated with respirator for 5 days. But thymectomy was performed without myasthenic crisis in these four patients between 25 days and 60 days after thyroidectomy. They have been doing well and no see-saw phenomenon was presented. Thymectomy is safe and effective even in the patients with Graves's disease, and we recommend to perform it after they become euthyroid by medical or surgical treatment.     

Histologic typing of non-Hodgkin's lymphomas by in situ hybridization with DNA probes of oncogenes

Expression of six proto-oncogenes (fos, myc, myb, Ki-ras, Ha-ras, and N- ras) in 43 cases of non-Hodgkin's lymphoma was analyzed by means of in situ hybridization. Biotinylated DNA probes of the six oncogenes and those of immunoglobulin H (IgH) gene and T-cell receptor beta (TCR beta) chain gene were used. The results of in situ hybridization performed under blind conditions by IgH gene and TCR beta chain gene probes were compatible with those of typing by cell surface markers. The nuclear protein-related proto-oncogenes, fos, myc, and myb, were expressed in about 70% to 80% of all cases regardless of phenotype, histology, or histologic grade. On the contrary, genes of ras family were expressed in more limited numbers of cases except for the Ki-ras gene, which was more frequently expressed by cases of the T-cell immunophenotype with a high malignancy grade. The results of dot hybridization with RNA extracted from some cases were compatible with those of in situ hybridization, further demonstrating the specificity of in situ hybridization.     

Use of antisera in the isolation of human specific conjugates of haloperidol

1. Three conjugated metabolites of haloperidol were isolated from urine of patients on haloperidol and purified by h.p.l.c. with immunological detection, using three types of anti-haloperidol antisera. 2. Structures of the metabolites were: a sulphate conjugate of the 2-hydroxylated 4-fluorophenyl ring of reduced haloperidol (MH-1), a glucuronide conjugate at the same position as MH-1 (MH-2), and a glucuronide conjugate of the hydroxy group of haloperidol (MH-3). 3. MH-3 was the main urinary metabolite in volunteers receiving haloperidol, who excreted 18% of the dose in the 24 h urine as MH-3, while other conjugates were less than 1%. MH-3 could not be hydrolysed with beta-glucuronidase, due to steric hindrance. 4. Immunological detection of conjugated metabolites is very useful in metabolic studies in humans because of its sensitivity and specificity.     

Pyloroplasty divides vagus nerve fibers to the greater curvature of the stomach. An axonal tracing study.

Recent studies have demonstrated the location in the dorsal motor nucleus of the vagus nerve (dmnX) of nerve cells that project preganglionic efferent vagus nerve fibers to the greater curvature of the stomach. Although it is clear that these fibers are contained within the vagus nerve trunks, the intra-abdominal pathways of these fibers are unknown. When a neurotracer was applied to the right gastroepiploic pedicle, nerve cells in the bilateral dmnX were labeled. If a preliminary anterior or posterior pyloroplasty was performed before the application of the neurotracer, cellular labeling was seen on the right or left side of the dmnX, respectively. Furthermore, division of the anterior Latarjet nerve eliminated labeling in cells of the left dmnX. This study demonstrates that the preganglionic vagus nerve fibers within the right gastroepiploic pedicle traverse an intramural course across the pylorus and are contained in the Latarjet nerve.     

Active oxygen species generated by monocytes and polymorphonuclear cells in Crohn's disease

Chemiluminescence (CL) analysis of monocytes and polymorphonuclear cells (PMNs) was performed on 13 patients with Crohn's disease (CD) and 10 healthy volunteers. The percentages of monocyte populations in mononuclear cells obtained from the patients with CD were greater than those from the healthy volunteers, but the numbers of PMNs were not different between the two groups. The peak level of phorbol myristate acetate (PMA)-induced CL activity generated by diluted whole blood from the patients with CD was more significantly elevated than that from the healthy volunteers, whereas the peak levels of opsonized zymosan-induced CL activity did not differ between the two groups. In monocytes, the peak levels of both PMA- and opsonized zymosan-induced CL activity were significantly higher in the patients with CD than in the healthy volunteers. CL in PMNs, however, showed no significant difference between CD and controls. It is suggested that monocytes of CD have a large capacity to generate active oxygen species. The present study suggests that excessive active oxygen species released by monocytes and perhaps macrophages may play an important role in formation of the intestinal lesions in CD.This work was supported by the Grant of Tokuteishitsukan from the Japanese Ministry of Welfare and Health.