Protein kinase C subspecies in hippocampus and striatum of reserpinized rat brain.

Protein kinase C (PKC) (alpha) and (beta) immunoreactivities were determined in the cytosolic and particulate fractions of the hippocampus and striatum after single and repetitive, intraperitoneal administration of reserpine. Significant decrease of PKC(alpha) immunoreactivities was observed in the particulate fractions of both striatum and hippocampus. Compared with the alteration of PKC(alpha), the decreased immunoreactivity of PKC(beta) was only observed in the particulate fraction of the hippocampus, associated with the increase in the cytosolic fraction. These findings suggest a novel mechanism regulating the distribution of PKC. The topographical selectivity in the present study may indicate the importance of the alteration of PKC(beta) in the pathophysiological mechanism in Alzheimer's disease.

Motor neuron disease with dementia and ophthalmoplegia. A clinical and pathological study.

Ophthalmoplegia and dementia are not usually observed in patients with amyotrophic lateral sclerosis. We report the case of a 60-year-old female with ophthalmoplegia and frontal-type dementia which appeared at an early stage of her illness that presented with dysarthria and weakness in the upper extremities. Notable autopsy findings in the central nervous system were, in addition to the degeneration of upper and lower motor neurons, moderate neuronal loss and spongy degeneration in layer II of the frontal cortex with prominent astrocytosis, and moderate neuronal loss with astrocytosis in both the substantia nigra and the red nucleus. Central chromatolysis of a few neurons in the oculomotor nucleus was seen. This case is considered to be a new subtype of motor neuron disease.

Reduced membrane-associated protein kinase C(beta) immunoreactivity in the hippocampus of reserpinized rat brain.

Protein kinase C(beta) immunoreactivity was determined in the membrane and cytosol fractions of the hippocampus, frontal cortex and cerebellum after repetitive, intraperitoneal administration of reserpine. A marked decrease in the immunoreactivity was observed in the membrane of the hippocampus, while no significant change was found in any other subfractions of the frontal cortex or cerebellum. These findings suggest a novel mechanism regulating the distribution of protein kinase C. The topographical selectivity in the present study may indicate the importance of the alteration of protein kinase C in the pathophysiological mechanism in Alzheimer's disease.

Radiation myelopathy: a clinicopathological study with special reference to correlation between MRI findings and neuropathology.

We describe magnetic resonance imaging (MRI) and neuropathological findings in a patient with chronic progressive radiation myelopathy (CPRM). An 81-year-old man with esophageal cancer underwent radiotherapy. Four years later he developed a progressive neurological deficit below the irradiated level of the spinal cord. Neurological examination revealed spastic paraplegia. MRI findings showed an area of high signal intensity on T2-weighted images of the thoracic spinal cord. On the basis of clinical and MRI findings, we diagnosed his condition as CPRM. MRI performed thirteen months after onset of neurological signs revealed mild atrophy of the spinal cord detected on T1-weighted images and an area of high signal intensity within the spinal cord detected on T2-weighted images. Neuropathological examination revealed findings consistent with radiation myelopathy. We speculate that the area of high signal intensity within the spinal cord detected on T2-weighted images might be a result of proliferation of small vessels, which was discovered upon autopsy.

Successful treatment of atypical mycobacterial meningitis by fluoroquinolone.

We report a case of restricted meningeal infection by atypical mycobacteria, identified by the polymerase chain reaction, in a non-immunocompromised adult successfully treated by multiple antibiotics including fluoroquinolone. New quinolones should be considered as a therapeutic option for such mycobacterial meningitis.

[A case of syphilitic meningitis presenting the seventh nerve and the eighth nerve palsies].

Here we described a case of syphilitic meningitis presenting the seventh nerve and the eighth nerve palsies. A 56-year-old man was admitted because of left facial palsy and hearing loss of bilateral ears. He had a penile chancre five months before admission. Cerebrospinal fluid examination showed high pressure, pleocytosis predominantly with mononuclear cells and high protein content. STS and TPHA of serum and CSF were positive. High dose penicillin G was effective, and he was discharged with only mild hearing loss in the left. Considering the penetration of penicillin G into the CSF and the minimum fully treponemicidal concentration of penicillin, the administration of large doses of aqueous penicillin G intravenously or intramuscularly was effective in such a case to prevent permanent deafness, though CDC recommends relatively low dose.

Processing of beta/A4 amyloid precursor protein is altered in the hippocampus of reserpinized rat brain.

Immunoreactivities of beta/A4 amyloid precursor protein (APP) and soluble derivative of APP (APPs) were determined in the hippocampus and the striatum of reserpinized rat brains. Significant decrease of APPs immunoreactivity was observed in the cytosolic fraction of hippocampus, but not of striatum, whereas APP immunoreactivity was found to be increased in the membrane fraction of hippocampus. These findings suggest that processing of APP in hippocampus may be regulated through the monoaminergic signal transduction system.

Induction of neuronal nitric oxide synthase by methylmercury in the cerebellum.

A free radical, nitric oxide (NO), besides being a messenger molecule in the brain, becomes a neurotoxin if overproduced. We recently reported that methylmercury (MeHg) induces neuronal NO synthase (nNOS) in Purkinje cells. In the present study, we examined the distribution and the mechanism of nNOS induction by MeHg. Subcutaneous administration of MeHg chloride to mice, 10 mg/kg/day for 9 days, increased calcium-dependent NOS activity to 60% more than the controls only in the cerebellum but not in other brain regions. The Western blots showed a comparable increase in nNOS protein in the cerebellum. A N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, did not block, but rather enhanced, the increase in the nNOS activity. Another NMDA antagonist, 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), did not affect the nNOS activity. The Western blots of protein kinase C (PKC), which is an important cofactor regulating nNOS, did not change after the administration of MeHg. These results show that MeHg induces biologically active nNOS selectively in the cerebellum. The induction is independent of PKC and is not reduced by the blockade of the NMDA receptor.

[Anti-inflammatory actions of proteases, bromelain, trypsin and their mixed preparation (author's transl)].

Anti-inflammatory actions of proteases, bromelain (BR), trypsin (TR) and their mixed preparation (KT) were studied mainly in rabbits using various experimental test methods. Inhibitory action of edema formation induced by carrageenin was observed to be dose dependent with oral administrations of KT. This inhibitory action of KT was more remarkable than actions of BR and TR, suggesting a possible synergism between the latter two. Such action was also observed with non-steroidal anti-rheumatic drugs, phenylbutazone (PB), indomethacin and acetylsalicylic acid. Oral administration of KT exerted definite inhibition or a tendency toward inhibition against paw edema induced by dextran, histamine or egg albumin or skin edema induced by anti-rabbit serum and thermal stimulation. Furthermore, inhibition of vascular permeability increase induced by histamine and bradykinin as well as a tendency toward inhibition against protein exudation in CMC-pouch method were observed. On the other hand, contrary to PB, potent inhibitory action was not manifested in the persistent proliferative inflammation models, the granuloma formation induced formalin soaked filter paper and cotton pellet and the mustard edema. Therefore, it can be deduced that the inhibitory action of KT against edema formation may be dependent mainly on the inhibitory action of vascular permeability increase and the anti-inflammatory action may be specific for acute exudative inflammation.