Gene organization of HLA and its association with ocular disease]

It is now evident that the human major histocompatibility complex (MHC), human leucocyte-associated antigen (HLA), regulates the immune response through discrimination between autologous and non autologous substances thereby displaying a high degree of genetic polymorphism. In recent years, the three-dimensional structure of HLA has been clarified by crystal analysis and provides the attractive hypothesis, the so-called hotdog model, explaining the interactions of foreign antigens (or autologous antigens), HLA and T cell receptors and has a great impact on various studies on immunogenetic mechanisms underlying the development of many diseases. Thus, several HLA-associated ocular diseases such as Beh?et's disease and Harada's disease have also been analyzed from this point of view by means of recombinant DNA techniques, enabling elucidation of molecular mechanisms of susceptibility to these diseases. This paper describes a general outline of HLA, especially its genetical structure, as well as recent analysis of molecular mechanisms of the predisposition to representative ocular diseases.     

Characterization of inhibition by haloperidol and chlorpromazine of a voltage-activated K+ current in rat phaeochromocytoma cells.

1. Inhibition by haloperidol and chlorpromazine of a voltage-activated K+ current was characterized in rat phaeochromocytoma PC12 cells by use of whole-cell voltage-clamp techniques. 2. Haloperidol or chlorpromazine (1 and 10 microM) inhibited a K+ current activated by a test potential of +20 mV applied from a holding potential of -60 mV. The K+ current inhibition did not exhibit voltage-dependence when test potentials were changed between -10 and +40 mV or when holding potentials were changed between -120 and -60 mV. 3. Effects of compounds that are related to haloperidol and chlorpromazine in their pharmacological actions were examined. Fluspirilene (1 and 10 microM), an antipsychotic drug, inhibited the K+ current, but pimozide (1 and 10 microM), another antipsychotic drug did not significantly inhibit the K+ current. Sulpiride (1 or 10 microM), an antagonist of dopamine D2 receptors, did not affect the K+ current whereas (+)-SCH-23390 (10 microM), an antagonist of dopamine D1 receptors, reduced the K+ current. As for calmodulin antagonists, W-7 (100 microM), but not calmidazolium (1 microM), reduced the K+ current. 4. The inhibition by haloperidol or chlorpromazine of the K+ current was abolished when GTP in intracellular solution was replaced with GDP beta S. Similarly, the inhibition by pimozide, fluspirilene, (+)-SCH-23390 or W-7 was abolished or attenuated in the presence of intracellular GDP beta S. The inhibition by haloperidol or chlorpromazine was not prevented when cells were pretreated with pertussis toxin or when K-252a, an inhibitor of a variety of protein kinases, was included in the intracellular solution. 5. Haloperidol and chlorpromazine reduced a Ba2+ current permeating through Ca2+ channels. Inhibition by haloperidol or chlorpromazine of the Ba2+ current was not affected by GDP beta S included in the intracellular solution. 6. It is concluded that haloperidol and chlorpromazine inhibit voltage-gated K+ channels in PC12 cells by a mechanism involving GTP-binding proteins. The inhibition may not be related to their activity as antagonists of dopamine D2 receptors or calmodulin antagonists.     

Clinical Course and Autopsy Findings of a Patient with Clival Chordoma Who Underwent Multiple Surgeries and Radiation during a 10-Year Period.

The management of clival chordoma remains problematic. We present the case of a 48-year-old woman with clival chordoma who underwent multiple surgeries and radiation therapy, including gamma knife stereotactic radiosurgery (GK-SRS), during a 10-year clinical course. The tumor was initially removed by gross total resection via the trans-sphenoidal approach, followed by external linac radiation therapy. The tumor recurred at the clivus 5 years after the initial operation. After repeated trans-sphenoidal removal of recurrent tumors, she twice underwent GK-SRS for a tumor remnant adjacent to the brainstem. Although this part of the tumor was controlled by GK-SRS, there was further tumor extension toward the sphenoid and maxillary sinuses. Ultimately, lower cranial nerve dysfunction developed due to tumor extension into the lower part of the clivus and the patient died of respiratory failure. Autopsy revealed the tumor to extend from the lower clivus to the bilateral middle fossae. The lower part of the tumor extended to the nasal cavity and to the posterior wall of the pharynx, resulting in compression of the upper pharyngeal region. The tumor around the jugular foramen compressed the lower cranial nerves bilaterally. Tumor cells did not, however, invade the intradural space microscopically. Although chordoma is not biologically malignant, this tumor can show massive extension with destruction of bony structures and extracranial invasion of connective tissues. Therefore, the optimal treatment strategy is to remove the tumor mass as extensively as possible, including normal bony structures and connective tissues surrounding the tumor, using skull base surgical techniques.     

Cavernous angioma with encapsulated intracerebral hematoma: report of two cases

Two cases of a cavernous angioma with an encapsulated intracerebral hematoma are presented. In both instances, computed tomography scan showed a ringlike appearance with a nodular lesion. Cerebral angiograms of the two cases, however, were normal. The preoperative diagnosis for both cases was a brain neoplasm. The diagnostic problems that this type of vascular malformation presents and its role in the development of the encapsulated hematoma are discussed.     

Monocytoid B lymphocytes and epithelioid cell clusters in abscess-forming granulomatous lymphadenitis. With special reference to cat scratch disease.

In order to clarify the appearance of monocytoid B lymphocytes (MBLs) in abscess-forming granulomatous lymphadenitis (AGL) and the relation between AGL and cat-scratch disease (CSD), 48 cases of AGL were studied histologically. MBLs were present in about 50% of AGL cases. Warthin-Starry (WS) silver stain-positive bacteria, which are the causative agent of CSD, were present in 52.4% of AGL cases with MBLs and 59.2% of AGL cases without MBLs. The appearance of MBLs in AGL was not related to various clinical features, including disease interval from initial lymphadenopathy to lymph node biopsy. Histologically, epithelioid cell clusters appeared in about 70% of MBL-positive AGL cases, but were not observed in MBL-negative AGL. Therefore, a close interaction between MBLs and epithelioid cells in AGL is suggested, and we emphasize that the histological features of some AGL cases resemble those of toxoplasmic lymphadenitis.     

11C-glucose metabolism in manic and depressed patients

The authors used positron emission tomography (PET) and 11C-labeled glucose to study 15 unmedicated patients with affective disorders and 7 control subjects. Diagnoses of affective disorders were based on DSM-III criteria, and symptomatology was evaluated by the Hamilton Rating Scale for Depression. Blood counts of 11C in both unipolar and bipolar patients did not differ from those in controls after oral administration of 11C-glucose. By contrast, brain counts of 11C in unipolar depressed patients were significantly lower, whereas those in bipolar manic patients were significantly higher, than in normal controls.     

A case of diphenylhydantoin-induced pneumonitis]

A 60-year-old man had been administered diphenylhydantoin (DPH) for prevention of convulsive seizures following clipping of an aneurysm of the middle cerebral artery. About one month after the commencement of DPH administration, he developed cough and low grade fever. He was treated with various antibiotics, but his condition increasingly worsened. Chest X-ray film revealed bilateral interstitial processes throughout the entire lung fields. Transbronchial lung biopsy was performed and the obtained specimen showed histological findings compatible with drug-induced pneumonitis. Administration of DPH was stopped immediately and 50 mg/day of prednisolone was started. The patient's condition rapidly improved, and the abnormal shadows on chest X-ray film gradually diminished. The lymphocyte stimulation test by DPH was positive with a stimulation index of 282%.     

Preliminary study on the effects of bar placement on the thorax after the nuss procedure for pectus excavatum using bone scintigraphy.

AIM: Bone scintigraphy was performed to elucidate the effects of the Nuss procedure for pectus excavatum on the bony thorax. METHODS: Eight boys and 6 girls (5 - 24 years of age) underwent bone scintigraphy, using (99m)Tc-HMDP. Eleven patients were studied 5 to 21 days after the Nuss procedure; 6 were studied 20 to 24 months after the operation before bar removal. Three of 14 were studied twice after the Nuss procedure and before bar removal. RESULTS: In the early postoperative phase, RI accumulation was found at the sternum and ribs in only 1 of 6 patients under 9 years of age, whereas in all 5 older patients, RI had accumulated at the sternum. Scintigrams before bar removal revealed, regardless of age, hot spots at the lateral ribs in contact with the bar and at the costochondral junctions where the bar passed through the intercostal spaces. Furthermore, chest roentgenograms showed the deformed lateral ribs in contact with the bar. CONCLUSIONS: The Nuss procedure creates minute fractures at the sternum and the ribs, especially in older patients. The bar deforms the ribs and restrains the growth of the thorax. Furthermore, it constantly rubs against the ribs and can therefore cause late complications. Bone scintigraphy may determine the appropriate timing for bar removal.