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Biomedical subjects

J Fujita

Publications and source records attributed to J Fujita.

At least 19 recordsLinked to original sources
PubMed1996

Characterization of a small-cell-lung-carcinoma cell line from a patient with cancer-associated retinopathy.

We examined the biologic properties of a small-cell-lung-carcinoma (SCLC) cell line (designated MN-1112) established from a patient with SCLC who showed paraneoplastic retinopathy syndrome. Morphologic and immunocytochemical analyses showed that MN-1112 cells possess features of the classic type of SCLC. MN-1112 cells grew in suspension forming relatively large clumps of cells with a doubling time of 72 hr. By light-microscope examination, the cells were relatively small and had scanty cytoplasm. The cells produced NSE, ACTH and CK (BB isozyme); they also expressed recoverin, a novel photoreceptor protein, detected by Northern-blot and Western-immunoblot analysis using human-recoverin-specific DNA probe and anti-bovine-recoverin polyclonal antibody. This report shows that human recoverin is expressed in cultured SCLC cells. Our results support the hypothesis that, in cancer-associated retinopathy (CAR) patients, auto-immune antibody targeting for ectopic recoverin in SCLC is initially produced and cross-reacts with the retinal protein, resulting in the retinal degeneration that occurs in CAR patients.

Aged↗
PubMed1996

Dose escalation study of carboplatin with fixed-dose etoposide plus granulocyte-colony stimulating factor in patients with small cell lung carcinoma. A study of the Lung Cancer Study Group of West Japan.

BACKGROUND: We performed a Phase I-II trial to determine the maximum tolerated dose of carboplatin (CBDCA) with a fixed dose of VP-16 and granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC) patients. METHODS: Treatment consisted of a starting dose of CBDCA, 400 mg/m2 (i.v., Day 1); VP-16, 100 mg/m2 (i.v., Days 1-3), and G-CSF, 2 micrograms/kg (s.c., Days 4-17) every 4 weeks for four cycles. The dose of CBDCA was escalated in increments of 50 mg/m2 until Grade IV toxicity on the World Health Organization scale developed in two-thirds or more of the patients. RESULTS: Seventy-five previously untreated patients with pathology confirmed SCLC were entered into the trial. Seventy-one patients were eligible and 70 patients were evaluated for response. Forty-five patients had limited disease (LD) and 26 had extensive disease (ED). The response rate of the 70 patients who could be evaluated was 81%, with 23% attaining a complete response (CR) and 58% attaining a partial response (PR). The response rate was 80% in LD patients (CR, 23%; PR, 57%) and 85% in ED patients (CR, 23%; PR, 62%). The major dose-limiting toxicity was thrombocytopenia. Nephrotoxicity, neurotoxicity, and ototoxicity were uncommon. The doses of CBDCA that resulted in unacceptable thrombocytopenia were 700 mg/m2 in patients younger than 70 years and 500 mg/m2 in patients older than 70 years. Overall median survival time (MST) was 9 months. MST of LD patients and ED patients were 11 months and 7 months, respectively. The dose-limiting toxicity of CBDCA with a fixed dose of VP-16 and using G-CSF as bone marrow rescue was age-related thrombocytopenia. The maximum tolerated dose of CBDCA was 650 mg/m2 if patients were younger than 70 years and 450 mg/m2 if they were 70 years or older. CONCLUSIONS: When we retrospectively compared our results with those using standard chemotherapy regimens, we saw no therapeutic benefit from increasing planned doses of CBDCA up to 700 mg/m2 in combination with G-CSF in patients with SCLC.

Aged↗
PubMed1996

Interleukin 6 receptor antibody inhibits muscle atrophy and modulates proteolytic systems in interleukin 6 transgenic mice.

The muscles of IL-6 transgenic mice suffer from atrophy. Experiments were carried out on these transgenic mice to elucidate activation of proteolytic systems in the gastrocnemius muscles and blockage of this activation by treatment with the anti-mouse IL-6 receptor (mIL-6R) antibody. Muscle atrophy observed in 16-wk-old transgenic mice was completely blocked by treatment with the mIL-6R antibody. In association with muscle atrophy, enzymatic activities and mRNA levels of cathepsins (B and L) and mRNA levels of ubiquitins (poly- and mono-ubiquitins) increased, whereas the mRNA level of muscle-specific calpain (calpain 3) decreased. All these changes were completely eliminated by treatment with the mIL-6R antibody. This IL-6 receptor antibody could, therefore, be effective against muscle wasting in sepsis and cancer cachexia, where IL-6 plays an important role.

Animals↗
PubMed1996

Elevated erythrocyte sodium-lithium countertransport activity correlates with increased intracellular sodium and free calcium-ion concentration in type 2 diabetes.

To explore the mechanism by which elevated sodium-lithium countertransport activity (SLC) associates with both predisposition to hypertension and diabetic nephropathy, we investigated the interrelationships among SLC, intracellular sodium concentration ([Na]i), intracellular free calcium-ion concentration ([Ca2+]i), diabetic nephropathy, hypertension, family history of hypertension, and other factors in 48 patients with Type 2 diabetes and 24 healthy controls. There was a significant correlation between SLC and [Na]i (r = 0.36, p < 0.05), [Na]i and [Ca2+]i (r = 0.47, p < 0.01), SLC and [Ca2+]i (r = 0.46, p < 0.01), and between HbA1c and [Ca2+]i (r = 0.38, p < 0.01). Both [Na]i and [Ca2+]i were significantly higher in the patients with elevated SLC than in those with normal SLC (p < 0.01 and p < 0.05, respectively). In stepwise multivariate regresssion analysis, [Na]i, HbA1c, and SLC appeared as independent determinants of [Ca2+]i. These data suggest a significant correlation of elevated SLC with increased [Na]i and [Ca2+]i. This may be a possible mechanism underlying the close association of elevated SLC with both predisposition to hypertension and diabetic nephropathy.

Adult↗
PubMed1996

Cancer-associated retinopathy syndrome: a case of small cell lung cancer expressing recoverin immunoreactivity.

Cancer-associated retinopathy (CAR) syndrome is a rare paraneoplastic neuropathy syndrome often found in patients with small cell lung cancer (SCLC). Serological studies have indicated that the process could include autoimmune reactions directing retinal antigens. Recently, the CAR antigen was identified as a photoreceptor protein, recoverin, by screening retinal proteins using the CAR patient's serum. The present case of SCLC showed rapidly deteriorated bilateral visual acuity lacking the inflammatory findings at the retina which were compatible with CAR. The immunohistochemical study revealed that the cancer cells expressed recoverin or recoverin-like immunoreactivity. This is the first observation in CAR syndrome. The presence of recoverin or recoverin-like immunoreactivity in SCLC with CAR syndrome supports the hypothesis that the cancer-retina immunologic cross-reaction contributes to visual loss in this syndrome.

Aged↗
PubMed1996

Detection of Pneumocystis carinii sequences in serum by polymerase chain reaction.

The clinical significance of the detection of Pneumocystis carinii DNA was evaluated, as well as the detection of circulating P. carinii antigen from serum using previously collected samples. Fourteen serum samples from 13 patients were diagnosed positively for P. carinii DNA by polymerase chain reaction (PCR). Ten of 14 episodes (71.4%) of pulmonary complications were compatible with P. carinii pneumonia. Two patients were definitely diagnosed as having had P. carinii pneumonia at autopsy. All patients positive for circulating antigens were also positive for P. carinii DNA, suggesting that the detection of P. carinii DNA by PCR is more sensitive compared to the detection of circulating antigens by the Ouchterlony method. It is concluded that the detection of P. carinii DNA in serum by PCR provides useful information for identifying P. carinii pneumonia.

Adult↗
PubMed1996

Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor.

Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. However, the relationship between the vascularity of HCC and the expression of angiogenic factors has not been investigated. In addition, no detailed studies have examined the possible involvement of angiogenic factors in the grade of malignancy of HCC. The aim of this study was to determine which angiogenic factors regulate tumor angiogenesis and contribute to the invasive ability of liver tumors, especially of HCC. Northern blot analysis was used to examine the transcriptional expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF), and acidic FGF in resected surgical specimens (20 HCC and 9 metastatic liver tumors). Correlations between messenger RNA (mRNA) expression and arteriographic findings, as well as histopathological findings, were evaluated. Immunohistochemistry was performed to identify the localization of cells expressing VEGF in HCC. Higher levels of VEGF mRNA were observed in 12 of 20 HCC and 2 of 9 metastatic liver tumors than in corresponding nontumorous tissues. The degree of VEGF mRNA expression was significantly correlated with the intensity of tumor staining in angiograms (P<.01). On immunohistochemical observation, VEGF protein was intensely detected in HCC cells. Furthermore, basic FGF mRNA was detected in 9 of 20 HCC and was related to the capsular infiltration of cancer cells (P<.05). In contrast, no significant difference was observed in the very low levels of acidic FGF mRNA found in the tumorous and nontumorous portions of the liver. In conclusion, these results suggest that VEGF contributes to angiogenesis of liver tumors, whereas basic FGF may be involved in the invasion of HCC into the surrounding tissues.

Aged↗
PubMed1996

Pregnancy-associated uterine granulated metrial gland cells in mutant and transgenic mice.

PROBLEM: Granulated metrial gland (GMG) cells are pregnancy-specific uterine lymphocytes found in rodents. The lineage relationships of GMG cells are incompletely defined, although genetic and immunophenotyping studies suggest membership in the natural killer (NK) cell lineage. Pregnancy-specific functions have been postulated for GMG cells, but no successful depletion of these cells has been achieved that would permit assessment of any critical roles that might influence gestational outcome. METHOD: Routine histological methods for light microscopy were used to assess implantation sites from wild-type mice and mice of the following genotypes: tgE26, mi/mi, and p53 knockout. RESULTS: GMG cells are transient, histamine-negative cells found in the pregnant uteri of most mice. Pregnancies in the NK and T-cell-deficient tgE26 were characterized by infrequent GMG cells, very small placentae, and an elevated rate of fetal and perinatal mortality. In term placentae of mi/mi with dystocia. GMG cells were found in a new location along the plane of placental separation, and they appeared degranulated. A normal life-history was observed for GMG cells in p53 knockout mice. CONCLUSION: Pregnancies in mutant and transgenic mice indicate that GMG cells are natural killer cells and have critical roles in placental development and pregnancy success. The disappearance of GMG cells at term is independent of p53 gene expression.

Animals↗
PubMed1996

Requirement for transglutaminase in progesterone-induced decidualization of human endometrial stromal cells.

Differentiation of endometrial stromal cells (decidualization) is essential for embryo implantation and maintenance of pregnancy. By sequential complementary DNA subtractive hybridization, one of the messenger RNAs (mRNA) induced by progesterone in human endometrial stromal cells decidualized in vitro was identified as that of a tissue transglutaminase type II (TGase). TGase mRNA was induced within 6 h after the addition of progesterone to the culture, and the effect was dose dependent. Both the TGase inhibitor monodansylcadaverine and oligodeoxynucleotide complementary to the TGase mRNA inhibited the decidualization, as assessed by PRL production and morphological transformation. Expression of TGase mRNA in human decidua and endometria exposed to high levels of progesterone in vivo was demonstrated by Northern blotting and in situ hybridization. These data suggest that TGase is necessary for the decidualization of human endometrial stromal cells and that clarification of the mechanism of action of TGase will facilitate further insight into the diagnosis and treatment of infertility.

Base Sequence↗
PubMed1996

Accounting for the peripartum loss of granulated metrial gland cells, a natural killer cell population, from the pregnant mouse uterus.

Natural killer (NK) cells become a prominent cell population in the rodent uterus during pregnancy. The mature, heavily granulated form of these cells is rare in virgin or postpartum uteri. Death, migration, or dedifferentiation could account for the disappearance of these cells from late gestation uteri. We asked whether uterine NK cells, also known as granulated metrial gland (GMG) cells, die in situ and if expression of Fas antigen is essential for their death. Late in gestation, fragmentation of nuclear DNA was detected histologically by OH-end labeling, as were ultrastructural changes suggesting cell death. NK cells developed in and were lost from the uteri of pregnant Fas antigen-deficient lpr/lpr mice. Postpartum samples of retained placentas contained some residual NK cells that had moved from regions of uterine musculature toward the uterine lumen and were being expelled with the placenta. Thus, both cell death and placental separation remove NK cells from the peripartum uterus.

Animals↗
PubMed1996

[Invasive pulmonary aspergillosis in a patient with acute leukemia--the role of neutrophil elastase in in cavity formation].

A 47-year-old man complaining of common cold-like symptoms was admitted to our hospital. Acute myelogenous leukemia was diagnosed and the patient was treated with induction chemotherapy. During granulocytopenia caused by induction chemotherapy, a nodular lesion appeared in the right upper lobe. The nodular lesion changed to a cavitary lesion after the recovery of peripheral white blood cell counts. A transbronchial biopsy specimen obtained from the right B3b showed Aspergillus. Oral itraconozole, flucytosine, and intravenous amphotericin B were given. The cavitary lesion in the right upper lobe regressed after anti-fungal therapy was started. During granulocytopenia caused by consolidation chemotherapy, the nodular lesion enlarged again. Thereafter, as bone marrow recovered, it changed to a cavitary lesion with a lung ball inside. In both episodes, a nodular lesion appeared during granulocytopenia, and changed to a cavitary lesion after bone marrow recovery. In addition, the level of neutrophil elastase reached its maximum at the time of the bone marrow recovery. These findings suggest that white blood cells of the host as well as neutrophil elastase play an important role in cavitation in pulmonary aspergillosis.

Aspergillosis↗
PubMed1996

[Comparative evaluation of 99mTc-MIBI (hexakis2-methoxy isobutyl isonitrile) and 201Tl-chloride in primary lung cancer].

We performed comparative study, using 99mTc-MIBI and 201Tl-chloride in patients with primary lung cancer. There were 42 patients with primary lung cancer. All patients underwent dual radionuclide imaging with 201Tl-chloride and 99mTc-MIBI. Regions of interest were placed over the tumor area (T) and contralateral normal lung area (N). A tumor to normal lung ratio (T/N ratio) and retention index were calculated by early and delayed ratios. In the SPECT images, the positive rate was 98% in both the early and delayed images for 201Tl-chloride and 95% in the early and 88% in the delayed images for 99mTc-MIBI. Both early and delayed T/N ratios of 201Tl-chloride were significantly higher than those of 99mTc-MIBI. The retention index of 201Tl-chloride was higher than that of 99mTc-MIBI. T/N ratio and retention index did not significantly correlated with reference to histological types. We conclude that 99mTc-MIBI SPECT can be helpful in localizing primary lung cancers. However, in our study the tumor accumulation of 99mTc-MIBI was significantly lower compared with 201Tl-chloride.

Adult↗
PubMed1996

[Comparison between high-resolution computed tomography and 99mTc-technegas SPECT pulmonary emphysema].

Scintigraphy with 99mTc-technegas was recently introduced for clinical imaging of lung ventilation. This method has been found to be useful in emergencies, to be more suitable for single photon emission computed tomography (SPECT) than other agents used in ventilation scintigraphy, and could reveal abnormalities in ventilation more easily than high resolusion computed tomography (HRCT) in pulmonary emphysema. We compared 99mTc-technegas SPECT with HRCT in six regions: the right upper, middle, and lower lobes, the left upper lobe, the lingula, and the left lower lobe, in 15 patients with pulmonary emphysema. Patients with centrilobular emphysema tended to show stronger changes in upper lobes than in lower lobes on both 99mTc-technegas SPECT and HRCT. Some regions showed no change on HRCT but various changes on 99mTc-SPECT. Patients with panlobular emphysema showed severe changes on 99mTc-SPECT in lower lung fields in which well-demarcated areas of low attenuation were not seen on HRCT. We conclude that 99mTc-SPECT is useful for detecting early changes and panlobular changes in pulmonary emphysema.

Adult↗
PubMed1995

Reduced expression of kan-1 (encoding putative bile acid-CoA-amino acid N-acyltransferase) mRNA in livers of rats after partial hepatectomy and during sepsis.

We isolated a cDNA clone, kan-1, from a rat liver cDNA library using a reverse transcriptase PCR cloning method. The kan-1 cDNA encoded a polypeptide of 420 amino acids, and was 70 and 69% identical in nucleotide and amino acid sequences respectively with human liver bile acid-CoA-amino acid N-acyltransferase (BAT). Thus Kan-1 is probably a rat homologue of human BAT (rBAT). Kan-1/rBAT mRNA was mainly expressed in the livers of adult rats and rats immediately after, but not before, birth. It was expressed in the hepatocytes, the sinusoidal endothelial cells and the Kupffer cells of the liver. An anti-Kan-1/rBAT polyclonal antibody detected a protein of molecular mass 46 kDa in the liver. After partial hepatectomy, the levels of Kan-1/rBAT mRNA decreased at 6 and 12 h in the regenerating liver. In a sepsis model, hepatic expression of Kan-1/rBAT mRNA decreased at 6 and 12 h after caecal ligation and puncture. The kinetics of Kan-1/rBAT mRNA expression suggests that it may play a role in acute-phase reactions.

Acyltransferases↗
PubMed1995

Autocatalytic inactivation of lysosomal cathepsins is associated with inhibition of protein breakdown by insulin-like growth factor-1 (IGF-1) in myotubes.

Protein breakdown was monitored in C2C12 myotubes as the rate of release of radioactivity after prelabeling cell protein with [3H] tyrosine. IGF-1 (13 nM) and insulin (100 nM) prolonged the half-life of long-lived proteins. Enzymatic activities of cathepsins B and B+L were inhibited by the addition of IGF-1 or insulin. Immunoblotting of cathepsins B and L revealed extensive degradation of heavy chain forms by IGF-1. However, neither expression of cathepsins B and L genes nor expression of cystatin beta, an intrinsic inhibitor for cathepsins, was influenced. The addition of E-64, L-3-carboxy-trans-2,3-epoxypropionyl-leucylamide-(4-guanidin o) butane, a inhibitor of cathepsins B and L, increased protein contents of heavy chains of cathepsins B and L in the IGF-1 treated cells. Inhibition of protein breakdown by IGF-1 is mediated by autocatalytic inactivation of lysosomal cathepsins B and L.

Analysis of Variance↗
PubMed1995

Presence of alternative 5' untranslated sequences and identification of cells expressing ctk transcripts in the brain and testis.

From a mouse brain cDNA library, two species of the Csk-type tyrosine kinase (ctk) gene containing different 5' untranslated sequences were cloned. Using the common as well as specific nucleotide sequences of the two clones as probes, we examined the expression of ctk in various mouse tissues by Northern blot analysis. The results indicated that both species of ctk were expressed in the brain, testis and bone marrow. By in situ histochemistry of the brain, ctk transcript was detected in neurons throughout the entire brain, especially those of the cortex, the hippocampus and the cerebellum. This distribution pattern is similar to that of the Src family kinases including Yes, Src, Fyn and Lyn. In the testis, the major transcript (0.7 kb) was shorter than that expressed in the brain and the bone marrow (2.0 kb). A subsequent Northern blot analysis of fractionated germ cell populations and in situ histochemistry revealed that the short and long transcripts were expressed in germ cells and somatic cells, respectively, and that the expression level was quantitatively regulated during germ cell development. These results suggest that Ctk is involved in the regulation of neural function and differentiation of male germ cells through interactions with member(s) of the Src family kinases.

Alternative Splicing↗