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Biomedical subjects

K Komai

Publications and source records attributed to K Komai.

At least 55 records · Page 3Linked to original sources

Anthropometric and other risk factors for ovarian cancer in a case-control study.

Because it has been suggested that an environmental factor may play a role in the etiology of ovarian cancer, a case-control study was conducted to assess some environmental and other risk factors for ovarian cancer from 1994 to 1996 in northern Kyushu, Japan. We analyzed the data of 89 cases with epithelial ovarian cancer and 323 controls without any cancer or ovarian disorder. After controlling for the effect of potential confounders, the odds ratios of ovarian cancer across increasing quartiles of the heaviest body weight were 1.00, 1.15, 1.71, 2.29 (P = 0.008, test for trend). Significantly increased risks were noted for a history of diabetes mellitus (P < 0.05), and for a family history of ovarian cancer (P < 0.05). Significantly decreased trends for risk were obtained for the number of pregnancies (P < 0.01) and the number of live births (P < 0.001). This study provides additional support for an association between obesity and the risk of ovarian cancer. This relationship may at least partly explain the recent increase in the incidence of ovarian cancer in Japan, although possible contributions of other factors can not be ruled out.

Adult↗

[Serial MRI study on a case of anterior spinal artery syndrome].

A 63-year-old woman suddenly began to suffer from left chest pain. She gradually became unable to walk and was admitted to the emergency room at another hospital. When she became paraplegic in spite of steroid therapy, she was admitted to our hospital. Her affliction was diagnosed as anterior spinal artery syndrome because of flaccid paraplegia and dissociated sensory loss below the Th4 dermatome. Hematological study indicated a compensated DIC and hepatic enzyme abnormality, while the CSF examinations showed an elevation of protein and positive myelin basic protein (MBP) elevation. The initial MRI taken in the acute stage showed no abnormal signals on T1-weighted (T1) and Gd-enhanced images. The sagittal T2-weighted image (T2) revealed central high intensity (HI) with longitudinal extension from Th2 through the Th11 vertebral level. On axial T2, HI was located on the gray matter at the Th3 and Th4 vertebral level, the ventral two-thirds at the Th8 vertebral level, the central ventral side at the Th9 and Th10 vertebral level, and the entire cross section at the Th12 and L1. A follow-up MRI examination showed that the range of HI on the sagittal T2 had been reduced to 5 segments from Th6 through Th10 vertebral level. The T2 HI lesion on the axial aspect had become reduced so as to localize on the left ventral side at the Th8 vertebral level and on the central ventral side at Th9 and Th10.

Female↗

[A patient with amnesic syndrome with defective route finding due to left posterior cerebral artery territory infarction].

We report a right-handed 67-year-old woman with an infarction in the left posterior cerebral artery territory presenting amnesic syndrome, right homonymous hemianopsia, pure alexia, color anomia, and defective route finding. The patient often walked in wrong directions out of her hospital room as well as in her home. She was able to recognize her own house and nearby streets by looking at them. Prosopagnosia and constructional impairment was not observed. Wechsler memory scale revised (WMS-R) revealed that she had marked disturbance in both visual and verbal recent memory. Brain MRI revealed an infarction involving the left medial inferior temporal and left medial occipital lobe, the left splenium of corpus callosum, and the left retrosplenial region. SPECT indicated a defect in the left medial occipital lobe and hypoperfusion in the left medial temporal lobe. Cerebral angiography demonstrated stenosis of the left medial occipital artery and occlusion of the left dorsal corpus callosal branches and the left calcarine artery. We conclude that left hippocampus, left parahippocampal gyrus and the left retrosplenial region may cause memory disturbance in our case. The lesion in the left retrosplenial region may have contributed to the occurrence of defective route finding. The relation between defective route finding and the retrosplenial amnesia is discussed.

Aged↗

[Successive subcortical hemorrhages in the superior parietal lobule and postcentral gyrus in a 23-year-old female].

We report a non-hypertensive 23-year-old female with successive hemorrhages in parietal subcortical regions. She had first experienced a transient pain in the left upper extremity one month before admission. She noticed dysesthesia in the same limb and weakness on her left hand, and, five days after, visited our hospital because of suddenly developed convulsion in the limb and loss of consciousness for a few minutes. Neurological examination revealed distal dominant flaccid paresis, positive pathological reflex and touch and position sense disturbances in the affected limb. Brain CT detected two high-density areas in the parietal lobe. Brain MRI demonstrated an acute phase subcortical hematoma in the left postcentral gyrus and a subacute phase one in the left superior parietal lobule. SPECT indicated hypoperfusion in the left frontal and parietal cortex. Cerebral angiography showed no abnormal findings. Her symptoms gradually improved, but left ulnar-type pseudoradicular sensory impairment remained on discharge. We considered the hemorrhage in this patient have arisen from rupture of cavernous hemangioma, because she was relatively young, the hematomas were oval in shape and successively developed in the left parietal lobe. Our patient suggests that a subcortical hemorrhage in the post-central gyrus causes flaccid paresis and pyramidal tract involvement.

Adult↗

[Diagnostic muscle MRI abnormality in a patient with inclusion body myositis].

A 64-year-old woman was admitted to our hospital because of muscle weakness and atrophy in the extremities. Four years before admission, he was noticed to have elevated creatine kinase (CK) level, but had no further evaluation. Two years later, she became difficult in standing up and needed a wheelchair. Six months before admission, she noticed muscle wasting in the buttock, thigh, bilateral forearms, and weakness in the upper limbs. On neurologic examination, she had weakness in sternocleidomastoid and all limb muscles, predominantly in the distal portion of the upper extremities. Laboratory study revealed elevated CK, LDH, and aldolase levels, and myogenic change with fibrillation on needle EMG. Muscle biopsy showed myopathic changes with infiltration of mononuclear cells and rimmed vacuoles. The clinical manifestations as well as poor response to corticosteroids therapy were supportive of the diagnosis of inclusion body myositis. However, the distribution of muscle weakness in her wrist, weaker in the extensors than in the flexors, was not characteristic to IBM. This problem was solved by the right forearm MRI which showed a high signal intensity area in flexor muscles, but not in extensors on T1 and T2 weighted images. Accordingly, the muscle MRI of forearm was a diagnostic aid of IBM in this patient.

Female↗

Antibodies to synthetic peptides of the alpha1A subunit of the voltage-gated calcium channel in Lambert-Eaton myasthenic syndrome.

To search for antigenic sites in the molecular structure of alpha1A subunit of the voltage-gated calcium channel (VGCC) (P/Q-type) in the Lambert-Eaton myasthenic syndrome (LEMS), we studied by immunoprecipitation assay serum samples from 30 LEMS patients (16 with small cell lung carcinoma (SCLC), 20 disease controls (10 with SCLC without LEMS and 10 with myasthenia gravis), and 15 healthy controls. Synthetic peptide antigens corresponded to the extracellular region (S5-S6 linker region) of each of the four domains forming the alpha1 subunit of P/Q-type VGCC. In addition, we studied serum samples for anti-P/Q-type VGCC antibodies by using omega-conotoxin MVIIC-labeled extract of human cerebellum as an antigen. Among sera of 30 LEMS patients, nine samples (30%) (six with SCLC) were positive for antibodies to the domain IV S5-S6 linker peptide, and six samples (20%) (five with SCLC) were positive for antibodies to the domain II S5-S6 linker peptide. Only two of 15 antipeptide-positive sera were positive for both antibodies. Titers for antibodies to domain IV, as well as those for antibodies to domain II, correlated with those of anti-P/Q-type VGCC (human cerebellum extract) antibodies. The antipeptide antibody was present in only one of 20 disease controls, a patient with SCLC without LEMS. Our observations suggest two potential epitopes of LEMS antibodies.

Antibodies↗

Optimal timing of a second-look operation for advanced epithelial ovarian cancer.

To clarify the optimal timing of second look operation (SLO) for advanced ovarian cancer, we retrospectively reviewed the records of 53 patients with FIGO stage 2, 3 and 4 epithelial ovarian cancer. SLOs were performed more than 12 months after primary surgery in 35 patients (late SLOs), and immediately after first-line chemotherapy in 18 patients (early SLOs). We examined data on SLO findings and patients' clinical courses. SLO findings were positive 5 (27.7%) of 18 in the early SLO group and in 11 (31.4%) of 35 in late SLO group. Positive findings were detected by washing cytology in 3 (60%) of the 5 in the early SLO group compared with 2 (18.2%) of the 11 in the late SLO group. Patients with microscopic disease had better prognosis than patients with macro lesions. False-negative SLO findings were 30.8% in the early SLO group and 12.5% in the late SLO group. All patients who recurred after negative SLOs had grade 2 and 3 tumors. The benefits of SLO were limited to accurate evaluation of first-line chemotherapy and early detection of persistent disease. In these implications, early performance of SLO is recommended.

Adult↗

[Mixed transcortical aphasia due to multiple deep white matter infarction in the dominant cerebral hemisphere: a case report].

We report a case of mixed transcortical aphasia (MTA) due to multiple cerebral infarction in the dominant hemisphere in an 80-year-old right-handed woman without hemiplegia. Her spontaneous speech was markedly reduced and auditory comprehension, reading and writing were severely disturbed. Although the repetition of sentences (at most 3 words) was relatively preserved, her speech was echolalic. Brain MRI showed bilateral multiple deep white matter infarction and subcortical infarction of the left parietal lobe, including left angular gyrus, but no abnormal signal intensities were detected in either Wernicke's or Broca's area. SPECT indicated a significant decrease in mean cerebral blood flow in both hemispheres, but there was no focal hypoperfusion in either speech area. We thought that the focal hypoperfusion observed in the right cerebellum indicated crossed cerebellar diaschisis. Electroencephalogram showed a diffuse reduction in the incidence of alpha waves in the left cerebral hemisphere. From these findings, we suggest that widespread hypofunction in the dominant hemisphere was important for the occurrence of MTA.

Aged↗

[Molecular biology and immunology of acetylcholine receptor in relation to myasthenia gravis].

In search for the myasthenogenic sites in the molecular structure of acetylcholine receptor (AChR) alpha-subunit, the conformation-dependent B-cell epitopes, and the MHC class II-restricted, immune cofactors-modified T-cell epitopes were studied. Using the peptides synthesized corresponding to AChR amino acid sequence, the alpha 183-200 (as an antigen to raise "blocking antibody") and the alpha 70-90, alpha 125-147 and alpha 67-76 with alpha 107-116 (as antigens to raise "binding antibody") were found immunogenic in the induction of the disease in animals. Phenotypic changes in the T-cell lineages in the thymus were discussed. An impairment of excitation-contraction coupling in some of myasthenic muscles was attributed to a defect caused by antibodies raised against ryanodine receptor protein. Myasthenia gravis patients' sera containing anti-ryanodine receptor antibodies inhibited the calcium-induced release of calcium in response to caffeine in human rhabdomyosarcoma cell line. Buffalo/Mna rats with spontaneous benign thymoma showed (1) ryanodine receptor expressed in the thymic epithelial cells, (2) anti-ryanodine receptor antibodies in serum, and (3) reduced twitch and tetanic force without abnormality in synaptic transmission and muscle membrane properties. It is suggested that thymic epithelial cell and skeletal muscle share common ryanodine receptor antigen. The finding seen in this rat strain can be a counterpart of the feature reflecting an immune attack directed against a compartment of skeletal muscle in myasthenia gravis.

Animals↗

[Molecular immunology of voltage-gated calcium channel and Lambert-Eaton myasthenic syndrome].

Lambert-Eaton myasthenic syndrome(LEMS), an autoimmune disease that is often associated with small cell lung carcinoma(SCLC), impairs the quantal release of acetylcholine by directing antibodies against voltage-gated calcium channels (VGCC) in the motor nerve terminal. We focused attention on the P/Q type VGCC, to which there are antibodies in LEMS patients in higher frequency than antibodies to other types of VGCC. To search for antigenic sites in the molecular structure of alpha 1A subuuit of P/Q type VGCC in LEMS, we synthesized 4 peptides corresponding to the extracellular region (S5-S6 linker) of each of 4 domains that form alpha 1A subunit of VGCC. Also, LEMS patients' sera were studied by immunoprecipitation assay using these antigens. Peptides corresponding to the extracellular region (S5-S6 linker) of domains II and IV were specifically reactive with LEMS antibodies; their titiers respectively correlated with those of anti-P/Q type calcium channel (omega-conotoxin MVIIC-sensitive human cerebellum extret). Lewis rats were immunized with the domain II S5-S6 linker peptides conjugated with KLH. The immunized rats showed LEMS features characterized by reduced acetylcholine quantum content of endplate potentials and antibodies reactive with P/Q type VGCC. Our observations suggest 2 potential epitopes of LEMS antibodies. Synaptotagmin is a Ca2+ and phospholipid binding protein integrated in synaptic vesicle membranes. It plays a crucial role in neurotransmitter release, probably as a Ca2+ sensor for exocytosis of synaptic vesicles. The extracellular region of synaptotagmin was found antigenic for the induction of a rat model of LEMS. A proportion of human LEMS antibodies reacted with the recombinant synaptotagmin in immunoblot.

Acetylcholine↗

Comparison of CA 125 assays with abdominopelvic computed tomography and transvaginal ultrasound in monitoring of ovarian cancer.

OBJECTIVE: To compare serum CA 125 assays with computed tomography (CT) and transvaginal ultrasound (TVUS) for early detection of disease recurrence in patients with ovarian cancer. METHODS: Sixty-two patients with non-mucinous epithelial ovarian cancer who had positive CA 125 levels (> 35 U/ml) were studied. We performed a retrospective review to determine the usefulness of serum CA 125 measurements. Setting the cut-off limit at either 35 U/ml or 16 U/ml, the accuracy of CA 125 measurements was compared with that of CT scanning, TVUS and operative findings at second-look laparotomy (SLL) in the early detection of recurrent tumors. RESULTS: Compared with SLL, both the specificity and the positive predictive value of CA 125 measurements were 100% at 16 and 35 U/ml. The sensitivity and the negative predictive value were 30.8 and 71.9%, respectively, below 35 U/ml and 53.8 and 79.3%, respectively, below 16 U/ml. The false-negative rate of CT was 36.1%. When the cut-off limit was reduced from 35 to 16 U/ml, 57.1% of patients considered to be in remission were reclassified as having persistent disease. A complete response confirmed by CT did not represent remission: CA 125 levels were 7.5-fold higher at the time of re-evaluation by CT. TVUS also lagged behind CA 125 assays in detecting disease recurrence. The sensitivity of ultrasound appeared to be lower than that of CT because it failed to detect extrapelvic lesions. CONCLUSION: A screening threshold (cut-off level) of 16 U/ml for CA 125 should be used to detect recurrent serous ovarian adenocarcinoma. Although ultrasound is a convenient method of detecting intrapelvic lesions, and has cost benefit, CT is necessary to detect extrapelvic recurrence. Neither CT nor ultrasound are more accurate than serial CA 125 assays in detecting disease recurrence.

Biomarkers, Tumor↗

Colocalization of NOS and SOD1 in neurofilament accumulation within motor neurons of amyotrophic lateral sclerosis: an immunohistochemical study.

Peroxynitrite, formed from nitric oxide and superoxide, may affect neurofilament assembly and cause neurofilament accumulation in motoneurons. This hypothesis may reconcile the mutations of two genes: superoxide dismutase-1 in some patients with familial amyotrophic lateral sclerosis, and the gene for the heavy neurofilament in some patients with sporadic amyotrophic lateral sclerosis previously reported. We found colocalization of superoxide dismutase-1 and nitric oxide synthase in the foci of neurofilament accumulation as 'conglomerates' in upper motor neurons and 'axonal spheroids' in lower motor neurons. In addition, all the specific molecules related to the reactions, including calmodulin, 3', 5'-cyclic guanosine-monophosphate, citrulline, and nitrotyrosine were found strongly immunopositive in the site of neurofilament accumulation. Our data support the view that the neurofilament aggregates are tightly linked with superoxide dismutase-1 and nitric oxide synthase activities. Both enzymes may focally contribute to peroxynitrite formation at light neurofilament, which is rich in both tyrosine and arginine residues and hence considered as the vulnerable site for nitrotyrosine formation. Nitrotyrosine is known to inhibit phosphorylation and if it impairs phosphorylation of neurofilament subunits, either light or heavy, may alter the slow axonal transport culminating in proximo-distal accumulation of NF and slowly progressive motoneuron death.

Amyotrophic Lateral Sclerosis↗

[Combination of irinotecan hydrochloride (CPT-11) and cisplatin as a new regimen for patients with advanced ovarian cancer].

It has been reported that the antitumor effect of CPT-11 is manifested through the inhibition of topoisomerase I by SN-38 which is an active metabolite of CPT-11 produced by intracellular carboxylesterase, and that CPT-11 is effective against recurrent ovarian carcinoma. We investigated the antitumor effect and adverse reactions in the combined therapy with CPT-11 and CDDP in patients with prior chemotherapy for recurrent carcinoma, and in 7 patients without prior chemotherapy, consisting of 4 patients with postoperative adjuvant chemotherapy for clear cell carcinoma and 3 patients with metastatic ovarian carcinoma. CDDP was administered on day 1 and CPT-11 was administered three times on days 1, 8 and 15. The dose of both CDDP and CPT-11 was 50 mg/m2 or 60 mg/m2. Adverse reactions were investigated in all patients and the antitumor effect was assessed in 12 patients with recurrent carcinoma who had measurable lesions. (1) The DLF was neutropenia. The neutrophil count nadiar occurred on day 18 or 19. Grade 3 or 4 adverse reactions were observed in 60% or more of the patients, but they disappeared following short term administration of G-CSF. In patients with recurrent carcinoma given CDDP and CPT-11 at 60 mg/m2, the incidence of grade 3 or 4 adverse reactions and number of occasions on which CPT-11 administration had to be postponed were higher than those in patients given 50 mg/m2. (2) Mild platelet reduction was observed. (3) Grade 3 or 4 diarrhea was observed in 3.2% of patients with recurrent carcinoma and in 7.7% of patients with metastatic ovarian carcinoma. (4) The antitumor effect was evaluated in 12 patients with recurrent carcinoma: CR in 2 patients. PR in 3, NC in 6, and PD in one. The response rate was 41.7%. (5) An antitumor effect was observed in 2 patients with serous carcinoma and in one patient each with mucous carcinoma, clear cell carcinoma and endometrial carcinoma. In conclusion, adverse reactions caused by the combination therapy with CPT-11 and CDDP (CPT-11: 50-60 mg/m2 on days 1, 8 and 15, CDDP: 50-60 mg/m2 on day 1) can be relieved by short term administration of G-CSF and it is suggested that the combination therapy may be effective in treating ovarian carcinoma.

Adult↗

[A case-control study of ovarian cancer to identify its risk factors].

To analyze the association between the potential risk factors and ovarian cancer, we conducted a case-control study from October, 1994 to January, 1996 in northern Kyushu. We interviewed 78 patients whose ovarian cancer was histologically confirmed, and 346 controls, selected from women at mass screening, who had not ever suffered from a cancer or an ovarian disorder. An odds ratio (OR) and its 95% confidence interval (95% CI) were estimated by the conditional logistic regression method. As a result, it was found that the risk was significantly increased for a family history of ovarian cancer in a mother or a sister (OR = 2.85, 95% CI 1.01-8.08), for heavier maximum body weight in the past (trend, OR = 1.31, 95% CI 1.06-1.63), and for larger maximum body mass index (trend, OR = 1.30, 95% CI 1.06-1.60). Conversely, the risk was significantly decreased with the number of parities (trend, OR = 0.57, 95% CI 0.39-0.83), and with experience in having ever taken oral contraceptive pills (OR could not be calculated, p < 0.05). The positive relationship of maximum body weight or maximum body mass index to the ovarian cancer risk may in part explain the recent increase in the incidence of ovarian cancer in Japan.

Alcohol Drinking↗