Investigation of clinical utility of contrast-enhanced MRI in the diagnosis of ectopic pregnancy.

AIM: To investigate whether contrast-enhanced (CE)-magnetic resonance imaging (MRI) improves identification of implantation site of ectopic pregnancy. MATERIALS AND METHODS: This retrospective study enrolled 63 patients in whom implantation sites had been confirmed at histopathology. Two expert radiologists for gynaecological imaging and two inexpert radiologists independently reviewed non-CE MRI and a combination of non-CE and CE-MRI (non-CE+CE-MRI), then determined implantation site with a confidence level. The following MRI features were also evaluated: extrauterine gestational sac (GS)-like structure (shape, signal intensities at T1-weighted imaging [WI], T2WI, and diffusion-weighted imaging [DWI], presence of the three rings appearance, and distinct low intensity areas at T2WI, presence of tree or dot-like components, degree of contrast enhancement), fallopian tube (dilatation, dilatation with haematoma, degree of contrast enhancement, enhanced components within the tube), and ascites. These findings were compared for non-CE and non-CE+CE-MRI data, and for expert and inexpert groups. RESULTS: The expert group identified implantation sites correctly in 58/63 (92%) cases for non-CE and non-CE+CE-MRI. In the inexpert group, the correct identification was improved from 54/63 (86%) using non-CE MRI to 58/63 (92%) using non-CE+CE-MRI, but was not significant (p=0.29). In comparison between non-CE and non-CE+CE-MRI, dilation of the fallopian tubes was observed more frequently (p=0.004) and the confidence level was elevated significantly in the non-CE+CE-MRI (p<0.0001) in the inexpert group. Intergroup comparison revealed that confidence level was significantly higher in the expert group than in the inexpert group using non-CE MRI (p<0.0001), although the difference was not significant at non-CE+CE MRI (p=0.49). CONCLUSION: CE-MRI did not significantly improve correct identification of ectopic pregnancy implantation sites, although the addition of contrast enhancement did enable inexpert radiologists to diagnose confidently.

Less maintenance immunosuppression in lung transplantation following hematopoietic stem cell transplantation from the same living donor.

Living-donor lobar lung transplantation (LDLLT) is one of the final options for saving patients with pulmonary complications after hematopoietic stem cell transplantation (HSCT). We retrospectively investigated 19 patients who had undergone LDLLT after HSCT in Japan. Eight patients underwent LDLLT after HSCT in which one of the donors was the same living donor as in HSCT (SD group), while 11 received LDLLT from relatives who were not the HSCT donors (non-SD group). In the SD group, three patients underwent single LDLLT. The 5-year survival rate was 100% and 58% in the SD and non-SD groups, respectively. In the SD group, postoperative immunosuppression was significantly lower than in the non-SD group. Two patients died of infection and one died of post-transplant lymphoproliferative disease (PTLD) in the non-SD group, while only one patient died of PTLD 7 years after LDLLT in the SD group. Hematologic malignancy relapsed in two patients in the non-SD group. For the three single LDLLTs in the SD group, immunosuppression was carefully tapered. In our study, LDLLT involving the same donor as for HSCT appeared to have advantages related to lower immunosuppression compared to LDLLT from relatives who were not the HSCT donors.

Low incidence of cardiovascular events in Japanese patients with Type 2 diabetes in primary care settings: a prospective cohort study (JDDM 20).

AIMS: To investigate whether a reduced incidence of cardiovascular disease in Type 2 diabetes can be achieved in a newly recruited cohort following the recently advanced concept of multifactorial treatment and followed in primary care settings as compared with earlier cohorts. METHODS: A prospective study was performed in primary care settings at multiple clinics nationwide in the Japan Diabetes Clinical Data Management (JDDM) study group. Subjects were 2984 patients with Type 2 diabetes without prevalent cardiovascular disease. The main outcome measure was the first event of non-fatal or fatal coronary heart disease, ischaemic stroke or peripheral artery disease, and the incidence was compared with other representative cohorts. RESULTS: There were 90 cardiovascular events over 10,827 person-years of follow-up with a dropout rate of 6%. The incidences (per 1000 person-years, 95% confidence interval) of composite, coronary heart disease, ischaemic stroke and peripheral artery disease in the JDDM study were 8.3 (6.6-10.0), 4.4 (3.2-5.6), 3.1 (2.1-4.2), and 0.7 (0.2-1.2), respectively. Each incidence was lowest in the JDDM study compared with other cohorts (P < 0.01 vs. each cohort). In the JDDM study, significant variables predictive of the occurrence of a cardiovascular event were age, duration of diabetes, HbA(1c), HDL cholesterol and urinary albumin. CONCLUSION: The novel finding of low cardiovascular disease occurrence in this study may be conferred by the feasibility at primary care settings for providing patients with Type 2 diabetes with favourable control of blood glucose, blood pressure and lipids, coupled with unique ethnicity/country factors.

Redox and metal-regulated oligomeric state for human porphobilinogen synthase activation.

The oligomeric state of human porphobilinogen synthase (PBGS) [EC.4.2.1.24] is homooctamer, which consists of conformationally heterogenous subunits in the tertiary structure under air-saturated conditions. When PBGS is activated by reducing agent with zinc ion, a reservoir zinc ion coordinated by Cys(223) is transferred in the active center to be coordinated by Cys(122), Cys(124), and Cys(132) (Sawada et al. in J Biol Inorg Chem 10:199-207, 2005). The latter zinc ion serves as an electrophilic catalysis. In this study, we investigated a conformational change associated with the PBGS activation by reducing agent and zinc ion using analytical ultracentrifugation, negative staining electron microscopy, native PAGE, and enzyme activity staining. The results are in good agreement with our notion that the main component of PBGS is octamer with a few percent of hexamer and that the octamer changes spatial subunit arrangement upon reduction and further addition of zinc ion, accompanying decrease in f/f (0). It is concluded that redox-regulated PBGS activation via cleavage of disulfide bonds among Cys(122), Cys(124), and Cys(132) and coordination with zinc ion is closely linked to change in the oligomeric state.

A mechanism responsible for the induction of H-2 restricted second order suppressor T cells.

The mechanism by which I-J restrictions were imposed on second-order suppressor cells (Ts2) was analyzed. The induction of Ts2 cells requires presentation of an inducer suppressor factor by a specialized population of factor-presenting cells. The I-J phenotype of this factor-presenting population controls the H-2 restriction of the Ts2 cells. The splenic cells responsible for presenting inducer factor appear to be of macrophage or dendritic cell lineage. Several homologies exist between the mechanism responsible for the induction of H-2-restricted suppressor and helper T cells. Thus, the I region products on specialized presenting cells determine the specificity and genetic restrictions of the T cell. In an H-2 heterozygous F1 animal, two distinct populations of cells can be induced, one specific for each parental H-2 heplotype. Furthermore, the data suggest that the suppressor cells also bear receptors for self H-2 products. The ramifications of these observations for the suppressor cell cascade are discussed.

Mechanism responsible for the induction of I-J restriction on TS3 suppressor cells.

The mechanisms responsible for the induction of I-J restrictions on third-order suppressor T cells (TS3) were analyzed. The I-J phenotype of the antigen-coupled cells used for priming restricted the specificity of the TS3 population. Thus, TS3 cells were only generated after priming with antigen-coupled I-J homologous cells. Identity at the I-JM (and I-E) subregions was sufficient for TS3 induction. Furthermore, priming of H-2 heterozygous mice with antigen-coupled parental cells generated TS3 that were restricted to the parental haplotype used for priming. The splenic cell population responsible for antigen presentation and induction of TS3 cells was fractionated. The cells involved in antigen presentation were found in the splenic adherent population and were absent in the fraction containing splenic nonadherent T and B cells. The subsequent activation and interaction of TS3 cells is also restricted by genes in the H-2 complex. The results are discussed in terms of a general mechanism responsible for the induction of restrictions in T helper and TS3 cells.

I-J restrictions on the activation and interaction of parental and F1-derived TS3 suppressor cells.

An experimental system was developed to independently analyze the H-2 and Igh genetic restrictions at two steps of the 4-hydroxy-3-nitrophenylacetyl hapten (NP) suppressor cell pathway. This experimental system allowed genetic analysis of the activation of TS3 cells by hybridoma-derived TsF2 and independent analysis of the genetic restrictions that controlled the interaction of the TS3 cells with their target population. Thus, TS3 cells were activated in vitro with monoclonal H-2b or H-2k-derived TsF2. The activated TS3 cells were then adoptively transferred to TS3-depleted (cyclophosphamide-treated) recipients of various genotypes. When the TS3-containing lymph node population was activated in vitro for 2 h, suppressive activity was only noted in combinations of TSF2, TS3, and recipients that were matched at both the I-J and Igh gene complexes. The data indicate that TsF2 can activate TS3 cells and that both the activation and the interaction of TS3 cells are I-J and Igh restricted. Using (B10 x B10.BR)F1 mice as TS3 donors, we noted that H-2b-derived TsF2 activated these F1 TS3 cells to suppress NP-specific cutaneous sensitivity responses in H-2b but not in H-2k recipients. Reciprocal experiments using H-2k-derived TsF2 demonstrated that only an H-2k-restricted population was activated in the F1-derived TS3 cells. The simplest explanation to account for these observations is that two distinct populations, each of which is restricted to a parental I-J determinants, exists in the heterozygous F1 TS3 population. Furthermore, we demonstrated that both I-Jb and I-Jk determinants are expressed on F1-derived TS3 cells. These observations are discussed in terms of the mechanisms involved in immunoregulation.

Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. XI. Pseudogenetic restrictions of hybridoma suppressor factors.

Suppressor factor derived from three different murine T cell hybridomas were characterized . They specifically inhibited 4-hydroxy-3-nitrophenyl acetyl cutaneous sensitivity responses. The factors bind antigen and bear I-J and idiotypic determinants, but lack conventional immunoglobulin constant-region determinants. The factors function during the induction phase of the immune response, by inducing a second population of suppressor cells (Ts(e)). Suppressor factor can inhibit both cellular and plaque-forming cell responses in appropriate strains of mice. These hybridoma suppressor factors directly suppress strains of mice that are Igh-V homologous with the strain producing the factor. Thus, there is an apparent Igh-V restriction in the activity of these factors. However, this is a pseudogenetic restriction because these factors generate second order suppressor cells (Ts(e)) in Igh-incompatible mice, but in order to express the suppressive activity, the cells must be adoptively transferred into recipients that are Igh compatible with the strain producing the suppressor factor. Finally, it was shown that the factor-induced Ts(e) population is under an apparent dual genetic restriction. Thus, Igh and H-2 homology is required in order for the Ts(e) population to express its suppressive activity.

Analysis of T cell hybridomas. IV. Characterization of inducible suppressor cell hybridomas.

The Ts3 subset of suppressor cells is generated after antigen priming, but, in order to express suppressor activity these cells require an additional activation step involving triggering with specific suppressor factors (TsF2). This report characterizes two cloned hybridoma cell lines (pTs3 hybridomas) that represent this stage of Ts3 cell differentiation. These hybridoma cells could be specifically activated with TsF2 to release another antigen-specific suppressor factor (TsF3) within 6 h. The inducible feature of these cells permitted analysis of the signals necessary for Ts3 activation. Antigen was not required for activation. Only TsF2 factors derived from antiidiotypic second-order suppressor cells could activate pTs3 hybridoma cells. There were stringent genetic restrictions on the ability of Ts2 to activate pTs3 cells. Triggering of pTs3 required corecognition of two determinants on the TsF2 molecular complex, i.e., the I-J and Igh-related idiotypic determinants. Thus, although pTs3 cells could absorb TsF2 from an I-J-mismatched source, these pTs3 were not activated by the allogeneic TsF2. For activation to occur, the H-2 (I-J) and Igh complexes of the TsF2 donor had to match those of the strain from which the pTs3 cells were derived. Mixing two distinct TsF2, one derived from an H-2-matched source and the other from an Igh-matched source, failed to activate pTs3 cells. Once activated, the pTs3 cells released a suppressive material that was indistinguishable from the TsF3 factors previously characterized in this system. Finally, the activation of the pTs3 cells apparently does not induce the de novo synthesis of TsF3 since the suppressive activity could be extracted from nonactivated pTs3 cells. Thus, the inducible pTs3 hybridomas represent a mature stage in the differentiation cycle of Ts3 cells and provide a means for studying the nature of the specific signals required for Ts3 activation.

Analysis of T cell hybridomas. III. Distinctions between two types of hapten-specific suppressor factors that affect plaque-forming cell responses.

The ability of two cloned T cell hybridomas and their products to specifically suppress the in vitro plaque-forming cell (PFC) response to the 4-hydroxy-3-nitrophenyl acetyl hapten (NP) was studied. Supernatant from one hybridoma (TS1) was shown to suppress in the induction but not the effector phase of the immune response. Supernatant from the TS1 hybridoma was capable of inducing second-order (TS2) effector-phase suppressor cells in vitro but did not suppress the response of anti-I-J plus C-treated responder cells. In contrast, supernatant from a second hybridoma (TS3) was capable of suppressing PFC responses when added either in the induction or the effector phase of the response. TS3 supernatant was unable to induce effector-phase suppressor cells but was capable of suppressing the response of anti-I-J plus C-treated responder cells. In addition, specific suppressor factors isolated from supernatants of the TS1 and TS3 hybridomas were shown to bind to NP, bear NPb idiotypic and I-J-encoded but not immunoglobulin-constant region determinants. The factor secreted by the TS3 hybridoma appears to act directly on B cell targets. Mild reduction of this factor results in two separable moieties, only one of which binds NP. Reconstitution experiments suggest that both chains are required for function. The collective data indicate that these hybridomas represent cells from first- and third-order suppressor T cell populations described previously in contact sensitivity and in vitro PFC systems. The implications of the ability of these hybridoma products to affect both T and B cell-mediated immune responses are discussed.

Analysis of T cell hybridomas. II. Comparisons among three distinct types of monoclonal suppressor factors.

Five hybridoma T cell lines were prepared by fusion of Ts3 cells with the BW 5147 thymoma. The culture supernatants from these T cell hybrids contained a factor, TsF3, which specifically suppressed 4-hydroxy-3-nitrophenyl acetyl hapten (NP(-hapten cutaneous sensitivity responses. The properties of this new series of hybridoma factors was compared with those of two previously characterized types of NP-specific suppressor factors (TsF1 and TsF2). TsF3 activity was only observed if the factor was administered during the effector phases of the immune response. TsF3 bears I-J and C57BL anti-NP antibody idiotypic determinants and has binding specificity for the NP hapten. Furthermore, TsF3 does not suppress H-2 (I-J)-incompatible mice. In addition to this H-2 restriction, the monoclonal TsF3 factors also demonstrated an Igh genetic restriction. Finally, the TsF3 factors could be distinguished by their ability to suppress cyclophosphamide-treated recipients.

Analysis of T cell hybridomas. I. Characterization of H-2 and Igh-restricted monoclonal suppressor factors.

Five hybridoma T cell lines were prepared by fusion of second order suppressor T cells (Ts2) with the BW5147 thymoma. The culture supernates from these T cell hybrids contained a factor, TsF2, which specifically suppressed 4-hydroxy-3-nitrophenyl acetyl hapten (NP)-induced cutaneous sensitivity responses. TsF2 activity was observed when the factor was administered during the effector phases of the immune response. TsF2 bears I-J determinants and has binding specificity for NPb idiotypic determinants. TsF2 suppressor activity could be absorbed on antigen-primed H-2-incompatible T cells but cannot suppress H-2-incompatible mice. In addition to this H-2 restriction, which maps to the I-J subregion, monoclonal TsF2 also has an Igh genetic restriction. The present results are combined with previous data to describe the cellular interactions leading to immune suppression.

The role of I-J and Igh determinants on F1-derived suppressor factor in controlling restriction specificity.

In the 4-hydroxy-3-nitrophenyl acetyl (NP) contact sensitivity system, the activity of third-order suppressor cells and their factors is restricted by H-2(I-J) and Igh linked genes. The present report analyzes the specificity of NP-specific Ts3 cells and factors derived from H-2 and Igh heterozygous (B6 X C3H)F1 mice. Two approaches were used. First, heterogeneous populations of F1 Ts3 cells were activated in vitro and then assayed in Ts3-depleted recipients which carried different combinations of H-2 and Igh alleles. The second approach was to hybridize the Ts3 cells and analyze the specificity of the F1-derived TsF3. The combined data demonstrated four functionally distinct populations of Ts3 cells. The activity of each population was restricted by a particular combination of H-2 and Igh haplotypes. Thus, Ts3 cells derived from F1 donors can demonstrate an apparent scrambling of H-2 and Igh restriction specificities. There was functional allelic exclusion of the H-2(I-J) and Igh determinants expressed on (B6 X C3H)F1 hybridoma-derived TsF3. Thus, TsF3 from each cloned hybridoma line expressed only one set of I-J and Igh determinants. Furthermore, there was a complete correlation between the I-J and Igh linked determinants expressed on TsF3 and the restriction specificity. In view of the recent findings on the molecular biology of the I-J region, an alternative interpretation of the role of I-J determinants on suppressor cells and factors is offered.

Influence of factors related to implant stability detected by wireless resonance frequency analysis device.

Resonance frequency analysis (RFA) was introduced as a method for measuring implant stability more than a decade ago. Implant stability quotient (ISQ) values obtained using a recently introduced wireless RFA device have made it possible to evaluate stability in a non-invasive technique; however, there are few studies of the factors that affect ISQ values determined using this device. The aim of the present study was to evaluate the association between ISQ values determined by wireless RFA and various factors related to dental implant stability using a pig cortical bone model. Dental implants (Replace) Select Tapered implants) with a length of 10 mm were placed into pig cortical bone samples, then, ISQ values were determined using wireless RFA under various conditions (probe orientation, diameter of implant, insertion torque and peri-implant bone loss). The results of this study showed that ISQ values were not affected by the direction of the probe from parallel to perpendicular to the long axis of the pig bone or to the smart peg. In addition, the diameter of the implant did not have a significant effect on the measured ISQ values. Statistically significant correlations were found between insertion torque and ISQ values (Spearman's test, P < 0.05), and lower ISQ values were observed for deeper peri-implant vertical defects (Mann-Whitney U-test, P < 0.05). A wireless RFA device appears to be useful for measuring implant stability within the limits of the present in vitro study.

The NOD mouse: recessive diabetogenic gene in the major histocompatibility complex.

Examination of the histocompatibility region of the nonobese diabetic (NOD) mouse with antibodies against class II glycoproteins (products of immune response genes of the major histocompatibility complex I-A and I-E), hybrid T-cell clones, and mixed-lymphocyte cultures and analysis of restriction fragment length polymorphisms indicate that the NOD mouse has a unique class II major histocompatibility complex with no expression of surface I-E, no messenger RNA for I-E alpha, and an I-A not recognized by any monoclonal antibodies or hybrid T-cell clones studied. In crosses of NOD mice with control C3H mice, the development of diabetes was dependent on homozygosity for the NOD mouse's unique major histocompatibility region.

Strategies for maximizing heart and lung transplantation opportunities in Japan.

INTRODUCTION: Because the donor shortage is extremely severe in Japan because of a strict organ transplantation law, special strategies must be established to maximize heart transplantation (HTx) and lung transplantation (LTx) opportunities. The purpose of this study was to review our strategies to identify and manage heart and lung donors. METHOD: Transplantation doctors themselves assessed their own donor heart and lung function before starting the procurement operation; skillful staff surgeons harvested the organs. Since November 2002, a special transplantation consultant doctor assessed donor organ function to identify useful organs and intensively cared for the donor to improve cardiac and lung function. RESULTS: Only 63 brain-dead donors have been available in Japan. However, 49 HTx (77.7%) and 39 LTx (19 bilateral and 20 single) were performed from 36 donors (57.1%). Thirty-six HTx donors were marginal, requiring sustained high doses of inotropes (n = 26), low left ventricular ejection fraction (n = 5), cardiopulmonary resuscitation (n = 15), and age older than 55 years (n = 6). Twenty LTx donors had infected sputa or showed pneumonia using chest X-ray. None of 49 HTx recipients died of primary graft failure (PGF). Patient survival at 3 years after HTx was 98.0%. Although 5/39 LTx died early, including 2 of PGF, patient survival rate at 3 years was 66.9%. CONCLUSION: Although the number of cases was still small, the availability of hearts and lungs has been high and the transplantation outcomes were acceptable. These strategies may be useful to maximize HTx/LTx opportunities.

Preoperative evaluation of enterovesical fistula using magnetic resonance imaging: case report.

We report a case of sigmoido-vesical fistula due to sigmoid diverticulitis. Magnetic resonance imaging enabled us to visualize the fistula itself in the bladder wall. Magnetic resonance imaging was highly effective in making a precise diagnosis and also provided important additional information for the preoperative work-up of the patient.

Influence of radiologic expertise in detecting lung tumors on chest radiographs.

PURPOSE: To analyze the influence of radiologic expertise in detecting lung tumors on chest radiographs. MATERIALS AND METHODS: We retrieved posteroanterior chest radiographs and CT examination obtained from 283 patients with solitary primary malignant lung tumors who underwent surgical resection. There were 176 men and 107 women with a mean age of 67.0±9.1 (SD) years (range: 33-88 years). Thirteen first-year post-graduate (PGY-1) trainees and nine pulmonary specialists (three radiologists, three thoracic surgeons, and three pulmonologists) interpreted the chest radiographs. Detection rates among trainees and specialists were compared using Student t test. RESULTS: The total numbers of detected tumors ranged from 103 (36.4%) to 136 (48.1%) with a mean of 127.9±9.1 (45.2±3.2%) in the trainee group, and 137 (48.4%) to 182 (64.3%) with a mean of 161.6±13.1 (57.1±4.6%) in the specialist group; the intergroup difference was statistically significant (P<0.001). Significant intergroup detectability differences of >10% were noted for tumors in the peripheral zone with (i) ground glass opacity (GGO) ratio ≥10% and <70% and any size, or (ii) GGO ratio <10% and size ≤2cm; and for tumors hidden by the mediastinum, heart, or diaphragm with (i) GGO ratio ≥10% and <30% and size >3cm, or (ii) GGO ratio <10% and size >2cm. CONCLUSION: Our study demonstrates significant differences in lung tumor detectability on chest radiographs between PGY-1 trainees and pulmonary specialists according to tumor size, extent of GGO, and tumor location.

[Outcomes of bronchoplasty procedures for lung cancer].

A sleeve lobectomy is an established general thoracic surgical procedure. To improve clinical outcomes following the procedure, we reviewed the records of 60 patients who underwent a bronchoplasty procedure in our department from 1992 to 2007. Induction chemotherapy was performed for 20, of whom 10 underwent radiotherapy as well. For all subjects, the postoperative mortality and morbidity rates were 1.7% and 33.3%, respectively. Induction therapy did not significantly affect those rates, though complications related to bronchial anastomoses occurred exclusively in subjects who received that therapy. The overall 5-year survival rate was 51.0%, while subjects with pN0 (67.9%) and pN1 (60.0%) disease, and those in stage I (79.1%) and stage II (59.9%) had better survival as compared with patients with pN2 (16.9%) disease, and those in stage III (21.8%) and stage IV (0%). Furthermore, the survival rate of yp-stage I and II patients was significantly greater than that of those in yp-stage III and IV (59.9% vs. 14.3%, p = 0.0158). We concluded that patients in stages I, II or with pN0-1 disease are good candidates for a bronchoplasty procedure, though induction therapy should be considered thereafter. In addition, due diligence for postoperative complications is necessary.

Fe-oxide concretions formed by interacting carbonate and acidic waters on Earth and Mars.

Spherical Fe-oxide concretions on Earth, especially in Utah, USA, have been investigated as an analog of hematite spherules found in Meridiani Planum on Mars to support interpretations of water-rock interactions in early Mars. Although several formation mechanisms have been proposed for the Fe-oxide concretions on Earth, it is still unclear whether these mechanisms are viable because a precise formation process and precursor of the concretions are missing. This paper presents evidence that Fe-oxide concretions in Utah and newly found Fe-oxide concretions in Mongolia had spherical calcite concretions as precursors. Different formation stages of calcite and Fe-oxide concretions observed, both in Utah and Mongolia, indicate that calcite concretions initially formed within eolian sandstone strata and were dissolved by infiltrating Fe-rich acidic waters to form spherical FeO(OH) crusts due to pH buffering. The similarity between these Fe-oxide concretions on Earth and the hematite spherule occurrences in Meridiani Planum, combined with evidence of acid sulfate water influences on Mars, suggest that the hematite spherules also formed from dissolution of preexisting carbonate spherules possibly formed under a dense carbon dioxide early martian atmosphere.