Biomedical subjects
Publications and source records attributed to A Yamaguchi.
We report two cases of surgically proven supravesical hernia, one an internal supravesical hernia and the other an external supravesical hernia. Abdominal computed tomography showed the relation of the incarcerated intestine anterior to and compressing the urinary bladder. Although neither case was diagnosable preoperatively, we believe that the preoperative diagnosis of supravesical hernia by abdominal computed tomography is possible.
Three different types of beta-lactamases--TEM-2 type penicillinase, a typical cephalosporinase of Citrobacter freundii, and a Proteus vulgaris cephalosporinase with broad substrate range--were studied to determine the inactivation and reactivation kinetics for beta-lactamase inhibitors of these enzymes. Sulbactam, cloxacillin sulfone, clavulanic acid, imipenem, and aztreonam were evaluated. On the basis of the kinetic parameters a minimum scheme for the inactivation of these beta-lactamases by each compound was proposed, and the difference in the features of each of these as progressive and competitive inhibitors were evaluated. The relationship between the kinetic parameters and the synergistic effects of the inhibitors in combination with traditional beta-lactam antibiotics on the bacterial strains producing these beta-lactamases was examined. A close relationship between the synergistic effect, expressed as the FIC index, and a proposed parameter, TN x Ki/Km, was demonstrated. The results of this analysis suggest that sulbactam is a beta-lactamase inhibitor applicable to a wide range of beta-lactamase types.
In order to examine the mechanism of the anabolic effect of parathyroid hormone (PTH) on bone formation, human PTH(1-34) [hPTH(1-34)] (30 micrograms/kg) was injected subcutaneously to 9-week-old rats 5 times a week for 1 or 3 weeks. Trabecular bone volume (BV/TV) in the tibial metaphysis was not significantly different between the PTH- and vehicle-treated groups, but the parameters related to bone formation, including osteoid surface (OS/BS), mineralizing surface (MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR/BS), were significantly increased as early as 1 week after PTH treatment. And the parameters related to bone resorption including eroded surface (ES/BS) and osteoclast number (N.Oc/BS) were also significantly increased as early as 1 week after PTH treatment. Treatment with PTH for 1 week induced no significant increase in bone mineral density at the femoral metaphysis, whereas the same treatment for 3 weeks induced a significant increase. When bone marrow cells isolated from femora and tibiae of either PTH- or vehicle-treated rats were cultured at a high density (2 x 10(7) cells/one well of 24-multiwell plate), cellular alkaline phosphatase (ALP) activity was significantly increased in the cells isolated from PTH-treated rats compared with vehicle-treated rats. When bone marrow cells were cultured at a low density (4 x 10(6) cells/a one well of 6-multiwell plate) to generate colonies (colony forming unit-fibroblastic, CFU-F), PTH induced apparent increases in both the total number of CFU-F and the number of ALP-positive CFU-F.(ABSTRACT TRUNCATED AT 250 WORDS)
The preparation, X-ray structure, and detailed physical characterization are presented for a new type of single-molecule magnet [Mn4(O2CMe)2(pdmH)6](ClO4)2 (1). Complex 1.2MeCN.Et2O crystallizes in the triclinic space group P1, with cell dimensions at 130 K of a = 11.914(3) A, b = 15.347(4) A, c = 9.660(3) A, alpha = 104.58(1) degree, beta = 93.42(1) degree, gamma = 106.06(1) degree, and Z = 1. The cation lies on an inversion center and consists of a planar Mn4 rhombus that is mixed-valent, MnIII2MnII2. The pdmH- ligands (pdmH2 is pyridine-2,6-dimethanol) function as either bidentate or tridentate ligands. The bridging between Mn atoms is established by either a deprotonated oxygen atom of a pdmH- ligand or an acetate ligand. The solvated complex readily loses all acetonitrile and ether solvate molecules to give complex 1, which with time becomes hydrated to give 1.2.5H2O. Direct current and alternating current magnetic susceptibility data are given for 1 and 1.2.5H2O and indicate that the desolvated complex has a S = 8 ground state, whereas the hydrated 1.2.5H2O has a S = 9 ground state. Ferromagnetic interactions between MnIII-MnII and MnIII-MnIII pairs result in parallel spin alignments of the S = 5/2 MnII and S = 2 MnIII ions. High-frequency EPR spectra were run for complex 1.2.5H2O at frequencies of 218, 328, and 436 GHz in the 4.5-30 K range. A magnetic-field-oriented polycrystallite sample was employed. Fine structure is clearly seen in this parallel-field EPR spectrum. The transition fields were least-squares-fit to give g = 1.99, D = -0.451 K, and B4 degrees = 2.94 x 10(-5) K for the S = 9 ground state of 1.2.5H2O. A molecule with a large-spin ground state with D < 0 can function as a single-molecule magnet, as detected by techniques such as ac magnetic susceptibility. Out-of-phase ac signals (chi'' M) were seen for complexes 1 and 1.2.5H2O to show that these complexes are single-molecule magnets. A sample of 1 was studied by ac susceptibility in the 0.4-6.4 K range with the ac field oscillating at frequencies in the 1.1-1000 Hz range. A single peak in chi'' M vs temperature plots was seen for each frequency; the temperature of the chi'' M peak varies from 2.03 K at 995 Hz to 1.16 K at 1.1 Hz. Magnetization relaxation rates were evaluated in this way. An Arrhenius plot gave an activation energy of 17.3 K, which, as expected, is less than the 22.4 K value calculated for the thermodynamic barrier for magnetization direction reversal for an S = 8 complex with D = -0.35 K. The 1.2.5H2O complex with an S = 9 ground state has its chi'' M peaks at higher temperatures.
The structural gene for a cephalosporinase of Citrobacter freundii GN346 was sequenced. From the nucleotide sequence, the entire amino acid sequence of the mature enzyme with 361 amino acids and a molecular weight of 39,867 was determined. The active-site serine was directly confirmed to be serine 64 by studies in which the enzyme was labeled with dansylpenicillin. In investigations comparing the inhibitory effect of sulbactam (penicillanic acid sulfone) and cloxacillin sulfone on the cephalosporinase and on TEM-2-type penicillinase, sulbactam was found to be an effective progressive inhibitor but a poor competitive inhibitor for the cephalosporinase. The cephalosporinase and the inhibitor formed a long-lived complex with a half-life of 550 minutes. Cloxacillin sulfone could not inactivate the cephalosporinase progressively but irreversibly inactivated the penicillinase.
The effect of the interaction of beta-lactamase production and outer membrane permeability on the bacterial resistance to beta-lactam antibiotics was investigated using the Escherichia coli K12 substrains, which have outer membrane mutation and produce TEM-type penicillinase. Experiments confirmed that the cefazolin concentrations in the periplasm of cells exposed to the MIC were restricted to 2.4-4.6 microM among the bacteria, even though the MICs for the bacterial strains were distributed from 13 microM to 1,726 microM. The drug concentrations in the periplasm could be calculated on the basis of parameters obtained experimentally, and the calculated values were in fair agreement with the experimental values. The effect of beta-lactamase activity (Vmax/Km) and the outer membrane barrier on the elevation of MICs was observed to be synergistic, and the contribution of beta-lactamase was more effectively expressed in the bacterial cells with higher outer membrane barrier.
DNA ploidy and the labeling index (LI) of proliferating cell nuclear antigen (PCNA) in gastric cancers were determined using cytofluorometry and immunohistochemistry, respectively, and the prognostic value of these two parameters was evaluated. Of 66 patients with advanced gastric cancers treated with radical resection, 27 with aneuploidy and a high PCNA-LI (> or = 40) showed the lowest 5-year survival rate (38%). Twenty patients with diploid cancers and a high LI showed a lower 5-year survival rate (59%) than the 15 patients with diploid cancers and a low LI (<40), who had the highest 5-year survival rate (86%). A multivariate analysis showed that the grouping based on the ploidy and the LI was an independent prognostic factor. Thus, the combination of DNA ploidy and PCNA-LI may be a useful prognostic indicator for advanced gastric cancers.
The nm23 gene has been proposed as a candidate tumor metastasis suppressor in some human cancers. Sialyl Lewis X (sLex) has been demonstrated to play an important role in the adhesion of human cancer cells to human vascular endothelium, inducing metastasis. Little information has been reported about the correlation between the expression of nm23 and sialylated carbohydrate antigens. In the present study, 102 surgically resected primary breast cancer tissues were sectioned and stained with antibody against nm23-H1 and sLex. Of the 102 cases, 39 (38.2%) cases with a reduced expression of nm23-H1 were observed, and the numbers of sLex-positive cases were 61 (59.8%), respectively. The reduced expression of nm23-H1 and the positive expression of sLex were significantly associated with lymph node involvement. Among the 100 patients who underwent curative surgery, the disease-free survival rate was significantly correlated to both the nm23-H1 and sLex expressions. No interrelated expressions were found between nm23-H1 and sLex. In multivariate analysis using Cox regression model, combination assay of nm23-H1 and sLex expression emerged as independent significant prognostic factors. These results suggest that nm23-H 1 gene and sLex may be involved in different steps of the metastatic process in human breast cancer, and immunohistochemical detection of the combination of sLex and nm23-H1 may be a biologic marker of prognostic significance.
To evaluate their prognostic value, the expressions of CD44v and sialyl LeX (SLX) in colorectal cancers were studied immunohistochemically. Tissue specimens were reacted with monoclonal antibodies (mAb) CD44-1V and CSLEX-1. Of the 145 colorectal cancer patients undergoing curative resection, 59 (40.7%) were positive for mAb CD44-1V, and 40 (27.6%) were positive for mAb CSLEX-1. There was a significant correlation between the combined expression of SLX and CD44v8-10 and lymph node metastasis. The patients with tumors negative for CD44v8-10 and SLX had the most favorable prognoses. Conversely, the patients with tumors positive for both CD44v8-10 and SLX had a high recurrence rate and the poorest prognoses. In a multivariate analysis using the Cox regression model, the combined expression of SLX and CD44v8-10 emerged as an independent prognostic indicator. These results suggested that the combined expression of CD44v8-10 and SLX may be a biologic marker of prognostic significance.
We studied the proliferative activity in endoscopically biopsied tumors by means of argyrophil-protein nucleolar organizer region (AgNOR) scores. AgNOR scores of 109 colorectal cancers ranged from 2.48 to 6.72 (mean: 3.27 +/- 0.52). The 109 tumors were divided into two groups by the median value of AgNOR counts. There was no significant correlation between the AgNOR scores and the histologic type, invasion of bowel wall, lymph node metastases or peritoneal metastases. There was a significant association between the AgNOR scores and lymphatic invasion or liver metastases. Patients with higher AgNOR score tumors had significantly poorer prognoses than those with lower AgNOR score tumors. In Dukes' stage C, especially, the survival rate for patients with higher AgNOR score tumors was significantly lower than for those with lower AgNOR score tumors. Recurrence was found in 8.7% of the tumors with lower AgNOR scores and 19.4% of the tumors with higher scores. Aneuploid tumors had higher AgNOR scores than tumors with the diploid pattern. The results suggest that the AgNOR scores may possibly be a useful prognostic marker of colorectal cancer.
Overexpression of p53 was studied immunohistochemically in colorectal tumors. We found p53-positive cells in 17 (58.6%) of 29 specimens of cancer in adenoma. Expression of p53 protein was detected in the nuclei of the tumor cells. We also found p53-positive cells in 7 (7.1%) of 99 specimens of adenoma. p53 immunoreactivity for severe dysplasia was higher than that for mild or moderate dysplasia. p53 expression in adenomas was restricted to a few glands, and the proliferating-cell nuclear antigen (PCNA)-positive rate for the p53-positive glands was significantly higher than that for p53-negative glands. The results suggested that the p53-positive glands might have high growth fractions, and that immunohistochemical detection of p53 expression in tubular adenomas might contribute to identifying the potential for malignant transformation.
Immunohistochemical detection of p53 was performed in archival material of 129 early gastric cancers. Positive staining was detected in 22.5% (29/129) of the cases. No significant association could be established with any clinicopathological criteria but a trend of a higher rate of p53 detection was observed among large tumors (> 6 cm) and in cases with lymph node involvement. Prognosis was significantly worse for patients with p53-positive staining tumors. The 5-year survival rate was 92.1% for patients with p53-negative tumors and 71.2% for those with positive malignancies (p = 0.001). p53 detection and lymph node involvement emerged as independent prognostic factors in a Cox model including other clinicopathological criteria. Immunochemical detection of p53 may become an important aid in the preoperative evaluation of patients with early gastric cancer.
The expression of epidermal growth factor receptor (EGFR), epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha) and the labeling index of proliferating cell nuclear antigen (PCNA LI) were examined immunohistochemically in 288 gastric cancer patients, and the relationships between these results and the lymph node metastasis were studied. To investigate the relation between the expression of EGFR and PCNA LI, we divided the patients into the following three groups according to the immunohistochemical findings: group A, EGFR (+); group B, EGFR (-), and EGF(+) or TGF alpha(+); group C, EGFR(-), EGF(-) and TGF alpha(-). In the cancers invading submucosal or proper muscle layer, high-PCNA tumors (PCNA LI > or = 70) in both groups A and B had more frequent lymph node metastasis than in the intermediate-(40-69) and low- (< or = 39) PCNA tumors. In the cancers invading subserosal layer or further, the frequency of metastasis in group A was over 78% and was not related to the PCNA range. In group B, metastasis was more frequent in high- and intermediate-PCNA tumors (about 80%) than in low-PCNA tumors (44%). These results suggest that growth regulation by EGFR is related to lymph node metastasis in gastric cancer, and the higher the PCNA LI of cancer cells becomes, the more frequent the occurrence of lymph node metastasis.
We conducted a phase III randomized study to investigate effects of supportive chemotherapy with oral doxifluridine (group A, 75 patients) or 5-fluorouracil (group B, 75 patients) in advanced gastric cancer when intensive chemotherapy was not an option. Although there were no significant differences between the groups with regard to survival, hospital-free survival and time to progression, median values of 3 endpoints were superior in group A. Secondary analysis showed that group A patients with prior chemotherapy tended to have longer survival and hospital-free survival and significantly longer time to progression.
We studied the Cd44v8-10 expression in gallbladder cancer immunohistochemically. Eighteen of 37 gallbladder cancer tissues expressed CD44v8-10. There were significant correlations between CD44v8-10 immunoreactivity and perineural invasion, venous invasion, and lymph node metastasis. Patients with CD44v8-10-positive tumors showed poor prognoses, whereas those with CD44v8-10-negative tumors had favorable prognoses. A multivariate analysis using the Cox regression model showed the immunoreactivity of CD44v8-10 to be an independent prognostic indicator of gallbladder cancer. The results suggest that CD44v8-10 expression may be a biologic marker of prognostic significance in gallbladder cancer.
Using in situ hybridization with a chromosome-specific DNA probe, we investigated the numerical aberrations of chromosome 17 in differentiated gastric cancers. In 75 cancers that invaded the submucosal or deeper layer, the frequency of an increased hybridized signal (hyperdiploid nuclei) on chromosome 17 was significantly associated with lymph node metastasis. Multivariate analysis showed that the classification of numerical aberration (disomy and polysomy) based on the percentage of hyperdiploid nuclei was an independent prognostic factor for the postoperative survival of 58 patients with invasive gastric cancer treated with radical gastrectomy. Thus, numerical aberrations of chromosome 17 may be a useful prognostic indicator of differentiated gastric cancer.
Pancreaticoduodenectomy (PD) was performed as a radical operation on 10 patients who had stage III or IV carcinoma of the distal third of the stomach which invaded the pancreas head (T4) or had level 3 lymph node metastasis. The surgical results of the PD were compared with those of 69 patients treated with subtotal gastrectomy (SG). Although the postoperative morbidity was higher (70%) in the PD group than in the SG group (32%), no hospital death occurred. The overall postoperative survival provided by PD was as good as that provided by SG for 43 patients who had stage III or IV tumors (the 5-year survival rates, 40 versus 45%). Regarding the T4 tumors invading the pancreas, the survival of the 9 patients with PD was better than that of the 12 patients with SG (median survival time, 19 versus 9 months). Thus, PD might improve the postoperative survival of patients with carcinoma of the distal stomach invading the pancreas.
A total of 25 patients with severe peritoneal dissemination underwent chemohyperthermic peritoneal perfusion (CHPP). The primary tumors in these patients comprised colorectal cancer (n = 14), ovarian cancer (n = 6), cervical cancer, (n = 1), small bowel cancer (n = 1), pseudomyxoma retroperitonei (n = 1), cystoadenocarcinoma of liver (n = 1), and pancreas cancer (n = 1). The intraperitoneal perfusion was carried out with a magnet pump for 60 min. The heated perfusate contained anticancer drugs to act synergistically with the hyperthermia. The intraperitoneal temperature was maintained at 42.0-42.5 degrees C. Eight of 25 patients showed CR, four PR, ten NC, and three PD, and the percentage (CR+PR) representing the overall efficacy rate was 48.0%. The morbidity rate was 8% (2/25) and there was no treatment-associated mortality. The percentage (CR+PR) of the patients with colorectal cancer was 57%; ovarian cancer, 50%; and other malignancies, 20%. The 1 year-and 3 year-survival rates of all the patients were 55% and 26%, respectively. The median survival periods of the CR, PR, NC, and PD groups were 4.0, 1.0, 1.0, and 0.7 years, respectively. The survival curve of the CR group was the best of all the groups (P = 0.02). These results indicated that CHPP was a feasible therapy and exerted a direct anticancer effect on peritoneal dissemination especially in the case of ovarian cancer, and the prognosis of complete responders was improved.