Biomedical subjects
Publications and source records attributed to Y Tsuchiya.
A 2 1/2-year-old Japanese boy with glycogen storage disease, type 9, developed proximal renal tubular acidosis (RTA). The RTA significantly improved in response to cornstarch therapy, implying a direct causal relationship between subtle metabolic derangements in glycogen storage disease, type 9, and proximal RTA.
Blood spot 17 alpha-hydroxyprogesterone (17-OHP) concentrations were measured in 515 infants aged from the 4th to the 81st day of life, using a fluorescence enzyme immunoassay method, and the values obtained were analyzed with respect to birth weight, gestational age at birth and sampling age, to obtain accurate reference ranges and to decide appropriate cut-off limits in a neonatal mass screening for steroid 21-hydroxylase deficiency. The results obtained indicate that the blood spot 17-OHP values in neonates should be interpreted using several different reference ranges obtained on the basis of the equivalent age of gestation at blood sampling. In the mass screening, therefore, the cut-off limits for recall are decided by these reference ranges as follows: (1) for blood resampling, 120, 30 and 25 nmol/l for the equivalent sampling ages of 31 weeks or less, 32-41 weeks and 42 weeks or more, respectively, and (2) for rapid confirmation of the disease by means of physical and laboratory examinations, 210, 60 and 60 nmol/l, respectively.
Doppler ultrasound detection of the blood flow associated with liver tumours was studied in primary hepatocellular carcinoma as well as in metastatic liver cancer and haemangioma. Doppler signals were detected from 48 of 55 hepatocellular carcinomas (87.3%), seven of 25 metastatic liver cancers (28.0%) and four of 30 haemangiomas (13.3%). The waveforms of Doppler signals were divided into two types: the pulsatile wave, which was detected from hepatocellular carcinoma (in 35 of the 48 with Doppler signals) and metastatic liver cancer (in all seven with positive signals), and the continuous wave, which was seen from hepatocellular carcinoma (41 out of 48) and haemangioma (in all four with signals). In six patients with hepatocellular carcinoma who underwent transcatheter arterial embolization, the pulsatile wave detected before therapy disappeared immediately thereafter and it is possible that this type of wave originates from tumour vessels. In the study of small, hypoechoic, mass lesions appearing in liver cirrhosis, such signals were also demonstrated, even in eight of 10 small hepatocellular carcinomas less than 2 cm in diameter, whilst they were not detected from nine regenerative nodules related to cirrhotic change. In conclusion, the Doppler ultrasound method may be a useful technique in detecting blood flow within liver tumours and may offer the possibility of a differential diagnosis of small tumours.
The effect of iodide on growth of rat thyroid cells (FRTL-5) was studied. TSH-stimulated cell growth was inhibited by iodide in a concentration-dependent manner, and an effect of iodide was detected at 10(-6) mol/l. KClO4 or 1-methylimidazole-2-thiol blocked the effect of iodide, suggesting that iodide uptake and its organification are required to produce the inhibitory effect of iodide on cell growth. Iodide not only decreased TSH-stimulated cAMP production in FRTL-5 cells but also cell growth induced by cAMP. These observations suggest that iodide inhibits TSH-stimulated growth of the cells by attenuating cAMP production and also by acting on the step(s) distal to cAMP generation. The inhibitory effect of iodide was also seen in growth stimulated by insulin, insulin-like growth factor-I or 12-O-tetradecanoyl phorbol 13-acetate, suggesting multiple sites of action of iodide in the process of growth of FRTL-5 cells.
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Primary cultured rat Kupffer cells stimulated with lipopolysaccharide (LPS) produced a hepatocyte stimulating factor (HSF), which enhanced the synthesis of acute phase protein, alpha 2-macroglobulin (alpha 2M), in adult rat hepatocytes. The Kupffer cell derived-HSF (KC-HSF), enhanced the synthesis of alpha 2M over 100 fold by primary cultured adult rat hepatocytes, in the presence of dexamethasone (Dex). The synthesis of albumin was not stimulated by the factor, even in the presence of Dex. The alpha 2M mRNA increased exponentially starting at 3 hr after addition of the factor. Therefore, the synthesis of alpha 2M stimulated by KC-HSF is probably controlled at the pretranslational phase. The LPS stimulated production of the KC-HSF was inhibited by actinomycin D. The HSF was precipitated between 35% and 65% saturation with ammonium sulfate and collected in the over 30,000 daltons fraction, by molecular sieving. Sephacryl S-200 gel chromatography revealed two distinct forms of HSF with apparent molecular weights of approximately 30,000 and 100,000 daltons. The majority of the activity was recovered in the latter fraction. Isoelectric chromatofocusing of the 100,000 daltons form of HSF yielded a single peak of activity with an apparent isoelectric point (pI) of 4.2. Each fraction contained the interleukin-1 (IL-1) activity, determined by thymocyte proliferation assay. These results show that Kupffer cells produce a cytokine, KC-HSF with IL-1 activity but different properties, as seen on the on Sephacryl S-200 gel filtration and isoelectrofocusing from known mouse or human IL-1.
Rat Kupffer cells stimulated with bacterial lipopolysaccharide (LPS) produced high levels of interleukin 1 (IL-1), determined by assaying the thymocyte proliferating activity. The unstimulated Kupffer cells secreted no detectable activity. LPS-induced production of IL-1 activity was dose-dependent and as little as 0.1 micrograms/ml of LPS induced the IL-1 production. Thirty minutes were required for LPS to induce sufficient amounts of IL-1 activity. IL-2 activity was not detected in the Kupffer cell culture medium. Another soluble agent, N-acetylmuramyl-L-alanyl-D-isoglutamine, or phagocytable agents, silica and zymosan, also stimulated IL-1 production by Kupffer cells, whereas phorbol myristate acetate did not. Kinetic studies revealed a rapid increase in both intra- and extracellular IL-1 activity within 1 hr following the addition of LPS, with a peak at 6 hr. This IL-1 activity produced by Kupffer cells was heat labile, resistant to freezing and thawing and precipitated with 65% ammonium sulfate. Upon gel filtration, the activity was present in three peaks of approximately 110, 35 and 15 kd. The hepatocyte stimulating activity, when assayed by alpha 2-macroglobulin inducing activity, was detected in the first two peaks but not in the third peak. These studies suggest that LAF activity is distinct from hepatocyte stimulating activity at least in the molecular weight.
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Apparent reduction of leukocyte counts was observed in mice irradiated with 1,500 approximately 3,000 rads of X-ray on the left hind leg. This reduction of leukocyte counts was completely protected by the pre-treatment with lentinan before X-ray irradiation. Suppressive effect of X-ray on the antitumor function of lentinan seems to be weak. When treatment with X-ray irradiation and lentinan was applied for mice bearing solid type sarcoma 180, additive effect was obtained by the combination of lentinan before or after X-ray irradiation.
C3H/He mice transplanted syngeneic MM102 tumor subcutaneously in the footpad were used to study the timing of administration of lentinan when combined with local irradiation of X-ray. In combination with 1,000 rads irradiation, the administration of lentinan after X-ray was not effective. When lentinan was administered in combination with 2,000 to 3,000 rads irradiation, the growth of tumor was decreased significantly in comparison with the groups which received radiotherapy alone and those that received lentinan alone. The administration of lentinan before irradiation was effective at the same degree in the group that received lentinan after irradiation. Life prolongation effect was also observed in the group that received lentinan before and after irradiation, and 4 mice among 8 tested mice were survived at 70th day after tumor transplantation.
Combination effect of lentinan with X-ray irradiation on the metastatic mouse tumors, L1210, KLN205 and Lewis lung carcinoma were studied. Combination use of lentinan with X-ray therapy prolonged the life of BDF1 mice bearing L1210 leukemia in the suitable combination conditions. Combination effects of lentinan with X-ray therapy were also observed on the suppression of the growth of KLN205 squamous cell carcinoma and on the suppression of the metastasis of Lewis lung carcinoma. Especially, in the case that lentinan was administered before or after X-ray local irradiation in the pulmonary metastasis system of Lewis lung carcinoma, a marked suppression of pulmonary metastasis was observed and 2 to 4 mice among 8 tested mice were tumor free.
Rat alpha 2-macroglobulin (alpha 2M) is an acute-phase reactant, concentration of which in serum increases more than 100-fold in the course of inflammation. Glucocorticoid and some protein factors such as interleukin 1 (IL-1) have been known to be involved in the regulation of this plasma protein synthesis. To understand the regulatory mechanism of alpha 2M production at the molecular level, we isolated genomic DNA clones of rat alpha 2M gene and characterized the promoter region of the gene by comparing the nucleotide sequence with those of other acute-phase reactant genes. Several possible regulatory signals were identified. Particularly, a sequence (T/A)T(C/G)TGGGA(A/T) was found about at 170 bp upstream from a putative capping site, which was also found in the 5'flanking region of various acute-phase reactant genes.
Venous blood sera from children infected with Mycoplasma pneumoniae (MP) responded with a high titer to MP antibodies, affected healthy normal erythrocytes in vitro, and gave rise to changes in erythrocyte osmotic fragility. When serum was inactivated at 56 degrees C for 30 min or preincubated with anti-human C1 esterase inhibitor, the changes in the osmotic properties were suppressed at the lower level. The total sialic acid content and the intracellular ATP concentration of the treated erythrocytes were analyzed.
This is a report of three cases using the Y-shaped anastomotic technique. Y-shaped anastomoses were found to be extremely useful in selected clinical situations for free flap transfers.
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When stimulated with lipopolysaccharide (LPS), primary cultures of Kupffer cells from the rat secreted a hepatocyte-stimulating factor (Kupffer factor) which induced the synthesis of alpha 2-macroglobulin (a2M) by hepatocytes. The effect of this Kupffer factor was found only when dexamethasone was present in the hepatocyte culture medium. Dexamethasone alone stimulated the a2M synthesis, to some extent, in a dose-dependent manner. When both Dex and the Kupffer factor were added to the medium, cultured hepatocytes synthesized 100-fold a2M, quantitative evidence that explains the in vivo phenomenon in which the serum a2M concentration increases more than 100-fold in the acute phase. A co-culture study with hepatocytes and Kupffer cells indicated that the latter cells have a major function in the induction of a2M synthesis in vivo. A hybridization study with rat a2M cDNA showed that the concentration of mRNA increased in cultured hepatocytes in the presence of the Kupffer factor, but only when dexamethasone was present. From these results we concluded that Kupffer cells secrete a hepatocyte-stimulating factor when stimulated by LPS and that glucocorticoid is essential for the induction of a2M in rat hepatocytes. The effect of the Kupffer factor and glucocorticoid appears to be regulated in the pretranslational, probably the transcriptional, phase.