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Biomedical subjects

M Noguchi

Publications and source records attributed to M Noguchi.

At least 19 recordsLinked to original sources

Intrapulmonary sublesions detected before surgery in patients with lung cancer.

BACKGROUND: The treatment of patients with multiple intrapulmonary lesions remains controversial. METHODS: Fifty-three patients with lung cancer, in whom preoperative evaluation disclosed intrapulmonary nodules distinct from the main tumor, were analyzed retrospectively to establish the optimal treatment in such cases. RESULTS: These sublesions proved to be intrapulmonary metastases (PM) in 16 cases (30%), multiple primary lung cancers in 7 cases (13%), and various nonmalignant lesions in the others. The survival of the 53 patients, and of patients with clinical Stage I/II disease in particular, compared favorably with that of all patients with resected lung cancer. Those with multiple sublesions had a poorer prognosis, irrespective of their nature. Although patients with PM as sublesions often had clinically advanced cancer, metastatic foci, per se, did not influence the survival data as calculated by a multivariate analysis. CONCLUSIONS: The authors conclude that the existence of a solitary intrapulmonary sublesion should not preclude surgical treatment, unless surgery is contraindicated because of other clinical and radiologic findings.

Humans

Mitochondrial changes in phospholipid molecular species during the increased oxidative phosphorylation after hepatectomy.

The changes in liver mitochondrial and microsomal phospholipid molecular species were analyzed during the period of remarkably increased oxidative phosphorylation following partial hepatectomy in rabbits. At 24 hours after hepatectomy, phosphorylative activity increased significantly from 69.7 +/- 5.5 to 118.5 +/- 5.7 nmol of ATP synthesized/min/mg protein, compared to the sham operated group. The ratio of phosphatidylethanolamine to phosphatidylcholine (PE/PC) in mitochondria increased significantly in the hepatectomy group compared with the sham operated group. Remarkable changes in molecular species were observed in mitochondrial phosphatidylethanolamine. 1-Stearoyl-2-arachidonoyl species decreased in the hepatectomy group. On the other hand, microsomal phospholipids hardly changed compared with mitochondrial ones. The change in content of 1-stearoyl-2-arachidonyl phosphatidylethanolamine in mitochondria tended to return to normal levels concomitant with the normalization of phosphorylative activity. The changes in content of mitochondrial phospholipids, especially phosphatidylethanolamine, might also be related to enhancement of phosphorylative activity.

Animals

[Evaluation of the internal mammary nodes by lymphoscintigraphy and ultrasonography in patients with breast cancer].

The efficacy of lymphoscintigraphy and ultrasonography was evaluated in the detection of internal mammary lymph node (IMN) metastases in patients with breast cancer. On histological examination of IMN, 10 patients had metastases (positive group) and 47 did not (negative group). On lymphoscintigraphy, lack of uptake in the parasternal region of the affected side was classified as abnormal. The frequency of this abnormal finding was not significantly different between both groups. On sonography, the thickness of the sonolucent internal mammary area was measured. The thickness of the affected side was 6 mm or more in two patients of the positive group and only one of the negative group. A thickness of over 6 mm on the affected side was statistically significant (p less than 0.05). The difference in thickness between the affected side and the healthy side was 3 mm or more in four patients of the positive group, and was less than 3 mm in all patients of the negative group. A difference in thickness of more than 3 mm between the two sides was extremely significant (p less than 0.001). In conclusion, sonography is valuable in detecting IMN metastases, while lymphoscintigraphy is not useful. Sonography is recommended as an efficient diagnostic modality for IMN metastases.

Adult

C-erbB-2 oncoprotein expression versus internal mammary lymph node metastases as additional prognostic factors in patients with axillary lymph node-positive breast cancer.

The relationship was assessed between c-erbB-2 oncoprotein expression and other prognostic factors in breast cancer, such as axillary and internal mammary node metastases. The value of these indicators was analyzed in estimating prognosis, especially in patients with axillary node-positive breast cancer. These results showed that c-erbB-2 is significantly related to clinical stage and axillary node metastases. A univariate study revealed that disease-free and overall survival were correlated significantly with clinical stage, tumor size, axillary and internal mammary node metastases, and 21N status. Among the patients with axillary node involvement, however, 21N status did not appear to be a significant additional prognostic factor. Internal mammary node metastases were significant. In a multivariate study, only axillary and internal mammary node metastases were significant prognostic factors for either the entire group of patients or those with positive axillary nodes. Therefore, axillary node dissection and biopsy of the internal mammary nodes may provide important prognostic information for patients with breast cancer.

Adult

Frequent loss of heterozygosity at the DCC locus in gastric cancer.

We examined 28 cases of surgically resected gastric cancer, excluding the diffuse type, for loss of heterozygosity (LOH) on 12 chromosomal arms using polymorphic DNA markers. LOH on chromosome 18q was detected in 61% (14 of 23) of the cases by the probes OLVIIA8, OLVIIE10, p15-65, SAM 1.1, and OS-4, and a putative common region showing LOH included the locus of the DCC tumor suppressor gene. LOH on chromosome 17p was also frequently found (8 of 19 or 42% of the cases) by the probes p10-3 and pHF12-1, and in 5 of these 6 cases the LOH on chromosome 17p was accompanied by LOH on chromosome 18q. On the other hand, the incidence of LOH was 30% or less using probes pHRnES, pHF12-65, p-c-mybE2.6, NJ3 3.2, pHF12-8, pHINS6.0, p9D11, hp2-alpha, pCMM6, and P1A5 on chromosomes 1q, 5, 6q, 7q, 9, 11p, 13q, 16q, 20, and 22q, respectively. LOH on chromosome 18q was frequent irrespective of the depth of tumor invasion, whereas the incidence of LOH on chromosome 17p was higher in the cases in which the tumor invaded beyond the muscularis propria than in those in which tumor invasion was limited to the submucosa and muscularis propria. These results suggest that LOH on chromosome 18q occurs at an earlier stage than LOH on chromosome 17p and that the inactivation of tumor suppressor genes located on chromosome 17p and 18q (e.g., the p53 and DCC genes) is critically involved in the development of the majority of gastric cancers. While alteration of the p53 gene is observed in various human cancers, that of the DCC gene is considered to occur more selectively in gastrointestinal cancers.

Chromosome Deletion

Role of sequences within the first intron in the regulation of expression of eukaryotic initiation factor 2 alpha.

Resting human peripheral blood T cells synthesize proteins at very low rates and contain very low levels of eukaryotic initiation factor (eIF) 2 alpha mRNA. During mitogenic activation, the level of eIF-2 alpha mRNA increases at least 50-fold, an effect thought to be due primarily to intranuclear stabilization of the primary transcript (Cohen, R. B., Boal, T. R., and Safer, B. (1990) EMBO J. 9, 3831-3837). Analysis of sequences within the first intron revealed a region with homology to the "initiator" (Inr) sequence first described by Smale and Baltimore (Smale, S. T., and Baltimore, D. (1989) Cell 57, 103-113). This Inr element is positioned 450 bases downstream of the eIF-2 alpha promoter and is oriented to generate an overlapping antisense transcript. Deletion or mutation of the Inr element results in a reproducible 5-8-fold increase in the activity of an eIF-2 alpha promoter-driven CAT reporter gene and a corresponding 2.5-fold decrease in activity of an antisense driven luciferase reporter gene in vivo in 293 cells. In vitro transcription analysis also reveals antisense transcripts which depend on an intact Inr element and whose 5' ends map to sequences surrounding the Inr consensus sequence. A potential role for double-stranded RNA generated by these overlapping divergent transcription units in the regulation of eIF-2 alpha gene expression in T cells is suggested.

Base Sequence

The source of the oxygen atom in the alpha-hydroxyglycine intermediate of the peptidylglycine alpha-amidating reaction.

Peptidylglycine alpha-amidating activity catalyses the oxidation of a C-terminally glycine-extended peptide to a desglycine alpha-amidated peptide at the expense of ascorbate and O2 in the presence of Cu2+. The reaction involves oxidative N-dealkylation within the terminal glycine residue, with retention of the glycine N atom and release of the remainder as glyoxylate. Recent studies by us and others have revealed that the reaction consists of two steps via a carbinolamide as an intermediate (peptidyl alpha-hydroxyglycine), and also that two separate enzymes derived from a common precursor protein catalyse these steps, formation of the carbinolamide and its conversion into alpha-amide and glyoxylate. As for the mechanism of carbinolamide formation, two distinct pathways can be considered: direct mono-oxygenation at the glycine alpha-C atom and dehydrogenation leading to an imine followed by hydration. To draw a distinction between them, we carried out the reaction with D-Tyr-Val-Gly as the substrate either in the H2(18)O-enriched medium or under an atmosphere of 18O2, and isolated the alpha-hydroxylglycine intermediate. The fast-atom-bombardment mass-spectral analysis demonstrated that the hydroxy O atom comes from O2, but not from H2O, indicating that the alpha-hydroxylation should be a monooxygenase reaction.

Amidine-Lyases

Mutagenesis studies on the amino acid residues involved in the iron-binding and the activity of human 5-lipoxygenase.

Human 5-lipoxygenase contains a non-heme iron essential for its activity. In order to determine which amino acid residues are involved in the iron-binding and the lipoxygenase activity, nine amino acid residues in highly homologous regions among the lipoxygenases were individually replaced by means of site-directed mutagenesis. Mutant 5-lipoxygenases in which His-367 or His-550 was replaced by either Asn or Ala, His-372 by either Asn or Ser, or Glu-376 by Gln were completely devoid of the activity. Though mutants containing an alanine residue instead of His-390 or His-399 lacked the activity, the corresponding asparagine substituted mutants exhibited. The other mutants retained the enzyme activity. These results strongly suggest that His-367, His-372, His-550 and Glu-376 are crucial for 5-lipoxygenase activity and coordinate to the essential iron.

Amino Acid Sequence

Papillary thyroid cancer and its surgical management.

The surgical management in papillary thyroid cancer has been highly controversial. In the Department of Surgery (II), Kanazawa University Hospital, the surgical management especially for cervical lymph node metastases has changed since 1973 from a conservative approach to an aggressive one. In order to determine whether an aggressive approach is warranted, a retrospective multivariate analysis was carried out on 106 cases of papillary thyroid cancer. The patients have been followed for 10-28 years. Multivariate analysis was conducted following Cox's model. By this analysis, aggressive management appeared to have no impact on survival or relapse-free survival. However, age, sex, tumor size, and cervical lymphadenopathy were confirmed to be important prognostic factors in survival and/or relapse-free survival.

Adult

Oncological aspect of immediate breast reconstruction in mastectomy patients.

In this study, we compared the relapse-free and overall survival of 83 patients who underwent mastectomy with immediate reconstruction (MIBR) using a musculocutaneous flap with or without silicone implant with those of 153 patients with breast cancer who underwent mastectomy without immediate reconstruction. In univariate analysis, the overall and/or relapse-free survival of reconstructed patients with four or more positive axillary lymph nodes or those with menopausal status were significantly inferior compared with those of nonreconstructed patients. In multivariate analysis, however, the immediate breast reconstruction did not appear to have a significant adverse influence on all patients, and on the subgroups stratified by menopausal status or axillary lymph node metastases. Therefore, it was concluded that MIBR using a musculocutaneous flap did not compromise the survival of patients with breast cancer.

Adult

The relationship between lymph node metastases and DNA-ploidy status as prognostic factors in invasive breast cancer.

We evaluated the relationship between the regional lymph node metastases and the DNA ploidy status in 207 patients with invasive breast cancer, as well as their prognostic values in estimating the prognosis of breast cancer. A significantly higher incidence of aneuploidy was found in patients with a large T3 or T4 tumor, a positive axillary lymph node status, more than 4 positive axillary lymph nodes or positive internal mammary lymph nodes. In a univariate study, the overall survival was significantly correlated with tumor size, axillary lymph node status, axillary and internal mammary lymph node metastases, and DNA ploidy status. In the multivariate analysis, however, only axillary and internal mammary lymph node metastases were recognized as important independent prognostic factors on survival. In this series, the DNA ploidy status did not appear to be an independent prognostic factor either in the entire series or in negative axillary node patients, since it was closely correlated with the axillary or internal mammary lymph node metastases, and the axillary node negative patients had an extremely favorable prognosis.

Adult

Pharmaceutical characterization of corticosteroid suppository treatment for ulcerative colitis.

The dose and method of administration of a corticosteroid given for the treatment of patients with ulcerative colitis are determined according to the range of the diseased area and its severity. In this study, we prepared a hydrophilic suppository consisting of water-soluble prednisolone sodium succinate (PSL-SS) and a hydrophilic base, polyethylene glycol (PEG), and a hydrophobic suppository consisting of water-insoluble prednisolone (PSL) and a hydrophobic base, Witepsol (WT). We determined the spread of the drugs after intrarectal administration and their therapeutic effect. When rats received the hydrophilic suppository, the drug spread farther oral than when they received the hydrophobic suppository. Moreover, more than half of the PSL-SS recovered was observed to have changed into PSL. A therapeutic effect on the colitis induced in rats by acetic acid was noted in the area up to 10 cm from the anus in the case of the hydrophilic suppository, while the effect of the hydrophobic suppository was seen only in the area up to 2.5 cm from the anus. In patients with ulcerative colitis, the hydrophilic suppository showed retrograde spread to a site 34.4 +/- 5.3 cm from the anus, while the hydrophobic suppository spread to a site 19.0 +/- 2.4 cm from the anus. These results suggest that a hydrophobic suppository should be used for patients in whom inflammation is confined to the rectum, and a hydrophilic suppository used for patients in whom inflammation reaches the rectum and the middle part of the sigmoid colon.

Administration, Oral

Non-arthritic rheumatoid valvulitis with coronary arteritis causing myocardial infarction.

Rheumatoid valvulitis occurring in an individual without arthritis has rarely been reported. A 62-year-old woman died after repeated myocardial infarction, with no articular symptoms but with a fever of unknown origin and a positive rheumatoid factor. Autopsy examination revealed granulomatous inflammatory lesions with rheumatoid nodules present in the aortic valve and the base of the left coronary artery. Wide-spread myocardial infarction was found in the septal and anterolateral walls of the left ventricle.

Aged

Growth potential of endometrial cancers assessed by a Ki-67 Ag/DNA dual-color flow-cytometric assay.

Ki-67 is a monoclonal antibody directed against a nuclear antigen present only in proliferating cells. To assess the growth potential of uterine endometrial cancer, the population of cells in proliferating cycle (%PC) was examined with Ki-67, using flow cytometry. The %PC of 27.18 +/- 12.00% in 22 endometrial cancers was significantly higher than the 14.5 +/- 5.94% found in 28 normal endometrial tissues. In premenopausal endometrial tissue, the %PC in the proliferatory phase was significantly higher than the %PC found in the secretory phase. In endometrial cancers, an increase of %PC was found in cases with deep myometrial invasion, and the %PC was elevated in groups containing histologically poorly differentiated types when compared to groups of well-differentiated and moderately differentiated types. Sorted cells reactive with Ki-67 antibody were large and had a high nuclear/cytoplasmic ratio. On the bases of these results, it was concluded that a Ki-67 Ag/DNA dual-color assay would be useful to examine the growth fraction in endometrial carcinoma and that an increased growth fraction was related to deep myometrial invasion or poorly differentiated types.

Adenocarcinoma

Wide resection with latissimus dorsi muscle transposition in breast conserving surgery.

In this study we evaluated whether the immediate transposition of the latissimus dorsi muscle (LDM) improves breast appearance and patient satisfaction after quadrantectomy. Twenty-three patients (transposed group) had the transposition of LDM immediately after quadrantectomy, but eight patients (non-transposed group) had quadrantectomy alone. For evaluation, breast size was classified as small (A or B cup) and large (C or D cup). Consequently, the cosmetic result was evaluated as excellent in 73% of the patients with transposed small breasts, but in only 25% of the patients with non-transposed small breasts and by none of the patients with transposed large breasts. On the other hand, all patients with transposed small breasts reported that they are satisfied with their operation, as opposed to 88% of the patients with transposed large breasts and 63% of the patients with transposed large breasts and 63% of the patients with non-transposed small breasts. It was concluded therefore, that the transposition of LDM is useful in correcting post-quadrantectomy breast deformity, especially in patients with small breasts.

Adult