Cerebral atherosclerosis in Japanese. 1. Lipids and glycosaminoglycans in cerebral arteries.
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Biomedical subjects
Publications and source records attributed to Y Kikuchi.
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We examined changes in the blood flow velocity of brain stem artery (BSA) and middle cerebral artery (MCA) in response to hypercapnic, normocapnic and hypocapnic hyperventilation in seven awake subjects with a transcranial Doppler to determine if there are differences in blood flow control in regional brain perfused by these respective arteries, and to separate the effects of CO2 and ventilation itself on blood flow velocity during CO2 loading. During hypercapnic hyperventilation, BSA flow velocity increased linearly with an increase in end-tidal partial pressure of CO2 (PETCO2). During hypocapnic hyperventilation, BSA flow velocity decreased linearly with decrease in PETCO2, but did not change during normocapnic hyperventilation. The mean CO2 reactivity of BSA was 2.8%/mmHg. The responses of MCA to these hyperventilations and CO2 reactivity were similar to those of BSA. These findings suggest that CO2 rather than ventilation per se is the important stimulus to changes in brain blood flow velocity and that the CO2 responses of brain arteries are not affected by differences in vascular beds.
We retrospectively reviewed 15 gadolinium-enhanced magnetic resonance imaging examinations of the cervical spine in eight patients who had spinal cord injury. Enhancement was demonstrated at the periphery of the intramedullary lesion in three patients at 1 to 14 weeks after injury. The enhancement might reflect vascularized granulation in a reparative phase. Spinal cord injury should be considered in the differential diagnosis of enhanced intramedullary spinal cord lesions.
We investigated the effect of artificial parafoveal scotomata on the multifocal electroretinogram (M-ERG). M-ERGs were recorded from normal subjects using a monitor with several different sizes of black paper attached. A lower response density area around the 10 to 15 degree parafoveal region was not recognized for scotomata up to 3 degrees but was observed in scotomata above 5 degrees (visual angle) in the field topography of M-ERG. The shape of the scotomata was not circular but somewhat oval. The results from two cases of parafoveal retinal degeneration accorded well with this basic study.
PURPOSE: To investigate the reproducibility as well as the effect of luminance in multifocal electroretinogram (mERG). METHODS: Multifocal electroretinogram recordings were repeated on different days in 6 normal subjects using the Veris III system. The mean luminance of the monitor displaying the stimuli was randomly varied by five kinds of neutral density (ND) filters. RESULTS: The standard deviation of mERG amplitude from the macular region was approximately 10% of the mean value for each normal subject. Reproducibility largely depended on the condition of the subject and placement of the contact lens electrode. With decreases in the mean luminance of the monitor, the amplitude of mERG decreased exponentially, whereas the peak latency increased linearly. mERGs elicited from a patient with mild cortical cataract resembled the mERGs obtained from the control group using an ND filter between -0.30 and -0.52 log, whereas two patients with typical retinitis pigmentosa showed much lower response densities in mERGs. CONCLUSIONS: It is necessary to pay attention to the reproducibility and the luminance effect to obtain reliable mERGs.
Drosophila cells contain virus-like particles (VLPs) containing 5 kilobases (kb) of RNA (VLP H-RNA) homologous to the transposable element copia. The identity between VLP H-RNA and copia DNA has previously been confirmed at the nucleotide sequence level and reverse transcriptase activity is also detected in the VLPs. These results suggest that VLPs and copia are derivatives of viral particle and provirus forms, respectively, of the copia retrovirus-like particle. If the copia retrovirus-like particle replicates by a mechanism similar to the mechanism of vertebrate retroviral replication, a cellular transfer RNA would prime synthesis of the first DNA strand. We show that this is indeed so but that copia retrovirus-like particle has a novel type of priming mechanism; the first DNA extension does not start from the 3' end of a tRNA, but from an internal site (two nucleotides after the anticodon loop) of the Drosophila initiator methionine tRNA (tRNAMeti).
To determine the role of immobilization in the pathogenesis of burn-associated bone disease, we selected the sheep as a model to study the effects of burn injury compared with a sham-burned control group. Seven of the sheep were subjected to controlled 40% flame burn, and seven underwent anesthesia with arterial and venous cannulation but without burn. After labeling newly formed bone with tetracycline and calcein, the sheep were killed 2 weeks after burn or sham burn, and the iliac crest and lumbar vertebrae were analyzed for histomorphometry. Analysis failed to demonstrate a significant reduction of bone formation rate in the burned sheep. Osteoid area and surface and osteoblast surface, which correlated significantly with bone formation rate (r = 0.49, p < 0.025), were reduced in the burned sheep. Results suggest that immobilization may play a primary role in the pathogenesis of burn-associated bone disease, but the presence of differences in other histomorphometric features indicates the bone disease is multifactorial.
We describe a very rare case of synchronous mucinous tumor of the endometrium and ovaries presenting during ovulation induction. A 31-year-old woman received ovulation induction for 5-year primary infertility. Ultrasonography revealed mucus retention in the uterine cavity and bilateral multicystic ovaries during ovulation induction. Atypical hyperplasia was diagnosed by endometrial curettage. Repeated procedures including ovarian cystectomy, endometrial curettage and in vitro fertilization combined with progestine therapy resulted in no pregnancy but rapid recurrences. She finally underwent simple hysterectomy and bilateral salpingo-oophorectomy. Microscopic examination revealed mucinous cystadenoma in the both ovaries and well differentiated mucinous adenocarcinoma of the endometrium.
The mechanism of cis-diamminedichloroplatinum (II) (CDDP) resistance was examined by using a CDDP-resistant (KFr) cell line established by continuous exposure of KF cells (derived from serous cystadenocarcinoma of the ovary) to escalating doses of CDDP. When KFr cells were incubated with 66.7 microM CDDP, the uptake of CDDP was significantly inhibited and the cellular content in the KFr cells was about a half of that in KF cells after incubation for 4 h. When the KF or KFr cells were incubated for 4 h with 100 microM CDDP, the release pattern of CDDP from KFr cells was similar to that from KF cells. In addition, the DNA histogram of both KF and KFr cells revealed that KF cells seemed to contain two clones of cell population and the KFr cells may have been selected by exposure to CDDP. At 3 h after intraperitoneal administration of 0.5 mg of CDDP per mouse to nude mice with KF or KFr tumor, the CDDP content in the KFr tumor was significantly lower than that in the KF tumor. In contrast, at 6 or 9 h after CDDP administration the CDDP content in the KFr tumor was significantly higher than that in the KF tumor. Furthermore, the KFr cells had cross-resistance to various CDDP analogues including carboplatin. It was shown that cellular uptakes of two CDDP analogues into KFr cells were significantly lower than those into KF cells.
Accurate preoperative diagnosis for gastrointestinal stromal tumor (GIST) was obtained using the endoscopic approach in about 50% of the cases. Preoperative assessment is quite important in reproductive women for the treatment of pelvic tumor. We report the first case of GIST of the rectum that was accurately diagnosed with preoperative needle biopsy from the vaginal wall. The case was a 38-year-old woman who presented with a history of genital bleeding. Internal examination revealed a round and elastic mass (7 x 7 cm) in the left pelvic cavity. The biopsy specimen from the left sidewall of the vagina using a manually manipulated biopsy needle showed strong reaction for CD34 and CD117 (c-KIT). The patient underwent low anterior resection of the rectum, tumor resection, and partial resection of the posterior vagina. Preoperative biopsy with vaginal approach might be helpful to make a diagnosis for pelvic tumor of unknown origin and unknown malignant potential.
Immunohistochemical staining of human and rat brains for metallothionein (MT) using a monoclonal anti-MT antibody (MT45) revealed that protoplasmic astrocytes, which are densely localized in the gray matter, contain high levels of MT. Human U373MG astrocytoma cells were stimulated with interleukin (IL)-1 or heavy metals to produce MT. When expression of MT in U373MG cells was analyzed by Northern blotting or indirect immunofluorescence using the MT45 antibody, it was found that IL-1 (> or = 10 U/ml), CdCl2 (50 microM) and high concentrations of ZnCl2 (500 microM) induced marked biosynthesis of MT.IL-6 (up to 3,000 U/ml) and lower concentrations of ZnCl2 (10-50 microM), however, showed little inducing activity. Hippocampal astrocytes in primary culture produced a relatively high basal level of MT. The MT level increased in response to addition of IL-1 (> or = 10 U/ml), ZnCl2 (50 microM) and CdCl2 (5 microM). However, the increase induced by IL-6 (1,000 U/ml) was not very marked. The in vivo induction of MT in the brain by cytokines is not fully understood. However, our data and other indirect evidence suggest that IL-1 may be a potent stimulator of MT induction in astrocytes. Furthermore, the astrocytoma cell line, U373MG, is a suitable in vitro system to analyze the expression of MT in astrocytes.
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In order to evaluate chemically the macroscopic scoring methods for severity of arteriosclerosis in the cerebral arteries, concentrations of total lipids, esterified and free cholesterol and lipid phosphorus were compared to the macroscopic severity of lesions in the cerebral arteries obtained from 376 Japanese persons after unexpected death. An increase of cholesterol content was correlated significantly with an increase of Baker's score and/or Gore's atherosclerotic index. The correlation coefficient between Baker's score and total or esterified cholesterol was the highest among the tested correlations (r = 0.82, n = 376).
Concentrations of various lipids and glycosaminoglycans (GAG) in the intima of the grossly normal and atherosclerotic cerebral arteries were compared with those of the aorta and coronary arteries. The lowest percentage of esterified cholesterol (EC) in total cholesterol, and of chondroitin sulfate-4/6 (CS-4/6) in total glycosaminoglycans and the highest percentage of heparin sulfate (HS) in total GAG are the characteristic features of the normal intima of normal cerebral arteries when compared with those in the aorta and coronary artery. In the cerebral arterial intimas, but not in the aorta or coronary arteries, there was a significant positive correlation between contents of EC and percentage and total content of CS-4/6. Atherogenesis in cerebral arteries is discussed in comparison to that of the aorta and coronary vessels.
Tape-recorded voices of 30 patients were acoustically analysed: 10 had glottic Tla carcinoma, 10 unilateral vocal fold polyp and 10 unilateral recurrent laryngeal nerve paralysis. The carcinoma cases were treated with laser surgery with/without radiotherapy, the polyp cases with endolaryngeal microsurgery and the paralysis cases with intrafold silicone injection. The acoustic analysis was conducted before and after the treatment for each patient. Three acoustic parameters, viz. pitch perturbation quotient (PPQ), amplitude perturbation quotient (APQ) and normalized noise energy (NNE), were employed. The results were as follows: (1) PPQ and APQ were greater in paralysis cases than in carcinoma and polyp cases; (2) none of the parameters was useful in differentiating the three disease groups investigated; (3) all three parameters proved to be useful in monitoring the effects of treatments; (4) all three parameters were positively correlated to the grade of hoarseness, rough and breathy quality of hoarseness, mean airflow rate and regularity of vocal fold vibration viewed under stroboscopy; (5) PPQ, APQ and NNE were positively related to each other.
A case is reported of Wilms' tumor associated with multiple pulmonary metastases histologically showing maturation of the tumor cells at 9 years after the resection of the primary tumor and intensive therapy. A huge tumor of a 22-month-old patient's right kidney was resected. The tumor was diagnosed as Wilms' tumor of mesenchymal type (stage 1), which consisted of predominantly immature mesenchymal tissue including rhabdomyoblasts, smooth muscle and fibrous tissue, and few blastemal and epithelial components. Intensive preoperative and postoperative chemotherapy with actinomycin D and vincristine and postoperative irradiation therapy totaling 16 Gy were carried out. The patient was regularly followed up uneventfully until 9 years after the surgery. On routine chest x ray at the age of 10 years 11 months, multiple pulmonary nodules were found. The excised nodules from the bilateral lungs disclosed similar histology, exclusively composed of dense collagen bundles and fibrocytes intermingled with mature striated muscle bundles. No immature tumor components were detected. The possible effect of intensive therapy in this maturation was stressed, although spontaneous benign differentiation of tumor cells cannot be excluded.
The purpose of the present study was to evaluate cytotoxic agents active for mucinous adenocarcinoma of the ovary (MACO) which is considered to be intrinsically platinum-resistant. We first conducted in vitro chemosensitivity tests assessing cytotoxic activities of various anti-cancer agents against MACO using a cell line, designated OMC-3, established from ascites of a patient with histologically pure MACO. The most active single agent was SN-38 (active substance of CPT-11 in vivo). The second most potent agent was mitomycin-C (MMC) followed by doxorubicin (DOX). In vivo chemo-sensitivity test of agents on OMC-3 transplanted into Balb/c nude mice demonstrated that MMC was most potent, followed by DOX. Moreover, a combination of CPT-11 and MMC exhibited the highest anti-tumor activity in this animal model. Cisplatin was found to be ineffective in both the in vitro and in vivo experimental system. Clinical trial with a combination of MMC and CPT-11 are justified in patients with MACO.