Katsuhiko Hamaguchi

Cause of death among patients with Parkinson's disease: a rare mortality due to cerebral haemorrhage

SummaryCauses of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinsons disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinsons disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.

Aging and superoxide dismutase activity in cerebrospinal fluid

We investigated superoxide dismutase (SOD) activity in human cerebrospinal fluid (CSF) as an index of the aging process in the central nervous system (CNS). The subjects were 61 individuals aged 21-77 years, comprising 24 men and 37 women without organic disorders of the nervous system. SOD activity in CSF was measured by the nitrite method modified by Oyanagui. The results showed that SOD activity in CSF gradually increased with age and that the values of SOD activity after the fifth decade were significantly higher than those in the third and fourth decades. It might suggest that the productivity of SOD in the CNS gradually increased with age due to stimulation of various types of oxidative stress which accumulated in vivo especially after the fifth decade.

Monoclonal antibodies specific to the integral membrane protein P0 of bovine peripheral nerve myelin

Two monoclonal antibodies (mAbs), 58A and 46E, were generated against the major protein P0 of bovine peripheral nervous system myelin (PNSM). The reactivities of the mAbs were assessed by enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemistry. Both mAbs, 58A and 46E, reacted to PNSM of bovine, human, rat and rabbit, but not to chicken PNSM or the brains of rat and rabbit. In the Western blot, these mAbs showed specific binding to bovine P0 as well as deglycosylated P0, but not to myelin-associated glycoprotein (MAG) of bovine spinal cord. The analyses of the lysylendopeptidase-digested peptides of bovine P0 revealed that the epitopes for the mAbs 58A and 46E were located on the amino acid residues 68-79 and 210-216, respectively. Since the mAbs 58A and 46E recognize the extracellular domain and the cytoplasmic domain of P0, respectively, they could be useful for studies on P0s role in myelin formation, its adhesive properties, and functions of the N-terminal extracellular and C-terminal cytoplasmic domains of the protein.

Hypotensive effect of long-term levodopa in patients with Parkinson's disease.

To study the hypotensive effect of L-dopa in patients with Parkinsons disease on long-term L-dopa, the blood pressure (BP) was measured in 14 patients and 6 controls before 100 mg L-dopa plus decarboxylase inhibitor and for up to 180 min after dosing. Plasma monoamines and motor functions were assessed. The mean BP was reduced between 60 and 180 min after dosing in the patients, whereas such a reduction was not observed in 5 patients from whom L-dopa was withheld and in controls who showed a high ratio of plasma dopamine compared to plasma L-dopa after dosing. The L-dopa-induced reduction in BP was thought to be due to a central nervous mechanism.

Cell-mediated immunity to bovine P2 protein and neuritogenic synthetic peptide in experimental allergic neuritis

Cellular reactivity to bovine P2 protein (P2) and its two synthetic peptides, SP66-78 and SP70-78, was serially examined by the lymphocyte proliferation test in animals with experimental allergic neuritis (EAN). SP66-78 and SP70-78 correspond to residues 66-78 and 70-78 of bovine P2. Proliferative response to SP66-78 as well as P2 appeared at day 7 before the onset of EAN and was clearly manifested at day 14 in the active stage, thereafter disappearing in the stable stage, whereas no response to SP70-78 was detected during the course of the disease. These results suggest that cell-mediated immune response to P2 and the specific part residues 66-78 of P2 play an important role in the pathogenesis of EAN.

Activated T lymphocyte subsets in experimental allergic neuritis

Changes in activated T cell subsets in peripheral blood were examined during the course of experimental allergic neuritis (EAN), using two-color immunofluorescence flow cytometry. Both CD4+ and CD8+ activated T cells decreased transiently before the onset of clinical signs, and increased just around the time of onset of the disease. In contrast, during the recovery phase, the numbers of CD4+ activated T cells returned to the normal range, whereas CD8+ activated T cells continued to increase. These findings imply that activation of CD4+ helper/inducer cells contributes mainly to the evolution of EAN, and that of CD8+ suppressor cells are necessary for recovery.

Cellular hypersensitivity to nervous antigens in Guillain-Barré syndrome.

Cell-mediated immune responses to various nervous antigens were examined in 12 cases of Guillain-Barré syndrome (GBS), 24 cases of noninflammatory peripheral neuropathy (NIPN), and 18 cases of degenerative disorders of central nervous system (CNSDD), using the lymphocyte-transformation technique. Cellular hypersensitivity to bovine P2 protein (P2) and a synthetic peptide, SP66-78, corresponding to the residues 66-78 of P2, was detected in about two-thirds of GBS cases, especially in the active or improving stages, but not in NIPN and CNSDD. The lymphocytes sensitized to these nervous antigens might play an important role in the pathogenesis of GBS.

Serum Antibodies to Peripheral Nerve Antigens in Guillain‐Barré Syndrome

We previously reported that cellular hypersensitivity to P2 protein (P2) might play an important role in the evolution of experimental allergic neuritis’ and the GuillainBarri syndrome (GBS).’ In the present study, we examined serum antibodies to three different nervous antigens, P2, a synthetic tridecapeptide (SP66-78) corresponding to residues 66-78 of bovine P2, and galactocerebroside (GC), in GBS and other neurologic diseases. Myelin fraction was prepared from bovine peripheral nerve roots, as previously described,’ and P2 was purified by acid extraction of myelin using the method of Kitamura et aL4 SP66-78 was synthesized in a liquid phase by stepwise elongation according to the method of Suzuki et aL5 Antibody titers were measured by enzyme-linked immunosorbent assay (ELISA) in the sera of 11 patients with GBS,

Changes in T‐Cell Subsets in Experimental Allergic Neuritis

FIGURE 1. Clinical course of experimental allergic neuritis and immune responses to P2 protein. Upper column shows changes in mean values of clinical scores on the scale of Hughes et ~ l . , ~ with slight modification. The mean time of onset was 10.5 days, and the clinical scores rapidly reached their maximum on day 14, continued to be high until day 16, and thereafter gradually declined. Lower column shows the results of the lymphocyte proliferation test and enzyme-linked immunosorbent assay in peripheral blood from another 15 animals sacrificed on days 7, 12, and 21 after immunization. Vertical bars indicate the mean ? 1 standard deviation. CS = clinical score; SI = stimulated index; OD = optical density at 405 nm.

Immune responses in experimental allergic neuritis treated with corticosteroids

ABSTRACT— The preventive and suppressive effects of methylprednisolone (MP) were investigated in 22 rabbits immunized with peripheral nerve myelin. Cellular reactivity to bovine P2 protein (P2) and anti‐P2 antibody were also examined serially in these animals, using the lymphocyte proliferation test or enzyme‐linked immu‐nosorbent assay. Seven animals (preventive group), given 15 mg/day of MP sub‐cutaneously from Days 0–28, showed a significant reduction in maximal severity and a delay in onset in comparison with 8 control animals. The remaining 7 animals (suppressive group), given the same dose of MP from Days 11–28, also showed significantly milder clinical signs than those observed in the controls. However, cellular hypersensitivity to P2 were manifested at Day 14 (just after clinical onset) in the controls, as well as in the preventive or suppressive groups. Furthermore, anti‐P2 antibody was detected in each group after Day 14. These results suggested that the interference of inflammatory processes of immune‐mediated disease might respond to the preventive and suppressive effects of MP.