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Biomedical subjects

Y Toh

Publications and source records attributed to Y Toh.

At least 55 records · Page 3Linked to original sources

Electron microscopic study of chronic eosinophilic pneumonia.

Two cases of chronic eosinophilic pneumonia were examined electron microscopically to study the role of eosinophil granulocytes. Eosinophils, together with macrophages and lymphocytes, were observed to have infiltrated prominently in the lung tissues of the two cases. Degeneration and necrosis of pneumocytes were observed, and denuded basement membranes and destroyed alveolar structures were occasionally found. In the alveolar septa, swelling of the endothelial cells of the blood capillaries, edema of the stroma and fibrin deposition were observed. Eosinophils, released eosinophil granules and macrophages phagocytosing eosinophil granules were found frequently near the degenerated and necrotic alveolar tissues. These findings suggest that the tissue injuries were induced by the cytotoxic effects of the eosinophil granules.

Adult↗

[Tracheal carcinoma causing severe tracheal stenosis].

A 47-year-old woman was admitted to our hospital because of shortness of breath. She had wheezed for a long time before admission. A flow-volume curve showed a pattern consistent with a fixed obstruction of the trachea. CT findings also revealed severe stenosis of the trachea caused by a tumor mass. Tracheal carcinoma was diagnosed after transbronchoscopic biopsy. The patient received chemotherapy and radiation therapy concurrently for about six weeks. Her symptoms resolved, and a second flow-volume curve had a normal pattern. Tracheal carcinoma should be included in the differential diagnosis of airway obstruction. In such cases, the flow-volume curve can be useful as a screening test.

Adenocarcinoma↗

[Rigid spine syndrome associated with marked hypoxemia and hypercapnia].

A 48-year-old man was referred to our hospital because of hypoxemia (PaO2 = 43 mmHg), hypercapnia (PaCO2 = 70 mmHg), complete atrio-ventricular block, and heart failure. He also had limitation of spine flexion, scoliosis, deformity of the rib cage, and constriction of the ankle joints, complicated by cor pulmonale. These findings were compatible with rigid spine syndrome. To avoid progressive pulmonary hypertension and hypoxemia, nasal BiPAP and home oxygen therapy (0.5 liters/minute) were begun. Rigid spine syndrome is clinically characterized by limitation of spine flexion, and the limitation of thoracic movement often causes severe constrictive respiratory dysfunction. This syndrome should be considered when evaluating patients who have both thoracic deformity, especially scoliosis, and respiratory failure.

Heart Block↗

HLA A2601-restricted CTLs recognize a peptide antigen expressed on squamous cell carcinoma.

The CD4-CD8+ CTL (KE-4 CTL) cell line against autologous tumor cells was established in a patient with esophageal cancer. This KE-4 CTL recognized a peptide antigen on esophageal and lung squamous cell carcinomas in an HLA A2601-restricted manner, as evaluated by cytotoxicity against a panel of tumor cells, transfection experiments with HLA A2601 cDNA, and reconstitution with eluted peptides. None of the normal cells tested was lysed by this CTL. These results suggest the existence of HLA A2601-restricted CTL precursors recognizing a peptide antigen on SCC in a patient with esophageal cancer.

Antigens, Neoplasm↗

Analysis of the complete sequence of the novel metastasis-associated candidate gene, mta1, differentially expressed in mammary adenocarcinoma and breast cancer cell lines.

To understand the genes and gene products involved in breast cancer invasion and metastasis, we previously isolated ten differentially expressed genes by differential cDNA library screening techniques, using the 13762NF rat mammary adenocarcinoma metastatic system. In this study, we further analysed a novel candidate metastasis-associated gene, mta1, previously designated clone 10.14. Northern blotting analyses showed that the steady-state mRNA expression level of mta1 was fourfold higher in a highly metastatic line (MTLn3) than in a nonmetastatic line (MTC.4). The mta1 gene was expressed at low levels in various normal rat organs, except testis, where it was expressed in high amounts. The mRNA expression levels of the human homologue of this gene were also examined in two human breast cancer metastatic systems; the ratios of mRNA were estimated to be MCF-7 (nonmetastatic):MCF7/LCC1 (invasive):MCF7/LCC2 (metastatic) = 1:2:4 and MDA-MB-468 (nonmetastatic):MDA231 (metastatic) = 1:4. Thus, the expression of this gene directly correlated with metastatic potential in two human systems, as well as in the rat metastatic system. Clone 10.14 was used to isolate a full-length cDNA clone for mta1, yielding the clone p10.14-C4.5, which was sequenced and analysed. Clone p10.14-C4.5 was 2756-bp long and contained a single open reading frame that could encode a protein of 703 amino acid (aa) residues. The aa sequence of mta1 was found to be novel by database homology search and contained possible phosphorylation sites for tyrosine kinase, protein kinase C and casein kinase II. A Pro-rich stretch was found at the C-terminal end that completely matched the consensus sequence for the SH3-binding motif.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Mortality and morbidity rates, postoperative course, quality of life, and prognosis after extended radical lymphadenectomy for esophageal cancer. Comparison of three-field lymphadenectomy with two-field lymphadenectomy.

PURPOSE: The authors evaluated the efficacy of extended radical (three-field) lymphadenectomy for esophageal cancer compared with less radical (two-field) lymphadenectomy. STUDY SUBJECTS AND ANALYTIC METHODS: The mortality and morbidity rates, postoperative courses, and survival rates were compared between 63 patients who underwent three-field lymph node dissection and 65 who underwent two-field lymph node dissection at Kurume University Hospital from 1986 to 1991. Long-term quality of life after surgery was compared between 37 patients who underwent three-field dissection and 35 who underwent two-field dissection from 1980 to 1991. RESULTS: Three-field dissection resulted in better survival for patients with positive lymph node metastasis from a carcinoma in the upper thoracic or midthoracic esophagus compared with two-field dissection. The mortality rates, postoperative courses and quality of life were the same for both procedures. CONCLUSIONS: Three-field dissection is preferred for upper thoracic or midthoracic esophageal cancer because of improved survival, acceptable mortality and morbidity rates, and good postoperative course and quality of life.

Aged↗

Expression of MAGE-1 gene by esophageal carcinomas.

Expression of the MAGE genes encoding tumor-rejection antigens on HLA-A1 and -Cw1601 recognized by cytotoxic T lymphocytes was investigated in esophageal carcinomas at the mRNA level by the semiquantitative reverse transcription-polymerase chain reaction method. MAGE-1 and -2 genes, but not MAGE-3, -3/-6 and -4a/-4b genes, were expressed in substantial proportions of the primary esophageal carcinomas and their metastatic lymph nodes. The proportion of MAGE-positive samples in the primary esophageal carcinomas correlated with the T factor of the TNM classification (pT1: 2 of 12 tumors, pT2: 1 of 6, pT3: 12 of 29, and pT4: 7 of 18). These results have important implications for specific immunotherapy of esophageal carcinomas using MAGE-1 gene product.

Antigens, Neoplasm↗

[Tumor-rejection antigens expressed on human squamous cell carcinoma].

Squamous cell carcinoma (SCC) is one of the most common cancers in human. SCC, particularly, esophageal and lung SCC are relatively resistant to currently available regimens of chemotherapy or radiation therapy. Therefore, development of a specific immunotherapy using tumor specific cytotoxic T lymphocytes (CTL) would be important to offer other treatment modalities. However, generation of HLA class I-restricted CTL recognizing SCC has been rarely reported. We established the HLA A2601-restricted CTL cell line recognizing a peptide antigen expressed on SCC. This CD4- CD8+ cytotoxic T lymphocyte (KE-4 CTL) cell line was established in a patient with esophageal cancer. The KE-4 CTL recognized a peptide antigen on esohageal and lung SCC in an HLA A2601-restricted manner as evaluated by cytotoxity against a panel of tumor cells, transfection experiments with HLA A2601 cDNA, and reconstitution with eleted peptides. None of normal cells tested was lysed by this CTL. These results suggest the exstence of HLA A2601-restricted CTL precursors recognizing a peptide antigen on SCC in a patient with esophageal cancer.

Antigens, Neoplasm↗

A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses.

To understand the genes involved in breast cancer invasion and metastasis, we analyzed a novel candidate metastasis-associated gene, mta1, which was isolated by differential cDNA library screening using the 13762NF rat mammary adenocarcinoma metastatic system. Northern blot analyses showed that the mRNA expression level of the mta1 gene was 4-fold higher in the highly metastatic cell line MTLn3 than in the nonmetastatic cell line MTC.4. The mta1 gene was expressed in various normal rat organs, especially in the testis, suggesting its essential normal function. The mRNA expression levels of the human homologue of this gene also correlated with the metastatic potential in two human breast cancer metastatic systems. The full-length mta1 cDNA sequence contained an open reading frame encoding a protein of 703 amino acid residues, and sequence analysis by data base homology search indicated that mta1 is a novel gene. The Mta1 protein contained several possible phosphorylation sites, and a proline-rich amino acid stretch at the carboxyl-terminal end completely matched the consensus sequence for the src homology 3 domain-binding motif. Using antibodies raised against glutathione S-transferase-Mta1 fusion protein or a synthetic oligopeptide, Western blots showed that the molecular mass of the Mta1 protein was approximately 80 kDa, and the levels of the Mta1 protein also correlated with the metastatic potential, results similar to those obtained from the Northern analyses. Thus, the novel gene mta1 may encode a molecule that is functional in normal cells as well as in breast cancer invasion and metastasis.

Adenocarcinoma↗

Immunohistochemical detection of CEA, CA19-9, and DF3 in esophageal carcinoma limited to the submucosal layer.

The immunohistochemical expression of CEA, CA19-9, and DF3 was studied in 20 normal epithelia, 11 cases of dysplasia, 32 squamous cell carcinomas restricted within the submucosal layer (SM carcinoma), and 42 advanced squamous cell carcinomas of the esophagus. The modes of expression were grouped into three patterns, i.e., negative, focal, and diffuse patterns. No diffuse expression of CEA, CA19-9, or DF3 was found in the normal squamous epithelium and dysplasia. In the carcinomas (32 SM carcinomas and 42 advanced carcinomas) the diffuse expression of CEA and CA19-9 was found in four lesions, and only one of the four lesions was an SM carcinoma, while the diffuse expression of DF3 was found in 16 of the 32 SM carcinomas and 25 of the 42 advanced carcinomas. These results indicated that the diffuse expression of these tumor-associated antigens were characteristic of tumor tissue in the esophagus, and particularly DF3 was diffusely expressed earlier than CEA or CA19-9. The expression of DF3 in the esophagus may, therefore, be a marker of the early stage of tumor growth.

Antigens, Neoplasm↗

Dipyridamole inhibits early wound healing in rat skin incisions.

In an effort to investigate the significance of platelet aggregation on early wound healing, the inhibitory effects of an antiplatelet drug (dipyridamole) on tensile wound strength was assessed. The breaking strength of the dorsal incisional wounds in Donryu rats both with and without the administration of dipyridamole was measured. In experiment I, the intraperitoneal administration of dipyridamole (100 mg/kg/day, Group A; 50 mg/kg/day, Group B) and saline (3 ml/day; Group C) was performed during the periods between the day of incision and the excision of the healing wound specimen in a 2.0-cm width on the third and seventh postoperative days (POD). The wound breaking strength was 229 +/- 44, 256 +/- 39, and 352 +/- 38 g/cm2 on POD 3 and 477 +/- 67, 578 +/- 60, and 764 +/- 31.9 g/cm2 on POD 7, in Groups A, B, and C, respectively. In experiment II, we performed the intraperitoneal administration of either dipyridamole (100 mg/kg) or 3 ml of saline as a control just before incision (Group a) as well as at 4 hr (Group b), and 12 hr (Group c) after incision, and the percentages of tensile strength compared with the control were 72 +/- 8, 89 +/- 13, and 103 +/- 23% in Groups a, b, and c, respectively. The administration of dipyridamole significantly inhibited the wound healing and, therefore, platelet aggregation would appear to play an important role in the early phase of wound healing.

Animals↗

The clinical characteristics of patients with synchronous squamous cell carcinoma of the esophagus and hepatocellular carcinoma.

An ongoing analysis of 762 patients with esophageal cancer revealed 4 (0.52%) male patients with synchronous hepatocellular carcinoma (HCC). A long history of habitual alcohol intake and heavy cigarette smoking was recognized in all four patients and, therefore, the possibility of these two factors being independent risk factors for this double cancer was suggested. Palliative treatment was undertaken since either one or both cancers were too far advanced, or because liver function was poor even in those patients with resectable cancers. The prognosis correlated more closely to the TNM stage of esophageal cancer rather than the HCC and the causes of death were related to the esophageal cancer in all four patients. These findings suggest that, in patients with this combination of double cancer, the state of the esophageal cancer may be a more reliable prognostic factor than that of the HCC and thus, the curability of esophageal cancer is of primary importance.

Aged↗

Analysis by RNA-PCR of latency and reactivation of herpes simplex virus in multiple neuronal tissues.

Following intracameral inoculation with herpes simplex virus type 1 (HSV-1), BALB/c mice develop acute necrotizing chorioretinitis and infectious virus is detected in the eyes, trigeminal ganglia, brain, spinal cord and adrenal glands during acute infection. In this study, we analysed the latent phase of this experimental animal system. In mice which survived the acute infection, latent HSV-1 was recovered from the trigeminal ganglia, brain and adrenal glands by co-cultivation with Vero cells. In these tissues, both the unspliced latency-associated transcript (LAT) and the spliced LAT were detected by RNA-PCR. Following in vivo administration of cyclophosphamide and dexamethasone to induce viral reactivation, ICP0 mRNA became detectable in the multiple neural tissues, and the spliced LAT disappeared whereas the unspliced LAT remained detectable by RNA-PCR. Sequence analysis of the RNA-PCR products revealed that the GC-AG splicing signal previously reported for LATs from trigeminal ganglia was also detected in LATs from the brain and adrenal glands, suggesting that the splicing of LATs might be associated with the maintenance of and/or reactivation from latency. The generalized latent infection of HSV-1 described in this study might serve as an experimental model of possible viral reactivation from organs that do not innervate the primary port of entry.

Adrenal Glands↗

Detection of herpes simplex virus type 1-encoded RNA by polymerase chain reaction: different pattern of viral RNA detection in latently infected murine trigeminal ganglia following in vitro or in vivo reactivation.

Herpes simplex virus type 1 (HSV-1) establishes latent infection in the sensory ganglia. To investigate the process of reactivation from latency, we used the RNA polymerase chain reaction (RNA-PCR) to detect the expression of several HSV genes. BALB/c mice were inoculated in the anterior ocular chamber with HSV-1 strain KOS and the trigeminal ganglia were examined at least 8 weeks after inoculation. Latency-associated transcripts (LATs) were found in the latently infected ganglia and remained detectable 120 h after explantation. Besides LATs, we detected transcripts for infected cell protein 0 (ICP0) (Vmw110) 24 h after explantation, but RNAs encoding ICP4 (Vmw175), ICP27, thymidine kinase and VP16 (ICP25; Vmw65) remained undetectable for 120 h after explantation. Following in vivo reactivation of HSV-1 by administration of cyclophosphamide and dexamethasone, all viral transcripts including ICP0 RNA became detectable. The RNA-PCR enabled us to detect ICP0 RNA much earlier than has been previously reported in studies using the Northern blot technique and has laid a foundation for further study of viral and cellular transcripts during reactivation. Our results suggest that the process of reactivation of HSV-1 from trigeminal ganglia may be divided into at least two steps: (i) initiation of ICP0 gene transcription and (ii) detectable transcription of the other genes. The second step may be regulated in part by the host immune system, since cyclophosphamide and dexamethasone administration enabled the detection of several viral transcripts.

Animals↗

Detection of herpes simplex virus (HSV) in the saliva from 1,000 oral surgery outpatients by the polymerase chain reaction (PCR) and virus isolation.

Herpes simplex virus (HSV) was detected by a polymerase chain reaction (PCR) in 47 (4.7%) out of 1,000 saliva samples from the outpatients of an oral and maxillofacial surgery department compared with 27 (2.7%) by conventional virus isolation. There were 20 PCR-positive, culture-negative cases but no culture-positive, PCR-negative cases. Patients younger than 10 years or older than 60 years secreted HSV more frequently than the others. Those with inflammatory diseases showed higher positivity for HSV than those with malignancy, trauma or other complaints. All 27 virus isolates were typed as HSV type 1 and none were resistant to acyclovir, arabinofuranosyl-adenine, iododeoxyuridine or phosphonoacetic acid.

Acyclovir↗

Tumor progression in hepatocellular carcinoma may be mediated by p53 mutation.

Human hepatocellular carcinoma (HCC) often contains intratumoral subpopulations of heterogeneous cellular differentiations within each tumor. To analyze the genetic alterations of p53 in the heterogeneous subpopulations, we examined 68 intratumoral nodular lesions within 34 HCCs composed of two distinct subpopulations. The cellular differentiations were determined histologically by Edmondson's grading system. Nine (26.5%) of 34 HCCs examined were found to have genetic alterations in exons 5 to 8 of the p53 gene, resulting in amino acid substitutions. Three of these nine HCCs with p53 mutations showed genetic heterogeneity of the p53 gene within each tumor; one HCC had a single missense mutation at codon 210 (asparginine to 210-serine) in an intratumoral lesion of Edmondson Grade II and double missense mutations at codons 210 and 217 (asparginine to 210-serine and valine to 217-alanine) in another intratumoral lesion of Edmondson Grade III. The remaining two HCCs had p53 mutations only in lesions of a higher grade. In total, the p53 mutations were detected in none of eight Edmondson Grade I lesions, in five of 29 Grade III lesions (17.2%), in eight of 26 Grade III lesions (30.8%), and in three of five Grade IV lesions (60.0%). Thus, our data revealed that the p53 mutations were closely related to the progression of HCC and that, in certain cases, malignant cells which acquired the p53 mutations might develop into dedifferentiated subpopulations within individual HCC.

Amino Acid Sequence↗

Surgical treatment of esophageal carcinoma in patients eighty years of age and older.

Before 1979, no patient 80 years of age or older had been operated on at our institution for esophageal cancer, while in the middle period (1980-1984), three patients were operated on, and postoperative pulmonary complications and operative death occurred in 66.7 and 33.3%, respectively. However, in the recent period (1985-1990), there was no postoperative morbidity or mortality in the five cases over age 80. On the other hand, there were 12 patients over age 80 who did not undergo operation, of whom all died of cancer. In the eight operated patients over age 80, two cases are still alive 17 and 34 months after operation. According to the above findings, when the patient's general condition is evaluated to be sufficient to tolerate the operation and the cancer is judged to be resectable, esophageal resection is thought to be indicative in all patients over eighty.

Aged↗