Sequential changes of [3H]cyclic AMP binding in the gerbil brain following transient cerebral ischaemia

Abstract— Sequential alterations in the binding of [³H]cyclic AMP (cAMP) as an indicator of cAMP-dependent protein kinase (cAMP-DPK) binding activity following transient cerebral ischaemia were studied in the gerbil brain using receptor autoradiography. Transient ischaemia was induced for 10 min. [³H]cAMP binding in the stratum oriens and pyramidale of the hippocampal CA1 sector significantly decreased in the early post-ischaemic stage and showed severe reduction 7 days and 1 month after recirculation. By contrast, [³H]cAMP binding showed no significant alterations in the stratum radiatum of the hippocampal CA1 sector and the stratum pyramidale of the hippocampal CA3 sector up to 48 h after ischaemia. However, the binding in these areas significantly decreased 7 days and 1 month after ischaemia. The stratum lacunosum-moleculare of the hippocampal CA1 sector and dentate gyrus showed no significant changes in [³H]cAMP binding throughout the recirculation period. However, in the dorsolateral part of the striatum, where severe neuronal damage was seen morphologically, [³H]cAMP binding was significantly reduced only one month after ischaemia. These results indicate that marked alteration of intracellular signal transduction precedes neuronal damage in the hippocampal CA1 sector, but not in the striatum. Furthermore, our autoradiographic data suggest that post-ischaemic alteration in [³H]cAMP binding between the hippocampal CA1 sector and striatum may be produced by different mechanisms.     

Treatment of Malignant Tumor in the Head and Neck: --Interdisciplinary Collaboration of Surgery and Radiotherapy--

Although the prime importance in treatment of head and neckcancer is eradication of tumors, due attention should be paidto the conservation of many important structures and functionsin the region. Just to mention a few of these important humanfunctions, there are phonation, digestion and facial expression.Simple surgical procedures specialized by otolaryngologistsare no longer satisfactory. Recently, radiotherapy of head and neck cancer has developedto a superlative degree and chemotherapy to a practical degreealthough much still remains to be satisfied. Our aim was toorganize an interdisciplinary group of specialists in surgery,radiotherapy and regional chemotherapy into a composite attackforce. We aimed at most effective treatment with the least ofside effects. Since 1961, our combined approach to cancer of the head andneck in close collaboration with radiotherapists has yieldedmuch improved results. This has led to an increasing numberof patients with satisfactory rehabilitation.

1. 1. Cancer of the maxilla: Even in the advanced cases combinedsurgery, radiotherapy and regional chemotherapy has led to thepreservation of important structures and functions. Many patientsare now allowed to return to social life and to their previousjobs.
2. 2. Cancer of the nasopharynx: Radiotherapy is the firstchoice.When the effect is less satisfactory, chemotherapy anda window-operationof the palate are performed.
3. 3. Tumorsof the tonsils: The majority of patients suffer fromthe reticulumcell sarcoma. Radiotherapy is the first choice.
4. 4. Cancerof the larynx: A full dose of radiotherapy is thefirst choice.Partial resections are done when indicated.
5. 5. Cancer of thetongue, hypopharynx and esophagus: Radiotherapyis the firstchoice in the majority of cases. Some need plasticsurgery.

     

Role of γδ T lymphocytes in the development of Behçet's disease

Phenotypic and functional properties of γδ T cells, which play an important role in mucocutaneous immunity, were examined to elucidate whether immunological abnormality in Behc¸et's disease may be related to a specific T cell population. We found that CD45RA⁺Vγ9⁺Vδ2⁺γδ T cells, which constitute a minor population of γδ T cells in healthy individuals, were increased in number in Behc¸et's disease irrespective of disease activity. This CD45RA⁺ subset of γδ T cells in the active, but not inactive, phase of this disease expressed IL-2Rβ and HLA-DR, suggesting that they are activated in vivo in active Behc¸et's disease. In addition, the CD45RA⁺γδ T cells produced extreme amounts of tumour necrosis factor and contained perforin granules. These data indicate that a phenotypically distinct subset of γδ T cells, CD45RA⁺CD45RO⁻Vγ9⁺Vδ2⁺, may contribute to immunological abnormalities which may lead to complexity of pathophysiology in Behc¸et's disease.     

Liver cell adenoma: A case report and a review of 30 cases reported in Japan

A 38 year old man with a huge liver cell adenoma extending to the pelvis was treated by left lateral lobectomy. The tumour, which was well-encapsulated by fibrous membrane, was 18 × 19 × 6 cm in size and weighed 1500g. Histopathologically, this tumour was composed of well-differentiated liver cell trabeculae and a small number of pseudobiliary ducts, but no Glisson sheaths. For the past 4 years 8 months he has remained asymptomatic. Thirty cases of liver cell adenoma found in Japanese literature are reviewed here and possible pathogenic implications are discussed.     

Antitumor Effect of 3-[(4-Amino-2-Methyl-5-Pyrimidinyl) Methyl]-1-(2-Chloroethyl)-1-Nitrosourea (ACNU) on Human Colon Carcinomas Transplanted into Nude Mice

Two human colon carcinomas serially transplanted into nude micewere used for experimental chemotherapy by 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea(ACNU). Human colon carcinomas Co-3 (well-differentiated adenocarcinoma)and Co-4 (poorly differentiated adenocarcinoma), were transplantedsubcutaneously into the backs of BALB/c male nude mice. Tumorsize was measured three times a week, and treatment was startedwhen the estimated tumor weight reached 100 to 300 mg. Twentyand 40 mg of ACNU per kg was administered intravenously, once,dissolved in 0.2 ml of normal saline. There were marked tumorregression and histological tumor cell destruction in Co-4,whereas no effect was observed in Co-3. Microangiography revealed a similar vascular network in Co-3and Co-4. Whole-body autoradiography was performed 5, 30, 180and 360 minutes after 20 mg (286 µC₁) of [ethylene-2-¹⁴C]-ACNUper kg was injected. ACNU concentration in the Co-3 tumor reacheda peak 30 minutes after injection and diminished promptly withthe decrease of ACNU in the blood, whereas in Co-4 tumors ACNUwas retained in the tumor until 360 minutes after ad ministration.The effect of ACNU was thought to be correlated with the concentrationof the drug in the tumor. Present address: Department of Surgery, Kitasato InstituteHospital, Tokyo, Japan.     

Post-ischaemic Alteration of Excitatory Amino Acid Transport Sites in the Gerbil Hippocampus

Sodium-dependent [³H]d -aspartate binding as a marker of excitatory amino acid transport sites in the gerbil hippocampus was evaluated by quantitative receptor autoradiography 1 h to 7 days after transient cerebral ischaemia for 10 min. Sodium-dependent [³H]d -aspartate binding in the hippocampal CA1 and CA3 sectors significantly increased in the early post-ischaemic stage. After 7 days, a conspicuous elevation of sodium-dependent [³H]d -aspartate-binding was observed in the hippocampal CA1 sector and dentate gyrus. However, no significant change in the binding was found in the hippocampal CA3 sector. A histological study revealed that transient ischaemia caused severe neuronal damage in the hippocampal CA1 sector and mild damage in the hippocampal CA3 sector. However, no ischaemic neuronal damage was observed in the dentate gyrus. An immunohistochemical study also showed that numerous reactive astrocytes were evident in the hippocampus, particularly in the hippocampal CA1 sector, 7 days after ischaemia. These results demonstrate that transient cerebral ischaemia can cause marked elevation in excitatory amino-acid transport sites in the hippocampus. Furthermore, our results suggest that the post-ischaemic increase in excitatory amino acid transport sites might reflect expression of reactive astrocytes. These findings are of interest in relation to the mechanisms of ischaemic hippocampal damage.