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.     

Histological changes in the midbrain around the aqueduct in congenital hydrocephalic rat LEW/Jms

Primary aqueductal stenosis is one of the main causes of congenital hydrocephalus in humans and experimental models. The congenitally hydrocephalic rat strain LEW/Jms is one such model. In this report, we describe further detailed histological features of periaqueductal structure, including the posterior commissure, subcommissural organ (SCO), and ependyma, and discuss the changes in these structures in relation to the cause of hydrocephalus. Coronal sections of the aqueduct in normal rats showed that the usual ependyma was absent in the center of the base facing the dorsal side, which was replaced by tall columnar cells. On the other hand, in hydrocephalic rats the ependyma encircled the aqueductal cavity. In midline sagittal sections, normal and hydrocephalic rats showed the SCO, although the SCO in hydrocephalic rats was shorter than in normal rats. There was also a marked difference between normal and hydrocephalic rats in the dorsoventral dimension of the rostral midbrain. In hydrocephalus, this dimension was large in comparison with normal rats. The superior collicular commissure located caudal to the posterior commissure ran along the ventral side of the midbrain in rats with hydrocephalus, and there was a cell-depleted area just dorsal to the superior collicular commissure. The same findings were observed from the 17th day of gestation until the postnatal period. Although the role of the SCO has been widely discussed from the viewpoint of secretory function, the present study indicated that this organ might be involved in the formation of the shape of the aqueduct.     

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.     

Diagnostic imaging of spinal cord lesions

Magnetic resonance imaging (MRI) has greatly facilitated morphologic evaluation of spinal cord lesions. Eleven cases representative of inflammatory, demyelinating, neoplastic and vascular diseases, are presented which illustrate and summarize important abnormal features in spinal cord imaging, particularly MR findings. Recently, specialised techniques such as MR angiography, fat-inhibiting methods, dynamic MRI and functional imaging have been developed. These methods have facilitated not only lesion diagnosis but also qualitative assessment, and are being used to analyze pathophysiology. Comprehensive diagnoses based on such modalities may be important in determining indications for surgery or defining the extent of surgery or the intensity of other treatments.     

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%.