[Study on methemoglobin in extracorporeal circulation].
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Biomedical subjects
Publications and source records attributed to I Hashimoto.
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Thrombolytic therapy using tissue-type plasminogen activator was performed in a 7-month-old boy with massive mural thrombi in large coronary aneurysms due to Kawasaki disease. Magnetic resonance imaging successfully demonstrated mural thrombi in both proximal and distal coronary aneurysms and their disappearance after thrombolytic therapy. We conclude that for preventing acute myocardial infarction and sudden death intravenous and intracoronary thrombolytic therapy with tissue-type plasminogen activator may help in infants and children with Kawasaki disease who have thrombi in coronary aneurysms.
We report a case of pulmonary atresia in which the ductus arteriosus underwent aneurysmal dilatation after infusion of prostaglandin E1 incorporated in lipid microspheres. To our knowledge this is the first case in which this rare morphological change has been demonstrated with the noninvasive method of magnetic resonance imaging.
The achievement of keratinocyte gene therapy in clinical practice requires fundamental experiments using human keratinocytes or skin. We have recently demonstrated that the in vivo introduction of the interleukin 6 (IL-6) gene into rat keratinocytes induces epidermal proliferation and lymphocyte infiltration into the skin. In this study, we first amplified the human IL-6 cDNA from oligo-dT-primed keratinocyte cDNA and then detected the fully spliced (FS) form and the alternatively spliced (AS) form of IL-6 cDNA. Sequence analysis showed that the AS form, which was composed of the IL-6 coding region with all of exon II deleted except for the first guanine, was identical to that reported to be present in lymphocytes. We constructed the expression vectors phIL6 of the FS form and phIL6S of the AS form. We transplanted human skin onto nude rats and introduced phIL6 and phIL6S into the human keratinocytes using the naked DNA method. Keratinocytes prepared 24 h after introduction from the areas treated with them were examined by reverse transcriptase (RT)-PCR and enzyme linked immunosorbent assay (ELISA). RT-PCR showed that the amounts of FS IL-6 mRNA and AS IL-6 mRNA were similar, whereas the ELISA showed that the amount of FS IL-6 peptide was four times that of the AS IL-6 peptide. Histological examination 48 h after introduction showed that the FS form had induced epidermal proliferation, whereas the AS form had not. The epidermal thickening without lymphocyte infiltration induce by the FS form indicates that keratinocyte proliferation is caused by a direct effect of overexpressed IL-6, and not by a secondary effect of infiltrating lymphocytes. This is the first report of the introduction of a human gene into human keratinocytes to produce a biologically active transgenic gene product in human skin using the naked DNA method.
In order to develop a more efficient method of introducing genes into keratinocytes in vivo, we intradermally injected DNA bound to high mobility group 1 protein, thereby taking advantages of the naked DNA and hemagglutinating virus of the Japan-liposome method reported previously. First we performed a gel mobility shift assay, which confirmed DNA binding to high mobility group 1. Then we injected beta-galactosidase expression vector complexed with high mobility group 1 into the rat skin and the activity of sample with the protein was 2-3 times higher than that without the protein as control. Semiquantification of transferred-DNA content using polymerase chain reaction and a time course of transgene expression in keratinocytes suggested that high mobility group 1 protein increased transfer of the DNA from the cytoplasm to the nucleus. Direct injection of the DNA-high-mobility-group-1 complex is a highly efficient method for introducing genes into keratinocytes in connection with gene therapy.
Brainstem auditory-evoked potentials were studied within 6 hours after mild head injury in 17 children with post-traumatic vomiting. Compared with 8 control subjects, the children with frequent vomiting showed a significant shortening of peak latency for wave III. This mechanism appears to be essentially the reverse of that found in the post-concussion syndrome in which significant delay of wave III has been reported. These findings indicate transient facilitatory effects of trauma on brainstem auditory transmission in post-traumatic vomiting.
Congenital leukemia often provides insight into mechanisms of in utero leukemogenesis. A 10-day-old boy with clinical features of skin nodules, marked hepatosplenomegaly, and subcutaneous bleeding received a diagnosis of congenital leukemia. This patient initially had a dominant B progenitor lymphoblast population and minor monocyte component. Treatment with prednisolone, vincristine, and doxorubicin resulted in a loss of lymphoblast population and a rapid increase and dominance of the monocyte component within 10 days. Complete remission initially was obtained with additional combination chemotherapy with epipodophyllotoxin (VP-16) and cytosine arabinoside (Ara-C), but relapse characterized by a lymphoblastic population in the bone marrow was subsequently observed. The authors hypothesize that the leukemic cells originated from a common B-monocyte lineage stem cell during fetal hematopoiesis.
Ten cynomolgus monkeys were given enterovirus 71 (E71) by mouth. Clinically, only one monkey showed weakness of the lower extremities. Histopathologically, vascular lesions of variable intensity, perivascular cuffing, degeneration and necrosis of the neurons and neuronophagia were observed in the CNS of 7 monkeys. E71 was recovered from the CNS and specific immunofluorescence was detected in the neurons and in associated macrophages in the CNS. Serum neutralizing antibody titres rose from 14 to 21 days. These monkeys are as susceptible to E71 infection by the oral route as by the subcutaneous route as previously shown, and its neuronal virulence was confirmed by its producing CNS lesions after oral infection. The orally infected monkey with E71 appears to provide an excellent model for infection by this agent in man.
Although fetal hydrocephalus is commonly detected by prenatal ultrasonographic examination, posthemorrhagic hydrocephalus has rarely been observed in the fetus. We report a case of hydrocephalus secondary to intraventricular hemorrhage (IVH) diagnosed by in utero magnetic resonance imaging (MRI) at 37 + 1 weeks of gestation. Ultrasonography revealed enlargement of the bilateral ventricles and an irregular mass measuring 20 x 12 x 10 mm in the right lateral ventricle. T1-weighted images with two-dimensional fast low-angle shot (2D-FLASH) and T2-weighted images with half-Fourier single-shot turbo spin echo (HASTE) demonstrated that an old hemorrhagic clot existed in the right lateral ventricle of the fetus. Hydrocephalus secondary to IVH was confirmed by postnatal MRI and ventriculoscopy. Fast MRI is especially useful for prenatal diagnosis of fetal brain abnormalities because it minimizes the artifact of fetal movement.
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The aim of this study was to determine whether tumor-associated macrophages (TAMs) infiltration correlates with clinicopathological factors including microvessel, counts and clinical outcome in endometrial cancer. Overall 56 out of the 109 endometrial cancers (51.4%) expressed distinct tumor-associated macrophages infiltration in their tumor stroma. Tumor-associated macrophages infiltration was significantly high in tumors with deep myometrial invasion, high grade and elderly patients. Microvessel counts strongly correlated with tumor-associated macrophages infiltration in tumor stroma (p = 0.0002). However, tumor-associated macrophages infiltration was not a prognostic factor. In conclusion, tumor-associated macrophages may play a crucial role in the promotion of angiogenesis, but can not be used to prodict prognosis of patients with endometrial cancer.
BACKGROUND: The role of thrombospondin (TSP) in tumor progression remains controversial. The association of TSP with clinicopathological features regarding prognostic significance was examined in patients with epithelial ovarian tumor. MATERIALS AND METHODS: Gene expression of TSP-1 and TSP-2 was assessed by reverse transcriptase-polymerase chain reaction in 6 borderline and 29 malignant epithelial ovarian tumors. RESULTS: TSP-1 mRNA expression was detected in 14 out of the 29 malignant epithelial ovarian tumors (48.3%), whereas TSP-2 mRNA expression was detected in 7 malignant epithelial ovarian tumors (24.1%). In contrast, no specimen from the borderline epithelial ovarian tumors expressed TSP mRNA. TSP-1 expression was significantly higher in tumors with advanced stage, massive ascites, positive peritoneal cytology and high grade. TSP-2 expression was significantly higher in tumors with massive ascites. Patients exhibiting TSP-1 and -2 mRNA expression demonstrated a markedly poorer prognosis than those lacking TSP-1 and -2 mRNA expression. CONCLUSION: These findings provide evidence that TSP expression may be associated with an aggressive phenotype in this class of neoplasm.
It is reported that increasing metallothionein (MT) synthesis suppressed sunburn cell formation in the mouse skin after ultraviolet B (UVB) irradiation, implying a photo-protective effect of the cysteine-rich protein. To understand the mechanism of the defense by cutaneous MT against UVB injury, an immunohistological localization of MT in human normal skin was studied following examination of lesional skin. MT in the skin was localized in granular layer with diffuse staining pattern in normal skin, defect in psoriatic lesions, positive but thin in granular cells in the lesions of lichen planus. MT treatment showed a significant decrease in chemiluminescence induced by superoxide radicals and depressed signal intensity of hydroxyl radicals derived from the Fenton reaction system. From the viewpoint of characteristic localization and probable role in scavenging activity for reactive oxygen species, MT in the epidermis may contribute to the protection against phototoxic injury in association with enzymatic and non-enzymatic antioxidants. These findings may support the previous results of UV defense by cadmium-induced MT in the skin.
In an attempt to evaluate a quality of life (QL) grade of patients who underwent major gastrointestinal surgery, a physical activity index (PAI) representing their daily physical activity level was introduced in the present study. The relationship between the PAI and the QL grade, which was classified into four categories (excellent, good, fair, and poor) according to our diagnostic criteria, was investigated by using postoperative patients with total gastrectomy (n = 52) and other gastrointestinal major surgery (n = 54). The PAI value was derived from basal metabolic energy expenditure and whole day energy expenditure which was predicted by a 24 hours heart rate ratio method. The evaluation of the QL was based on clinical records and answers to a questionnaire submitted to the patient. The mean PAI of the gastrectomy patients (n = 15) was lowest during the postoperative 3 months (p less than 0.005), and was then gradually restored to nearly the preoperative value during the period between the 6th and 12th months. The four graded QL groups were compared with each other in terms of the mean PAI and energy expenditure. As a result, the QL grades were proportional to both of these values, indicating that the more favourable the QL grade, the higher the PAI and the energy expenditure (p less than 0.005). These results establish that if the evaluation of energy expenditure is valid the PAI could be potentially applicable to clinical use as one of the parameters that delineate the QL grade.
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