A new method for measurement of placental elasticity: acoustic radiation force impulse imaging.

INTRODUCTION: The velocities of the lateral shear waves (Vs; m s⁻¹) generated by an acoustic radiation force impulse (ARFI) correlate with Young's modulus. Therefore, ARFI can be used as a new method to evaluate tissue elasticity. The aim of this study was to investigate the safety of ARFI imaging and the differences in placental elasticity in complicated cases. METHODS: The study population included 115 patients between 26 and 41 weeks gestation, who were divided into three groups, namely normal, fetal growth restriction (FGR) and pregnancy-induced hypertension (PIH). After delivery, the Vs values of the placenta were measured ex vivo. After ARFI imaging, microscopic examination was performed, the Vs values were compared among the three groups and the relationship between the Vs values and neonatal birthweight Z-score was investigated. RESULTS: No histological changes were noted even after ARFI imaging. The Vs values in the FGR group were significantly higher than those in the normal group (1.94 ± 0.74 and 1.31 ± 0.35 m s⁻¹, respectively; p < 0.05). The Vs values demonstrated a significant negative correlation with the Z-score. Moreover, as the Z-score became lower, the Vs values became higher in the range of Z-scores under -0.5 standard deviation (SD). DISCUSSION: We speculate that the increased Vs values in the FGR group may have been caused by histological changes, and that a more severe FGR might result in increased Vs values. CONCLUSION: ARFI imaging was observed to have no apparent histological damage to the placental tissue. Ex vivo placentas from the FGR group were significantly more firm. Moreover, Vs values and Z-scores of birthweight had a significant negative correlation. Additional investigations are needed about the utility of this method for the evaluation of placental function in vivo.

Distinct functional regions of the human polymeric immunoglobulin receptor.

The polymeric immunoglobulin receptor (pIgR) is a type I transmembrane protein that is expressed on the surfaces of glandular and intestinal epithelial cells. The extracellular portion of the pIgR is composed of six different domains. Domain 6 is involved in the enzymatic cleavage and release of the pIgR into the intestinal lumen as a free secretory component (fSC). A highly conserved 9-amino acid sequence is present in this region in various species. Although mutations in domain 6 are associated with particular diseases, such as IgA nephropathy and Epstein-Barr virus-related nasopharyngeal cancer, and the glutamic acid residues in the conserved 9-amino acid sequence are expected to be indispensable for the secretion of fSC, the importance of these residues has not been examined. In the present study, we attempted to examine the role of these residues in the enzymatic cleavage of the pIgR. The enzymatic cleavage of the pIgR was not affected by the presence of an alanine to valine substitution at position 580 or glutamine to alanine substitutions at positions 606 and/or 607, or the deletion of the whole 9-amino acid conserved sequence. Intriguingly, the 10 amino acid sequences flanking the N- and C-terminal ends of the conserved 9-amino acid sequence had opposite effects on pIgR cleavage. Namely, the N-terminal and C-terminal sequences enhanced and reduced pIgR cleavage efficiency, respectively. These results indicated that the pIgR can be divided into several functionally distinct regions.

Multifaceted mechanisms for cell survival and drug targeting in chronic myelogenous leukemia.

Treatment outcomes for chronic myelogenous leukemia (CML) have shown major improvements as a result of the development of the tyrosine kinase inhibitors (TKIs) imatinib, nilotinib and dasatinib for the disease-specific molecular target BCR-ABL1 tyrosine kinase (TK), but a cure of CML by BCR-ABL1 TKIs has been rarely achieved. CML cells are protected from cytotoxic insults, including those by TKIs, through various collaborative BCR-ABL1- mediated and -independent mechanisms, as well as cell-intrinsic and -extrinsic molecular mechanisms. These protective mechanisms include overlapping cell signaling pathways for normal hematopoietic proliferation, modulation of molecules associated with the BCL2 family protein-regulated programmed cell death pathway, autophagic cell protection capability, bone marrow environment-mediated cell protective signaling, abnormally upregulated genetic instability and other BCR-ABL1- independent kinase activities. To develop a more effective treatment strategy for a cure by means of total leukemic cell killing, a thorough understanding of how CML cells survive and resist cytotoxic insults is essential. In this article, we review current knowledge about multifaceted BCR-ABL1-related and -unrelated mechanisms for survival and death of CML cells and present suggestions for the development of new therapeutic strategies for complete elimination of residual CML cells during TKI treatment.

Analyses of amino acid sequences in hypervariable region-1 of hepatitis C virus (HCV) in sera from chimpanzees infected three times with the same HCV strain.

BACKGROUND: To investigate whether or not the same strain of hepatitis C virus (HCV) can twice re-infect the same chimpanzee, we analyzed nucleic and amino acid sequences in HCV hypervariable region-1 (HVR1). Two chimpanzees were inoculated, three times each, with the same HCV strain during the 1983-1991. After each inoculation, chimpanzees developed acute hepatitis C, and then recovered. METHODS: Using sera, HVR1 cloning and antibody to HVR1 major clone measurement were performed. RESULTS: Clones from the first inoculum were divisible into major and minor types. Clones from the second and third inocula, as well as all post-inoculation sera, were essentially identical to the major type. Titers of antibody to HVR1 major clone were consistently low in pre- and post-inoculation sera. CONCLUSIONS: Both chimpanzees were re-infected twice with the same strain of HCV. The sequences from the second and third infections were similar to the major sequences in the first inoculum.

Sero-epidemiology of sporadic acute hepatitis in Bangladesh: high prevalences of infection with type-B, type-E and multiple types of hepatitis virus.

In a recent investigation of hepatitis in Bangladesh, the sera from 74 adult patients (aged 15-67 years) who had been clinically diagnosed as cases of sporadic acute hepatitis were collected at various hospitals in and around Dhaka. Five cases were positive for IgM antibody against the hepatitis A virus and 30 were positive both for the surface antigen of the hepatitis B virus (HBV) and for IgM antibody against the HBV core (HBc). The six cases found positive for antibodies against the hepatitis D virus were all also positive for the HBV surface antigen but negative for anti-HBc IgM. Thirteen patients harboured hepatitis C virus RNA and 29 were positive for IgM antibody against the hepatitis E virus (HEV). There were 14 non-A-to-E subjects, whose illness was of unknown aetiology. Of the 83 infections with hepatitis viruses detected in the other 60 patients, 6%, 36%, 16%, 7% and 35% were of types A, B, C, D and E, respectively. Each of 28 of the patients (47% of those confirmed to have viral hepatitis) had concomitant infection with more than one type of hepatitis virus. The predominance of HBV and HEV infections and the high prevalence of multiple infection seen among these Bangladeshi cases have not been observed among hepatitis cases in developed countries.

Ovarian Burkitt's lymphoma diagnosed by a combination of clinical features, morphology, immunophenotype, and molecular findings and successfully managed with surgery and chemotherapy.

Ovarian involvement as an initial manifestation of lymphoma, without detectable extraovarian disease, is a rare occurrence. The diagnosis of ovarian lymphoma is almost invariably unsuspected until the tumor has been examined histologically. A 25-year-old null gravid woman presented with abdominal distension. Presence of abnormal lymphoid cells in pleural effusion led to presurgical assumption that the pelvic mass noted on computerized tomography examination might be an ovarian lymphoma. We performed left salpingo-oophorectomy. Clinical, histologic, and molecular examination revealed Burkitt's lymphoma of the ovary with c-myc gene rearrangement and mRNA expression of multiple cytokines. She received dose-intensified combination chemotherapy. She is alive and free of disease 30 months after the diagnosis. Immunophenotype and molecular findings allowed reliable discrimination of Burkitt's lymphoma from diffuse large B-cell lymphoma and other lymphomas. If an ovarian tumor is solid and suspected to be of lymphoid origin, we suggest that it is necessary to obtain samples for genetic examination at surgery. This strategy often provides important information to establish therapeutic regimen and predict patient prognosis.

Pure red cell aplasia and myelofibrosis in B-cell neoplasm.

We describe an unusual case of B-cell neoplasm accompanied by pure red cell aplasia (PRCA) and myelofibrosis in a 67-year-old male presenting with severe anaemia. A few unclassified, myeloperoxidase-negative blastoid cells were seen on bone marrow aspiration, and erythroid cell hypoplasia and myelofibrosis on bone marrow biopsy. An autoimmune PRCA was suspected, as serum CH50, C3 and C4 levels were consistently low. Ciclosporin was effective in treating the anaemia, but anaemia returned when the drug was discontinued. Thirteen months later, the patient was admitted with pleural effusion and ascites that contained monoclonal CD19+ CD20+ immature blast cells with a complex karyotype, thought to be neoplastic B-cells. The unclassified blastoid cells seen earlier may therefore have been from the same origin. The patient deteriorated rapidly and died. Only one case of non-Hodgkin's lymphoma with PRCA and myelofibrosis has been reported previously. We discuss the possibility that dysregulated T-cells induced by neoplastic B-cells may have given rise to concomitant PRCA and myelofibrosis.

Compression of the common bile duct by the posterosuperior pancreaticoduodenal artery: case report.

We describe a unique case of a patient who presented with a linear, transverse filling defect in the common bile duct, detected by cholangiography, that was caused by the posterosuperior pancreaticoduodenal artery compressing the common bile duct associated with gallstones. We believe this case to be the first of its kind reported in the literature.

Randomized placebo-controlled trial assessing the effect of bifidobacteria-fermented milk on active ulcerative colitis.

BACKGROUND: Probiotics are efficacious for treating and maintaining remission of ulcerative colitis. AIM: To conduct a randomized placebo-controlled trial of bifidobacteria-fermented milk supplementation as a dietary adjunct in treating active ulcerative colitis. METHODS: Twenty patients with mild to moderate, active, ulcerative colitis randomly received 100 mL/day of bifidobacteria-fermented milk or placebo for 12 weeks with conventional treatment. RESULTS: Clinical and endoscopic activity indices and histological scores were similar in the two groups before treatment. Although improvements were significant in both groups, the clinical activity index was significantly lower in the bifidobacteria-fermented milk than in the placebo group after treatment. The post-treatment endoscopic activity index and histological score were significantly reduced in the bifidobacteria-fermented milk, but not the placebo group. Increases in faecal butyrate, propionate and short-chain fatty acid concentrations were significant in the bifidobacteria-fermented milk, but not the placebo group. No adverse effects were observed in either group. CONCLUSION: Supplementation with this bifidobacteria-fermented milk product is safe and more effective than conventional treatment alone, suggesting possible beneficial effects in managing active ulcerative colitis. This is a pilot study and further larger studies are required to confirm the result these preliminary results.

Huge IgD plasmacytoma in the abdomen presenting coagulation necrosis.

A 65-year-old Japanese woman was diagnosed in 1996 with a pathological fracture of the left femur caused by immunoglobulin D-type myeloma (IgD myeloma). She responded well to combination chemotherapy followed by irradiation. The patient experienced renal failure and became dependent on haemodialysis. In 1999, large plasmacytomas developed in the abdomen and left humerus. The abdominal tumour appeared to induce gastroduodenal ulcers and jejunal obstruction. We initiated irradiation therapy without chemotherapy to prevent further growth of the plasmacytoma, although treatment-resistant gastroduodenal ulcers developed. Continued blood loss from the gastroduodenal ulcers resulted in a deterioration in the patient's health, which prevented successful haemodialysis. An autopsy showed that the plasmacytoma had undergone coagulation necrosis. We conclude that the use of combination chemotherapy with topical irradiation was an acceptable treatment measure against IgD plasmacytoma; irradiation without chemotherapy was the most likely cause of the coagulation necrosis seen in the plasmacytoma at autopsy.

Sequences in the hypervariable region 1 of hepatitis C virus show only minimal variability in the presence of antibodies against hypervariable region 1 during acute infection in chimpanzees.

We analyzed sequences of hypervariable region 1 (HVR1) of hepatitis C virus (HCV) in six chimpanzees, experimentally infected with a single HCV inoculum, to clarify the correlation between HVR1 mutation and antibodies to HVR1. Two chimpanzees had been immunized with synthetic HVR1 peptides before HCV inoculation. All six animals became infected with HCV but cleared the infection within the acute phase. The major HVR1 sequences in longitudinal sera were unchanged in animals both with and without anti-HVR1 antibodies. Additionally, sequences of HVR1 variants in each chimpanzee converged after 11 to 19 weeks. The data show that anti-HVR1 antibodies are unlikely to drive variation in HVR1.

[Correlation between 5-fluorouracil (5-FU) sensitivity as measured by collagen gel droplet embedded culture drug sensitivity test (CD-DST) and expression of orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) in colorectal cancer].

The levels of OPRT, DPD, and TS were determined in colorectal cancer tissue specimens, and 5-FU sensitivity was measured by CD-DST. The correlation between enzyme activity and 5-FU sensitivity was then studied. Six patients with colorectal carcinoma who had undergone surgical resection in our institution between May and August 2000 were studied. The CD-DST method was used to measure the sensitivity to 5-FU under three sets of conditions: 0.2 microgram/ml x 5 days (A), 1.0 microgram/ml x 1 day (B), and 10.0 micrograms/ml x 3 h (C). The coefficients of correlation of tumor sensitivity to 5-FU and OPRT activity were A: 0.8246, B: 0.7670, and C: 0.7856, and to DPD activity were A: 0.2525, B: 0.3928, and C: 0.4337, while the coefficients of correlation to TS enzyme levels were A: -0.5240, B: -0.4770, and C: -0.6131. These findings demonstrate a high degree of correlation between OPRT activity at the tumor site and tumor sensitivity to 5-FU under a variety of conditions, suggesting that OPRT activity can be a useful indicator in predicting the anti-tumor effectiveness of 5-FU for a specific tumor.

[Expression and pathophysiologic features of orotate phosphoribosyl transferase activity (OPRT) in gastric carcinoma].

Orotate phosphoribosyl transferase (OPRT) is an enzyme that converts the pyrimidine fluoride-class anticancer drug 5-fluorouracil (5-FU) into the active nucleotide form. As such, it can be considered a primary enzyme in the first stage inhibiting DNA and RNA expression. The present study measured OPRT activity both in gastric carcinoma tissue and in surrounding normal tissue, and investigated the correlation between these findings and clinicopathologic characteristics in the patients. The study subjects were 20 patients with gastric carcinoma who were treated by surgical resection in our department. The relationship between OPRT activity in gastric carcinoma and surrounding normal tissue and patient age, sex, tissue type, extent of tumor invasion, extent of metastasis to the lymph nodes, lymphatic invasion and the existence of venous invasion of the gastric wall were investigated. The mean OPRT activity for all patients was 0.039 +/- 0.042 nmol/min/mg-prot in normal tissue and 0.120 +/- 0.099 nmol/min/mg-prot in tumor tissue, and the mean ORPT activity was significantly higher in tumor tissue than in surrounding normal tissue (p < 0.01). The OPRT ratio for tumor tissue/normal tissue (T/N) was significantly decreased as the invasiveness of the tumor increased, and was also significantly lower in patients with lymph node metastasis (p < 0.05) than in patients without lymph node metastasis. A decrease of OPRT activity in tumor tissue is a possible reason for the equivocal results of 5-FU-based chemotherapy in advanced gastric carcinoma.

Congenital dyserythropoietic anemia type 1 with fetal onset of severe anemia.

We report a patient with congenital dyserythropoietic anemia type 1 with characteristic anomalies and two novel clinicopathologic presentations: intrauterine onset of severe anemia resulting in cardiac failure and relatively mild dyserythropoietic features on bone marrow aspiration in contrast to severity of anemia. After repeated transfusions and a trial of erythropoietin administration, the patient died from respiratory infection at age 7 months. Autopsy revealed characteristic dyserythropoietic features of the bone marrow by light microscopy and electron microscopy, which confirmed a diagnosis of congenital dyserythropoietic anemia type 1.

Hepatitis G virus coinfection influences the liver histology of patients with chronic hepatitis C.

AIMS/BACKGROUND: The present investigation compared the histological features of the liver of chronic hepatitis C patients who are or are not coinfected with hepatitis G virus (HGV) to determine the histological and clinical characteristics of HGV infection. SUBJECTS AND METHODS: This study included 194 patients with chronic hepatitis C who visited our institution between 1993 and 1995. Detection of serum HGV RNA was performed by nested reverse transcription-polymerase chain reaction. Scores were assigned to indicate the severity of each of the following features on the liver biopsy of a patient: inflammatory cell infiltration in the periportal, parenchymal, and portal area; fibrous stage; lymphoid aggregates in the portal area; portal sclerotic change; perivenular fibrosis; pericellular fibrosis; bile duct damage; bridging necrosis; and irregular regeneration of hepatocytes (IR). RESULTS: HGV RNA was detected in the sera of 18 (9.3%) of the 194 patients. The histological features of the HGV RNA-positive patients show significantly more severe bile duct damage, perivenular fibrosis, pericellular fibrosis and IR than the liver of the HGV RNA-negative patients. The biochemical results in the two groups did not significantly differ. CONCLUSION: Our data suggest that chronic HGV coinfection worsens the histological features of liver disease.

[A case of giant sebaceous gland carcinoma without adequate treatment].

BACKGROUND: A patient with a sebaceous gland carcinoma without adequate treatment is reported. CASE: A 67-year-old man underwent an operation on his left upper eyelid after a diagnosis of chalazion in 1981. Two years after the initial operation, he noticed a tumor in the left upper eyelid. In 1987, he visited another hospital and was diagnosed with sebaceous gland carcinoma by a tissue biopsy. He left it untreated against medical advice. When he visited our hospital in 1996, the tumor was as large as 80 x 75 x 40 mm and the left upper and lower eyelids stuck together. After admission, he died of myocardial infarction 23 days after his visit to our hospital. Autopsy revealed that the tumor had extended into the orbital cavity, paranasal sinus, and base of the skull, with metastasis to the preauricular, submandibular, and cervical lymph nodes and both lungs. The pathology of the tumor was a moderately differentiated sebaceous gland carcinoma. CONCLUSION: This case showed the natural course of extension and metastasis of a sebaceous gland carcinoma.