[Intrafamilial epidemic of meningococcal meningitis].
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Biomedical subjects
Publications and source records attributed to M Masuda.
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The crystal structures of synthetic 1-galactosamide bolaamphiphiles, N,N'-bis(beta-D-galactopyranosyl)decane-1,10-dicarboxamide (1) and N,N'-bis(beta-D-galactopyranosyl)dodecane-1,12-dicarboxamide (2), were determined by single-crystal X-ray analysis. The space groups are P21, Z = 2 with cell dimensions: a = 13.624(2), b = 4.832(3), c = 21.178(3) Angstroms, beta = 98.57(1) degrees for 1; a = 13.521(2), b = 4.838(1), c = 23.706(2) Angstroms, beta = 104.945(10) degrees for 2. The galactopyranosyl rings of 1 and 2 are in a 4C1 chair conformation. The bolaamphiphile molecules are arranged in a layered structure for 1 and 2, with the alkylene chains packed parallel all over the layers. The hydroxyl groups of the galactopyranosyl rings in 1 and 2 form identical three-dimensional hydrogen-bond networks. The connecting decamethylene spacer of 1 has a kink conformation, while the dodecamethylene chain of 2 an all-trans zigzag conformation.
We attempted to clarify the relationship between cyclin E to p27(Kip1), Ki-67 and clinicopathologic features in transitional cell bladder carcinoma. Immunohistochemical staining of archival tissue specimens of transitional cell bladder carcinoma obtained from 94 patients was performed by the labeled streptavidin-biotin-peroxidase method. Overexpression of cyclin E protein was observed in 38 of the 94 (40.4%) specimens, and was positively correlated with histological grade, Ki-67 LI and p27(Kip1) labeling index (LI). These data suggest that cyclin E may be associated with aggressive tumor growth, and may have a relationship with p27(Kip1) for the regulation of cell cycle progression in transitional cell bladder carcinoma.
We examined the expression and significance of p27(Kip1) protein in 79 patients with transitional cell carcinoma of the renal pelvis and ureter. Immunohistochemical staining of archival tissue specimens was done using a labeled streptavidin-biotin-peroxidase method. There was no significant association between p27(Kip1) labeling index and histologic grade or pathologic stage. Patients with p27(Kip1) labeling indices of 27 or greater had more favorable prognoses in comparison to those with p27(kip1) labeling indices less than 27 (P<0.01). Multivariate analysis indicated that p27(Kip1) had an independent predictive prognostic value (P<0.05). The p27(Kip1) may be a novel prognostic marker for transitional cell carcinoma of the renal pelvis and ureter.
Lymphatic lipid transport in the intestine of adult and ageing rats was compared. Adult (8-10 months old) and old (24-26 months old) male Wistar rats were cannulated into the mesenteric lymph under ethrane anesthesia. On the following day, lipid emulsion containing 35.4 mg/h of olive oil was infused intraduodenally for 7 h and lymph collected hourly was assayed for triglyceride and apolipoprotein A-IV (apo A-IV). The results showed there was no difference in lymphatic lipid and apo A-IV transport between adult and old rats. Since apo A-IV synthesis in the enterocytes is linked to the intracellular assembly of lipoprotein, it is likely that in addition to lymphatic transport, production of chylomicrons is not impaired in ageing rats.
The small GTPase Rho, which regulates a variety of cell functions, also serves as a specific substrate for bacterial toxins. Here we demonstrate that Bordetella dermonecrotizing toxin (DNT) catalyzes cross-linking of Rho with ubiquitous polyamines such as putrescine, spermidine and spermine. Mass spectrometric analyses revealed that the cross-link occurred at Gln63, which had been reported to be deamidated by DNT in the absence of polyamines. Rac1 and Cdc42, other members of the Rho family GTPases, were also polyaminated by DNT. The polyamination, like the deamidation, markedly reduced the GTPase activity of Rho without affecting its GTP-binding activity, indicating that polyaminated Rho behaves as a constitutively active analog. Moreover, polyamine-linked Rho, even in the GDP-bound form, associated more effectively with its effector ROCK than deamidated Rho in the GTP-bound form and, when microinjected into cells, induced the anomalous formation of stress fibers indistinguishable from those seen in DNT-treated cells. The results imply that the polyamine-linked Rho, transducing signals to downstream ROCK in a novel GTP-independent manner, plays an important role in DNT cell toxicity.
An immunoprecipitation assay for autoantibodies (Abs) to the human islet cell antigen IA-2 has been developed using 125I-labelled recombinant IA-2 expressed in E. coli. With this assay IA-2 Abs were detected in 103/217 (47%) of IDDM patients of different ages and with different disease duration. IA-2 Ab prevalence was higher in younger patients (at the age of 15 years or below) with the recent onset IDDM (64/113; 57%) compared to patients above the age of 15 years (11/25; 44%). One of 40 (2.5%) Graves' disease patients and five of 204 (2.5%) of NIDDM patients were also positive. IA-2 Abs were not detected in sera from patients with Hashimoto's thyroiditis (n=32), myasthenia gravis (n=20) or systemic lupus erythematosus (n=10). IA-2 Ab measurements based on 125I-labelled IA-2 showed a good correlation with the results of an immunoprecipitation assay based on 35S-labelled IA-2 produced in the in vitro transcription/translation system (r=0.78; n=113; p<0.001). Out of 217 IDDM sera which were tested for IA-2 Abs, 140 (65%) were positive for Abs to glutamic acid decarboxylase (GAD) and 166 (76%) were positive for Abs to IA-2 and/or Abs to GAD. In addition, Abs to IA-2, to GAD and to insulin were analysed in sera from recent onset IDDM patients who had not been treated with insulin (n=117). In all, 76/117 (65%) of these sera were positive for GAD Abs, 66/117 (56%) for IA-2 Abs, 45/117 (38%) for insulin Abs. However, 98/117 (84%) were positive for at least one of the three Abs confirming earlier observations on the complementarity of Ab testing in IDDM. Overall, the IA-2 Ab assay based on 125I-labelled recombinant IA-2 showed good sensitivity, precision and specificity which, combined with an easy and convenient protocol, makes it attractive for routine use.
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BACKGROUND: Late nodal metastases is a critical factor that worsens the prognosis of T1/T2N0 tongue cancer treated by interstitial brachytherapy. If we could better predict the patients at high risk for late nodal metastases developing before treatment, more appropriate choices of treatment could be selected. In recent studies of colon cancer, prostate cancer, and laryngeal cancer, CD44H has been postulated to be a metastasis suppressor. METHODS: On the basis of this phenomenon, we immunohistochemically evaluated the expression of CD44H in 38 cases of primary T1/T2N0 tongue cancer treated by interstitial brachytherapy. Formalin-fixed, paraffin-embedded biopsy specimens obtained before treatment were examined. RESULTS: The group that had late nodal metastases revealed a significantly lower (p =.0035) CD44H expression. CONCLUSIONS: A decreased CD44H expression may therefore be useful as a new predictor of late nodal metastases in patients with T1/T2N0 tongue carcinoma. For patients with a decreased CD44H expression, a partial glossectomy and an elective neck dissection may therefore be an appropriate treatment modality.
Various natural carotenoids were proven to have anticarcinogenic activity. Epidemiological investigations have shown that cancer risk is inversely related to the consumption of green and yellow vegetables and fruits. Since beta-carotene is present in abundance in these vegetables and fruits, it has been investigated extensively as possible cancer preventive agent. However, various carotenoids which co-exist with beta-carotene in vegetables and fruits also have anti-carcinogenic activity. And some of them, such as alpha-carotene, showed higher potency than beta-carotene to suppress experimental carcinogenesis. Thus, we have carried out more extensive studies on cancer preventive activities of natural carotenoids in foods; i.e., lutein, lycopene, zeaxanthin and beta-cryptoxanthin. Analysis of the action mechanism of these natural carotenoids is now in progress, and some interesting results have already obtained; for example, beta-cryptoxanthin was suggested to stimulate the expression of RB gene, an anti-oncogene, and p73 gene, which is known as one of the p53-related genes. Based on these results, multi-carotenoids (mixture of natural carotenoids) seems to be of interest to evaluate its usefulness for practice in human cancer prevention.
OBJECTIVE: The operative management and long term outcome of mitral valve replacement in infancy remain a therapeutic challenge. The selection of a prosthetic valve for this particular age group might affect the clinical outcome. Here we present our experience of mitral valve replacement in 6 infants using small bileaflet mechanical prosthetic valves. METHODS: Between January 1994 and August 1997, 6 infants (their age ranged from 3 months to 11 months, and their body weight from 2978 g to 7403 g) underwent mitral valve replacement using a mechanical valve prosthesis (16 mm CarboMedics prosthetic valve in 5, and 17 mm St. Jude Medical prosthetic valve Hemodynamic Plus in 1). The preoperative morphological features of the mitral valve were stenosis in 1, regurgitation in 3, and a combination of these in 2. The prosthesis was fixed at the annulus in 3, and at the supra-annular position in 3. Anticoagulation was performed using warfarin. RESULTS: There was no operative mortality. Postoperative catheterization revealed an acceptable wedge pressure in the pulmonary arteries, ranging from 10 to 12 mmHg. During the mean follow-up period of 36 months, late death due to residual pulmonary hypertension occurred in 1 patient at 10 months after surgery. Excluding this patient, all remaining patients are doing well with no need for repeated operation with no thromboembolic complication. The actuarial survival rate and the reoperation free rate at 70 months are 83 +/- 15% and 100%, respectively. CONCLUSION: Mitral valve replacement using a small size bileaflet mechanical prosthetic valves in infancy can be performed with low operative mortality and with satisfactory mid-term results.
Videoendoscopic surgery is commonly used to obtain a definitive diagnosis in a patient with pleural lesions or pulmonary infiltration of unknown etiology. We have performed minimally invasive pleural and lung biopsies, using 2-mm mini-videoscopic instruments supported by standard thoracoscopy via one 11.5-mm port, in 10 patients. These involved 8 patients with diffuse pulmonary infiltration, and two with diffuse pleural thickening. They underwent thoracoscopic pulmonary wedge resection and pleural biopsy using one 11.5-mm port and two or three 2-mm mini-ports. The mean operating time was 37 minutes. This procedure was successful in establishing a definitive diagnosis in each patient. Complications included subacute acceleration in pulmonary infiltration in one patient. No patient complained of pain or discomfort at the 2 mm-thoraco port sites. Healing of this port site resulted in excellent cosmesis. Mini-videoscopic surgery supported by standard thoracoscopic equipment can be used to perform lung or pleural biopsy less invasively than standard thoracoscopic approach.
The differences in the cardioprotective effects of nucleoside transport inhibitor (NTI) which is known to accumulate endogenous adenosine, on moderate and deep hypothermic ischemia, were examined. Using the Langendorff model, isolated, perfused rat hearts were arrested with cold cardioplegia and subjected to 90 min of global ischemia followed by 40 min of reperfusion. The temperature during ischemia was maintained at either 10 degrees C (groups 1 and 2) or 25 degrees C (groups 3 and 4). In groups 2 and 4, NTI in the form of R75231, 1 mg/l, was added to the cardioplegic solution. The intramyocardial adenosine triphosphate content at the end of ischemia was significantly lower in the moderate hypothermia groups than in the deep hypothermia groups. In the moderate hypothermia groups, NTI significantly enhanced the adenosine accumulation at the end of ischemia. Moreover, the recovery of both the contractile function and coronary flow rate in group 4 was superior to that in group 3, and was similar to those in groups 1 and 2. The addition of NTI to the cardioplegic solution generated a sufficient cardioprotective effect in moderate hypothermic ischemia, but not in deep hypothermic ischemia. The mechanism of this discrepancy is attributed to the differences in the levels of endogenous adenosine accumulated during ischemia.
G1 cyclins and cyclin-dependent kinase (CDK) complexes play important roles in G1 cell cycle transition, and their overexpression is implicated for neoplasia. The p27 protein (p27) negatively regulates G1 progression by binding to G1 cyclins/CDK complexes and inhibits their activity, resulting in inhibition of entry to the cell cycle. We investigated overexpression of cyclin D1 (CCND1), cyclin D2 (CCND2), cyclin E (CCNE), CDK2, and CDK4, in addition to p27, in 260 gastric cancer cases on the basis of Western blots, reverse transcriptase-polymerase chain reaction Southern blots, and immunohistochemistry to clarify the roles of these proteins in tumor progression and prognosis. Examination of 20 cases of fresh cancer and matched normal tissues demonstrated a clear tendency for increased mRNA synthesis to be more frequent than expected from protein levels, and a direct correlation between p27 protein and mRNA was not found. Immunohistochemistry demonstrated 21. 5%, 34.2%, 30.4%, 44.2%, and 48.0% positivity for CCND1, CCND2, CCNE, CDK2, and CDK4, respectively, in the 260 gastric cancer cases. Overexpression of CCND2 and CDK4 significantly correlated with tumor progression. Moreover, CCND2 cytoplasmic staining (26.2%) appeared to be strictly linked with progression, whereas nuclear staining (7. 8%) demonstrated an inverse correlation. Survival curves showed CCND2 (especially cytoplasmic staining) and CDK4 positivity to be associated with a poor prognosis and CCNE positivity with a better prognosis. Tumors with high p27 labeling indices (LIs) were well differentiated, with low levels of invasion and lymph node metastasis. p27-negative cases (37.3%) demonstrated a poor prognosis. Multivariate analysis revealed positivity for CCND2 and negativity for p27 to be independent prognostic factors. There were no direct links among CCND2, CCNE, CDK4, and p27. The results indicate that CCND2 cytoplasmic localization might reflect an important physiological role in tumor progression, whereas CCNE overexpression correlates with differentiation and a good prognosis, possibly because of accumulation of inactive forms of CCNE-CDK2 complexes. Loss of p27 caused by degradation activity may affect tumor cell growth in the presence of an altered extracellular matrix, facilitating metastasis. Cell-cycle-regulatory proteins appear to work independently.
BACKGROUND: In beating heart coronary artery bypass grafting (CABG) the effect of ischemic insult during coronary occlusion could not be evaluated immediately. Using transesophageal echocardiography, myocardial performance can be evaluated with analysis of integrated backscatter. METHODS: In 15 beating heart CABGs, cyclic variation (CV) of integrated backscatter of the anterior wall before, during, and after the left internal thoracic artery to left anterior descending (LAD) branch anastomosis was measured with transesophageal echocardiography. The patients were divided into two groups according to collateral vessels status (good collateral group n = 6, poor collateral group n = 9). RESULTS: In all patients, CV increased significantly after revascularization (8.56+/-2.50 to 11.47+/-3.32 dB, p < 0.0001). During LAD occlusion, significant decrease in CV was found in patients who had poor collateral arteries. At 15 minutes of LAD occlusion, CV decreased from the preocclusion value of 7.51+/-2.21 to 3.23+/-4.03 dB (p < 0.01). CONCLUSIONS: Measurement of CV can detect the ischemic insult during coronary occlusion and the effect of revascularization in beating heart CABG.
A 73-year-old woman with a large esophagorespiratory fistula underwent bronchoscopy and computed tomographic (CT) virtual endoscopy before stenting. Noninvasive CT virtual endoscopy showed the large fistula, and the CT findings agreed with the bronchoscopic findings.
Continuous production of sialyllactose, as a typical sialylsaccharide, was examined using a membrane reactor. The synthesis of sialyllactose through the transfer reaction catalyzed by neuraminidase, has been reported to be a suitable process for industrial production, but it still has drawbacks such as a low yield, high enzyme cost, and hydrolysis by the enzyme of sialyllactose formed. We attempted to solve these problems by utilizing an appropriate membrane reactor system. We first investigated the effects of various reaction conditions on sialyllactose productivity, and found that the productivity was independent of the enzyme concentration and reaction temperature but dependent on the substrate and buffer concentrations and the hydraulic retention time (HRT). We then selected a suitable membrane that allowed sialyllactose to permeate but rejected the substrate and enzyme. Finally, we constructed a membrane reactor system with a cut-off molecular weight of 3000 and applied it to continuous sialyllactose production from colominic acid at an HRT of 80 min. Using substrate concentration of 25 g/l the system performed with a high level of productivity and gave a good yield, while maintaining high transfer ratio of 4-5% over a 160-h test period.
Reactive nitrogen species, including nitrogen oxides (N(2)O(3) and N(2)O(4)), peroxynitrite (ONOO(-)), and nitryl chloride (NO(2)Cl), have been implicated as causes of inflammation and cancer. We studied reactions of secondary amines with peroxynitrite and found that both N-nitrosamines and N-nitramines were formed. Morpholine was more easily nitrosated by peroxynitrite at alkaline pH than at neutral pH, whereas its nitration by peroxynitrite was optimal at pH 8.5. The yield of nitrosomorpholine in this reaction was 3 times higher than that of nitromorpholine at alkaline pH, whereas 2 times more nitromorpholine than nitrosomorpholine was formed at pH <7.5. For the morpholine-peroxynitrite reaction, nitration was enhanced by low concentrations of bicarbonate, but was inhibited by excess bicarbonate. Nitrosation was inhibited by excess bicarbonate. On this basis, we propose a free radical mechanism, involving one-electron oxidation by peroxynitrite of secondary amines to form amino radicals (R(2)N(*)), which react with nitric oxide ((*)NO) or nitrogen dioxide ((*)NO(2)) to yield nitroso and nitro secondary amines, respectively. Reaction of morpholine with NO(*) and superoxide anion (O(2)(*)(-)), which were concomitantly produced from spermine NONOate and by the xanthine oxidase systems, respectively, also yielded nitromorpholine, but its yield was <1% of that of nitrosomorpholine. NO(*) alone increased the extent of nitrosomorpholine formation in a dose-dependent manner, and concomitant production of O(2)(*)(-) inhibited its formation. Reactions of morpholine with nitrite plus HOCl or nitrite plus H(2)O(2), with or without addition of myeloperoxidase or horseradish peroxidase, also yielded nitration and nitrosation products, in yields that depended on the reactants. Tyrosine was nitrated easily by synthetic peroxynitrite, by NaNO(2) plus H(2)O(2) with myeloperoxidase, and by NaNO(2) plus H(2)O(2) under acidic conditions. Nitrated secondary amines, e.g., N-nitroproline, could be identified as specific markers for endogenous nitration mediated by reactive nitrogen species.