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Biomedical subjects

S Yoshida

Publications and source records attributed to S Yoshida.

At least 919 records · Page 51Linked to original sources

Growth inhibition of human glioma cells modulated by retrovirus gene transfection with antisense IL-8.

The human glioma cell line, NP-1, expresses IL-8 mRNA and constitutively secretes IL-8 protein. Administration of recombinant IL-8 increased the proliferation of NP-1 cells in a dose-dependent manner. In the presence of anti-IL-8 antiserum, the IL-8 mediated proliferation of NP-1 cell growth was inhibited. Further, NP-1 cell growth was inhibited by transfection of retroviral constructs encoding antisense IL-8 both in vitro and in vivo models. These results suggest that antisense IL-8 gene therapy could be beneficial in gliomas where autocrine stimulation by IL-8 is implicated.

3T3 Cells↗

Clinicopathologic features of early rectal carcinoma and indications for endoscopic treatment.

PURPOSE: This study was undertaken to clarify the indications for endoscopic treatment. METHODS: Clinical and pathologic features of 191 lesions in 180 patients with early rectal carcinoma were examined, including 110 intramucosal carcinomas and 81 carcinomas with submucosal invasion (submucosal carcinomas). All lesions had been endoscopically or surgically resected at the National Cancer Center Hospital between 1976 and 1990. RESULTS: Metastasis to regional lymph nodes (LN metastasis) was seen in 0 percent (0/39) of intramucosal carcinomas and 9.2 percent (6/65) of submucosal carcinomas in the surgically treated patients. The incidence of LN metastasis was higher for lesions larger than 10 mm in diameter, for those showing massive submucosal invasion, and for moderately differentiated adenocarcinomas. LN metastases were associated significantly with lymphatic invasion. CONCLUSIONS: These results suggest that early rectal carcinomas should be resected surgically if they 1) show massive submucosal invasion, 2) are classified as moderately differentiated adenocarcinomas, and 3) are larger than 10 mm in diameter. In patients with both scanty submucosal invasion and features of well-differentiated adenocarcinoma or intramucosal carcinoma and if no other risk factors for LN metastasis are present, such as lymphatic invasion by the primary lesion, surveillance may suffice after endoscopic resection.

Adult↗

Bunina body formation in amyotrophic lateral sclerosis: a morphometric-statistical and trace element study featuring aluminum.

Clinico-environmental and pathological variables were obtained from 10 patients with amyotrophic lateral sclerosis using particle-induced X-ray emission spectrometry (PIXE) and morphometric-statistical analysis. Statistical analysis identified a model that maximally predicts the Bb% (frequency of Bunina bodies) from a selected set, four variables: (1) nucleolar index, (2) magnesium (Mg) content, (3) aluminum (Al) content, and (4) duration of illness. Among them, only the Al content proved important. To determine their chemical nature, electron energy loss spectrometry (EELS) was applied at the ultrastructural level; it revealed that within the motor neuron, Al strongly binds to the Bunina body as well as rough endoplasmic reticulum (rER), and lesser strongly to mitochondria and lipofuscin granule. Thus, it is chemically similar to the rER, providing preferential binding sites to aluminum. The Bunina bodies may be an end-product of the nucleic acid dysmetabolism at rER caused by Al along with Mg depletion.

Adult↗

Ontogeny of neuropsin mRNA expression in the mouse brain.

In our previous study, we found a novel gene encoding a serine protease termed neuropsin (NP) which exhibited activity-dependent gene expression or repression in the mouse hippocampus (Chen et al., 1995). In the present study, we examined the ontogeny of NP mRNA expression by in situ hybridization in the brain. Weak hybridization signals were also observed in the choroid plexus at this stage in addition to neuronal labeling. The signals continued to show this localization pattern until postnatal day 12. After embryonic day 18, the number of hybridization signals localized in the neurons of the forebrain limbic area were more predominant than those in the lower brainstem. NP gene expression spread in the anterior olfactory nucleus, hippocampus, septal nuclei, diagonal band of Broca, amygdala and limbic cortex successively from early embryonic to adult stage, though signals in the other brain regions were gradually decreased after birth. Thus, the widespread localization and two types of expression pattern, constitutive or transient, suggest that NP is a multiple functional protein involved in development, neuronal plasticity and cerebrospinal fluid production.

Animals↗

Developmental changes in the electrophysiological properties of neonatal rat oculomotor neurons studied in vitro.

The electrophysiological properties of oculomotor neurons were studied in neonatal rats aged 1-15 days. Action potentials were recorded from brainstem slices (frontal section) using the intracellular recording method at 35 degrees C. No significant age-dependent differences were detected in the resting potential (around -55 mV) and in the amplitude of the action potential (approximately 60 mV). However, the input resistance of oculomotor neurons declined with age from a mean of 60.8 M omega for rats 1-3 days old to 17.0 M omega for rats 14-15 days old. In addition, the duration of the action potential measured at the half-amplitude gradually decreased from 0.74 ms to 0.34 ms with increasing age. Increases were detected in the maximum rate of rise (from 117 V/s to 181 V/s) and the maximum rate of fall (from -67 V/s to -103 V/s) of the action potential. When long-lasting (500 ms) depolarizing current pulses were applied to oculomotor neurons, some neurons exhibited continuous repetitive discharge (i.e. tonic firing) while others showed transient discharge (phasic firing). The proportion of tonic-type neurons increased with age: the value was 9% for rats 1-5 days old, 37% for rats 6-10 days old and 54% for rats 11-15 days old. Concomitantly, the number of neurons showing a time-dependent inward rectification increased and the average maximum frequency of the discharge rose from 150 to 420 Hz, approximately, with age. Furthermore, it was found that the electrophysiological properties of oculomotor neurons of rats 14-15 days old were similar to those in adult rats. It is concluded that oculomotor neurons in neonatal rats show rapid alterations in their electrophysiological properties and that the ratio of tonic-type to phasic-type neurons changes during the early stages of development.

Action Potentials↗

A female heterozygous patient with Fabry's disease with renal accumulation of trihexosylceramide detected with a monoclonal antibody.

We describe a female patient with heterozygous Fabry's disease. The patient had persistent proteinuria and microhematuria but lacked any other diagnostic signs such as corneal and cutaneous involvement. Kidney tissue obtained at biopsy showed the segmentally distributed enlarged glomerular epithelia. These cells were filled with vacuolated foamy cytoplasm, which had lamellar and myelinoid structures under electronmicroscopic observation. Accumulation of trihexosylceramide (CTH) in these foamy epithelial cells was confirmed with immunohistochemical staining with the use of anti-CTH monoclonal antibody. Alpha-galactosidase activity of leukocytes was 67 nmol/mg protein/hr, which was approximately half that of the normal population (mean +/- SD, 147 +/- 65 nmol/mg protein/hr, n = 20). All of these findings were compatible with the diagnosis of heterozygous Fabry's disease. We recommend that kidney tissue biopsy specimens suggesting Fabry's disease be immunostained with anti-CTH antibody.

Antibodies, Monoclonal↗

Mice deficient for the IL-3/GM-CSF/IL-5 beta c receptor exhibit lung pathology and impaired immune response, while beta IL3 receptor-deficient mice are normal.

The receptors for IL-3, GM-CSF, and IL-5 share a common beta subunit (beta c), and mice have an additional IL-3 beta subunit (beta IL3). We have independently generated mice carrying null mutations of each molecule. beta c mutant bone marrow showed no response to GM-CSF or IL-5, whereas IL-3 stimulation of beta c or beta IL3 mutant bone marrow was normal. beta c mutant mice showed lung pathology consisting of lymphocytic infiltration and areas resembling alveolar proteinosis, and also exhibited low basal numbers of eosinophils. Infection of beta c mutant mice by Nippostrongylus brasiliensis resulted in the absence of blood and lung eosinophilia. Animals repopulated with beta c mutant bone marrow cells showed slower leukocyte recovery and reduced eosinophil numbers. These data define the role of beta c in vivo, and show a phenotype that is likely to be the cumulative effect of loss of GM-CSF and IL-5 stimulation.

Animals↗

Gene transfer and expression in progeny after intravenous DNA injection into pregnant mice.

Several methods that enable foreign genes to be transferred directly into germ cells and adult animals have been developed, which have stimulated great interest in manipulating genes in vivo. However, there have been no methods available for introducing genes into fetuses. We report here that a single intravenous injection of expression plasmid: lipopolyamine complexes into pregnant mice resulted in successful gene transfer into the embryos. The transgenes thus introduced were expressed in the fetuses and newborn progeny. This simple and new method of gene transfer into embryos will facilitate rapid analysis of transgene effects in the fetuses and will be useful for studying gene-deficient animal models to gain transgene functions at desired stages of embryogenesis.

Animals↗

Roles of stem cell factor in the in vitro growth of blast clonogenic cells from patients with acute myeloblastic leukemia.

We investigated the effects of stem cell factor (SCF) on the growth of blast clonogenic cells from 27 patients with acute myeloblastic leukemia (AML) and 3 patients with chronic myelocytic leukemia in myeloid crisis. SCF alone showed a significant stimulatory activity in 15 of 30 patients (50%). A marked reduction in the number of blast cell colonies supported by SCF alone was noted by the addition of neutralizing antibody (Ab) against granulocyte-macrophage colony-stimulating factor (GM-CSF). Ab against interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) also moderately reduced the number of colonies, whereas Ab against granulocyte CSF (G-CSF) failed to do so. All four Ab together completely abolished the growth in 5 of 6 patients tested. c-kit antisense oligonucleotides reduced the colony formation supported by IL-3 or G-CSF or, in the absence of growth factor, in only 2 of 10 patients tested. SCF caused stimulation by acting synergistically with G-CSF, GM-CSF, IL-3, IL-6, IL-9, IL-11, and IL-12 in 20 of 27 (74%), 17 of 27 (63%), 14 of 28 (50%), 9 of 28 (32%), 1 of 15 (7%), 3 of 28 (11%), and 2 of 15 (13%) patients, respectively. Thus, SCF alone or in combination with some other factor stimulated the growth in 27 of 30 (90%) patients. Of 3 nonresponders, 2 were AML, M3 at presentation. G-CSF at the optimal concentration increased the sensitivity of blasts to SCF. Taken together, SCF acting in combination with other factors, but not alone, stimulates the growth of blast clonogenic cells. GM-CSF, IL-6, and TNF-alpha may be produced endogenously, whereas G-CSF and SCF may be supplied exogenously. Autocrine regulation of the growth of blasts seems to increase the responsiveness of the cells to any of these factors, allowing them to achieve a highly active growth state.

Base Sequence↗

Reduced implantation rate associated with a subtle rise in serum progesterone concentration during the follicular phase of cycles stimulated with a combination of a gonadotrophin-releasing hormone agonist and gonadotrophin.

Our objective was to assess the effects of subtle increases in serum progesterone concentration (1.0-2.0 ng/ml) on the outcome of in-vitro fertilization (IVF), particularly on the quality of embryos, during the follicular phase of cycles stimulated with gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG). A total of 97 patients underwent 116 cycles of IVF and were stimulated with a combination of HMG and GnRHa. They were divided into two groups: those with a subtle progesterone rise and those with no progesterone rise. The two groups were compared with respect to serum oestradiol, progesterone, immunoreactive luteinizing hormone (I-LH), bioactive LH (B-LH), and results of IVF. The groups did not differ significantly in mean age or in total dose of HMG received. On the day that human chorionic gonadotrophin was administered, concentrations of oestradiol and progesterone were significantly higher in the subtle progesterone rise cycles than in the no progesterone rise cycles. In the no progesterone rise cycles, the percentages for embryos beyond the 4-cell stage, grade 1 embryos, and implantation rates were significantly higher than those in subtle progesterone rise cycles. The combination of GnRHa and HMG eliminated any significant rise in serum I-LH or B-LH concentration during the follicular phase, but did not suppress the subtle rise in progesterone. These results confirm our previous finding that a subtle progesterone rise adversely affects the outcome of IVF. It is also suggested that a reduction in embryo quality may influence the lower rate of implantation in subtle progesterone rise cycles.

Adult↗

Selective inhibition of DNA polymerase epsilon by phosphatidylinositol.

We studied the effects of various phospholipids on the DNA synthesizing reactions by calf thymus DNA polymerases alpha, delta, and epsilon. Of these three enzymes, DNA polymerase epsilon was most sensitive to acidic phospholipids, i.e., phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP), phosphatidylserine (PS), phosphatidic acid (PA), and cardiolipin (CAR). Of these acidic phospholipids, PI (from bovine liver) is of special interest because it inhibited DNA polymerase epsilon much strongly than DNA polymerase alpha and delta. The inhibition of DNA polymerase epsilon by PI was competitive with the DNA template-primer and was noncompetitive with dTTP substrate. The Ki value was estimated to be 16 microM. These results indicate that PI from bovine liver can be used as a specific inhibitor for DNA polymerase epsilon to analyze its role in DNA replication. Interestingly, the PI isolated from soybean, which has a different fatty acid composition, inhibited not only DNA polymerase epsilon but also DNA polymerase alpha.

Animals↗

Mucin-producing tumor of the lung: CT findings.

Primary lung tumors and pulmonary metastases with a large mucin content are relatively rare, and reports of CT findings are scarce. We present the CT images of patients with mucinous bronchioloalveolar carcinoma and lung metastasis of mucinous adenocarcinoma of the colon. The CT findings include a uniform low attenuation (4.5 and 7.8 HU), irregular margins, and slight enhancement after intravenous injection of contrast medium.

Adenocarcinoma, Bronchiolo-Alveolar↗

Temperature effects on Legionella pneumophila killing by and multiplication in phagocytes of guinea pigs.

We examined the effects of temperature on the interaction between Legionella pneumophila and phagocytes of guinea pigs. The body temperatures of guinea pigs infected with a sublethal dose (1.2 x 10(4) CFU) or a lethal dose (1.0 x 10(5) CFU) of L. pneumophila elevated from 38.4 +/- 0.15 C to 40.2 +/- 0.42 C or 40.3 +/- 0.62 C, respectively. The intracellular bacterial killing by and bacterial proliferation in the phagocytes were examined at 33, 37, 40, and 42 C, using in vitro culture systems of peritoneal macrophages or polymorphonuclear leukocytes (PMN) of guinea pigs. In all the macrophages incubated at different temperatures, significant intracellular bacterial killings were observed at 4 hr after in vitro phagocytosis. After 24 hr of incubation, there was about a 100-fold increase of CFU and the number reached a maximum after 48 hr of incubation in the macrophages incubated at 42 C as well as 37 and 40 C, suggesting that macrophages support the intracellular bacterial growth in hyperthermia. In the PMN, L. pneumophila CFU 4 hr or 12 hr after the infection were significantly lower at 42 C than those at 37 C (P < 0.05), indicating that the bactericidal capacity of PMN was enhanced at 42 C compared to 37 C. However, in all the PMN incubated at different temperatures, there were about 10-fold increases of CFU 24 hr after the infection, suggesting that PMN as well as macrophages support intracellular bacterial growth in hyperthermia. The extracellular bacterial growth was examined at 33, 37, 40, and 42 C in buffered yeast extract (BYE) broth or RPMI 1640 medium containing 50% guinea pig serum as a permissive or non-permissive liquid medium for the bacterial growth, respectively. Inhibition of bacterial growth in BYE broth at 42 C, and a decrease of CFU in RPMI 1640 medium containing 50% guinea pig serum at 42 C were observed. In conclusion, hyperthermia may be beneficial by restricting extracellular bacterial survival, but it exerts no beneficial effect on the restriction of intracellular bacterial growth in phagocytes, though PMN showed enhanced initial killing at 42 C. These results suggest that fever, or hyperthermia itself, may not largely contribute as a nonspecific host defense early in the course of legionellosis.

Animals↗

Helicobacter pylori infection, serum pepsinogen level and gastric cancer: a case-control study in Japan.

We conducted a case-control study to evaluate the effect of Helicobacter pylori (HP) infection on the risk of gastric cancer in Tokyo, Japan. The sera at the time of diagnosis from 282 gastric cancer cases and 767 sex- and age-matched cancer-free controls were tested for the presence of anti-HP IgG antibody (HM-CAP ELISA kit) and serum pepsinogen (PG) level (PG I and PG II Riabead). No significant association was observed in all sets [matched odds ratio (OR) = 1.04, 95% confidence interval: 0.73-1.49]. In subgroup analyses, however, an association was suggested in females [OR = 1.57], a younger population (< 50 years) [OR = 1.86], early cancer [OR = 1.53] and small cancer (< 40 mm) [OR = 1.55]. Furthermore, we observed a tendency for odds ratios to decrease with an increase in age or cancer growth (depth of tumor invasion and tumor size). Considering that the spontaneous disappearance of HP due to extended mucosal atrophy may lead to these decreasing odds ratios, we applied the conditional logistic model adjusted for the PG I/II ratio as a measure of atrophic gastritis. This analysis showed a positive association with HP infection in all sets [OR = 1.69; 1.01-2.81], distal cancer [OR = 1.88; 1.07-3.31] and intestinal-type cancer [OR = 3.76; 1.39-10.18]. We concluded that the risk of cancer associated with HP infection may be underestimated in studies with cross-sectional exposure because of spontaneous disappearance of HP due to extended mucosal atrophy.

Adult↗

Expression of integrin alpha 3 in gastric and colorectal cancers: its relation to wall contraction and mode of invasion.

We macroscopically classified 25 gastric and 23 colorectal advanced cancers into "contracted" and "uncontracted" types, and found immunohistochemically that integrin subunit alpha 3 was more frequently expressed in the extracellular matrix (ECM) in the former than in the latter (75%:9/12 vs. 38%: 5/13 in gastric and 86%:6/7 vs. 25%:4/16 in colorectal cancers, respectively). Integrin subunit alpha 3 was also expressed more frequently in cancers producing transforming growth factor-beta (TGF-beta), which is related to ECM deposition, integrin expression and cell mobility, than in those which did not produce TGF-beta (67%:10/15 vs. 40%:4/10 in gastric and 57%:4/7 vs. 38%:6/16 in colorectal cancers, respectively). In addition, integrin subunit alpha 3 was not expressed in 2 benign gastric ulcers combined with gastric cancer elsewhere in the stomach. On the other hand, a retrospective analysis of 107 cases of rectal cancer which recurred after a curative operation revealed that local recurrence was more frequent in "contracted" than "uncontracted" types (44%:11/25 vs. 26%:21/82). These results may suggest that the abundant interstitial fibrosis which leads to remarkable gastric or colorectal wall contraction is a result of the interaction between cancer cells and ECM, along with the expression of integrin and/or the production of TGF-beta. This fibrosis may also be closely related to the mode of gastric and colorectal cancer invasion.

Antigens, CD↗