Search PubMed⌕ Search

Biomedical subjects

T Kosuge

Publications and source records attributed to T Kosuge.

At least 55 records · Page 3Linked to original sources
PubMed1999

Repeat liver resection for recurrent colorectal liver metastases.

BACKGROUND: This study aimed to delineate the role of surgery for recurrent colorectal cancer in the liver and to identify prognosticators for better patient selection and outcome. METHODS: Data from 90 repeat hepatectomies (second = 75; third = 12; fourth = 3) for recurrent colorectal cancer were collected. RESULTS: After the second hepatectomy, the 3-and 5-year survival rates were 48% and 31%, respectively. Twenty-seven percent (20 of 75) of patients are alive without recurrence after a median follow-up of 27 months, and 9 survived more than 5 years. Four or more tumors, positive regional lymph node metastases, concomitant extrahepatic disease, and residual tumor were independent poor prognostic factors after the second hepatectomy. CONCLUSIONS: Repeat hepatectomy should be applied for recurrent colorectal cancer, when curative removal of the tumor is possible, although the benefit from treatment was limited in a patient with regional lymph node metastases, 4 or more metastases, or extrahepatic disease.

Adult↗
PubMed1999

The alpha-aminoadipate pathway for lysine biosynthesis is widely distributed among Thermus strains.

We previously reported that lysine is synthesized through the alpha-aminoadipate pathway in Thermus thermophilus HB27 (T. Kosuge and T. Hoshino, FEMS Microbiol. Lett., 169, 361-367, 1998), which was the first report demonstrating the synthesis of lysine through the alpha-aminoadipate pathway in Bacteria. LYS20 and LYS4, which respectively encode homocitrate synthase and homoaconitate hydratase have already been identified as the lysine biosynthetic genes in T. thermophilus HB27. In the present work, we examined eight other Thermus strains for the existence of genes belonging to the alpha-aminoadipate pathway. BamHI- or BglII-digested total DNAs from the eight strains were analyzed by Southern hybridization using LYS20 or LYS4 as a DNA probe. DNA fragments that hybridized with one or both of the genes were detected in seven of the Thermus strains but not in T. ruber. The sizes of the fragments that hybridized with the LYS20 and LYS4 probes were the same among T. thermophilus HB27, T. thermophilus HB8, "T. caldophilus" GK24, and four "T. flavus" strains. For example, a similar 4.3-kb fragment was detected in each of the above seven strains. In this fragment, four open reading frames were found downstream of the LYS4 gene in T. thermophilus HB27. Gene disruption experiments revealed that three open reading frames are involved in lysine biosynthesis in T. thermophilus HB27. These results strongly suggest that the lysine biosynthetic gene cluster for the alpha-aminoadipate pathway is widely distributed in the genus Thermus.

Journal Article↗
PubMed1999

Factors influencing survival of patients undergoing hepatectomy for colorectal metastases.

BACKGROUND: The extent of surgical margin is still a matter of controversy with regard to outcome after liver resection for metastatic disease. The aim of this study was to clarify the significant prognostic factors after hepatectomy for colorectal metastases, with special reference to the surgical margin. METHODS: Ninety-six patients who underwent initial hepatic resection for liver metastases from colorectal cancer between 1992 and 1994 were studied. RESULTS: Overall 1-, 3- and 5-year survival rates were 94, 61 and 51 per cent respectively. All of the independent factors associated with poor prognosis after hepatic resection were tumour-related factors, such as the number of tumours (four or more), presence of portal vein invasion, hepatic vein invasion and absence of a fibrous pseudocapsule. A positive resection margin was not an independent prognostic factor, because of its strong relationship with the number of tumours resected. CONCLUSION: A generous surgical margin is not essential for curative hepatic resection, although positive surgical margins should be avoided. New potential risk factors which affect survival, such as the presence of portal vein or hepatic vein invasion and the absence of a pseudocapsule, may be helpful for defining the indications for postoperative adjuvant treatment.

Adult↗
PubMed1999

Improved surgical results for hilar cholangiocarcinoma with procedures including major hepatic resection.

OBJECTIVE: To evaluate the long-term outcome of aggressive surgery incorporating hepatic resection and systematic nodal dissection for advanced carcinoma involving the hepatic hilus. SUMMARY BACKGROUND DATA: Few long-term results are available regarding radical surgery incorporating major hepatectomy and nodal dissection. METHODS: A retrospective analysis was undertaken in 107 patients with carcinoma involving the hepatic hilus treated between 1980 and 1997. Resectional surgery was performed in 65 patients, 52 of whom underwent major hepatectomies. The effects of clinical and pathologic factors were assessed by univariate and multivariate analyses. RESULTS: Sixty percent of the patients with resectional surgery had stage IVA or IVB disease, and 92.3% of them underwent major hepatectomies. No in-hospital deaths were encountered in the 35 most recent resections, whereas there were six deaths in the early period. Resectional surgery was associated with a survival benefit, especially when resection margins were free from cancerous infiltration. The estimated 5-year survival rate after resection, including all deaths, was 34.8%; this was 51.6% when the margins were clear. Nodal involvement was documented in 44.6% of the resections. However, patients with metastases limited to the regional nodes showed a survival rate similar to that in patients without nodal involvement. Significant predictive factors for survival after resection were extension to the gallbladder, nodal status, resectional margins, histologic type, and gender. CONCLUSIONS: The combination of major hepatectomy with systematic nodal dissection gave a good chance of prolonged survival for patients with carcinoma involving the hepatic hilus, even when the disease was advanced. Less-extensive procedures were also beneficial for less-advanced disease if clear resectional margins were secured.

Adult↗
PubMed1999

A prokaryotic gene cluster involved in synthesis of lysine through the amino adipate pathway: a key to the evolution of amino acid biosynthesis.

In previous studies we determined the nucleotide sequence of the gene cluster containing lys20, hacA (lys4A), hacB (lys4B), orfE, orfF, rimK, argC, and argB of Thermus thermophilus, an extremely thermophilic bacterium. In this study, we characterized the role of each gene in the cluster by gene disruption and examined auxotrophy in the disruptants. All disruptants except for the orfE disruption showed a lysine auxotrophic phenotype. This was surprising because this cluster consists of genes coding for unrelated proteins based on their names, which had been tentatively designated by homology analysis. Although the newly found pathway contains alpha-aminoadipic acid as a lysine biosynthetic intermediate, this pathway is not the same as the eukaryotic one. When each of the gene products was phylogenetically analyzed, we found that genes evolutionarily-related to the lysine biosynthetic genes in T. thermophilus were all present in a hyperthermophilic and anaerobic archaeon, Pyrococcus horikoshii, and formed a gene cluster in a manner similar to that in T. thermophilus. Furthermore, this gene cluster was analogous in part to the present leucine and arginine biosyntheses pathways. This lysine biosynthesis cluster is assumed to be one of the origins of lysine biosynthesis and could therefore become a key to the evolution of amino acid biosynthesis.

2-Aminoadipic Acid↗
PubMed1999

Macroscopic intrabiliary growth of liver metastases from colorectal cancer.

BACKGROUND: The clinicopathologic features of colorectal liver metastases that invade the bile duct were evaluated. METHODS: From 1992 to 1996, 149 patients who underwent a first hepatic resection were studied for a total of 377 colorectal liver metastases. Twenty-one second hepatic resections in these patients were also analyzed. RESULTS: Bile duct invasion was histologically observed in 62 (42%) of 149 patients with first colorectal liver metastasis. Eighteen patients (12%) had gross extension of the tumor in the bile duct ranging from 4 mm to 42 mm (median 17.0 mm). Histologically, two thirds (12 of 18) of the tumors with macroscopic bile duct invasion were well-differentiated adenocarcinomas with a tendency for less vascular involvement. The actuarial 3- and 5-year survivals were 62% and 57% for patients with no bile duct invasion, 56% and 48% for patients with microscopic bile duct invasion, and 94% and 80% for patients with macroscopic bile duct invasion. The 5-year survival rate was better for patients with macroscopic bile duct invasion than for those with only microscopic (P = .02) or no bile duct invasion (P = .03). In a multivariate analysis, macroscopic bile duct invasion was an independent prognostic variable for favorable outcome after hepatic resection. CONCLUSIONS: Macroscopic bile duct invasion of colorectal liver metastases may reflect an indolent biologic behavior, warrants an aggressive surgical approach, and confers a better prognosis.

Adenocarcinoma↗
PubMed1998

Lysine is synthesized through the alpha-aminoadipate pathway in Thermus thermophilus.

A 3.8-kb DNA fragment which was able to complement the mutation of a lysine auxotrophic Thermus thermophilus mutant was cloned from T. thermophilus HB27. Sequence analysis of the 3.8-kb fragment indicated the presence of three open reading frames including a truncated one. The predicted amino acid sequences of two of the three open reading frames showed 55.2% and 45.0% identity with homocitrate synthase and homoaconitate hydratase of Saccharomyces cerevisiae, respectively. These two enzymes act as lysine biosynthetic enzymes through the alpha-aminoadipate pathway which has been reported in S. cerevisiae and fungi. Each of the two open reading frames in T. thermophilus was disrupted by integration of the heat-stable kanamycin nucleotidyltransferase gene. The resulting mutants showed lysine auxotrophy, which could be complemented with alpha-aminoadipate but not with diaminopimelate. These results indicate that lysine was synthesized through the alpha-aminoadipate pathway and not through the diaminopimelate pathway in T. thermophilus.

2-Aminoadipic Acid↗
PubMed1998

A soft X-ray (80-1500 eV) grazing-incidence monochromator with varied-line-spacing plane gratings at PF-BL-11A.

The design and performance of a new soft X-ray beamline BL-11A at the Photon Factory (PF) are presented. A Hettrick-type grazing-incidence monochromator equipped with three varied-line-spacing plane gratings was designed and constructed at a bending-magnet source of the PF 2.5 GeV storage ring. An 800 lines mm(-1) laminar grating produced by aspheric-wavefront holographic recording optics, as well as a mechanically ruled blazed one, were tested. A resolving power of more than 4500 was achieved at 400 eV with either grating, and approximately 10(10) photons s(-1) are available at a resolving power of 2000. High photon flux enables low-concentration samples, such as surface adsorbates, to be studied. A simple scanning mechanism for a wide energy range is quite useful for EXAFS measurements on light elements such as C, N and O.

Journal Article↗
PubMed1998

Helical computed tomography in the diagnosis of portal vein invasion by pancreatic head carcinoma: usefulness for selecting surgical procedures and predicting the outcome.

OBJECTIVE: To evaluate the use of helical computed tomography (CT) in diagnosing portal vein (PV) invasion by pancreatic head carcinoma and its usefulness in predicting outcome. DESIGN: Validation cohort study. SETTING: Tertiary care public hospital. PATIENTS: Twenty-seven patients with carcinoma involving the pancreatic head were preoperatively studied with helical CT. All patients underwent resection. MAIN OUTCOME MEASURE: By quantifying the contact between the tumor and PV on helical CT, the relationship between them was classified into 1 of 4 types: type 1, visible fat layer between PV and the tumor; type 2, with the total PV circumference defined as 360 degrees, contact between the tumor and PV was considered to be 90 degrees or less; type 3, contact ranged between 91 degrees and 180 degrees; and type 4, contact greater than 180 degrees. Helical CT results were compared with intraoperative observation, histological findings of the resected specimen, and postoperative course. RESULTS: When helical CT showed type 3 or 4, the case was diagnosed as positive for PV invasion. Sensitivity, specificity, and overall accuracy were 83%, 100%, and 89% when compared with the intraoperative assessment, and 92%, 79%, and 85% with the histological assessment, respectively. One- and 2-year survival rates were 86% and 69% for type 1, 100% and 75% for type 2, and 33% and 12% for type 3, respectively. The survival rates of patients with types 1 and 2 were significantly higher than that of those with type 3 (P<.05). All 3 patients with type 4 died within 9 months. CONCLUSIONS: Helical CT facilitates detection of PV invasion by pancreatic head carcinoma. The extent of PV involvement reflected the outcome after pancreatectomy.

Adenocarcinoma↗
PubMed1998

Small polypoid lesions of the gallbladder: differential diagnosis and surgical indications by helical computed tomography.

OBJECTIVES: To demonstrate the helical computed tomographic (CT) features of small polypoid lesions of the gallbladder and to establish a clinical strategy based on CT findings for the treatment of such lesions. DESIGN: Validation cohort study. SETTING: Tertiary care public hospital. PATIENTS: Thirty-one patients with polypoid lesions of the gallbladder (< or = 3 cm) underwent CT followed by resection. MAIN OUTCOME MEASURE: The detectability of the lesions on both unenhanced and enhanced CT and the configuration of the lesions on enhanced CT were prospectively evaluated in comparison with the histopathological findings. RESULTS: Unenhanced CT detected 14 (45%) of the 31 lesions, whereas enhanced CT detected all of the lesions. The detection rates of the neoplastic lesions (adenoma, adenocarcinoma, and metastatic tumor) and cholesterol polyps were 81% (13/16) and 7% (1/15), respectively (P<.001). Among the 20 lesions demonstrated as pedunculated, 6 (30%) were neoplastic, whereas 10 (91%) of the 11 lesions demonstrated as sessile were neoplastic (P<.001). When a lesion was demonstrated on unenhanced CT or its shape was sessile on enhanced CT, the case was diagnosed as a neoplastic lesion. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the CT diagnosis of the neoplastic lesions were 88% (14/16), 87% (13/15), 88% (14/16), 87% (13/15), and 87% (27/31), respectively. CONCLUSION: Computed tomography can differentiate neoplastic and nonneoplastic small polypoid lesions of the gallbladder and reliably identify the presence of neoplastic lesions that should be resected.

Adult↗
PubMed1998

Early hepatocellular carcinoma as an entity with a high rate of surgical cure.

Early hepatocellular carcinoma (HCC) has been defined as a well-differentiated cancer containing Glisson's triad, but it remains unknown whether this lesion is curable. We prospectively studied 70 patients (enrolled from 1,172 referrals between 1982 and 1991) who had a diagnosis of a single HCC 2 cm or less in diameter (Stage T1) and who underwent curative hepatectomy and long-term follow-up (range, 0.2 to 14.3 years). Patients were eligible for surgery if they had a tumor that met the diagnostic criteria for HCC and were in Child-Pugh class A (n = 59) or B (n = 11) status. Among the 70 patients, there was 1 operative death. Based on our typing system, the tumors were assigned as early HCC (n = 15), overt HCC (n = 52), and non-HCC tumor (n = 3). The rate of microscopic regional spread was lower in early HCCs than in overt HCCs (7% vs. 42%; P = .01). The early HCC group had a longer time to recurrence than did the overt HCC group (3.9 vs. 1.7 years; P < .001) and had no local recurrence. After a median follow-up of 6.3 years, both overall survival and recurrence-free survival in the early HCC group were significantly better than those in the overt HCC group (P = .01; P = .001). In these two groups, the 5-year rates of overall survival were 93% and 54% (P = .01), and those of recurrence-free survival were 47% and 16% (P = .05), respectively; a significant survival benefit persisted over a decade (57% vs. 21%; P = .05). The early HCC group was at a lower risk of recurrence (relative risk, 0.31; 95% CI, 0.15 to 0.65; P = .002) and death (relative risk, 0.26; 95% CI, 0.09 to 0.73; P = .01) than was the overt HCC group. Early HCC is a distinct clinical entity with a high rate of surgical cure, thereby justifying its definition. It can be a lesion that corresponds to "Stage 0" cancer in other organs.

Carcinoma, Hepatocellular↗
PubMed1998

Succinylated collagen crosslinked by thermal treatment for coating vascular prostheses.

Vascular prostheses coated with collagen carefully prepared to avoid contamination were tested to see if it could induce endothelial cell lining throughout the graft surface in a natural way. The collagen fibers were succinylated. Hydrogel produced with the succinylated collagen was used for the sealant to reduce the amount of solid substance. To avoid contamination and the side effects of chemical reagents, the collagen thermally crosslinked under sterile conditions. A suspension of the collagen fibers was enmeshed in the interstices of Dacron fibers of fabric prostheses, which were then thermally crosslinked at 130 degrees C for 20 h. The prostheses were porous when the collagen fiber network was dry. Under wet conditions, however, the water permeability of the grafts was reduced to 0.1 ml/min from the 1,250 ml/min of the original prostheses. Three weeks after implantation in the abdominal aortas of dogs, 81.2 +/- 11% of the luminal surface was macroscopically thrombus free, and 56 +/- 14% was endothelialized. More than 95% of the coated collagen had been absorbed. Numerous fibroblasts had migrated into the graft walls, and capillary blood vessels had infiltrated the inside of the graft walls without foreign body reaction. In the controls, thrombus free areas averaged 9.0 +/- 5%, and endothelialized areas averaged 5.2 +/- 4%. Many giant cells, plasma cells, and lymphocytes had migrated into the graft walls, but no fibroblasts. These results suggest that rapid endothelialization is possible when clean collagen is used.

Animals↗
PubMed1998

Nonfunctioning islet cell tumors of the pancreas: clinical, imaging and pathological aspects in 16 patients.

BACKGROUND: Nonfunctioning islet cell tumors (NFICTs) usually reach a large size prior to detection, at which stage patients have some symptoms or signs. Recently, NFICTs have been discovered in asymptomatic patients with increasing frequency owing to advances in diagnostic imaging techniques. This study investigated clinical, imaging and pathological features in recent cases of NFICT. METHODS: The medical records, radiographs and pathological specimens of 16 patients with NFICT who were evaluated between April 1991 and March 1996 were reviewed. RESULTS: Tumor sizes ranged from 0.8 to 17 cm (average, 5.2 cm). Five patients (31%) had some symptoms or signs at the time of diagnosis; however, the other 11 (69%) had no symptoms. Of 10 patients with a tumor of size 5 cm or less, nine were asymptomatic and all tumors were histologically benign. In contrast, in six patients with a tumor larger than 5 cm, four had some symptoms and five tumors were malignant. The detection rates of pancreatic tumor mass on ultrasonography and computed tomography were 94% (15/16) each. All 14 patients in whom the tumor was completely resected survived without recurrence; however, the remaining two patients with liver metastases died following recurrence. CONCLUSIONS: US and CT are useful in detecting NFICTs even if the tumor is small and the patient is asymptomatic. The detection of NFICTs of small size and their complete removal are essential for a successful cure.

Adenoma, Islet Cell↗
PubMed1998

Expression of CD44 variants and its association with survival in pancreatic cancer.

Since the CD44 variant 6(v6) molecule has been noted as a marker for tumor metastasis and prognosis in several tumors, we examined whether or not v6 is a useful marker for evaluating the prognosis of pancreatic cancer patients. In addition, we attempted to assess the clinicopathological implications for pancreatic cancer of the variant 2 (v2) isoform using a recently developed monoclonal antibody against a v2 epitope. The expression of CD44 variants was evaluated immunohistochemically in paraffin-embedded pancreatic cancer tissues from 42 patients who were confirmed surgically and histologically to have received curative resection. An indirect immunoperoxidase method was used with monoclonal antibodies against epitopes of the standard (CD44s) portion, v6 and v2. Protein expression data were evaluated statistically for any correlations with the length of survival or with histological parameters. The expression of CD44v6 and v2 was observed only in tumor cells, if at all. On the other hand, expression of total CD44 (including CD44v, as well as CD44s) was observed in both tumors and adjacent normal sites. Tumor tissue from 21 (50%) and 16 (38%) patients showed positive immunoreactivity with mAb 2F10 (anti-CD44v6) and mAb M23.6.1 (anti-CD44v2), respectively. The expression of CD44v6 and v2 was correlated with decreased overall survival (P = 0.0160 and P = 0.0125, respectively). A significant correlation was obtained between CD44v2 peptide expression and vessel invasion (P = 0.026). These results suggest that CD44v2 and CD44v6 may be useful markers for poor prognosis in curatively resected primary pancreatic cancer.

Antigens, CD↗
PubMed1998

Construction of a proline-producing mutant of the extremely thermophilic eubacterium Thermus thermophilus HB27.

Growth of Thermus thermophilus HB27 was inhibited by a proline analog, 3,4-dehydroproline (DHP). This result suggested that the gamma-glutamyl kinase (the product of the proB gene) was inhibited by feedback inhibition in T. thermophilus. DHP-resistant mutants were reported previously for Escherichia coli (A. M. Dandekar and S. L. Uratsu, J. Bacteriol. 170:5943-5945, 1988) and Serratia marcescens (K. Omori, S. Suzuki, Y. Imai, and S. Komatsubara, J. Gen. Microbiol. 138:693-699, 1992), and their mutated sites in the proB gene were identified. Comparison of the amino acid sequence of T. thermophilus gamma-glutamyl kinase with those of E. coli and S. marcescens mutants revealed that the DHP resistance mutations occurred in the amino acids conserved among the three organisms. For eliminating the feedback inhibition, we first constructed a DHP-resistant mutant, TH401, by site-directed mutagenesis at the proB gene as reported for the proline-producing mutant of S. marcescens. The mutant, TH401, excreted about 1 mg of L-proline per liter at 70 degreesC after 12 h of incubation. It was also suggested that T. thermophilus had a proline degradation and transport pathway since it was able to grow in minimal medium containing L-proline as sole nitrogen source. In order to disrupt the proline degradation or transport genes, TH401 was mutated by UV irradiation. Seven mutants unable to utilize L-proline for their growth were isolated. One of the mutants, TH4017, excreted about 2 mg of L-proline per liter in minimal medium at 70 degreesC after 12 h of incubation.

Amino Acid Sequence↗