Chihiro Koga

Corticotropin-releasing factor activates the noradrenergic neuron system in the rat brain

The effect of corticotropin-releasing factor (CRF) on central noradrenaline (NA) metabolism was examined by measuring levels of the major metabolite of NA, 3-methoxy-4-hydroxy-phenylethyleneglycol sulfate (MHPG-SO4) in several rat brain regions. Various doses of CRF ranging from 0.5-10 micrograms injected ICV significantly increased MHPG-SO4 levels in several brain regions including the hypothalamus, amygdala, midbrain, locus coeruleus (LC) region, and pons + medulla oblongata excluding the LC region. Plasma corticosterone levels were also significantly increased after ICV CRF administration up to 0.5 micrograms. The present results that CRF not only elevates plasma corticosterone levels but also increases NA metabolism in many brain regions suggest its neurotransmitter and/or neuromodulator role exerting the excitatory action on central NA neurons.

A CRF antagonist attenuates stress-induced increases in NA turnover in extended brain regions in rats

We investigated the effects of intracerebroventricular (i.c.v.) administration of corticotropin-releasing factor (CRF) antagonist, alpha-helical CRF9-41 (ahCRF), on increases in noradrenaline (NA) turnover caused by immobilization stress in rat brain regions. Pretreatment with ahCRF (50 or 100 micrograms) significantly attenuated increases in levels of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), the major metabolite of NA in rat brain, in the locus coeruleus (LC) region, and attenuated the MHPG-SO4/NA ratio after immobilization stress for 50 min in the cerebral cortex, hippocampus, amygdala, midbrain and hypothalamus. However, stress-induced increases in plasma corticosterone levels were not decreased significantly by pretreatment with ahCRF. These results suggest that CRF, released during stress, causes increases in NA release in extended brain regions of stressed rats.

Effect of opioid peptides on dopamine release from nucleus accumbens after repeated treatment with methamphetamine

The effect of opioid peptides on extracellular dopamine levels in the nucleus accumbens was compared between rats treated with methamphetamine and saline repeatedly (for 9 days) by using microdialysis. After the period of repeated treatment, the rats in both groups were kept for an additional 9 days without further treatment. Repeated administration of methamphetamine reduced the decreasing effect of dynorphin (10 microM), applied locally in the perfusate, and enhanced the increasing effect of [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO, 10 microM) on the extracellular dopamine levels in the nucleus accumbens. It is possible that repeated treatment with methamphetamine leads to attenuation of the inhibition and enhancement of the stimulation of dopamine release from the nucleus accumbens via presynaptic dynorphin- and enkephalin-sensitive receptors, respectively.

Muscimol-induced increase in dopamine release and metabolism is not observed in kainic acid-lesioned striatum of conscious rats: An in vivo microdialysis study

Local application of muscimol through the striatal dialysis membrane caused a significant increase in both dopamine release and dopamine metabolism in the striatum of conscious rats, however, both elevations induced by muscimol were significantly lower in the kainic acid-lesioned striatum when assessed with in vivo brain microdialysis. These findings show that intra-striatal muscimol indirectly stimulates nigrostriatal dopaminergic function by possibly causing an inhibition of striatal gamma-aminobutyric acid neurons.

Clinical relevance of thymidylate synthase (TS) activity for S-1-based chemotherapy in squamous cell carcinoma of the oral cavity

S-1 is a newly developed oral fluoropyrimidine derivative that is now widely used as a chemotherapeutic agent in the treatment of oral squamous cell carcinoma (SCC). Thymidylate synthase (TS) is the rate-limiting enzyme in the de novo DNA biosynthetic pathway, and improves clinical response to chemotherapy with fluoropyrimidines. We have retrospectively evaluated the predictive value of thymidylate synthase activity in 75 patients with oral SCC with an enzyme-linked immunosorbent assay (ELISA). Mean (SD) activity (pmol/mg) in the specimens was 0.078 (0.080) (median 0.059). The median value was taken as the cut-off value based on which the patients were divided into high and low activity groups. Both the clinical and histopathological responses to chemotherapy and radiochemotherapy were higher in the group with low TS activity. The group with low TS activity also differed significantly in their clinical response to S-1-based chemotherapy (p<0.05). However, there was no significant difference in cause-specific survival. Measurement of TS activity may aid in predicting the clinical response to chemotherapy including S-1 for oral SCC.

Coffin-Siris Syndrome

Abstract A 9-month-old boy with Coffin Siris syndrome is described. Characteristic features include eyebrow hypertrichosis, long eyelashes, flat nasal bridge, prominent philtrum, hypoplasia or absence of the distal phalanges, high palate, and enlarged gingiva. The childs condition worsened and he ultimately died of multiple organ failure at the age of 5 years and 3 months.

Aberrant Expression of p56lck in Primary Oral Cancer

Objective: To examine whether p56lck is expressed in primary oral cancer and whether cytotoxic T-lymphocyte precursors reactive to p56lck peptides are present in the peripheral blood mononuclear cells of these patients. Materials and Methods: Oral tissue specimens were surgically obtained from 54 patients with oral squamous cell carcinoma and 20 patients with benign oral tumours. Six oral squamous cell carcinoma cell lines were used (HSC-2, HSC-3, HSC-4, OSC-20, Ca9-22, and SAS). The expression of p56lck was investigated by reverse transcriptase-polymerase chain reaction and immunohistochemical staining, and the level of interferon-gamma in the peripheral blood mononuclear cells of 10 patients with oral squamous cell carcinoma evaluated by enzyme-linked immunosorbent assay to ascertain the presence of cytotoxic T-lymphocyte precursors reactive to p56lck peptides. Results: p56lck was expressed in 38.9% (21/54) of the 54 primary oral cancer specimens obtained, but not in the benign oral tumour cells adjacent to the surrounding T cells. Only type II transcripts were expressed in the peripheral blood mononuclear cells, whereas only type I transcripts were expressed in all oral squamous cell carcinoma tissues and cell lines. Peripheral blood mononuclear cells from 7 (70%) out of 10 patients with oral cancer produced interferon-gamma in response to p56lck-derived peptides in vitro, suggesting an immune response to aberrantly expressed p56lck in these patients. Conclusion: These results may provide insight into the immunopathology of oral cancer. Further studies that demonstrate the activity of p56lck peptide-specific cytotoxic T lymphocytes may lead to the development of vaccines specific to individual oral cancer patients.

Argon Plasma Coagulation Therapy for Oral Leukoplakia

Abstract Objective: To evaluate the clinical applicability of argon plasma coagulation therapy for oral leukoplakia. Patients and Methods: Twelve patients with oral leukoplakia were treated by argon plasma coagulation and examined clinicopathologically. Argon plasma coagulation was performed more than once inpatients with multiple or extensive lesions. Results: After argon plasma coagulation, the lesions completely disappeared. Postoperative scar formation was not observed. However, slight retraction of the attached gingiva occurred 4 weeks after argon plasma coagulation for gingival leukoplakia. Patients were followed-up for a mean of 47 months after operation. The postoperative course was uneventful, with no recurrence or malignant transformation. Conclusion: Argon plasma coagulation appears to be an effective treatment for oral leukoplakia. Key words: Electrocoagulation, Laser, Leukoplakia