Yeast virus propagation depends critically on free 60S ribosomal subunit concentration.

Over 30 MAK (maintenance of killer) genes are necessary for propagation of the killer toxin-encoding M1 satellite double-stranded RNA of the L-A virus. Sequence analysis revealed that MAK7 is RPL4A, one of the two genes encoding ribosomal protein L4 of the 60S subunit. We further found that mutants with mutations in 18 MAK genes (including mak1 [top1], mak7 [rpl4A], mak8 [rpl3], mak11, and mak16) had decreased free 60S subunits. Mutants with another three mak mutations had half-mer polysomes, indicative of poor association of 60S and 40S subunits. The rest of the mak mutants, including the mak3 (N-acetyltransferase) mutant, showed a normal profile. The free 60S subunits, L-A copy number, and the amount of L-A coat protein in the mak1, mak7, mak11, and mak16 mutants were raised to the normal level by the respective normal single-copy gene. Our data suggest that most mak mutations affect M1 propagation by their effects on the supply of proteins from the L-A virus and that the translation of the non-poly(A) L-A mRNA depends critically on the amount of free 60S ribosomal subunits, probably because 60S association with the 40S subunit waiting at the initiator AUG is facilitated by the 3' poly(A).

Transglutaminase differentially regulates growth signalling in rat perivenous and periportal hepatocytes.

The influence of transglutaminase 2 (TG2) activity on the proliferative effect of epidermal growth factor (EGF) and on EGF receptor affinity in periportal hepatocytes (PPH) and perivenous hepatocytes (PVH) has been investigated using a primary culture system. PPH and PVH subpopulations have been isolated using the digitonin/collagenase perfusion technique. DNA synthesis was assessed by [3H] thymidine incorporation into hepatocytes. The assay for binding of [125I] EGF to cultured hepatocytes was analysed by Scatchard plot analysis. Pretreatment with the TG2 inhibitor monodansylcadaverine (MDC) greatly increased EGF-induced DNA synthesis in both PPH and PVH. Furthermore, [125I] EGF binding studies in PVH treated with MDC indicated that high-affinity EGF receptor expression was markedly up-regulated, whereas in PPH, there was no significant effect. Treatment with retinoic acid (RA), an inducer of TG2 expression, significantly decreased EGF-induced DNA synthesis in both PPH and PVH. Binding studies in the presence of RA revealed that the high-affinity EGF receptor was down-regulated and completely absent in both PPH and PVH. These results suggest that TG2 was involved in the differential growth capacities of PPH and PVH through down-regulation of high-affinity EGF receptors.

Prognostic significance of apoptotic index in completely resected non-small-cell lung cancer.

PURPOSE: To evaluate the significance of apoptotic index (AI) as a prognostic factor after surgery for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 236 patients who underwent surgery for previously untreated pathologic stage I to IIIa NSCLC between 1985 and 1990 were reviewed. AI was defined as the number of apoptotic cells, detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling, per 1,000 tumor cells. Proliferative index (PI) and aberrant p53 expression were also evaluated immunohistochemically. RESULTS: The 5-year survival rate for the lowest-AI group (AI < 5.0) was 74.7%; those for the lower-AI group (5.0 < or = AI < 11.0) and the higher-AI group (11.0 < or = AI < 25.0) were 51.6% and 57.8%, respectively. These survival rates were significantly lower than that of the lowest-AI group (P =.021 and P =.043, respectively). The highest-AI group (25.0 < or = AI), however, showed the most favorable prognosis, with a 5-year survival rate of 83.2%. Multivariate analysis confirmed that a moderate AI (5.0 < or = AI < 11.0 or 11.0 < or = AI < 25.0) was a significant factor to predict poor prognosis. The PIs for the lowest-, the lower-, the higher-, and the highest-AI groups were 32.3%, 48.0%, 54.3%, and 50.7%, respectively. The lowest-AI group showed a favorable prognosis because of its low PI, whereas the lower- and the higher-AI groups had a poor prognosis caused by increased cancer-cell proliferation. The highest-AI group showed the most favorable prognosis because apoptotic cell death overcame cell proliferation. No significant correlation was observed between AI and aberrant p53 expression. CONCLUSION: AI proved to be an independent prognostic factor in NSCLC.

KRB1, a suppressor of mak7-1 (a mutant RPL4A), is RPL4B, a second ribosomal protein L4 gene, on a fragment of Saccharomyces chromosome XII.

The mak7-1 mutant loses the killer toxin-encoding M1 dsRNA. MAK7 is RPL4A, one of two genes encoding ribosomal protein L4. KRB1 is a dominant suppressor of mak7-1 that is tightly centromerelinked, but not linked to centromere markers of chromosomes I-XVI. Our orthogonal field agarose gel electrophoresis analysis of chromosomal DNA from strains with KRB1 shows a novel band of approximately 250 kb. This band hybridizes with an RPL4B-specific probe, but not an RPL4A (MAK7)-specific probe. The RPL4B-specific probe also hybridizes to chromosome XII where the original RPL4B is located. KRB1 is meiotically linked to this extra chromosome. Disruption of either the RPL4B gene on chromosome XII or that on the extra chromosome results in loss of the killer phenotype and a decreased concentration of free 60S subunits. Thus, the RPL4B on the extra chromosome is KRB1 and is active. The extra chromosome contains chromosome XII sequence between Lambda 5345 clone (ATCC70558) and Lambda 6639 clone (ATCC71085) of Olson's Lambda library, indicating that KRB1 represents a chromosomal rearrangement involving chromosome XII and explaining the earlier genetic data.

Targeted in vivo delivery of therapeutic gene into experimental squamous cell carcinomas using anti-epidermal growth factor receptor antibody: immunogene approach.

The "Fab immunogene" is a novel gene transfer vehicle in which the Fab fragment of anti-human epidermal growth factor (EGF) receptor antibody B4G7 is conjugated with poly-L-lysine to form an affinity complex with DNA. It was developed to target delivery of therapeutic genes into EGF receptor-hyperproducing tumor cells. Various characteristic features of the immunogene have been documented (Chen et al., 1998). Here we add further evidence to prove that in vitro transfer of beta-galactosidase/Fab immunogene is exclusively to EGF receptor-positive cells and that the herpes simplex virus thymidine kinase (TK)/Fab immunogene induces substantial suicide effects on A431 tumor cells when treated together with ganciclovir. The in vivo specificity of the immunogene transfer was examined using A431 tumor-bearing nude mice. When these nude mice were injected intraperitoneally with the chloramphenicol acetyltransferase (CAT)/Fab immunogene, CAT DNA was detected in the tumors as well as in liver and kidney but not brain, whereas CAT mRNA and enzyme activity were detected only in the tumors. Local and intraperitoneal injection of the TK/Fab immunogene and subsequent administration of ganciclovir effectively suppressed the growth of A431 tumors transplanted on the backs of nude mice. These observations suggest a possible application of the Fab immunogene system in cancer gene therapy.

Novel mutations in the myocilin gene in Japanese glaucoma patients.

Myocilin is a gene responsible for juvenile onset primary open angle glaucoma (POAG) mapped as the GLC1A locus and, many mutations have been reported worldwide. Some mutations were found not only in patients with juvenile onset POAG, but also in patients with late onset POAG and in patients with normal tension glaucoma. To investigate the mutation prevalence in Japan, we performed a mutation analysis in 140 unrelated Japanese patients. We have identified the 10 sequence variants, of which four were highly probable for disease-causing mutations (Arg46ter, Arg158Gln, Ile360Asn, and Ala363Thr), and six polymorphisms (Gln19His, Arg76Lys, Asp208Glu, Val439Val, Arg470His, and Ala488Ala). Thus, myocilin mutations were found at the rate of 4/140 (2.9%) probands, similar to previous reports with other ethnic populations.

Receptor-mediated gene delivery using the Fab fragments of anti-epidermal growth factor receptor antibodies: improved immunogene approach.

We previously developed the "immunogene" approach toward cancer gene therapy using epidermal growth factor receptor (EGFR)-mediated endocytosis. Here, we describe an improved immunogene system, in which the antigen-binding (Fab) fragments of the monoclonal antibody (Ab) B4G7 against the human EGFR were conjugated with poly-L-lysine to form a gene delivery vehicle (designated Fab "immunoporter"). Within 12 hours, the beta-galactosidase beta-gal) gene was transferred via the Fab immunoporter to virtually all of the nuclei of human squamous carcinoma A431 cells that overproduce the EGFR, and the beta-gal enzyme activity was detected within 24 hours and retained for more than 3 days. The beta-gal gene was not transferred into human and mouse cells that were deficient in EGFRs, but it was delivered if those mouse cells were transformed with human EGFR genes. Beta-gal gene transfer via the Fab immunoporter was inhibited by pretreatment with excess amounts of the Fab fragment. The transfer efficiency of the beta-gal gene to A431 cells via the Fab immunoporter was approximately 2%, which is as high as the lipofection method and 20- to 100-fold higher than the whole Ab immunoporter. The transfer of the herpes simplex virus thymidine kinase gene into A431 tumor cells as a form of the thymidine kinase/Fab immunogene was successful, and subsequent treatment with ganciclovir induced remarkable suicide effects which conferred 1000-fold higher drug sensitivity. Thus, the Fab immunogene was substantially improved with regard to the whole Ab immunogene and could be used as a potent gene transfer vehicle for the in vivo targeting of EGFR-hyperproducing tumor cells.

Metabolism substrate with negative myocardial uptake of iodine-123-BMIPP.

UNLABELLED: Iodine-123-BMIPP is an iodinated methyl-branched-chain fatty acid. Low uptake of BMIPP relative to thallium or other perfusion tracer indicates metabolically damaged but viable myocardium (for example, ischemic but viable myocardium). In some cases, however, negative myocardial uptake of BMIPP is observed. The main purposes of this study were to assess the frequency of such BMIPP findings and to clarify metabolism of such cases by using PET. METHODS: Among the 1258 patients who underwent BMIPP scintigraphy, 11 patients (0.9%) showed negative myocardial uptake of BMIPP. Under fasting condition, PET using [11C]palmitate, 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and [11C]acetate was performed in nine of these 11 patients. RESULTS: Global myocardial uptake of [11C]palmitate, expressed as the standardized uptake value, was significantly lower in the patients than in control (3.62 +/- 0.44 versus 5.49 +/- 1.62; p < 0.01). However, the early phase clearance rate of [11C]palmitate and oxidative metabolism was not significantly different. In the fasting state, PET studies showed increased FDG accumulation in seven of nine patients (high group) and decreased accumulation in two patients (low group). In the high group patients, glucose metabolism in the fasting state was similar to that in the normal volunteers after glucose loading (Kcomplex: 0.050 +/- 0.016 versus 0.038 +/- 0.015; p = ns). However, low glucose metabolism was noted in the low group patients (Kcomplex: 0.007 and 0.005). CONCLUSION: Negative myocardial uptake of BMIPP is occasionally, but not often, observed. Global uptake of [11C]palmitate was decreased in these patient. The majority of these patients showed "metabolic switching" from normal free fatty acid metabolism to abnormally enhanced glucose metabolism in the fasting state. However, some patients showed decreases in both exogenous glucose utilization and free fatty acid uptake in the fasting state.

Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with primary congenital glaucoma.

PURPOSE: To investigate CYP1B1 gene mutations in Japanese patients with primary congenital glaucoma (PCG). METHODS: Sixty-five unrelated Japanese patients with PCG were screened by PCR-single-strand conformational polymorphism (SSCP) analysis followed by direct sequencing. No patients were offspring of consanguineous marriages, a common occurrence among patients in previous reports. PCG haplotypes were constructed with intragenic polymorphisms in affected individuals. Three-dimensional atomic structures of human CYP1B1 and four mutant CYP1B1 sequences representing missense mutations were assembled using homology modeling and were regularized by an energy-minimization procedure. RESULTS: Eleven novel mutations, including seven definite and four probable mutations, were detected in 13 (20%) of the 65 unrelated patients. Of the seven definite mutations, three were predicted to truncate the CYP1B1 open reading frame. The other four were missense mutations (Asp192Val, Ala330Phe, Val364Met, and Arg444Gln), all located in conserved core structures determining proper folding and heme-binding ability of cytochrome P450 molecules. Molecular modeling demonstrated that two of four mutations in positions 330 and 364 were structurally neutral, but Arg444Gln caused significant structural change. Of the four probable mutations, three were missense (Val198Ile, Val320Leu, and Glu499Gly); the other was a base substitution in the noncoding region of exon 1. CONCLUSIONS: The 11 varied CYP1B1 mutations found in 13 unrelated Japanese patients with sporadic occurrence of PCG represent an allelic heterogeneity and may be unique to a specific population.

Heat shock protein 27 was up-regulated in cisplatin resistant human ovarian tumor cell line and associated with the cisplatin resistance.

To understand the molecular basis for failure of cisplatin (CDDP) based chemotherapy, we compared gene expressions between CDDP sensitive and resistant ovarian tumor cell line, 2008 and 2008/C13*5.25, by mRNA differential display. We detected both up-regulated and down-regulated bands in the resistant cell and found some of them to be positive on Northern blotting. DNA sequencing revealed one to be mitochondrial heat shock protein 75. We found that HSP27 and HSP70 were also up-regulated in the resistant cell by Western blotting. Further, transient transfection with the HSP27 sense gene made the sensitive cell more resistant, while transient transfection with the antisense gene made it more sensitive.

Anomalous systemic arterial supply to normal basal segments of the left lower lobe. A report of two cases.

Two cases of anomalous systemic arterial supply to the basal segments of the lower lobe of the left lung without sequestration are presented. In the first case, the final diagnosis was made during a surgical operation, and lobectomy of the lower lobe of the left lung was performed. In the second case, the preoperative diagnosis made by CT was confirmed by angiography. An anastomosis was performed between the anomalous artery and the pulmonary artery without resection of the basal segments. Six months after surgery, pulmonary angiography showed improved flow of the anastomosed vessel, but little improvement was evidenced in the perfusion scan.

Analyses of segmental lymph node metastases and intrapulmonary metastases of small lung cancer.

BACKGROUND: Curativity and indications for limited resection of small peripheral lung cancer remain controversial. METHODS: Pathologic investigations of segmental lymph node metastases and intrapulmonary metastases in the resected lobe were performed for 94 small peripheral lung cancers (3.0 cm or less in diameter). RESULTS: Nine patients had segmental lymph node metastases, 1 had intrapulmonary metastases, and 1 had both. Of these 11 patients, 5 had metastases limited to the primary tumor-bearing segments, 2 had metastases in nonprimary tumor-bearing segments, and 4 had metastases in both. Of the 10 patients with segmental lymph node metastases, 7 had metastases in both lobar-hilar and mediastinal lymph nodes, and 3 of 8 with adenocarcinoma had a tumor 2.0 cm or less. CONCLUSIONS: Segmentectomy seems more favorable than wedge resection, but the risk of remnant tumor remains as compared with lobectomy. Evaluation of lobar-hilar or mediastinal lymph nodes is helpful to determine the presence or absence of segmental lymph node metastases. Limited resection can be undertaken with smaller tumors to allow preservation of more lung function while accepting a somewhat enhanced risk of recurrence.

Lewis Y antigen expression and postoperative survival in non-small cell lung cancer.

BACKGROUND: In contrast to other Lewis blood group-related antigens, Lewis Y antigen (LeY) has not been fully investigated in non-small cell lung cancer. METHODS: To assess the significance of LeY expression, 236 patients with completely resected pathologic stage 1-3a were reviewed with immunohistochemical analysis. RESULTS: LeY expression was positive in 179 patients (75.8%). In poorly differentiated cancer, percentage of LeY-positive patients was lower than in moderately to well-differentiated cancer (67.2% versus 81.2%, p = 0.028). Five-year survival rate of LeY-positive patients was 78.2%, significantly higher than that of LeY-negative patients (59.7%, p = 0.001). Combined with p53 status, differences in survival proved to be marked; 5-year survival rate of patients with positive LeY expression and without aberrant p53 expression, was as high as 83.3%, whereas that of patients with negative LeY expression and with aberrant p53 expression was only 38.4% (p < 0.001). Multivariate analysis confirmed that LeY expression was a significant independent factor to predict better survival. CONCLUSIONS: LeY expression is a significant prognostic factor related to grade of cancer differentiation.

Scanning laser Doppler flowmeter study of retinal blood flow in macular area of healthy volunteers.

AIM: To compare the interocular and intraocular differences of capillary perfusion, and the intraocular regional differences of retinal blood flow in the macular area of healthy volunteers. METHODS: Tissue blood flow in the macula was examined in both eyes of 20 healthy volunteers with the Heidelberg retinal flowmeter. Blood flow measurements were made in a 10 degrees x 2.5 degrees area superior and inferior to the macula. The mean blood flow (MBF) was calculated by an automatic full field perfusion image analyser program. The MBF in the right and left eyes and in the superior and inferior macular areas of the same eye were compared. RESULTS: The ratios of the MBF in the right eye to the left eye in the macular areas were 1.00, and 1.03, respectively. The ratio of the MBF in the superior macular area to the inferior area was 1.01 for the right eyes and 1.04 for the left eyes. CONCLUSIONS: Because no significant differences were found in the MBF between the two eyes and between the superior and inferior macular areas in the same eye, interocular (for example, affected eye versus fellow eye) and intraocular (superior versus inferior macular areas) comparisons of MBF can be made to determine if changes in retinal perfusion have occurred.

Phenotype of cytochrome P4501B1 gene (CYP1B1) mutations in Japanese patients with primary congenital glaucoma.

AIM: To investigate the phenotypes associated with cytochrome P4501B1 gene (CYP1B1) mutations in Japanese patients with primary congenital glaucoma (PCG). METHODS: 66 Japanese patients with PCG were screened for sequence mutations in the CYP1B1 gene using single strand conformation polymorphism analysis followed by automated DNA sequencing. 11 cases had a CYP1B1 mutation in both alleles (the mutation group) and 21 cases did not have a CYP1B1 mutation (the "no mutation" group). The clinical features, such as age of onset, sex, intraocular pressure, and Descemet's membrane rupture, of the two groups were compared. RESULTS: The clinical symptoms and signs did not differ for the two groups. The mean age at onset was 1.7 months in the mutation group and 3.1 months in the no mutation group, and the male:female ratio was 6:5 in the mutation group and 19:2 in the no mutation group. Both of these differences were statistically significant. CONCLUSIONS: In clinically diagnosed cases of PCG, a subgroup shows a CYP1B1 gene mutation. Age at onset was earlier in PCG patients with CYP1B1 mutations than in patients without mutations. Women were more prevalent among patients with mutations than those without mutations.

Acute renal failure and hearing loss due to sodium bromate poisoning: a case report and review of the literature.

Acute renal failure with hearing loss due to sodium bromate intoxication is described. A 48-year-old woman who ingested permanent wave neutralizer in a suicide attempt and developed anuria was admitted to our hospital for hemodialysis. Bromate intoxication was suspected and hemodialysis was carried out; she required maintenance dialysis 3 times a week. Irreversible severe sensorineural hearing loss continued and peripheral polyneuropathy developed in the lower limbs. We measured the concentration of bromine in the serum before and after the first hemodialysis and found its removal rate to be 61.3%. This is the first report that proved the utility of hemodialysis for bromate intoxication in a clinical setting.

A new method of segmental resection for primary lung cancer: intermediate results.

OBJECTIVE: To improve the postoperative results of limited resection for small lung cancer, we have developed a new operative method, pulmonary artery-guided segmentectomy. This resection begins with identification of the pulmonary arterial branches involved in the tumor, then the pulmonary tissue is divided along the pulmonary arteries (i.e. guided by pulmonary arteries) from the hilum toward the periphery by electrocautery. The advantages of this method include the facilitation of securing adequate margin from the tumor, and the feasibility of intralobar lymph node dissection during operation. To examine the efficacy of the new method of segmental resection, we retrospectively reviewed 74 cases of T1N0M0 disease who underwent the pulmonary artery-guided segmentectomy. METHODS: From 1993 to 2000, 74 patients with pathological T1N0M0 lung cancer were treated by the pulmonary artery-guided segmentectomy. Forty-one patients (55.4%) who underwent the segmentectomy had been considered suitable candidates for lobectomy (intentional resection group). The other 33 patients (44.6%) were considered poor candidates for lobectomy because of poor cardiopulmonary reserve (compromised resection group). RESULTS: The overall survival rate at 5 years was 82.0%. The 5-year survivals in the intentional and the compromised resection groups were 81.6 and 77.6%, respectively, and no significant differences were detected between the groups. According to tumor size, the 5-year survival rate for patients with tumors of 20 mm or smaller (92.9%, n=53) was higher than that for the patients with tumors of 21-30 mm (63.0%, n=21), but the difference did not reach statistical significance. Median follow-up time of 27.0 months revealed eight locoregional recurrences and four deaths due to lung cancer. Sixty-three patients (85.1%) are alive with no evidence of disease, and six patients (8.1%) are alive with recurrent disease. Locoregional recurrences occurred in one of 53 patients (1.9%) with tumors 20 mm or smaller and in seven of 21 patients (33.3%) with tumors 21-30 mm, the difference being statistically significant (P<0.01). CONCLUSIONS: Our intermediate results demonstrated that the new pulmonary artery-guided segmentectomy could be an alternative method for selected patients with small lung cancer, particularly with tumors 20 mm or smaller in diameter.

Time trends and survival after surgery for p-stage IIIa, pN2 non-small cell lung cancer (NSCLC).

OBJECTIVE: To evaluate the role of surgery for p-stage IIIa, pN2 non-small cell lung cancer (NSCLC), time trends and survival after surgery and the prognostic factors were investigated retrospectively. METHODS: Consecutive patients, 155, with p-stage IIIa, pN2 NSCLC who underwent thoracotomy at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between January 1976 and December 1990 were divided into three groups by the period of operation (the earlier period: 1976-1980, n = 49; the middle period: 1981-1985, n = 55; and the later period: 1986-1990, n = 51), and were reviewed. Of the 155 patients, 84 (54.2%) were preoperatively evaluated to have mediastinal lymph nodes metastases (cN2 disease). RESULTS: The 5 year survival rates in the earlier, middle and later periods were 12.1, 18.6, and 43.8%, respectively, showing significant improvement in the later period (P < 0.001, for the later period versus the earlier period or the middle period). The improvement was caused by decrease in the rate of operation-related death (4.1, 1.8, and 0.0%, in the earlier, the middle, and the later period, respectively), increase in the rate of complete tumor resection (59.1, 76.4, and 96.1%, respectively), and decrease in the ratio of pT3N2M0 patients (44.9, 34.5, and 17.6%, respectively) having poor prognosis compared with pT1-2N2M0 patients. Decrease in the ratio of cT3N2M0 patients and for increase in the rate of complete resection could be realized by accurate preoperative diagnosis with introduction of chest computed tomography (CT). Based on the preoperative evaluation, the 5 year survival rates of cT1N2M0, cT2N2M0, and cT3N2M0 patients were 39.4, 30.5, and 10.2%, respectively, showing significant poor prognosis in cT3N2M0 patients. CONCLUSION: In cT1-2N2M0 or pT1-2N2M0 patients, a good prognosis can be realized by complete tumor resection with mediastinal lymph nodes dissection. In contrast, surgical treatment should not be justified in cT3N2M0 or pT3N2M0 patients.

Advantage of post-operative oral administration of UFT (tegafur and uracil) for completely resected p-stage I-IIIa non-small cell lung cancer (NSCLC).

OBJECTIVE: Although adjuvant therapy after surgery for non-small cell lung cancer (NSCLC) has been reported to be ineffective, it has been recently reported in prospective randomised studies conducted by two different groups in Japan that oral administration of a 5-fluorouracil (5-FU) derivative drug, UFT (a combination drug of tegafur and uracil) can improve the post-operative survival [The Study Group of Adjuvant Chemotherapy for Lung Cancer (Chubu, Japan). A randomized trial of postoperative adjuvant chemotherapy in non-small cell lung cancer (the second cooperative study). Eu J Surg Oncol 1995;21:69-77; Wada, H., Hitomi, S., Teramatsu, T, West Japan Study Group for Lung Cancer Surgery. Adjuvant chemotherapy after complete resection in non-small-cell lung cancer. J Clin Oncol 1996;14:1048-1054]. To examine the efficacy of UFT as post-operative adjuvant therapy, a retrospective study was performed. METHODS: A total of 655 consecutive patients who underwent complete tumor resection for pathologic stage I-IIIa, NSCLC at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between 1976 and 1992 were retrospectively reviewed. As post-operative adjuvant therapy, UFT was administrated to 98 patients (UFT group), and was not administered to the other 557 patients (Control group). RESULTS: The 5-year survival rate of the UFT group was 76.5%, which was significantly better than that of the Control group (5-year survival rate: 58.6%, P = 0.005). Stratified with pathologic stage, the efficacy of UFT was seen in the p-stage I disease (5-year survival rate: 88.6% for the UFT group, 72.0% for the Control group, P = 0.013) and in the p-stage IIIa, pN2 disease (5-year survival rate: 54.3% for the UFT group, 37.5% for the Control group, P = 0.037). Multivariate analysis of the prognostic factors also revealed the efficacy of UFT (P = 0.004, 95% confidence interval of relative risk: 0.325-0.840). Post-operative intravenous chemotherapy or radiation therapy did not prove to be significant factors affecting the prognosis. CONCLUSIONS: Efficacy of oral administration of UFT as post-operative adjuvant therapy for completely resected NSCLC was proposed. To confirm the efficacy, a prospective randomized study for a more homogenous patient group is needed.

The myocilin (MYOC) gene expression in the human trabecular meshwork.

PURPOSE: We previously reported a novel cytoskeletal protein with a myosin-like domain which is localized in the ciliary rootlet and basal body of connecting cilium of photoreceptor and hence we named it 'myocilin'. It was soon realized that myocilin is identical to a protein called TIGR (trabecular meshwork inducible glucocorticoid response protein) which was found to be responsible for the pathogenesis of juvenile open angle glaucoma. In this study, we employed in situ RNA hybridization to examine the myocilin (MYOC)/ TIGR gene expression in the trabecular meshworks of glaucomatous and nonglaucomatous eyes. METHODS: The glaucomatous specimens were obtained by trabeculectomy from the patients with primary open angle glaucoma (POAG), chronic angle closure glaucoma (CACG) and steroid glaucoma, respectively, and the nonglaucomatous specimens were obtained from a victim of traffic accident at autopsy and from a patient with maxillary sinus carcinoma at enucleation for the operation. The in situ RNA hybridization was carried out with digoxigenin-labeled sense and antisense RNA probes. RESULTS: In all cases, hybridization signals were detected primarily in the trabecular meshwork cells and secondarily in the fibroblast-like cells of corneoscleral wall. CONCLUSIONS: Myocilin gene is expressed clearly in the trabecular meshwork cells of both glaucomatous and nonglaucomatous eyes.