Biomedical subjects

H Shida

Publications and source records attributed to H Shida.

At least 37 records · Page 2Linked to original sources

PubMed1996

Radiologic and pathologic characteristics of mixed dust pneumoconiosis.

Modern radiologic technology has to led to increased diagnostic efficacy and accuracy in demonstrating pulmonary changes secondary to occupational dust exposure. This article presents three cases of typical and two cases of atypical silicosis with rounded atelectasis as seen in computed radiographic (CR), computed tomographic (CT), and scintigraphic images and autopsied lung specimens. Chest radiographs revealed both small rounded and small irregular opacities. Small irregular opacities on chest radiographs often proved to be reticular or honeycomb patterns on CT scans. Irregular opacities seen on CR and CT images represented interstitial fibrotic or mixed dust fibrotic changes associated with the accumulation of birefringent particles and emphysematous change, as noted at histologic analysis. CT scans and scintigrams were useful for visualizing parenchymal abnormalities, especially fibrotic change, emphysematous change, and pleural abnormalities.

Aged↗

PubMed1995

Vaccination of rabbits with recombinant vaccinia virus carrying the envelope gene of human T-cell lymphotropic virus type I.

Two groups of 3 rabbits each were immunized with either recombinant vaccinia virus, WR-SFB5env, carrying the human T-cell lymphotropic virus type I (HTLV-I) env gene at the site of the hemagglutinin gene of the WR strain, or control vaccinia virus, HA-WR, lacking the functional hemagglutinin gene. All 6 rabbits responded with anti-vaccinia virus antibodies. WR-SFB5env elicited anti-HTLV-I env antibodies but no vesicular stomatitis virus (HTLV-I) pseudotype neutralizing antibodies in all 3 rabbits. After 10 weeks, the animals were challenged by transfusion of blood from an HTLV-I-infected rabbit. Two of the 3 vaccinated rabbits and all 3 control rabbits became infected with HTLV-I, as indicated by seroconversion and detection of HTLV-I proviral sequences by polymerase chain reaction. The rabbit that had been protected from initial challenge became infected with HTLV-I upon rechallenge 12 weeks after the first challenge. In view of the proven prophylactic effect of passive immunization against HTLV-I, our vaccine trial failed because WR-SFB5env was incapable of inducing neutralizing antibodies against HTLV-I in the immunized animals. It remains to be studied whether cell-mediated immunity such as antibody-dependent cellular cytotoxicity was involved in the temporary protection of I vaccinated rabbit.

Animals↗

PubMed1995

In vitro induction of cytotoxic T lymphocytes against HTLV-I-infected T-cells from adult T-cell leukemia patients, asymptomatic HTLV-I carriers and seronegative healthy donors.

We investigated an in vitro method to produce cytotoxic T lymphocytes (CTLs) against HTLV-I-infected T-cells using peripheral blood mononuclear cells (PBMC) of adult T-cell leukemia (ATL) patients, asymptomatic HTLV-I carriers (AC) and seronegative healthy donors. The PBMC were restimulated repeatedly for 4 weeks with HLA-matched HTLV-I-infected T-cells which had been pretreated at 56 degrees C for 30 min to inactivate infectious HTLV-I. The culture medium included 10-100 units/ml of recombinant lymphokines (rIL-1, rIL-2, rIL-4, rIL-6 and rIL-7) and 10% fetal calf serum in RPMI-1640 medium. The cytotoxic activity was measured against HLA-matched HTLV-I-infected T-cell lines after CD4+ or CD8+ cells were positively panned from the cultured PBMC. The PBMC of ATL, AC and healthy donors were able to produce either CD4+ or CD8+ CTLs against HTLV-I-related antigens (env, gag, p21x, p27rex and p40tax) as well as the antigen(s) of as-yet unknown specificity expressed on HTLV-I-infected T-cells. All the CTLs recognized the specific antigens in the context of either class I or class II HLA types. These results indicated that ATL patients, AC and healthy donors were immunocompetent to generate CTLs against HTLV-I-infected T-cells and probably against HTLV-I-transformed T-cells.

Adult↗

PubMed1995

Effects of translation initiation factor eIF-5A on the functioning of human T-cell leukemia virus type I Rex and human immunodeficiency virus Rev inhibited trans dominantly by a Rex mutant deficient in RNA binding.

The viral transactivator proteins Rex and Rev are necessary for the expression of structural proteins of human T-cell leukemia virus type I and human immunodeficiency virus type 1, respectively. Although the interaction of Rex/Rev with a cellular cofactor(s) has been thought to be required for Rex/Rev action, there is no suitable system to search for the cofactor(s) in mammalian cells. We found that a Rex mutant, TAgRex, which contains a simian virus 40 nuclear localization signal in place of the N-terminal 19 amino acids of Rex, could dominantly inhibit wild-type Rex/Rev functions. The inhibition did not require either Rev response element/Rex response element binding or the oligomerization ability of the mutant, but it did require a region around amino acid 90 of the Rex protein, suggesting that TAgRex sequestered the cellular cofactor. Complementation with the eukaryotic translation initiation factor 5A (eIF-5A) in this system could restore the impaired Rex function. These results indicate that eIF-5A is the cofactor indispensable for Rex function. Additionally, by using a two-hybrid system, the homo-oligomer formation of Rex was found to be mediated by the region around amino acid 90 in addition to Tyr-64 and Trp-65 of Rex protein. Thus, eIF-5A may play a part in the formation of the Rex homo-oligomer.

Animals↗

PubMed1995

Rounded atelectasis associated with silicosis.

Two cases of autopsy-proven, silicosis-associated rounded atelectasis (SARA) are reported. Clinicopathologically, SARA shows a combination of rounded atelectasis and the typical features of silicosis. Pathologically, SARA is characterised by the presence of numerous silicotic nodules deposited throughout the atelectatic lung tissue, which otherwise shows the ordinary features of rounded atelectasis. SARA may contribute to the development of massive fibrosis in silicotic lungs.

Aged↗

PubMed1995

[Continuous intraarterial infusion of 5-fluorouracil plus leucovorin for liver metastases from colorectal cancer].

Between September 1990 and August 1994, 11 patients (pts) with liver metastases (mets) from colorectal cancer were treated with continuous hepatic arterial infusion chemotherapy of 5-fluorouracil (FU) plus leucovorin (LV). Eight pts had non-resectable liver mets (H3: 7, H2: 1), and 3 had residual small mets after resection of major mets. Drugs were administered via an extracorporeal infusion device connected to the hepatic arterial infusion port. 5-FU and LV were given through a 5- to 7-day continuous infusion at 500-750 mg/body/day and 30 mg/body/day, respectively, with a 3- to 4-week rest period. In the recent 6 pts, cisplatin was administered as a 2-hour infusion at 25 mg/body, one or two times simultaneously. Grade 2 toxicity was noted in two pts (18%). One was stomatitis and another was uncontrolled ascites in an advanced cirrhotic pt. The response rate in the 9 evaluable pts was 67% with 6 PR and no CR. The duration of the response was 5 to 9 months. One- and two-year survival rates were 75% and 22%, respectively. These results were superior to those of the intermittent bolus injection of 5-FU plus MMC (or epirubicin) in 40 pts from 1977 to 1994. These results suggest that continuous 5-FU plus LV arterial infusion is an effective regimen in pts with liver metastases from colorectal cancer. However, the infusion with an extracorporeal device limits the pts' quality of life. Further investigation is needed for a schedule that can be practiced for a longer period.

Aged↗

PubMed1995

[A case of multiple liver metastasis from remnant gastric cancer responding to leucovorin.5-FU+UFT therapy].

We report a case of a 67-year-old male patient who experienced multiple liver metastasis 6 months after undergoing an operation for remnant gastric cancer. The histological classification of the cancer in gastric remnant was poorly-differentiated adenocarcinoma. The patient was treated with a low dose of LV.5-FU once a week and oral UFT as an outpatient. As a result, after 3 months of the treatment, CT showed that multiple liver lesions almost disappeared, a condition that lasted about 3 years without relapse. Toxic effects due to this treatment were temporary slight liver disfunction, mild anorexia and stomatitis. This case indicates that the regimen of LV.5-FU+UFT may be effective for multiple liver metastasis from postoperative remnant gastric cancer, enabling the patient to maintain an excellent QOL (quality of life).

Adenocarcinoma↗

PubMed1994

Constructions of vaccinia virus A-type inclusion body protein, tandemly repeated mutant 7.5 kDa protein, and hemagglutinin gene promoters support high levels of expression.

We devised vaccinia virus (VV)-based vector systems that support higher levels of expression of cloned genes in the early and late phases of the infection cycle than reported previously. Enhanced expression can be obtained by combining the promoter of the A-type inclusion body protein gene, the mutated early region of the 7.5-kDa gene promoter (7.5-kDa promoter), and the promoter of the hemagglutinin (HA) gene. One construct produced 60 micrograms/10(6) cells of chloramphenicol acetyltransferase (CAT), equivalent to 10-18% of total cell protein. Another construct produced about seven times more CAT during the early phase than the amount synthesized under the control of the 7.5-kDa promoter alone. The envelope proteins of human immunodeficiency virus type I synthesized during the early phase of infection were more active as immunogens than these proteins synthesized during the late phase, regardless of the amounts produced.

Animals↗

PubMed1994

Assembly of vaccinia virus: the second wrapping cisterna is derived from the trans Golgi network.

During the assembly of vaccinia virus, the intracellular mature virus becomes enwrapped by a cellular cisterna to form the intracellular enveloped virus (IEV), the precursor of the extracellular enveloped virus (EEV). In this study, we have characterized the origin of this wrapping cisterna by electron microscopic immunocytochemistry using lectins, antibodies against endocytic organelles, and recombinant vaccinia viruses expressing proteins which behave as Golgi resident proteins. No labelling for endocytic marker proteins could be detected on the wrapping membrane. However, the wrapping membrane labelled significantly for a trans Golgi network (TGN) marker protein. The recycling pathway from endosomes to the TGN appears to be greatly increased following vaccinia virus infection, since significant amounts of endocytic fluid-phase tracers were found in the lumen of the TGN, Golgi complex, and the wrapping cisternae. Using immunoelectron microscopy, we localized the vaccinia virus membrane proteins VV-p37, VV-p42, VV-p21, and VV-hemagglutinin (VV-HA) in large amounts in the wrapping cisternae, in the outer membranes of the IEV, and in the outermost membrane of the EEV. The bulk of the cellular VV-p37, VV-p21, and VV-p42 were in the TGN, whereas VV-HA was also found in large amounts on the plasma membrane and in endosomes. Collectively, these data argue that the TGN becomes enriched in vaccinia virus membrane proteins that facilitate the wrapping event responsible for the formation of the IEV.

Animals↗

PubMed1994

Induction of antibody responses that neutralize human T-cell leukemia virus type I infection in vitro and in vivo by peptide immunization.

In order to define neutralization regions on the envelope antigen of human T-cell leukemia virus type I (HTLV-I), we have generated a number of new anti-envelope gp46 monoclonal antibodies from rats and mice. Epitopes recognized by new monoclonal antibodies which could neutralize HTLV-I in syncytium and transformation inhibition assays were localized to sequences in gp46 from amino acids 186 to 193, 190 to 195, 191 to 195, 191 to 196, and 194 to 199. Ovalbumin-conjugated synthetic gp46 peptides containing these neutralization epitopes, pep190-199 (a synthetic gp46 peptide containing amino acids 190 to 199) and pep180-204, but not pep185-194 or pep194-203, could give rise to HTLV-I-neutralizing antibody responses in rabbits. These immune or nonimmune rabbits were then challenged with HTLV-I by intravenous inoculation with 5 x 10(7) live HTLV-I-producing ILT-8M2 cells. By a PCR assay, it was revealed that HTLV-I provirus was detected in peripheral blood lymphocytes from nonimmune and pep288-312-immunized rabbits, whereas the provirus was not detected in peripheral blood lymphocytes from pep190-199- and pep180-204-immunized rabbits over an extended period. These results suggest that the induction of anti-gp46 neutralizing antibody responses by immunization with synthetic peptides has the potential to protect animals against HTLV-I infection in vivo.

Amino Acid Sequence↗

PubMed1994

Clonal expansion of CD8+ cytotoxic T lymphocytes against human T cell lymphotropic virus type I (HTLV-I) genome products in HTLV-I-associated myelopathy/tropical spastic paraparesis patients.

Short-term culture of peripheral blood mononuclear cells (PBMC) derived from patients with human T cell lymphotropic virus type I-associated myelopathy (HAM)/tropical spastic paraparesis resulted in dominance by DR+ activated CD8+ T cells. Variations in the T cell receptor (TCR) V alpha and V beta chains in these cells were analyzed, and in all 10 patients examined, 2-3 V gene families were dominant in both TCR V alpha and V beta. In five patients we examined, cultured lymphocytes contained cytotoxic lymphocytes for p40tax (patients HAM2, 3, 7, and 8) or env protein (patient HAM4) of human T lymphotropic virus type I. In patients HAM2 and HAM8, cultured lymphocytes contained a large proportion of V beta 8+ CD8+ and/or V beta 12+ CD8+ cells. The sequence of V beta 8+ and V beta 12+ cDNA revealed that they were oligoclonal with identical or similar sequences in each patient. Elimination experiments with monoclonal antibodies for TCR V beta 8 and V beta 12 showed that they were CD8+ cytotoxic T lymphocytes (CTL) for p40tax. In addition, flow cytometry and sequencing analysis of uncultured PBMC revealed that in HAM2, V beta 8+ CTL and their precursors account for 7% and V beta 12+ CTL and their precursors account for 18% of total CD8+ cells. This indicates the presence of two markedly expanded clones in vivo. No common dominant TCR V alpha or V beta were observed among 10 HAM patients analyzed.

Amino Acid Sequence↗

PubMed1994

Demonstration of desmosomal antigens by electron microscopy using cryofixed and cryosubstituted skin with silver-enhanced gold probe.

In a previous post-embedding immunogold electron microscopic (EM) studies, localization of various desmosomal antigens was possible at high but not at low magnification. We developed a method for simultaneous demonstration of epidermal desmosomal antigens at both low- and high-power EM magnifications by a method based on cryofixation and acetone cryosubstitution and the use of a 1-nm gold probe with silver enhancement. Ultra-thin sections of Lowicryl K11M were incubated with primary antibodies against desmoplakin, desmocollin, or desmoglein, followed by 1-nm gold-conjugated secondary antibody. Silver enhancement for 12 min provided the ideal labeling size for low-power visualization, whereas silver enhancement for 4-6 min was ideal for high-power EM observation. Each desmosome immunolabeled with the gold probe was clearly demonstrated, even at very low-power magnification. The level of background labeling could be determined easily and the area of interest for high-power observation selected accurately. The fine ultrastructural appearance of desmosomal molecules was precisely demonstrated on high-power observation. This system should be useful for the immunocytochemical study of a variety of desmosomal antigens as well as other molecules of interest.

Adult↗

PubMed1994

A cellular protein which is coprecipitated with HTLV-I rex protein in the presence of the target mRNA.

We examined the cellular protein(s) which can associate with Rex protein of human T cell leukemia virus type I (HTLV-I), using Rex-maltose binding protein (MBP) fusion protein. Immunoprecipitation of RexMBP with anti-MBP antibody revealed that a 24 kD protein (p24) associated with RexMBP only in the presence of Rex-responsive mRNA. The fact that p24 was present in both the nucleus and the cytoplasm is consistent with a role of Rex in the nucleo-cytoplasmic transport of viral mRNAs. P24 did not interact with nonfunctional Rex mutant proteins even if they had RNA binding activity in vitro. These results suggest the possible involvement of p24 in the Rex function through a complex formation with Rex on Rex-responsive mRNA.

Amino Acid Sequence↗

PubMed1994

Stress-induced expression of the c-fos proto-oncogene in the hippocampal formation.

To investigate the effects of stress on c-fos mRNA expression, rats were submitted to forced immobilization for 15, 30, 60 or 120 min before sacrifice. In situ hybridization was performed on sections containing the dorsal hippocampus with a 32P-labelled 50-base oligonucleotide probe (10(7)-10(9) cpm/micrograms) complementary to nucleotides 370-319 of rat c-fos. Forced restraint induced a time-dependent increase in c-fos mRNA expression which was most pronounced in the dentate gyrus and CA1-CA3 regions of the hippocampal formation, and which peaked after 30 min of immobilization (72.7 +/- 1.0 vs 24.1 +/- 0.8 cpm/mm2 in unrestrained animals). A positive but weaker signal was also detected in the amygdala, pyriform cortex and other parts of the cerebral cortex and habenulae. These results suggest that the hippocampal formation is activated during stress.

Animals↗

PubMed1994

Cytotoxic T cell response and expression of the target antigen in HTLV-I infection.

The cytotoxic T cell response of peripheral blood mononuclear cells (PBMC) to in vitro stimulation with human T cell leukemia virus type I (HTLV-I) was compared among HTLV-I-infected individuals with various clinical conditions. Induction of HTLV-I-specific cytotoxic T lymphocytes (CTL) was observed in 57% of asymptomatic HTLV-I carriers, 86% of patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) or other HTLV-I-related inflammatory diseases, and 18% of adult T cell leukemia (ATL) patients. HTLV-I p40tax, one of the major CTL target antigens, has an epitope strongly associated with HLA-A2. HTLV-I p40tax-specific CTL were frequently induced from HLA-A2-positive donors with HTLV-I-related inflammatory diseases regardless of neurological symptoms, but not from all the HLA-A2-positive HTLV-I-infected individuals tested. Leukemic cells of an ATL patient with HLA-A2, whose PBMC did not show an HTLV-I-specific CTL response, could be lyzed by p40tax-specific CTL derived from an HAM/TSP patient. This indicates that i) the presence of a certain HLA presenting CTL epitopes is not the sole determinant of the individual CTL response to HTLV-I, ii) HTLV-I-specific CTL act as potential effectors of anti-tumor surveillance in vivo. The role of HTLV-I-specific CTL, however, may be limited by another in vivo mechanism suppressing the expression of HTLV-I antigens. This suppression, presumably mediated by a plasma factor and commonly observed in HTLV-I-infected individuals, could be one reason for the persistence of HTLV-I-infection.

Base Sequence↗

PubMed1994

[5-Fluorouracil plus low-dose leucovorin in the treatment of advanced colorectal cancer].

From September 1989 to September 1992, 17 patients (pts) with non-curative or recurrent colorectal cancer were treated with 5-fluorouracil (FU) plus leucovorin (LV) systemic therapy. The sites of evaluable metastases were liver (10), peritoneum (4), lung (3) and others (6). The LV dosage was 30 mg/body (low-dose method) and the FU dosage was 500-750 mg/body. Both drugs were administered either 5 days/every 4 weeks or one day/every 1 to 2 weeks via protracted or bolus infusion. The regimen was generally well tolerated, although 9 pts (53%) experienced toxicity which required dose reductions. Overall response rate was 29% (5 PR). No CR was observed. Improvement in tumor-related symptoms was noted temporarily in 7 out of 10 pts. Serum CEA level decreased in 13 out of 14 pts. All the response sites were liver (5), with simultaneous lung (1) or peritoneum (1) metastasis. The response duration was 3 to 10 months (mean 6.2 months). Second-line therapy after progression of diseases, such as combination with CDDP, was attempted in some of the PR pts, but no re-response was observed. We conclude that FU plus low-dose LV regimen is an effective therapy for advanced colorectal cancer, but further attempts should be made to increase response rate, prolongation of response duration and effective second-line therapy after progression.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Induction of the c-fos proto-oncogene in the rat pineal gland during stress.

To investigate the effects of stressful stimuli on pineal gland activity, male Wistar albino rats (200-250 g, 2-4 per group) were submitted to 30 min of forced immobilization or to unilateral vibrissotomy 30 min before sacrifice. In situ hybridization was performed with a 35S-labelled 50-base oligonucleotide probe complementary to nucleotides 270-319 of rat c-fos on sections containing the pineal gland. Autoradiograms were quantified using a JAVA microdensitometer. Stressful stimuli induced a significant increase in the expression of c-fos mRNA in the pineal gland (restraint = 144.3 +/- 14.4 cpm/mm2; hemivibrissotomy = 206.7 +/- 29.5 cpm/mm2) as compared to no restraint animals (30.6 +/- 5.1 cpm/mm2), animals displaying tonic-clonic seizures after an ip (64 mg/kg) injection of pentylenetetrazole (34.0 +/- 4.7 cpm/mm2), or competition (70.6 +/- 11.4 cpm/mm2) and RNAase-treated (52.7 +/- 9.1 cpm/mm2) controls. These results raise the possibility that stressful stimuli may interfere with pineal gland function.

Animals↗

PubMed1993

Triple lung cancers in a patient with silicosis.

A case of pulmonary silicosis associated with triple lung cancers is presented. Two of the three tumors were unexpected clinically. The discussion deals with the diagnostic difficulty in radiological differentiation between the pneumoconiotic mass lesion and superimposed tumor shadows, as well as the possible causal relationship between the two conditions. From the practical point of view, elderly patients with pneumoconiosis should be carefully monitored for the development of lung cancer.

Adenocarcinoma, Bronchiolo-Alveolar↗