Invasive micropapillary carcinoma of the breast: clinicopathological and immunohistochemical study.

Invasive micropapillary carcinoma (IMPCa) of the breast refers to a unique variant of invasive ductal carcinoma, but its biological behavior has not been elucidated well. We analyzed 16 IMPCa cases (10 pure type, six mixed type). The incidence of IMPCa was 1.

Gene transfer of alpha1,3-fucosyltransferase increases tumor growth of the PC-3 human prostate cancer cell line through enhanced adhesion to prostatic stromal cells.

Elevated expression of sialyl Lewis X has been postulated to be a prognostic indicator of prostate cancer. However, direct evidence for the relationship between increased expression of sialyl Lewis X and malignancy of prostate cancer is still lacking. To determine whether increased levels of sialyl Lewis X leads to malignancy in prostate tumor, we transfected the human prostate cancer cell line PC-3 with alpha1,3-fucosyltransferase III (FTIII) to obtain stable transfectants, PC-3-FTIII lines, that highly express sialyl Lewis X.

Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities.

Heparin-binding EGF-like growth factor (HB-EGF) is first synthesized as a membrane-anchored form (proHB-EGF), and its soluble form (sHB-EGF) is released by ectodomain shedding from proHB-EGF. To examine the significance of proHB-EGF processing in vivo, we generated mutant mice by targeted gene replacement, expressing either an uncleavable form (HBuc) or a transmembrane domain-truncated form (HBdeltatm) of the molecule. HB(uc/uc) mice developed severe heart failure and enlarged heart valves, phenotypes similar to those in proHB-EGF null mice.

Factors involved in the development of hypertension induced by a low-protein diet in rats with renal injury.

Background/aims: While a low-protein diet (LPD) has been reported to increase blood pressure, the mechanism for its increase has not yet been clarified. We investigated the factors involved in the development of hypertension induced by LPD in rats with post-cyclosporine (CsA) nephropathy, and determined the appropriate composition for LPD that is to be utilized for renal research.

Methods: The rats were divided into 4 groups, each group being fed either a normal-protein diet (NPD), LPD with a low sucrose content as the main component of carbohydrate, LPD with a high-sucrose content, or LPD with low sucrose plus 2% L-arginine (Arg) for 12 weeks, and the blood pressure, urinary nitric oxide (NO) metabolite (NOx) excretion, renal NO-generating capacity and renal Arg content were compared among these groups.

Diffuse hepatic angiosarcoma with a portal venous supply mimicking hemangiomatosis.

We report a case of diffuse hepatic angiosarcoma. Dynamic computed tomography (CT) showed gradual contrast enhancement and homogeneity in the late phase. The tumor was homogeneously hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging, mimicking hemangiomatosis.

Immunostaining of stage-specific embryonic antigen-4 in intratubular germ cell neoplasia unclassified and in testicular germ-cell tumors.

Stage-specific embryonic antigen-4 (SSEA-4) is expressed in testicular germ-cell tumors (GCT) according to studies using thin-layer chromatography (TLC) immunostaining. To further understand the relationship between SSEA-4 and the histogenesis of testicular GCT, we examined the expression of SSEA-4 in 43 samples of testicular GCT either by immunohistochemical staining or by TLC immunostaining. Immunohistochemical staining detected SSEA-4 in spermatogonia from the non-tumor parts of the testis and in all of 8 samples of intratubular germ cell neoplasia unclassified (IGCNU).

Time-related changes of radiofrequency ablation lesion in the normal rabbit liver: findings of magnetic resonance imaging and histopathology.

Rationale And Objectives: To study time-related magnetic resonance imaging (MRI) and histopathological findings after radiofrequency ablation (RFA) in the normal liver.

Methods: Under ultrasound guidance, RFA was performed in 22 rabbits with a 15-gauge expandable probe inserted into the liver. The RF power was applied at 10 W initially with a 5-W increment every minute until RF power "roll-off" occurred.

Microinvasive ductal carcinoma (T1mic) of the breast. The clinicopathological profile and immunohistochemical features of 28 cases.

Microinvasive ductal carcinoma of the breast, namely ductal carcinoma in situ with microinvasion (T1mic) as defined by the American Joint Committee on Cancer (AJCC) Staging Manual, is a rare disease, although it is increasing because of widespread use of mammography. The aim of the present study was to describe the clinicopathological and immunohistochemical features of this entity. Twenty-eight patients who were diagnosed as T1mic from January 1997 to August 2002 were studied by using 3-5 mm-thick serial sections with hematoxylin-eosin staining.

Immunohistochemical expressions of mGluR5, P2Y2 receptor, PLC-beta1, and IP3R-I and -II in Merkel cells in rat sinus hair follicles.

We previously found that Merkel cells (MCs) of the rat and monkey show a strong immunoreaction of the alpha-subunit of Gq protein. The Galphaq-subunit isoform activates isozymes of phospholipase C-beta (PLC-beta), which produces inositol-(1,4,5)-triphosphate (IP3) which mobilizes intracellular Ca(++) from calcium stores via IP3 receptors. Glutamate and adenosine triphosphate (ATP), which are candidates for neurotransmitters in Merkel endings, are known to couple to Galphaq.

Quantitative and qualitative comparison of virulence traits, including murine lethality, among different M types of group A streptococci.

Epidemiological studies have proposed an association between group A streptococci (GAS) bearing a particular M serological type and pathologic conditions such as streptococcal toxic shock syndrome (STSS). M1 and M3 GAS are isolated from STSS cases more frequently, whereas M4 and M12 GAS are isolated from non-STSS cases more frequently. To investigate whether there is any difference contributing the M-type association among GAS, we compared various virulence traits, including the murine lethality of M4, M12, M1, and M3 GAS clinical isolates, which are not clonally related to one another.

Costimulatory molecules CD80 and CD86 in human crescentic glomerulonephritis.

Background: CD80 and CD86, cell-surface molecules found only on antigen-presenting cells (APCs), are required for activation of CD4-postitve (CD4+) T cells by interaction with CD28/cytotoxic T-lymphocyte-associated antigen 4 on T cells. The roles of these molecules in human glomerulonephritis (GN) presently are unknown.

Methods: Twelve cases of crescentic GN, thought to be a T helper cell-directed delayed-type hypersensitivity-like injury, and 10 controls with non-immunoglobulin A proliferative GN were used.

The therapeutic potential of novel cardiotonic agents.

During the course of treatment of heart failure patients, cardiotonic agents are inevitable for improvement of myocardial dysfunction. Clinically available agents, such as beta-adrenoceptor agonists and selective phosphodiesterase 3 inhibitors, act mainly via cyclic AMP/protein kinase A-mediated facilitation of Ca(2+) mobilisation (upstream mechanism). These agents are associated with the risk of Ca(2+) overload leading to arrhythmias, myocardial cell injury and premature cell death.

[Usefulness of urine analysis in clinical nephrology].

In chronic glomerular nephritis (CGN), it is important to estimate the renal function and 24 hr urinary protein excretion to estimate the effectiveness of the treatment. In this study, we evaluated the usefulness of a microscopic urine test in making pathological diagnosis. As a result, we found that IgA nephritis has a significantly higher urinary RBC count among the CGN group, and found focal glomerular sclerosis and membranoproliferatine GN patients have significantly higher urinary RBC count among nephrotic patients.

Signal transduction and Ca2+ signaling in contractile regulation induced by crosstalk between endothelin-1 and norepinephrine in dog ventricular myocardium.

In certain cardiovascular disorders, such as congestive heart failure and ischemic heart disease, several endogenous regulators, including norepinephrine (NE) and endothelin-1 (ET-1), are released from various types of cell. Because plasma levels of these regulators are elevated, it seems likely that cardiac contraction might be regulated by crosstalk among these endogenous regulators. We studied the regulation of cardiac contractile function by crosstalk between ET-1 and NE and its relationship to Ca2+ signaling in canine ventricular myocardium.

Inhibitory action of the phosphatase inhibitor cantharidin on the endothelin-1-induced and the carbachol-induced negative inotropic effect in the canine ventricular myocardium.

In the canine ventricular myocardium, endothelin-1 and the muscarinic agonist carbachol scarcely affect the basal force of contraction but do induce a pronounced negative inotropic effect in the presence of beta-adrenoceptor agonists. Experiments were performed to examine whether the protein phosphatase inhibitor cantharidin inhibits the negative inotropic effect induced by endothelin-1 and carbachol in isolated canine ventricular trabeculae. In the presence of 100 nM norepinephrine, endothelin-1 (10 nM) and carbachol (30 nM) decreased the norepinephrine-induced positive inotropic effect to about 40% of the norepinephrine-induced maximal response.

CSF hypovolemia vs intracranial hypotension in "spontaneous intracranial hypotension syndrome".

Objectives: To investigate the role of CSF hypovolemia in spontaneous intracranial hypotension (SIH) syndrome because so-called SIH syndrome sometimes lacks intracranial hypotension.

Methods: Ten women (aged from 28 to 49 years) with characteristic orthostatic headache without a previous history of dural tear were investigated. In addition to gadolinium (Gd)-enhanced brain MRI, spinal MRI with and without Gd enhancement was performed.

Dissociation of E-4031 from the HERG channel caused by mutations of an amino acid results in greater block at high stimulation frequency.

Objective: We have reported identification of the amino acid whose mutation reduces effects of quinidine on the HERG channel. Although the residue (isoleucine at 647) is not in the recently reported methanesulfonanilide binding site, a single concentration of E-4031 (10 microM) was less effective to I647 mutant channels than wild type HERG channel. We designed the present experiment to further investigate influence of mutations at 647 on the effects of methanesulfonanilides.

Design and synthesis of the tumor-activated prodrug of dihydropyrimidine dehydrogenase (DPD) inhibitor, RO0094889 for combination therapy with capecitabine.

A series of tumor-activated prodrugs of the inhibitors of dihydropyrimidine dehydrogenase (DPD), an enzyme catabolizing 5-fluorouracil (5-FU: 4g), has been designed and synthesized. RO0094889 (11c) is a prodrug of 5-vinyluracil (4c), a known DPD inhibitor, and was designed to generate 4c selectively in tumor tissues by sequential conversion of 11c by three enzymes: esterase, cytidine deaminase and thymidine phosphorylase, the latter two of which are known to be highly expressed in various tumor tissues. When capecitabine (1), a tumor-activated prodrug of 5-FU, was co-administered orally with 11c, 5-FU in tumor tissues was significantly increased with only a slight increase of 5-FU in plasma as compared with oral capecitabine alone.

Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex.

The multisubunit transcription elongation factor NELF (for negative elongation factor) acts together with DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) sensitivity-inducing factor (DSIF)/human Spt4-Spt5 to cause transcriptional pausing of RNA polymerase II (RNAPII). NELF activity is associated with five polypeptides, A to E. NELF-A has sequence similarity to hepatitis delta antigen (HDAg), the viral protein that binds to and activates RNAPII, whereas NELF-E is an RNA-binding protein whose RNA-binding activity is critical for NELF function.

Acute interstitial nephritis with polyclonal B cell infiltration and development of mantle cell lymphoma.

A 69-year-old man with proteinuria, hematuria and abnormal renal and hepatic function developed acute renal failure. His clinical and laboratory examinations showed splenomegaly, edema, anemia and polyclonal hypergammaglobulinemia with high IgG levels. Renal biopsy showed interstitial nephritis with predominant B cell and plasma cell infiltration without monoclonality.

Long-term neuroprotective effects of hypothermia on neonatal hypoxic-ischemic brain injury in rats, assessed by auditory brainstem response.

A method to assess long-term neurofunctional outcome of hypothermia on immature brains has not yet been clearly established. To investigate the effects of hypothermia on long-term neurofunctional outcome, we studied brainstem function using auditory brainstem response in adult rats after neonatal hypoxic-ischemic brain injury. Seven-day-old rats underwent a combination of left common carotid artery ligation and subsequent exposure to 8% O(2) for 1 h (n = 17).

HVJ-envelope vector for gene transfer into central nervous system.

To overcome some problems of virus vectors, we developed a novel non-viral vector system, the HVJ-envelope vector (HVJ-E). In this study, we investigated the feasibility of gene transfer into the CNS using the HVJ-E both in vitro and in vivo. Using the Venus reporter gene, fluorescence could be detected in cultured rat cerebral cortex neurons and glial cells.

SCL/tal-1-dependent process determines a competence to select the definitive hematopoietic lineage prior to endothelial differentiation.

Hematopoiesis in most vertebrate species occurs in two distinct phases, primitive and definitive, which diverge from FLK1(+)VE-cadherin(-) mesoderm and FLK1(+)VE-cadherin(+) endothelial cells (EC), respectively. This study aimed at determining the stage at which hematopoietic lineage fate is determined by manipulating the SCL/tal-1 expression that is known to be essential for the early development of the primitive and definitive hematopoietic systems. We established SCL-null ES cell lines in which SCL expression is rescued by tamoxifen-inducible Cre recombinase-loxP site-mediated recombination.

Effects of OR-1896, a metabolite of levosimendan, on force of contraction and Ca2+ transients under acidotic condition in aequorin-loaded canine ventricular myocardium.

We performed experiments in canine ventricular trabeculae loaded with aequorin to elucidate the influence of acidosis on the positive inotropic effect (PIE) of OR-1896 (R)- N-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenyl]-acetamide, an active metabolite of levosimendan. The concentration-response curve (CRC) for OR-1896 was biphasic in acidotic conditions (pH(o) 6.6) that was essentially the same as that in control conditions (pH(o) 7.

Clinical significance of ST3Gal IV expression in human renal cell carcinoma.

Alteration of sialyltransferase expression has been implicated in carcinogenesis. Out of sialyltransferases cloned to date, we focused on ST3Gal IV expression in human renal cell carcinoma (RCC). Levels of ST3Gal IV mRNA were examined in human RCC in comparison with non-tumor kidney.