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Background: In the eighth edition of the AJCC cancer staging classification, the T system for distal cholangiocarcinoma (DCC) has been revised from a layer‐based to a depth‐based approach. The aim of this study was to propose an optimal T classification using a measured depth in resectable DCC. Methods: Patients who underwent pancreatoduodenectomy for DCC at 32 hospitals between 2001 and 2010 were included. The distance between the level of the naive bile duct and the deepest cancer cells was measured as depth of invasion (DOI). Invasive cancer foci were measured as invasive tumour thickness (ITT). Log rank χ2 scores were used to determine the cut‐off points, and concordance index (C‐index) to assess the survival discrimination of each T system. Results: Among 404 patients, DOI was measurable in 182 (45·0 per cent) and ITT was measurable in all patients, with median values of 2·3 and 5·6 mm respectively. ITT showed a positive correlation with DOI (rS = 0·854, P < 0·001), and the cut‐off points for prognosis were 1, 5 and 10 mm. Median survival time was shorter with increased ITT: 12·4 years for ITT below 1 mm, 5·2 years for ITT at least 1 mm but less than 5 mm, 3·0 years for ITT at least 5 mm but less than 10 mm, and 1·5 years for ITT 10 mm or more (P < 0·001). This classification exhibited more favourable prognostic discrimination than the T systems of the seventh and eighth editions of the AJCC (C‐index 0·646, 0·622 and 0·624 respectively). Conclusion: ITT is an accurate approach for depth assessment in DCC. The four‐tier ITT classification with cut‐off points of 1, 5 and 10 mm seems to be a better T system than those in the seventh and eighth editions of the AJCC classification. [ABSTRACT FROM AUTHOR]

Background Many users in Japan of skin brightening/lightening cosmetics containing rhododendrol ( RD) have developed leucoderma. Leucoderma appears on skin areas repeatedly treated with RD-containing cosmetics. RD-induced leucoderma ( RDIL) presents different degrees of well-defined hypopigmentation. It is crucial to determine the degree of hypopigmentation to differentiate RDIL from vitiligo vulgaris ( VV). Objectives To quantitatively evaluate hypopigmentation of RDIL lesions and the recovery of pigmentation, and to compare the hypopigmentation with VV and normal skin. Materials and methods Sixteen cases of RDIL, nine cases of VV and 15 healthy controls were examined using a novel multispectral camera ( MSC) that can simultaneously obtain the reflection intensity at 10-nm wavelength intervals from 400 to 760 nm of the photographed area. ∆Absorbance was calculated by subtracting the log of reflection intensity of the target area from that of a white reflection standard. Results Most RDIL lesions showed lower ∆Absorbance than healthy skin and higher ∆Absorbance than VV lesions between 400 and 550 nm. Statistical comparison of the maximum ∆Absorbance from 420 to 460 nm (Max∆Absorbance) for VV, RDIL and control skin showed that the Max∆Absorbance of RDIL was significantly higher than that of VV and lower than that of control skin. The comparison of ∆Absorbance of the same sites in RDIL lesions between the initial visit and 6 months later showed significant improvement after 6 months. Conclusions These studies demonstrated quantitative changes in RDIL and its recovery phase and suggested the utility of a MSC in obtaining objective colour information of skin disorders. [ABSTRACT FROM AUTHOR]

Hybrid CT/angiography (angiography) system and C-arm cone beam CT provide cross-sectional imaging as an adjunct to angiography. Current interventional oncological procedures can be conducted precisely using these two technologies. In this article, several cases using a hybrid CT/angiography system are shown first, and then the advantages and disadvantages of the hybrid CT/angiography and C-arm cone beam CT are discussed with literature reviews. [ABSTRACT FROM AUTHOR]

Background. In previous studies, we made the unexpected finding that in mice, ultraviolet (UV)B irradiation of the eye increased the concentration of α-melanocyte-stimulating hormone (α-MSH) in plasma, and systemically stimulated epidermal melanocytes. Aims. To compare the extent of the pigmentation induced by social and restraint stress (which activate the hippocampus-pituitary system) with that induced by UVB irradiation. Methods. DBA/2 and sham-operated or hypophysectomized DBA/2 mice were subjected to local UVB exposure using a sunlamp directed at the eye, and two types of stress (social and restraint) were imposed. Results. UVB irradiation of the eye or exposure to stress loading both increased the number of Dopa-positive melanocytes in the epidermis, and hypophysectomy strongly inhibited the UVB-induced and stress-induced stimulation of melanocytes. Irradiation of the eye caused a much greater increase in dopamine than did the stress load. Both UVB eye irradiation and stress increased the blood levels of α-MSH and adrenocorticotropic hormone (ACTH). In addition, the increase in plasma α-MSH was greater in animals subjected to UVB eye irradiation than in those subjected to stress loading, whereas the reverse occurred for plasma ACTH. UVB irradiation to the eye and stress loading increased the expression of prohormone convertase (PC)1/3 and PC2 in the pituitary gland. The increase in expression of pituitary PC2 was greater in animals subjected to UVB eye irradiation than to stress, whereas no difference was seen between the two groups for the increase in PC1/3. Conclusions. UVB eye irradiation exerts a stronger effect on pigmentation than stress loading, and is related to increased levels of α-MSH and PC2. [ABSTRACT FROM AUTHOR]

ABSTRACT The radio galaxy 3C 84 is a representative of γ-ray-bright misaligned active galactic nuclei (AGNs) and one of the best laboratories to study the radio properties of the subparsec jet in connection with the γ-ray emission. In order to identify possible radio counterparts of γ-ray emissions in 3C 84, we study the change in structure within the central 1 pc and the light curve of subparsec-sized components C1, C2 and C3. We search for any correlation between changes in the radio components and the γ-ray flares by making use of the Very Long Baseline Interferometry (VLBI) and single-dish data. Throughout the radio monitoring spanning over two GeV γ-ray flares detected by the Fermi Large Area Telescope and the MAGIC Cherenkov Telescope during 2009 April-May and 2010 June-August, the total flux density in the radio band increases on average. This flux increase mostly originates in C3. Although γ-ray flares span the time-scale of days to weeks, no clear correlation with the radio light curve on this time-scale is found. No new prominent components and change in morphology associated with the γ-ray flares are found on VLBI images. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the long-term effects of patients with α-Fetoprotein (AFP)-producing gastric cancer. Criteria based on preoperative AFP levels and positive AFP production in the tumour were used to identify possible subjects. Results showed that tumour size, invasion depth, and stage of the disease are not associated to preoperative serum AFP levels. It also notes that an increase in AFP levels resulted to recurrence of the tumour.

Background Extramammary Paget disease is an uncommon skin tumour occurring mostly in the genitoperineal region. Previous reports have shown frequent expression of androgen receptor, suggesting a tumour-proliferative effect of androgens on Paget cells. Androgen-converting enzymes such as 5α-reductase, which locally produces a bioactive androgen, have recently gained attention in studies of the intratumoral actions of androgens. Objectives We investigated correlations between the androgenic microenvironment and invasiveness in extramammary Paget disease, particularly in terms of sex differences. Methods We examined 58 cases of extramammary Paget disease (32 men, 26 women; 42 noninvasive, 16 invasive) using immunohistochemistry for androgen receptor and 5α-reductase. Results In all 58 cases, expression rates were 57% for androgen receptor and 55% for 5α-reductase, with 38% double-positivity for androgen receptor and 5α-reductase. Only 5α-reductase expression rate was significantly higher in invasive cases (81%) than in noninvasive cases (45%; P = 0·042). For invasive cases, numbers of double-positive results for androgen receptor and 5α-reductase were significantly higher in men (70%) than in women (17%; P = 0·039). Conclusions Double positivity for androgen receptor and 5α-reductase in Paget cells suggests autocrine synthesis of androgens in extramammary Paget disease. The different hormonal microenvironments in male and female cases and intratumoral androgen levels affect the invasiveness of extramammary Paget disease. [ABSTRACT FROM AUTHOR]

The impact of total physical activity level on cancer risk has not been fully clarified, particularly in non-Western, relatively lean populations. The authors prospectively examined the association between daily total physical activity (using a metabolic equivalents/day score) and subsequent cancer risk in the Japan Public Health Center-based Prospective Study. A total of 79,771 general-population Japanese men and women aged 45-74 years who responded to a questionnaire in 1995-1999 were followed for total cancer incidence (4,334 cases) through 2004. Compared with subjects in the lowest quartile, increased daily physical activity was associated with a significantly decreased risk of cancer in both sexes. In men, hazard ratios for the second, third, and highest quartiles were 1.00 (95% confidence interval (CI): 0.90, 1.11), 0.96 (95% CI: 0.86, 1.07), and 0.87 (95% CI: 0.78, 0.96), respectively (p for trend = 0.005); in women, hazard ratios were 0.93 (95% CI: 0.82, 1.05), 0.84 (95% CI: 0.73, 0.96), and 0.84 (95% CI: 0.73, 0.97), respectively (p for trend = 0.007). The decreased risk was more clearly observed in women than in men, especially among the elderly and those who regularly engaged in leisure-time sports or physical exercise. By site, decreased risks were observed for cancers of the colon, liver, and pancreas in men and for cancer of the stomach in women. Increased daily physical activity may be beneficial in preventing cancer in a relatively lean population. [ABSTRACT FROM AUTHOR]

Aims:  To evaluate factors potentially contributing to the long-term persistence of Salmonella enterica serovar Enteritidis phage type (PT) 30 in an almond orchard. Methods and Results:  Surface and subsurface soil temperatures, and air temperatures in a radiation shelter, were recorded during a 12-month period, and were used to identify relevant storage temperatures (20 or 35°C) for microcosms of two different soil types (clay and sandy loams) with moisture levels near saturation or near field capacity. Salmonella Enteritidis PT 30 was inoculated into the microcosms at 6 log CFU g−1 dry weight. Between 14 and 180 days of incubation, counts of S. Enteritidis PT 30 decreased rapidly at 35°C and were significantly different ( P < 0·05) from counts at 20°C, regardless of the soil type or moisture level. Salmonella was detected by enrichment of 10-g samples from all microcosms after 180 days of incubation at 20°C, but from none of the microcosms held at 35°C. To measure the potential for the growth of S. Enteritidis PT 30 in clay loam soil, an aqueous extract of almond hulls (containing 1·6% mono and disaccharides) or equivalent volume of water was added 7 days after inoculation. Significant ( P < 0·05) growth of S. Enteritidis PT 30 was observed within 8 or 24 h of adding hull extract, but not water, to soil. Conclusions:  Opportunities may exist for S. Enteritidis PT 30 to survive for an extended time in almond orchard soils and to grow in these soils where hull nutrients are released. Significance and Impact of the Study:  Temperature has a significant impact on the long-term survival of S. Enteritidis PT 30 in soil, and nutrients leached from almond hulls may result in Salmonella growth. These factors should be considered in the design of Good Agricultural Practices for almonds. [ABSTRACT FROM AUTHOR]

Haematopoietic stem cell transplantation (HSCT) is performed for treatment of a broad spectrum of illnesses. Reconstitution of an intact immune system is crucial after transplantation to avoid infectious complications, and above all, the establishment of T cell receptor (TCR) diversity is the most important goal in the procedure. Until recently, little has been known of the mechanism of T cell reconstitution in the very early period after HSCT. In this study, we analysed TCR repertoires sequentially in four patients with severe combined immunodeficiency (SCID) before and after HSCT. In all patients, the TCR repertoires were extremely abnormal before HSCT, whereas after transplantation there was progressive improvement in TCR diversity, based on analysis of the TCR Vβ repertoire and CDR3 size distributions. Somewhat unexpectedly, there was a significant but transient expansion of TCR diversity 1 month after transplantation in all cases. Clonotypic analysis of TCRs performed in one case showed that many T cell clones shared identical CDR3 sequences at 1 month and that the shared fraction decreased progressively. These results indicate that early expansion of TCR diversity may reflect transient expansion of pre-existing mature T cells from the donor blood, independent of de novo T cell maturation through the thymus. [ABSTRACT FROM AUTHOR]

A limited number of therapeutic strategies are currently available for patients with inflammatory bowel disease (IBD). In particular, the maintenance therapy after remission in Crohn's disease (CD) is not satisfactory and new approaches are needed. Interleukin-10 gene-deficient (IL-10–/–) mice, a well-characterized experimental model of CD, develop severe chronic colitis due to an aberrant Th1 immune response. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), a new immunosuppressive reagent, has been used successfully in animal models for heart, liver, lung and kidney transplantation. In the present study, we examined the efficacy of everolimus in the treatment of chronic colitis in an IL-10–/– mouse model. Everolimus was administered orally for a period of 4 weeks to IL-10–/– mice with clinical signs of colitis. The gross and histological appearances of the colon and the numbers, phenotype and cytokine production of lymphocytes were compared with these characteristics in a control group. The 4-week administration of everolimus resulted in a significant decrease in the severity of colitis, together with a significant reduction in the number of CD4+ T cells in the colonic lamina propria as well as IFN-γ production in colonic lymphocytes. Everolimus treatment of established colitis in IL-10–/– mice ameliorated the colitis, probably as a result of decreasing the number of CD4+ T cells in the colonic mucosa and an associated reduction in IFN-γ production. [ABSTRACT FROM AUTHOR]

To evaluate the hypothesis that, in terms of all-cause death, drinking alcohol 1-4 days per week is less harmful than daily (5-7 days/week) drinking of the same quantity of alcohol, a prospective cohort study using a self-administered questionnaire was conducted in Japan between 1990 and 2003 of 88,746 subjects (41,702 men and 47,044 women) aged 40-69 years at baseline. Among male regular drinkers consuming alcohol more than 1 day per week, light drinkers (<300 g/week) showed no increase in all-cause mortality irrespective of frequency of alcohol intake. Heavy drinkers (> or = 300 g/week), however, showed an increased risk of all-cause mortality among those who consumed alcohol 5-7 days per week, while no obvious increase was observed among those who consumed alcohol less than 4 days per week. Hazard ratios for drinkers who consumed alcohol 5-7 days per week were 1.29 (95% confidence interval: 1.12, 1.50) for 300-449 g per week and 1.55 (95% confidence interval: 1.32, 1.81) for > or = 450 g per week when compared with those for occasional drinkers who consumed alcohol 1-3 days per month. These findings support the Japanese social belief that 'liver holidays,' abstaining from alcohol for more than 2 days per week, are important for heavy drinkers. [ABSTRACT FROM AUTHOR]

We investigate the high-frequency radio spectra of 20 low-luminosity active galactic nuclei (LLAGNs) with compact radio cores. Our millimetre survey with the Nobeyama Millimetre Array (NMA) and analyses of submillimetre archival data that had been obtained with the Submillimetre Common User Bolometer Array (SCUBA) on the James Clerk Maxwell Telescope (JCMT) reveal the following properties. At least half of the LLAGNs show inverted spectra between 15 and 96 GHz; we use the published data at 15 GHz with the Very Large Array (VLA) in a 0.15-arcsec resolution and our measurements at 96 GHz with the NMA in a 7-arcsec resolution. The inverted spectra are not artificially made due to their unmatched beam sizes, because of little diffuse contamination from dust, H ii regions, or extended jets in these LLAGNs. Such high-frequency inverted spectra are apparently consistent with a ‘submillimetre bump’, which is predicted by an advection-dominated accretion flow (ADAF) model. We find a strong correlation between the high-frequency spectral index and low-frequency core power measured with very-long-baseline-interferometry (VLBI) instruments. The inverted spectra are found exclusively in low-core-power sources, while steep spectra are in high-core-power ones with prominent pc-scale jets. This suggests that the ADAF and non-thermal jets may coexist. The flux ratios between disc and jet seem to be different from LLAGN to LLAGN; disc components can be seen in nuclear radio spectra only if the jets are faint. [ABSTRACT FROM AUTHOR]

Despite its decreasing trend in Japan, gastric cancer remains an important public health problem. Although the age standardised rates of gastric cancer have been declining for decades, the absolute numbers are increasing because of the rapid aging of the population. A large proportion of Japanese gastric cancers are detected at an early stage, with a better overall survival rate. As with Western developed countries, a change in the social environment such as reduced salt use and increased fresh vegetable and fruit intake as well as improvement of food storage may play an important part in the decline. Differences in Helicobacter pylori infection rates between generations presumably have contributed to the generation related variation in the declining trends. It is expected that most gastric cancers in Japan may be preventable by lifestyle modification such as salt reduction and increased fruit and vegetable intake, together with avoidance of smoking and countermeasures against H pylori infection so that the level now evident in Western developed countries can be reached. [ABSTRACT FROM AUTHOR]

We report multi-frequency and multi-epoch radio continuum observations with multi-spatial resolution for the low-luminosity active galactic nucleus (LLAGN) NGC 266. In the centimetre regime, we find diffuse components with Very Large Array (VLA) observations, and a variable compact core with a rising spectrum with Very Long Baseline Array (VLBA) observations. Although the spectral index of the rising spectrum is consistent with the prediction of the simple advection-dominated accretion flow (ADAF) model, the observed radio power is slightly high compared with that of the model prediction. A spectral break at centimetre-to-millimetre wavelengths is inferred from the upper limits of flux densities from Nobeyama Millimetre Array (NMA) and James Clerk Maxwell Telescope (JCMT) data at millimetre and submillimetre wavelengths, respectively. More complicated considerations are required for the theoretical model to interpret such observed radio properties. [ABSTRACT FROM AUTHOR]

t. yamazaki, m. inoue, m. ogawa, s. shiga, t. kishimoto, t. hagiwara, t. matsumoto and t. hayashi. 2004. To clarify the inhibitory effects of ozone on Chlamydia trachomatis and C. pneumoniae. Cell culture was performed using HeLa229 cells for C. trachomatis, and Human Line cells for C. pneumoniae. C. trachomatis strain D/UW-3/Cx and C. pneumoniae strain AR-39 were used. Ozone water was generated by an ozone water dispenser and diluted to desired concentration just before each experiment. Preinoculation minimum cidal concentration (MCC) and postinoculation MCC methods were employed. In preinoculation MCC, chlamydial strains were treated with serially diluted ozone water followed by inoculation to cells. In postinoculation method, chlamydial strains were inoculated to cells and incubated for 24 h. Then infected cells were treated with ozone water, followed by additional incubation for 48 h. Complete inactivation was obtained in preinoculation MCC method at 0·5 ppm of ozone water for 30 s, or 4 ppm for 5 s. Ozone at a concentration of 4 ppm was enough for immediate inactivation of both C. trachomatis and C. pneumoniae. Ozone water at 4 ppm should be applicable for prevention of C. trachomatis urogenital infections. [ABSTRACT FROM AUTHOR]

Summary We report a case of febrile ulceronecrotic Mucha–Habermann disease (FUMHD) in a 21-year-old man. This disease is a severe form of pityriasis lichenoides et varioliformis acuta (PLEVA) and is characterized by the sudden onset of diffuse ulcerations associated with high fever and systemic symptoms. It is sometimes lethal especially in elderly patients. In the present case, intense generalized maculopapular erythematous plaques with central necrosis developed progressively in association with a high fever. Initial treatment with systemic betamethasone had been unsuccessful and the skin lesions, which covered about 50% of the body surface, became severely ulcerated. Although the development of new lesions had ceased spontaneously, widespread ulceration of the skin remained. Debridement of the necrotic skin and skin grafting using cultured epidermal autografts and meshed allografts of cadaver skin led to prompt reepithelization. [ABSTRACT FROM AUTHOR]

This study examined whether recurrent nerve chain node metastasis serves as an indicative factor for cervical lymph node dissection in thoracic esophageal cancer. The association of recurrent nerve chain lymph node metastasis and cervical node metastasis was analyzed for 91 patients with thoracic esophageal cancer who had undergone three-field lymph node dissection. In patients with upper thoracic esophageal cancer, the incidence of cervical lymph node metastasis was similar regardless of recurrent nerve chain node metastasis. On the other hand, in patients with middle or lower esophageal cancer, the incidence was significantly higher in recurrent nerve-positive (16/31, 51.6%) than in recurrent nerve-negative (5/43, 11.6%) patients. The prognosis of patients with recurrent nerve chain node metastasis was significantly better in the three-field dissection group than in the two-field dissection group, while in patients with no recurrent nerve chain node metastasis, survival was similar between the two groups. In conclusion, cervical lymphadenectomy can be omitted for recurrent nerve chain node-negative patients with middle and lower thoracic esophageal cancer. [ABSTRACT FROM AUTHOR]

The effect of the superior mediastinal lymph node dissection was compared retrospectively with that of standard dissection in 108 esophageal cancer patients. Five-year survival rates were 46.3% in patients who underwent standard surgery (group A) and 39.3% in patients who underwent superior mediastinal lymph node dissection (group B). The survival curves were basically the same. Nineteen out of 42 (45.2%) tumors in group A and 24 out of 66 (36.4%) tumors in group B recurred. The distribution of the first sites of recurrence did not differ significantly between groups. However, 14 tumors (67%) in group A recurred in the lymph nodes, but only seven tumors recurred (28%) in the lymph nodes in group B. Eleven tumors (52%) in group A recurred to superior mediastinal nodes, but only one tumor (4%) recurred to a superior mediastinal node in group B. Fourteen of the group B patients showed metastasis to superior mediastinal lymph nodes and none of these patients survived for more than 5 years. Eleven of these 14 patients showed metastasis to only one or two nodes. Based on our data and other reported findings, we conclude that extended lymphadenectomy of the superior mediastinal region alone does not contribute to improved survival of esophageal cancer patients, but it does contribute to the prevention of lymph node recurrence in this region. [ABSTRACT FROM AUTHOR]

From July 1994 to July 1998, a larynx-preserving procedure was performed on 10 out of 22 (45%) patients in the surgical treatment of hypopharyngeal and cervical esophageal cancer. At first, all 10 patients were treated with concurrent radiochemotherapy with cisplatin (10 mg/m[sup 2]/day), 5-fluorouracil (500 mg/m[sup 2]/day) and radiation (2 Gy/day) five times per week for 4 weeks. After preoperative radiochemotherapy, the larynx-preserving procedure, combining laryngeal suspension and cricopharyngeal myotomy, was performed. The operative and hospital mortality rate was 0%. The incidence of post-operative morbidity with minor complications was 70% in the present study. Laryngeal speech and oral food intake were preserved in all patients after this procedure. The new larynx-preserving procedure combining laryngeal suspension and cricopharyngeal myotomy for cervical esophageal cancer is a favorable operative method for retaining intelligible laryngeal speech and good food intake. [ABSTRACT FROM AUTHOR]

Attempts to determine whether class II transactivator (CIITA) is responsible for the impaired up-regulation of major histocompatibility complex II molecules. Evaluation of the surface marker expression on thymic epithelial cells; Relationship between CIITA and the phenotypic characteristics of lymphocytes; Characteristics of thymoma.

The Hanshin-Awaji earthquake in January 1995 caused the greatest number of deaths and injuries in Japan since World War II. Various weaknesses of modern information systems were exposed during and after the earthquake. The authors carried out a questionnaire survey to investigate the current state of hospital information and to examine the kinds of information needed immediately after an earthquake. The survey results show that information about the ability to admit new patients and the availability of medical supplies is necessary immediately after such a disaster. These results will be useful for planning countermeasures against this kind of disaster. [ABSTRACT FROM PUBLISHER]

Background.Recently rat vascular smooth-muscle cells (VSMC) have been shown to possess Epo receptor, and respond to various cytokines for producing nitric oxide (NO). In the present study we examined the effect of pharmacological dose of human recombinant erythropoietin (rHuEpo) on the IL-1β-induced NO and cGMP production as well as inducible nitric oxide synthase (iNOS) in cultured rat VSMC. [ABSTRACT FROM PUBLISHER]

The cytolytic and/or cytostatic effects of hyperthermia, lymphokine-activated killer cells (LAK cells) and the combination of both were assayed using FI and F10B16 melanoma cell lines. F10 cells with a high metastatic potential showed a greater sensitivity to hyperthermia than F1 cells which have low metastatic potential. The F10 cells were lysed to a lesser extent by LAK cells than the F1-B16 cells. When the cell lines were subjected to hyperthermia at 43°C for 3 h and then interacted with LAK cells. the maximum cytolysis reached almost 100%. When the interaction with LAK cells was followed by hyperthermia at 43°C, the total release of 51Cr from the cell lines was 75–85%. The extent of 51Cr release from the B16 melanoma cell lines was inversely correlated with the survival rate as calculated by the plating efficiency of the incubated cells. The survival rate of mice intravenously injected with B16-F10 cells and subjected to hyperthermia at 41°C for 3 h in vitro increased compared to that of controls. This was further increased by the simultaneous administration of LAK cells. [ABSTRACT FROM AUTHOR]

We devised an accurate procedure with which to measure the affinities of beta-lactam antibiotics for penicillin-binding protein (PBP) 2' in methicillin-resistant Staphylococcus aureus (MRSA). In the present study, we used two isogenic strains of MRSA, on heterogeneous and the other homogeneous, derived from the methicillin-susceptible strain FDA209P, harbouring the mecA gene. In these MRSA strains, PBP2' was saturated by [14C]benzylpenicillin (PCG) at a concentration of 300 mg/L. In addition, the saturation of PBP2' by [14C]PCG required an incubation period of 30 min. According to these results, the precise affinities of beta-lactam antibiotics for PBP2' were determined by the 'accurate competition assay', using a high concentration of [14C]PCG and extending the reaction time. This procedure yielded lower IC50 values of beta-lactams than the 'usual competition assay'. However, each beta-lactam had almost the same affinity for PBP2' in heterogeneous and homogeneous strains. These results suggest there is a factor(s) other than PBP2' responsible for controlling resistance levels and the heterogeneity or homogeneity of MRSA strains. [ABSTRACT FROM AUTHOR]

The synergic activity of imipenem/cilastatin combined with cefotiam was studied in a mouse bacteraemia mod.el. Combinations of imipenem plus cefotiam in ratios from 1: 5 to I : 160 were more effective than either imipenem alone or cefotiam alone (P < 0·05). Synergy was observed against both β-lactamase producing and β-lactamase non-producing MRSA. Staggered combinations of imipenem with cefotiam (each drug was administered at a different time) were studied in an in-vitro pharmacokinetic system to clarify relationships between killing kinetics and pharmacodynamics of the combinations. In the in-vitro system, cefotiam (1 g over 30 mm) administered 2 h after imipenem administration (250 mg over 30 mm) reduced viable cell counts to an undetectable level and maintained this for 4 h, while the simultaneous administration of imipenem and cefotiam maintained an undetectable cell count for only 2 h. Furthermore, imipenem administered after cefotiam showed no synergy. These results indicate that the timing of dosing of each antibiotic influences synergy, and administration of cefotiam 2 h after imipenemis more effective than the other regimens. [ABSTRACT FROM PUBLISHER]

The in-vitro activity of imipenem combined with beta-lactam antibiotics was studied for 25 strains of methicillin and imipenem-resistant Staphylococcus aureus (MRSA) in comparison with that of fosfomycin combined with cefmetazole. Using the chequerboard agar dilution method, strong synergy was seen for all strains for imipenem with cefoperazone, cefotiam, cefpiramide or piperacillin. All fractional inhibitory concentration indices (FIC indices) of these combinations were less than or equal to 0.12. For the combination of imipenem with cefotiam the synergy was found to be bactericidal, but was not affected by the temperature of incubation, the concentration of sodium chloride in the medium or beta-lactamase production. However, for the combination of fosfomycin with cefmetazole only 44% of the strains with a mean FIC index of 0.55, showed synergy. The remaining 56% of strains showed either partial synergy (44%) or additive activity (12%). The combinations of imipenem with the beta-lactam antibiotics were more effective than that of fosfomycin with cefmetazole. [ABSTRACT FROM AUTHOR]

The effect of cyanide, arsenate, Mg++ or EDTA on the uptake of norfloxacin in Escherichia coli was measured. Uptake of norfloxacin was suppressed by either 0.1 mM MgSO4 or 0.1 mM EDTA, while the presence of 0.1 mM MgSO4 increased the minimum suppressive concentration of EDTA from 0.1 to 0.2 mM. Increased uptake in the presence of 10 mM cyanide was observed, but the addition of 10 mM arsenate had no significant effect. Concentration of norfloxacin in bacterial cells was observed even when uptake was suppressed by the addition of 10 mM EDTA. Uptake in mini-cells was comparable to that in whole cells. These results suggest that the uptake of norfloxacin in E. coli, in addition to influx by simple diffusion and energy-dependent efflux, is influenced by binding of norfloxacin to the cell surface as a result of chelating activity to Mg++, together with an unknown concentration step resulting from binding to cell components other than the chromosome. [ABSTRACT FROM AUTHOR]

DQ-2556, a new cephalosporin, showed a broad antibacterial spectrum over Gram-positive and -negative organisms. The activity of DQ-2556 against recent clinical isolates of Gram-positive cocci and Enterobacteriaceae was comparable with that of cefpirome, and superior to that of ceftazidime. DQ-2556 was almost as active as cefpirome against Pseudomonas aeruginosa, but was less active than ceftazidime. With the exception of Ps. aeruginosa, DQ-2556 was bactericidal against various organisms at either the MIC or twice the MIC. DQ-2556 bound preferentially to penicillin-binding proteins (PBPs) 2, 1 and 3 of Staphylococcus aureus, PBPs 3, 1A and 1B of Escherichia coli and PBPs 1A, 3 and 4 of Ps. aeruginosa. DQ-2556 was stable to various penicillinases and cephalosporinases, but was unstable to oxyiminocephalosporinases. The Km values of DQ-2556 for the cephalosporinases of Citrobacter freundii and Enterobacter cloacae were only two- or three-fold higher than those of ceftazidime, indicating that DQ-2556 had a relatively high affinity for these enzymes compared with other recently developed cephalosporins. The MIC of DQ-2556 for Esch. coli increased four-fold in an OmpF-deficient mutant, indicating that the OmpF porin was one of the major routes for penetration of DQ-2556 into Esch. coli cells. [ABSTRACT FROM AUTHOR]

The in-vitro synergistic activity of tazobactam, a new beta-lactamase inhibitor, combined with piperacillin was tested against various beta-lactamase-producing strains. The beta-lactamase inhibitory activity of tazobactam against various known types of beta-lactamase was also tested in comparison with clavulanic acid or sulbactam. Tazobactam caused a remarkable reduction of the piperacillin MICs for penicillinase- and oxyiminocephalosporinase-producing strains and also showed a moderate synergistic effect against cephalosporinase-producing strains. The bactericidal activity of piperacillin was enhanced in combination with tazobactam. Tazobactam inhibited the penicillinases, and the oxyiminocephalosporinase produced by Proteus vulgaris, at low concentration. In these cases its activity was comparable with that of clavulanic acid and stronger than that of sulbactam. Tazobactam demonstrated a better inhibitory capability than sulbactam against the cephalosporinases tested. Tazobactam was able to inactivate intracellular beta-lactamase in Prot. vulgaris and Morganella morganii, confirming its ability to penetrate the cell membrane of these species. [ABSTRACT FROM AUTHOR]

Rabbit antiserum was prepared to the penicillinase of Alcaligenes denitrificans subsp. xylosoxydans GN14062. The antibody gave a single precipitin line in double immunodiffusion assays with the penicillinases from strain GN14062 and from two other A. denitrificans subsp. xylosoxydans strains. The precipitin line given by the GN14062 enzyme gave a reaction of complete identity with the precipitin lines of the penicillinases from the other A. denitrificans subsp. xylosoxydans strains. Furthermore, activity of the penicillinases from all three A. dentrificans subsp. xylosoxydans strains was neutralized by the antiserum to the GN14062 enzyme. Thus it was proved that the penicillinases produced by the three A. denitrificans subsp. xylosoxydans strains were immunologically identical. Penicillinases types I, II, III, IV, V, SHV-1, TEM-1, TEM-2, and the chromosomal penicillinases of Klebsiella pneumoniae GN69 and A. faecalis GN14061 formed no immunoprecipitate with, nor were neutralized by, the antiserum to the GN14062 enzyme. From these results, it was concluded that the penicillinase produced by A. denitrificans subsp. xylosoxydans was immunologically distinct from the penicillinases produced by these other bacteria. [ABSTRACT FROM AUTHOR]

New monobactam compounds with fluoromethyl side chains at the 4-position were synthesized. These compounds showed strong antibacterial activity against Gram-negative bacteria including Pseudomonas aeruginosa and good stability to various beta-lactamases. The effect of replacement of the 1-carboxy-1-methylethoxyimino residue of aztreonam with various substituted groups, and of the configuration of the 3- and 4-position were examined. Substitution of a carboxycyclopropoxy group in the oxyimino moiety effected the most potent antibacterial activity. The cis congeners were not hydrolysed by any types of beta-lactamases including the oxyiminocephalosporin hydrolysing enzyme. Introduction of a fluorine atom in the methyl group at the 4-position increased the beta-lactamase stability of monobactams. [ABSTRACT FROM AUTHOR]

L-105 (sodium(-)-(6R, 7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyimino- acetamido]-3-[1,2,3-thiadiazol-5-yl)thiomethyl]-8-oxo-5-thia-1-aza bicyclo [4.2.0]oct-2-ene-2-carboxylate) is a new semisynthetic cephalosporin derivative. The in-vitro antibacterial activity of L-105 against clinical isolates of 18 bacterial species was compared with those of cefmenoxime, cefoperazone and cefazolin. Its spectrum against Gram-negative bacteria was similar to that of cefmenoxime. Moreover, against Gram-positive bacteria, including Staphylococcus aureus, coagulase negative staphylococci, Streptococcus faecalis, Str. pneumoniae and Str. pyogenes, L-105 was more potent than cefmenoxime and cefoperazone. Against Gram-positive bacteria, including Staph. aureus which is comparatively resistant to most third-generation cephalosporins, it was nearly equal in potency to cefazolin. L-105 was stable to various penicillinases and cephalosporinases. However, this compound was slightly hydrolyzed by oxyiminocephalosporinases, i.e., the enzymes produced by Pseudomonas cepacia and Ps. maltophilia. [ABSTRACT FROM AUTHOR]

The in-vitro antibacterial activity of AMA-1080 against both Gram-positive and Gram-negative clinical isolates was studied in comparison with that of aztreonam, cefotaxime, ceftazidime and cefoperazone. AMA-1080 showed a potent antibacterial activity against Gram-negative bacteria, particularly, the strains of Enterobacteriaceae. In addition, AMA-1080 inhibited the strains of genus Pseudomonas at the low concentrations. However, AMA-1080 showed less active against Gram-positive bacteria. It was found that AMA-1080 was highly resistant to hydrolysis by both chromosomal and plasmid-mediated beta-lactamases. [ABSTRACT FROM AUTHOR]

A penicillin beta-lactamase was purified from a strain of Alcaligenes dentrificans subsp. xylosoxydans resistant to beta-lactam antibiotics. The purified enzyme preparation gave a single protein band on polyacrylamide gel electrophoresis, and its molecular weight was 18,000 from sodium dodecylsulphate-acrylamide gel electrophoresis and gel filtration. Its isoelectric point was 9.8, the optimal pH was 8.5 and the optimal temperature was 35 degrees C. The enzyme hydrolyzed penicillin G and ampicillin more rapidly than cephalosporins. Relative rates, with penicillin G as 100, were: ampicillin, 102; carbenicillin, 15; cloxacillin, less than 1; piperacillin, 9; cephaloridine, 41; cefoperazone, 36; cefpiramide, 36 and cefmenoxime, 14. Clavulanic acid, sulbactam, imipenem, and cephamycins had low affinities for the enzyme. The enzyme activity was inhibited by iodine, Hg2+, clavulanic acid and sulbactam. [ABSTRACT FROM AUTHOR]

Cefotaxime (CTAX), a new cephalosporin derivative, has a broad antibacterial spectrum and is stable to β-lactamases produced by various species of bacteria. However, CTAX is hydrolysed by β-lactamases produced by Proteus vulgaris, Pseudomonas cepacia and Bacteroides fragilis, called cefuroxime-hydrolysing enzyme (Group III). Slightly low activity toward Pseudomonas aeruginosa is probably due to the low penetrability of the drug into the cells. The mechanism of action of CTAX was studied with respect to its binding affinities to penicillin-binding proteins (PBPs) and morphological changes of bacteria treated by CTAX in vitro. Cefotaxime showed especially high affinity for Escherichia coli PBP-1A, -1Bs, -3 and -4 and low affinities for PBP-2, -4, -5 and -6. Similar results were obtained with Ps. aeruginosa, in which this compound showed high affinities for PBP-3, -1A, -1B and 2. These results are compatible with morphological observations that at concentrations near its minimal inhibitory concentration or more, this antibiotic induced the formation of filamentous cells of E. coli and Ps. aeruginosa. At higher concentrations or after prolonged incubation, it induced lysis of the cells. [ABSTRACT FROM PUBLISHER]

The age-related changes in proportion of various subsets within lymphocytes were investigated in cord blood and peripheral blood from healthy children and adults. The percentages of T and B cells did not show age-related changes, whereas natural killer (NK) cells increased significantly with age. Within lymphocytes or the CD3+ T cell population the proportion of CD45RAbright+ lymphocytes decreased and that of CD45RO+ cells increased, while that of CD45RAdim+ cells showed no age-related change. Within lymphocytes, the percentage of CD45RAbright+ CD4+ cells decreased, together with a decline of that of CD4+ cells. The proportions of CD45RAbright+ CD8+ cells and S6F1bright+ CD8+ cells increased with age and the age-dependent increase of the proportion of CD8+ cells seems to be mainly attributable lo the increases in these subsets. The CD45RAdim+ CD4+ and CD45RAdim+ CD8+ cells co-expressing CD45RO at a low level nevertheless showed no age-related changes. In γδ T cells, both δTCSI+ and δTCSl- T cells increased with age, but the δTCSl- γδ T cells increased more than the δTCSl+ subset. Among lymphocytes, the percentages of CD20+, CD21+ and CD22+ cells remained similar, with no age-related changes, but the proportion of CD5+ cells within lymphocytes or B cells decreased. The proportions of CD16+ NK cells among lymphocytes increased with age, and this change was attributable to the increase of CD56+ cells. [ABSTRACT FROM AUTHOR]

We studied some of the requirements for production of immune interferon (IEN-γ) by human peripheral leucocytes following stimulation with concanavalin A (Con A). Synthesis of IFN-γ commenced 2 hr after the cells were exposed to the lectin and continued for about 20 hr thereafter. IFN-γ production during the latter period was independent of free Con A in the culture medium hut it was sustained by continued Con A binding and required active de novo protein synthesis. Egg lecithin, which inhibits the blastogenic response. did not affect IFN-γ production. [ABSTRACT FROM AUTHOR]

The zona-free hamster egg penetration test (HEPT) is widely used for evaluating the fertilizing ability of human spermatozoa. However, the relationship between the HEPT and microassisted fertilization has yet to be determined. To evaluate the efficiency of HEPT in selecting the most appropriate method of in-vitro fertilization (IVF), including intracytoplasmic sperm injection (ICSI) in couples with male factor infertility, clinical laboratory data was analysed retrospectively. The patients were divided into groups according to the sperm penetration index as determined by the HEPT: group A (sperm penetration index = 0), group B (sperm penetration index <15) and group C (sperm penetration index 15). A total of 405 oocytes were collected and inseminated by conventional methods in 69 couples with male factor infertility. In all, 31 out of 148 (20.9%) oocytes fertilized in group A; 35 out of 117 (29.9%) in group B; and 73 of 140 (52.1%) in group C. The clinical pregnancy rates per transfer in groups A, B and C were 0% (0/13), 0% (0/14) and 25.9% (7/27) respectively. Both the fertilization rate and pregnancy rate in group C was significantly higher than in groups A and B. ICSI was carried out in a total of 57 couples and 334 oocytes in metaphase II stage were manipulated. The normal fertilization (2 pronuclear) rate per oocyte was 65.6 ± 26.0% (mean ± SD). Out of 127 oocytes, 76 (59.8%) fertilized in group A, 57 out of 87 oocytes (65.5%) in group B and 86 out of 120 oocytes (71.7%) in group C. Of the 56 transfers, 17 clinical pregnancies were obtained, giving an average pregnancy rate of 30.4% per transfer. The clinical pregnancy rates per transfer in groups A, B and C were 17.4% (4/23), 40.0% (4/10) and 39.1% (9/23) respectively. No significant differences were observed in the fertilization rates or in the pregnancy rates between the three groups. In addition, there were no differences in the fertilization and pregnancy rates between the ICSI and IVF patients in group C. These findings suggest that the results of the HEPT are well correlated with the fertilizing ability of human spermatozoa in the patients treated by conventional IVF. Couples suffering from male factor infertility with a sperm penetration index of <15 (as determined by HEPT) should consider treatment with ICSI, while those with a sperm penetration index of 15 should attempt conventional IVF. [ABSTRACT FROM PUBLISHER]

The blocking effects of complement-dependent sperm immobilizing antibodies in the sera of infertile women and monoclonal antisperm antibodies against humans and mice on fertilization were investigated. The hemizona assay (HZA) and sperm penetration assay (SPA) were used to study the inhibitory effects of sera from 22 infertile patients positive for sperm immobilizing antibodies. Use of these tests allowed us to differentiate whether the antibody blocked sperm-zona pellucida tight binding and/or sperm penetration into the ooplasm. The zona pellucida penetration assay (ZPA) was also used to study the effects of four monoclonal antibodies (mAbs) on human sperm penetration into the zona pellucida. Seven mAbs against murine spermatozoa were tested for their inhibitory effects on in-vitro fertilization (IVF) and HZA in mice. Of 22 patient sera with sperm immobilizing antibodies, 21 (95.5%) inhibited HZA attachment and penetration, whereas this did not occur in any of 13 patient sera without these antibodies. However, 19 of 22 (86.4%) patient sera with sperm immobilizing antibodies and eight of 13 (61.5%) patient sera without these antibodies inhibited the SPA. Two (2C6, 1G12) of four mAbs against human spermatozoa showed strong inhibitory effects in all the assays (HZA, ZPA and SPA). One mAb (3B10) did not inhibit HZA but blocked ZPA and SPA. Another mAb (H6-3C4) seemed to have no inhibitory effects on fertilization. Two (Vx 5 and Vx 8) of seven mAbs against murine spermatozoa inhibited IVF in mice but did not block mouse HZA. These findings suggest that antisperm antibodies block fertilization at specific stages. Some of them may inhibit sperm capacitation and thus prevent all processes of fertilization that follow. Some other antibodies may not affect capacitation and sperm binding to zona pellucida but inhibit the acrosome reaction, followed by the blocking of sperm penetration through zona pellucida and ooplasm. [ABSTRACT FROM AUTHOR]