Biomedical subjects
Publications and source records attributed to K Komai.
A toxic substance was purified from larvae of the antilion, Myrmeleon bore, by DEAE Sephacel and Phenyl Superose column chromatography. The substance was a large polypeptide with a molecular weight of about 165-167 kDa. Its paralytic activity measured by injection against German cockroaches was about 130 times higher than that of tetrodotoxin on a molar basis.
Aminergic and cholinergic vasomotor nerves in vessels of the human optic nerve were studied morphologically. Aminergic nerve fibers were observed by the glyoxylic acid method. Cholinergic nerve fibers were observed by light microscopy after acetylcholinesterase staining by the Karnovsky-Roots method and Tago's modified method. In the retrobulbar optic nerve behind the bulbus, aminergic and cholinergic vasomotor nerves were observed to be dense in the central retinal artery and vein and posterior ciliary arteries. A large number of vasomotor nerves were also demonstrated in vessels in the septum of the optic nerve, but they were sparse in pial vessels. Further centrally, a few vasomotor nerves were found in pial vessels of the intracanalicular and intracranial optic nerve, but few were observed in the septum of the optic nerve. At the optic chiasm they were densely distributed in pial vessels.
The possible antigenicity of synaptotagmin, a synaptic vesicle protein acting as a cooperative calcium (Ca2+) receptor in exocytosis, was tested to determine whether it is involved in the induction of Lambert-Eaton myasthenic syndrome in which antibodies against voltage-dependent Ca2+ channels or related molecules play a pathogenic role. Repeated injections to Lewis rats with peptides of synaptotagmin residues 20 through 53 or 1 through 30 that are presumably exposed at the nerve terminal surface during exocytosis induced corresponding antipeptide antibodies; on immunoblots, antibodies recognized synaptotagmin that was expressed in the clonal cells. Electrophysiologically, the peptide (residues 20-53)-immunized rats showed (1) reduced acetylcholine quantal content of end-plate potential, (2) an increase in quantal content at high extracellular Ca2+ concentration, and (3) early facilitation followed by less marked depression of end-plate potential amplitude at a tetanic rate of repetitive nerve stimulation. Findings are similar to those in human Lambert-Eaton myasthenic syndrome and passively transferred Lambert-Eaton myasthenic syndrome in mice, and thus suggest that antibody to a synaptotagmin-voltage-dependent Ca2+ channel complex may be involved in the pathogenesis of Lambert-Eaton myasthenic syndrome. The peptide (residues 1-30)-immunized rats showed no electrophysiological abnormality.
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We report three related patients with autosomal dominant hereditary motor and sensory neuropathy (HMSN). An unusual and characteristic feature was calf enlargement, caused by muscle fiber hypertrophy predominantly of type 1 fibers. None of the family members showed atrophy of the legs. Sural nerve pathology disclosed marked loss of myelinated fibers and numerous onion bulb formations. While cases of HMSN with calf muscle hypertrophy have been reported, the present pedigree was different from that in any of the previous cases in that no family member showed clinically apparent leg atrophy.
The induction of myasthenia gravis depends on linked recognition of antigenic sites of acetylcholine receptor (AChR) by B-cells and T-cells. The former is conformationally restrained, and the latter is under the MHC class II restriction. We synthesized an artificially formed peptide (model peptide) by coupling the alpha 190-195 selected as B-cell site and cholinergic binding site and the alpha-107-116 selected as T-cell site and agretope with the intervening chain segment aligned as Asn-Pro-Gly-Gly (NPGG) to adopt beta-turn conformation. This model peptide, alpha 107-116-NPGG-alpha 190-195, was potently immunogenic in Lewis rats to provoke anti-peptide antibody reactive with native AChR and to induce the animal model of immunopharmacologic blockade of acetylcholine (ACh)-binding site. Low immunogenicity compared with this was found when using natural peptides predicted as sequences of B-cell site or T-cell site and the peptide synthesized by linking both without intervention of NPGG. The alpha 190-195 had no function of cholinergic binding either as a single segment or as part of the conformation-modified peptides; results suggest that the conformation modified for high immunogenicity does not assume the bioactive conformation for ACh-binding.
The African green monkey kidney-derived Vero cell line expresses a receptor activity for noninfectious hepatitis B surface antigen (HBsAg) particles containing the small S protein. (M.E. Peeples, K. Komai, R. Radek, and M.J. Bankowski, 1987, Virology 160, 135-142). In this report, the binding characteristics, the physiological requirements, and the functions of this receptor are further characterized. The association rate constant (ka) was determined by measuring binding during a short (10-min) incubation period to avoid the complication of dissociation. The results indicated an extremely high affinity binding: ka = 2.0 x 10(10) M-1 min-1. HBsAg particle binding to the Vero cells was also found to be slowly reversible, and dependent on temperature, pH, and Ca2+. After binding to Vero cells. HBsAg particles were quickly internalized as measured by trypsin removal from the cell surface. Once removed from the cell surface by proteolysis, regeneration of receptor activity required protein synthesis, indicating that there is no significant receptor pool within the cell. Receptor activity was also found to recycle to the cell surface after HBsAg particles were internalized.
Uterine papillary serous carcinoma (UPSC) is a recently recognized histologic variant of endometrial carcinoma with an aggressive clinical course. This study reviews 7 patients with the diagnosis of UPSC treated at the National Kokura Hospital between 1987 and 1989. The mean age was 60 years. Clinically, 4 patients presented as Stage I, one as Stage II, one as Stage III, and one as Stage IV. Surgery upstaged 28.7% (2/7) of these patients. All 7 patients underwent a staging laparotomy followed by chemotherapy. Deep myometrial invasion was found in 5/7 (72%) of the specimens. Four of these 5 specimens demonstrated up to the uterine serosa. Lymph nodal involvement was observed in 1/4 (25%) of the specimens. Furthermore, positive peritoneal washings were obtained in 4/7 (57%) of the specimens. All patients received an adjuvant combination chemotherapy with cisplatin 50 mg/m2 on day 1, adriamycin 50 mg/m2 on day 1, and ifosfamide 1.0 g/m2 on day 1 to day 5 (PAI). Recurrence and relapse of the disease developed in the 2 patients within 6 months. Two patients had a negative second look operation with no evidence of disease (NED) at 18 months after the initial treatment. Serial determination of the serum CA125 was seen to have great value in monitoring treatment in 4 patients. However, additional accrual and follow-up are needed to determine whether or not PAI therapy has an impact on this disease.
A case of spastic paraplegia in Sjögren's syndrome associated with mixed connective tissue disease is reported. In this 49-year-old woman spastic gait and arthralgia developed at the age of 23 years and progressed chronically. On neurologic examination, supranuclear paresis of facial nerve was observed. Deep tendon reflexes were hyperactive in the jaw, upper and lower extremities. Serological tests showed that anti-nuclear, anti-RNP, and anti-SS-A antibodies were positive. Spinal fluid analysis showed that rate of de novo central nervous system (CNS) IgG synthesis was increased, and C3/C4 ratio was elevated. CT scans of the brain showed calcifications at bilateral basal ganglia, dentate nucleus and cerebellar vermis. An electroencephalogram revealed diffuse slowing, and 123I-IMP brain scans revealed decreased cerebral blood flow. MRI of brainstem and cervical cord were normal. These findings suggested that corticospinal tracts upper the brainstem were severely affected, and that there were multifocal latent lesions in the CNS. Mechanisms of the CNS involvement were supposed to be both autoimmune abnormality in the CNS, and vascular impairment.
The Vero (African green monkey kidney-derived) cell line is capable of binding recombinant hepatitis B surface antigen (rHBsAg) particles containing only the small surface (S) protein of hepatitis B virus (HBV). This binding activity appears to be due to a single major population of receptors (M. E. Peeples et al., Virology 160, 135-142 (1987]. Since infectious HBV particles also contain the small S protein, it is possible that the Vero cell receptor might also function as an HBV receptor. The initial physical characterization of this receptor is reported here. Treatment of Vero cells with each of four proteases reduced their binding activity by 70% or greater, indicating that the receptor is partially protein in nature. Binding activity was also reduced by pretreating cells with neuraminidase or low levels of sodium periodate, indicating that sialic acid also plays a major role in the receptor activity. Consistent with this interpretation, N-acetylneuraminic acid and N-acetylneuraminyl-lactose were able to competitively inhibit rHBsAg particle attachment to Vero cells. The protein nature of the Vero cell receptor was confirmed by the demonstration that chymotrypsin treatment which resulted in 70% loss of binding had little effect on the cell sialic acid content. Therefore, the Vero cell receptor for rHBsAg particles is a sialoglycoprotein.
Extrahepatic biliary obstruction in humans and rats leads to hypertriglyceridemia. The observed hypertriglyceridemia could result from either a defect of plasma triglyceride (TG) catabolism or hepatic over-production of TG. To examine these questions we have used the rat model to determine hepatic TG secretion by the Triton WR-1339 methodology (inhibition of peripheral lipolysis) and exogenous TG clearance (after i.v. injection of Intralipid). Four groups of rats were studied: group OB--48 h post-operative--bile-duct obstructed; group DV--bile diverted; group SC--sham-operated controls; and group FC--48 h fasted, unoperated controls. The hepatic TG secretion rate for group OB rats was a factor of 7 lower than that of either group SC or FC, and 5 times lower than that for group DV. There were no differences between the hepatic TG secretion rates of groups DV and FC or SC. After i.v. injection of Intralipid, plasma TG decreased with first-order kinetics. The rate constant was taken as the exogenous TG clearance rate (ETGCR). Mean ETGCR for group OB was a factor of 3 lower than that for either control group; while the ETGCR for group DV was equivalent to the control groups. Thus biliary diversion does not affect hepatic TG secretion or the ETGCR. The apparent cause of the hypertriglyceridemia of cholestasis in the bile-obstructed rat is impaired plasma TG catabolism.
Human hepatitis B virus (HBV) has not been passaged in established cell culture systems. To determine whether this inability results from the lack of a receptor, 30 cell lines were examined for their abilities to bind 125I-labeled recombinant hepatitis B virus surface antigen (rHBsAg) particles. These particles contained only the small surface (S) protein, which is also found in the envelope of infectious HBV particles. Only two cells lines, both derived from African green monkey kidney, were able to bind a large portion of the 125I-rHBsAg particles. Binding to one of these cell lines, Vero, was found to be specific by three criteria: it was competitively inhibited by nonradioactive particles, it was saturable, and it could be blocked by chimpanzee antiserum raised against the rHBsAg particles. Analysis of the binding data indicated a single major population of high affinity receptor sites: 2.7 X 10(5) sites/cell, Kd = 2.8 nM. Binding was not due to the covalently linked 125I tracer isotope because unlabeled particles also bound, as detected with a monoclonal antibody. Binding was not unique to this recombinant particle preparation since serum-derived particles also bound to Vero cells. These results indicate that the Vero cell line expresses a receptor for the small S protein of HBV and that the small S protein, alone, may function as the HBV attachment protein.
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We evaluated the possible role of prostaglandin E2 (PGE2) in the calcium(Ca++)-mediated damage of skeletal muscle by a calcium ionophore (A23187) that induces excessive Ca++ influx. Twitch and tetanus of rat diaphragms were depressed with either PGE2 or A23187. A23187-induced depression was reduced by PG synthesis inhibitors, aspirin, or indomethacin, though less than that by a protease inhibitor, leupeptin. PGE2-induced depression was also inhibited by leupeptin. Damage of the muscle cell by excessive intracellular free Ca++ may thus be mediated via a PGE2 pathway besides other mechanisms including non-lysosomal, Ca++-activated proteases.
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We report the use of paclitaxel in the successful treatment of a patient with recurrent adenocarcinoma of the cervix. Paclitaxel, 70 mg/m2 by 1-h infusion weekly, was administered to a 59-year-old patient with cervical adenocarcinoma showing lung metastasis. She showed partial clinical response after seven cycles, and at the completion of 20 cycles she showed complete response, which was confirmed by chest X-ray and computed tomography scan. Toxicities including neurotoxicity were mild. She showed an objective response to treatment for over 8 months, and she enjoyed a favorable quality of life during and after treatment. Weekly paclitaxel was very well tolerated, yet was effective for recurrent cervical adenocarcinoma.