Influence of splenomegaly on aortic and liver parenchymal CT numbers during contrast-enhance CT in patients with cirrhosis.

INTRODUCTION: To compare CT (computed tomography) values for enhancement of the abdominal aorta and liver parenchyma during dynamic contrast enhancement (CE) CT in cirrhotic patients with and without splenomegaly (SM). METHODS: We considered 258 patients (83 males and 46 females for the splenomegaly group, and 83 males and 46 females for the control group) for this retrospective study. We measured CT values in the abdominal aorta and hepatic parenchyma during the hepatic arterial (HAP) and portal venous (PVP) phases. The aortic CE at HAP and the hepatic parenchymal CE at PVP were compared between the two groups. For success rate of scans, we also calculated the optimal CE rates (>280 HU in the abdominal aorta and >50 HU in the hepatic parenchyma) for each group. RESULTS: In the SM group, the CE for abdominal aorta was decreased during the aortic phase for a dynamic CE-CT (p < 0.05). When evaluating the success rates, they were found to be 65.1 % and 58.9 % in the SM group and 81.4 % and 72.3 % in the non-SM group (p < 0.05). CONCLUSION: The success rate of scans and CE for the abdominal aorta during the aortic phase exhibited a significant decrease during dynamic CE-CT scans on patients with SM. Patients with SM may have reduced diagnostic ability with typical contrast injection protocols. IMPLICATIONS FOR PRACTICE: It may be necessary to change the injection rates and contrast medium volume during CE-CT depending on the presence or absence of SM.

Morphologic changes in hepatitis virus-related liver cirrhosis: Relationship to hemodynamics of portal vein on dynamic contrast-enhanced CT.

INTRODUCTION: The morphologic changes in the compensated stage of liver cirrhosis (cLC) are not diffuse atrophic changes. With cLC lobar or segmental changes combined with atrophy of the right lobe and medial segment together with hypertrophy of the caudate lobe and lateral segment are commonly seen. The purpose of this study was to evaluate the morphologic changes in hepatitis virus-related liver cirrhosis in relationship to haemodynamics of the portal vein on dynamic contrast-enhanced computed tomography (DCE-CT) METHODS: This study included 72 patients, 46 with hepatitis virus-related cirrhosis and 26 with a normally functioning liver, who underwent DCE-CT. In cirrhosis patients, the morphologic change index (MCI) of the liver was calculated and categorised into two groups, high-MCI (MCI ≥ 0.4) (n = 21) and low-MCI (MCI < 0.4) (n = 25). Cross-sectional areas of the main, right and left portal veins and the intra-portal distribution from splenic venous flow were evaluated for their relationships with the MCI and compared among three groups (normal-control, low MCI and high MCI). RESULTS: There was a significant difference in the cross-sectional area of the left portal vein between the high-MCI group and the low-MCI group (p = 0.013) and the control group (p = 0.008). A significant correlation was identified between the cross-sectional area of the left portal vein and the MCI (r = 0.508, p < 0.001). CONCLUSION: Cross-sectional area of the left portal vein may be a factor related to morphologic changes in hepatitis virus-related liver cirrhosis and could be a possible index of the left portal venous flow volume. IMPLICATIONS FOR PRACTICE: This study may be useful for predicting the degree of hepatic morphologic changes and the condition of cirrhosis in association with regional hepatic morphologic changes.

Management of De Novo Mycobacterial Infection After Lung Transplantation Without Rifampicin: Case Series of a Single Institution.

BACKGROUND AND OBJECTIVES: To treat organ transplant patients with mycobacterial infection, physicians need to pay attention to interaction between drugs used against mycobacteria and immunosuppressants. The purpose of this report is to describe the clinical features of and treatment for mycobacterial infection in lung transplant (LTx) recipients. METHODS: To investigate the incidence, treatment, and outcome for mycobacterial infection, we retrospectively reviewed 100 LTx recipients in our program since 2000. RESULTS: Four recipients (4.0%) developed mycobacterial infection. Three recipients took tacrolimus, and 1 received cyclosporine with mycophenolate mofetil and a steroid for immunosuppression. Tuberculosis (TB) was isolated from 2 recipients, and non-tuberculous mycobacteriosis (NTM) was detected in the other 2. We treated the patients with levofloxacin + isoniazid + pyrazinamide + ethambutol (EB) for TB and clarithromycin (CLM) + EB for NTM to avoid interaction of calcineurin inhibitors (CNI: 8-10 ng/mL in trough level) with rifampicin (RFP). In treating the patients with NTM, we were able to maintain an adequate blood concentration of CNI by decreasing the dosage from one-half to one-quarter. All mycobacterial infections were controlled with treatment. In 1 patient with chronic obstructive pulmonary disease (COPD) infected with TB in the native lung, the forced expiratory volume in 1 second (FEV1) unexpectedly increased from 1890 mL before infection to 2320 mL possibly due to organization of the native lung. CONCLUSIONS: We were able to manage the mycobacterial infections using drugs other than RFP without any cases of acute rejection under adequate immunosuppression. Organization of the native lung with TB infection unexpectedly resulted in improvement of FEV1 in a COPD patient.

Mycobacterium avium genotype is associated with the therapeutic response to lung infection.

Factors that can interfere with the successful treatment of Mycobacterium avium lung infection have been inadequately studied. To identify a potent predictor of therapeutic responses of M. avium lung infection, we analyzed variable number tandem repeats (VNTR) at 16 minisatellite loci of M. avium clinical isolates. Associations between the VNTR profiling data and a therapeutic response were evaluated in 59 subjects with M. avium lung infection. M. avium lung infection of 30 subjects in whom clarithromycin-containing regimens produced microbiological and radiographic improvement was defined as responsive disease, while that of the remaining 29 subjects was defined as refractory disease. In phylogenetic analysis using the genotypic distance aggregated from 16-dimensional VNTR data, 59 M. avium isolates were divided into three clusters, which showed a nearly significant association with therapeutic responses (p 0.06). We then subjected the raw 16-dimensional VNTR data directly to principal component analysis, and identified the genetic features that were significantly associated with the therapeutic response (p <0.05). By further analysis of logistic regression with a stepwise variable-selection, we constructed the highest likelihood multivariate model, adjusted for age, to predict a therapeutic response, using VNTR data from only four minisatellite loci. In conclusion, we identified four mycobacterial minisatellite loci that together were associated with the therapeutic response of M. avium lung infections.

Rapid improvement of osseous sarcoidosis after the treatment of pulmonary aspergillosis by itraconazole.

Osseous sarcoidosis is relatively uncommon, and treatment with corticosteroids is not always effective. Moreover, patients with an advanced stage of pulmonary sarcoidosis are sometimes infected with aspergillus in the cavities of the pulmonary lesions, and long-term use of corticosteroids should be prohibited to prevent the development of fatal invasive pulmonary aspergillosis. Here, we described a unique case of osseous sarcoidosis with pulmonary aspergillosis, showing a rapid improvement of the osseous symptoms just after the administration of the antifungal agent, itraconazole. Itraconazole is likely to become a candidate among new therapeutic agents for osseous sarcoidosis.

Secondary bronchiolitis obliterans organising pneumonia in a patient with carbamazepine-induced hypogammaglobulinaemia.

Here we describe a case of a secondary bronchiolitis obliterans organizing pneumonia (BOOP), which was associated with repeated respiratory infections caused by carbamazepine (CBZ)- induced hypogammaglobulinaemia. A 49-year-old woman had been treated with CBZ (400 mg/day). Two and a half years later, she developed of dyspnea with productive cough and high-grade fever. Chest roentgenogram and computed tomography showed bilateral infiltrates in lower lung fields. Her laboratory findings revealed severe hypogammaglobulinaemia, suggesting that an immune system disorder caused pulmonary infection. Histological examination by trans-bronchial lung biopsy (TBLB) demonstrated that many foamed alveolar macrophages were obstructing the alveolar ducts and adjacent alveoli, suggesting BOOP. After cessation of CBZ, the hypogammaglobulinaemia and chest roentgenogram findings markedly improved. The present case suggests that CBZ may have some adverse effects on the immune system and cause frequent airway infections, and that secondary BOOP could be induced by repeated infections caused by CBZ-induced hypogammaglobulinaemia.

MRI appearance of primary giant ovarian leiomyoma in a hysterectomised woman.

Primary leiomyoma is a rare, benign tumour of the ovary. We describe the MRI features of an ovarian leiomyoma identified in a 51-year-old woman after hysterectomy. The tumour appeared as a well-circumscribed low signal intensity mass on T(1) weighted imaging, with mixed signal intensity on T2 weighted imaging. Areas of high signal intensity on T2 weighted imaging corresponded to degeneration of leiomyoma. Dynamic contrast-enhanced imaging revealed early enhancement of the lesion. MRI appearance was thus similar to that of uterine leiomyoma. This case suggests the potential usefulness of dynamic contrast-enhanced MRI for the diagnosis of ovarian leiomyoma.

[Whole-body MR imaging for evaluation of bone marrow cellularity in aplastic anemia].

The aim of this study was to investigate the usefulness of whole-body MRI(WB-MRI) in the evaluation of cellularity in bone marrow and the distribution of fatty marrow in aplastic anemia. WB-MRI was performed on five patients with aplastic anemia who ranged in age from 62 to 70 years of age, and on four controls with malignant lymphoma who ranged in age from 59 to 67 years. Coronal images were obtained using a body coil with an FOV of 48 cm x 48 cm, and with both fast short T1 inversion recovery(STIR) and spin-echo T1-weighted(T1-WI) in three regions: (1) head to thorax, (2) abdomen to pelvis, and (3) lower extremities. The findings on WB-MRI were compared with those of histological studies of bone marrow at the sternum and the posterior iliac crest. The results were as follows: (1) there was a correlation between the cellularity of histological studies of bone marrow and signal intensity on WB-MRI; (2) WB-MRI could detect the activity of bone marrow; and (3) in a comparison of signal intensity in aplastic anemia and control subjects, there were differences of signal intensity in the central marrow.

[The role of airway submucosal glands in the airway mucosal defense system].

Despite constant inhalation of air-borne particles including a variety of microbes and antigens, the normal lungs hardly ever develop infection or airway injury. This is because the normal lung is equipped with sophisticated defense mechanisms against foreign substances. It has been reported that the airway mucosa, especially the submucosal glands, play important roles not only in nonspecific defense using airway secretions but also in specific defense in cooperation with immune cells. In contrast to the nasopharyngeal or intestinal mucosa, which is always exposed to many foreign antigens, the mucosal surface of the lower respiratory tract in known to be kept in a germ-free condition. This fact indicates that immunological information derived from the antigen-rich mucosa, such as the intestine, might be transmitted to the airway mucosa, thus resulting in efficient removal of unwanted substances. This immunological elimination requires specific antibodies (Abs) against harmful antigens, and the major population of Abs in the airway is dimeric IgA. Airway submucosal glands synthesize a secretory component (SC), a transporter of secretory IgA, and immunoglobulin-containing plasma cells have been identified preferentially around the glandular tissue. Overall, the submucosal glands play a key role in the integrity of airway mucosal immunity.

Biochemical markers for the detection of bone metastasis in patients with prostate cancer: diagnostic efficacy and the effect of hormonal therapy.

In the present study, we investigated the diagnostic effectiveness of biochemical markers of bone turnover for the detection of bone metastasis from prostate cancer and changes in the levels of these markers caused by hormonal therapy. Ninety-five patients with prostate cancer were divided into one of three groups: 26 patients with bone metastasis (BM(+)), 35 patients without bone metastasis on nonhormonal therapy (BM(-)HT(-)) and 34 patients without bone metastasis on hormonal therapy (BM(-)HT(+)). All patients in the BM(+) group had received hormonal therapy. Serum or urinary levels of the following biochemical markers of bone turnover were examined: bone-specific alkaline phosphatase (B-ALP), osteocalcin (OC), type I procoIlagen C-propeptide (PICP), type I collagen cross-linked C-telopeptide (ICTP), C-telopeptide fragment (CTx), N-telopeptide fragment (NTx), total pyridinoline (T-Pyr), total deoxypyridinoline (T-D-Pyr) and free deoxypyridinoline (F-D-Pyr). The BM(+) group showed significantly higher values than the BM(-)HT(-) group for B-ALP, PICP, NTx, CTx, T-Pyr, T-D-Pyr, and F-D-Pyr. Compared with the BM(-)HT(+) group, the BM(-) group showed significantly higher values for B-ALP, ICTP, NTx, T-Pyr and T-D-Pyr. The levels of B-ALP, NTx, CTx, T-D-Pyr and F-D-Pyr were significantly different between the BM(-)HT(-) and BM(-)HT(+) groups. All markers, except OC and CTx, significantly were correlated with the extent of bone metastasis on bone scintigraphy. Of all markers, receiver operating characteristic (ROC) analyses revealed B-ALP and F-D-Pyr to be the most sensitive and specific for differentiation between the BM(+) and BM(-)HT(-) groups with regard to bone formation and resorption. respectively. In contrast, B-ALP and ICTP were most sensitive and specific for differentiation between the BM(+) and BM(-)HT(+) groups. The results suggest that hormonal therapy greatly affects the efficacy of PICP, CTx and F-D-Pyr in the diagnosis of bone metastasis, whereas its effects on ICTP are small. Although bone metabolic markers would be useful in the diagnosis of bone metastasis from prostate cancer, the effects of hormonal therapy on bone metabolism should be kept in mind in their evaluation.

Microelectrode and impedance analysis of anion secretion in Calu-3 cells.

Calu-3 cells secrete HCO(3)(-) in response to cAMP agonists but can be stimulated to secrete Cl(-) with K(+) channel activating agonists. Microelectrode and impedance analysis experiments were performed to obtain a better understanding of the conductances and driving forces involved in these different modes of anion secretion in Calu-3 cells. Microelectrode studies revealed apical and basolateral membrane depolarizations upon the addition of forskolin (V(ap) -52 mV vs. -21 mV; V(bl) -60 mV vs. -44 mV) that paralleled the hyperpolarization of the mucosal negative transepithelial voltage (V(T) -8 mV vs. -23 mV). These changes were accompanied by a decrease in the apical membrane fractional resistance (F(Rap)) from approximately 0.50 to 0.08, consistent with the activation of an apical membrane conductance. The subsequent addition of 1-ethyl-2-benzimidazolinone (1-EBIO), a K(+) channel activator, hyperpolarized V(ap) to -27 mV, V(bl) to -60 mV and V(T) to -33 mV. Impedance analysis revealed the apical membrane resistance (R(ap)) of the forskolin-stimulated cells was less than 20 ohm cm(2), indeed in most monolayers R(ap) fell to less than 5 ohm cm(2). The impedance derived estimate of the basolateral membrane resistance (R(bl)) was approximately 170 ohm cm(2) in forskolin treated cells and fell to 50 ohm cm(2) with the addition of 1-EBIO. Using these values for the R(bl) and the F(Rap) value of 0.08 yields a R(ap) of approximately 14 ohm cm(2) in the presence of forskolin and 4 ohm cm(2) in the presence of forskolin plus 1-EBIO. Thus, by two independent methods, forskolin-stimulated Calu-3 cells are seen to have a very high apical membrane conductance of 50 to 200 mS/cm(2). Therefore, we would assert that even at one-tenth the anion selectivity for Cl(-), this high conductance could support the conductive exit of HCO(3)(-) across the apical membrane. We further propose that this high apical membrane conductance serves to clamp the apical membrane potential near the equilibrium potential for Cl(-) and thereby provides the driving force for HCO(3)(-) secretion in forskolin-stimulated Calu-3 cells. The hyperpolarization of V(ap) and V(bl) caused by 1-EBIO provides a driving force for Cl(-) exit across the apical membrane, inhibits the influx of HCO(3)(-) on the Na(+):HCO(3)(-) cotransporter across the basolateral membrane, activates the basolateral membrane Na(+):K:2Cl(-) cotransporter and thereby provides the switch from HCO(3)(-) secretion to Cl(-) secretion.

Crystal structure of glycosyltrehalose trehalohydrolase from the hyperthermophilic archaeum Sulfolobus solfataricus.

The crystal structure of glycosyltrehalose trehalohydrolase from the hyperthermophilic archaeum Sulfolobus solfataricus KM1 has been solved by multiple isomorphous replacement. The enzyme is an alpha-amylase (family 13) with unique exo-amylolytic activity for glycosyltrehalosides. It cleaves the alpha-1,4 glycosidic bond adjacent to the trehalose moiety to release trehalose and maltooligo saccharide. Unlike most other family 13 glycosidases, the enzyme does not require Ca(2+) for activity, and it contains an N-terminal extension of approximately 100 amino acid residues that is homologous to N-terminal domains found in many glycosidases that recognize branched oligosaccharides. Crystallography revealed the enzyme to exist as a homodimer covalently linked by an intermolecular disulfide bond at residue C298. The existence of the intermolecular disulfide bond was confirmed by biochemical analysis and mutagenesis. The N-terminal extension forms an independent domain connected to the catalytic domain by an extended linker. The functionally essential Ca(2+) binding site found in the B domain of alpha-amylases and many other family 13 glycosidases was found to be replaced by hydrophobic packing interactions. The enzyme also contains a very unusual excursion in the (beta/alpha)(8) barrel structure of the catalytic domain. This excursion originates from the bottom of the (beta/alpha)(8) barrel between helix 6 and strand 7, but folds upward in a distorted alpha-hairpin structure to form a part of the substrate binding cleft wall that is possibly critical for the enzyme's unique substrate selectivity. Participation of an alpha-beta loop in the formation of the substrate binding cleft is a novel feature that is not observed in other known (beta/alpha)(8) enzymes.

[Comparison of whole-body MR imaging and bone scintigraphy in the detection of bone metastases from breast cancer].

The aim of this study was to investigate the usefulness of whole body MR imaging (WB-MRI) in the detection of bone metastases from breast cancer and to compare the results with those from bone scintigraphy. In 21 patients with suspected bone metastasis from breast cancer, both bone scintigraphy and WB-MRI were performed. With WB-MRI, coronal images were obtained using a body coil in an FOV of 48 cm, and sequences of fast short TI inversion recovery (STIR) and gadolinium-enhanced fast spoiled GRASS (SPGR) were used in three parts: from the head to the thorax, the abdomen to the pelvis, and the lower extremities. Of the total 105 metastatic bone lesions, 65 (61.9%) were detected by bone scintigraphy, 98 (93.3%) by fast STIR, and 74 (70.5%) by fast SPGR. Thus, the detection of bone metastases by WB-MRI was excellent. However, detectability in the ribs was lower for WB-MRI than for bone scintigraphy. Contrast-enhanced MRI was useful in the differentiation of osteosclerotic lesions, in which high signal intensity is rare, pleural effusion, which has high signal intensity on STIR, and bone metastatic lesions. In conclusion, WB-MRI showed high reliability in the detection of bone metastatic lesions from breast cancer.

Suppression of maxi-K channel and membrane depolarization by synthetic polycations in single tracheal myocytes.

Polycationic proteins, e.g., major basic protein from eosinophils or cathepsin G from neutrophils, have been shown to increase nonspecific airway responsiveness. Along with several indirect manners of action, polycations were reported to contract smooth-muscle strips and to raise the cellular Ca(2+) concentration as a direct action on airway smooth muscle. However, the mechanistic basis for the direct behavior remains to be elucidated. To address this issue, we examined the effects of synthetic cationic polypeptides poly-L-arginine and poly-L-lysine on fresh single smooth-muscle cells from bovine trachea using a patch-clamp technique. Both of the polycations significantly depolarized the membrane from a baseline of about -40 to -20 mV in a dose-dependent manner. The polycations also suppressed whole-cell spontaneous transient outward currents as well as both the conductance (from a baseline of about 130 to 70 pS) and open-state probability (about 25% of control values) of large-conductance Ca(2+)-dependent K(+) channel (maxi-K channel) on excised outside-out patch membranes. The polycations were without effect on the whole-cell Ca(2+) currents induced by depolarizing voltage pulses. We concluded that the synthetic polycations had at least two sites of action; one is the delayed rectifier K(+) channel that is responsible for the membrane depolarization that increases Ca(2+) influx, and the other is the maxi-K channel the suppression of which inhibits muscle relaxation. These results may explain the direct contractile action and, therefore, one of the mechanisms underlying the airway hyperresponsiveness induced by various polycationic proteins.

A novel function of thyrotropin as a potentiator of electrolyte secretion from the tracheal gland.

Accumulating evidence suggests that thyrotropin (thyroid-stimulating hormone [TSH]) plays some roles in immunoregulation by an extrathyroidal action. Because airway submucosal glands are responsible for nonspecific and specific airway defense, we tested the effect of TSH on feline tracheal submucosal gland using a whole-cell patch-clamp technique, immunohistochemistry, and reverse transcription/polymerase chain reaction (RT-PCR). TSH potentiated neurotransmitter-induced ionic currents significantly in a dose-dependent manner. Acetylcholine (10(-)(8) M)- and norepinephrine (10(-)(7) M)-induced inward current (I(i)), which we previously showed to be a Cl(-) current, were increased to about 3-fold the pre-TSH control responses, respectively, by 2.0 ng/ml TSH; and to 6- and 23-fold the control values by 20.0 ng/ml TSH, respectively. TSH alone was without effect up to 20.0 ng/ml. Follicular stimulating hormone only slightly affected the I(i) (1. 5-fold the control). Analyses with immunohistochemistry and RT-PCR failed to identify TSH receptors on the glandular tissue. Maneuvers to raise the cellular adenosine 3',5'-cyclic monophosphate also failed to mimic the TSH-mediated potentiation. The TSH effect appeared to be mediated by a signaling pathway involving tyrosine kinase because its inhibitors (genistein and herbimycin A) abolished the augmentation completely, and interferon-gamma, a tyrosine kinase activator, imitated the TSH action on submucosal gland. Thus, TSH may be an important regulator of airway fluid secretion.

What and when: parallel and convergent processing in motor control.

Successful motor behavior requires making appropriate response (response selection) at the right time (timing adjustment). Earlier psychological studies have suggested that the response selection and timing adjustment processes are performed serially in separate stages. We tested this hypothesis using functional magnetic resonance imaging. The subjects performed a choice reaction time task in four conditions: two (on-line response selection required or not) by two (on-line timing adjustment required or not). We found that the neural correlates for the two processes were indeed separate: the anterior medial premotor cortex (presupplementary motor area) was selectively active in response selection, whereas the cerebellar posterior lobe was selectively active in timing adjustment. However, the functional separation was only partial in that the lateral premotor cortex and the intraparietal sulcus were active equally for response selection and timing adjustment. The lateral premotor cortex was most active when both processes were required, suggesting that it integrates the information on response selection and the information on timing adjustment; alternatively, it might contribute to the allocation of attentional resources during dual information processing. The intraparietal sulcus was equally active when either response selection or timing adjustment was required, suggesting that it modifies, rather than integrates, these processes. Furthermore, our results suggest that these activations related to response selection and timing adjustment were distinct from sensory or motor processes.

Identification of quantitative trait loci for serum cholesterol levels in stroke-prone spontaneously hypertensive rats.

The stroke-prone spontaneously hypertensive rat (SHRSP) has been reported to show significantly lower levels of serum total cholesterol than the normotensive control strain Wistar-Kyoto rat (WKY). Because selective inbreeding was conducted for stroke proneness, this concomitantly inherited characteristic of SHRSP may play some pathophysiological role in stroke. We evaluated the genetic determinants of the cholesterol trait by estimating heritability and subsequently by undertaking a genome-wide screen with 161 genetic markers in F(2) progeny involving SHRSP and WKY (104 male and 106 female rats). Three quantitative trait loci (QTLs) were detected on rat chromosomes 5, 7, and 15. Markers from the linked region on chromosome 15 indicated significant evidence of linkage with a maximal log of the odds (LOD) score of 7.7, whereas those on chromosomes 5 and 7 cosegregated with the trait in a sex-specific manner (the QTL close to genetic marker D5 Mit5 reached an LOD score of 7.3 in males, and that close to D7 Mit10 reached an LOD score of 3.2 in females). The male-specific QTL on chromosome 5 appeared to overlap with previously reported QTLs for stroke-associated phenotypes, but an identical gene (or genes) appeared unlikely to control these and the cholesterol traits simultaneously. In the present study, serum cholesterol levels were shown to be highly genetically determined in SHRSP (the heritability estimates are 76% in males and 83% in females), and 3 QTLs with substantial effects were identified. Further work, however, is required to clarify whether the cholesterol trait is related to the etiology of stroke or has been retained by chance through the inbreeding process in SHRSP.