Histochemical Study of Hyaluronate in Alcoholic Liver Disease

Recently, it has been reported that serum hyaluronate (hyaluronic acid; HA) concentrations increase in various liver diseases, especially in alcoholic liver disease (ALD), and serum HA concentration has been used as a marker for hepatic fibrosis. However, it is unknown whether hepatic HA contents in ALD increase by alcohol or not. In this study, we histochemically stained HA in liver biopsy specimens obtained from ALD patients while actively drinking and after abstinence to clarify the effects of alcohol on hepatic HA contents. Liver biopsy specimens were obtained from 13 patients with ALD and 10 patients with non-ALD. In ALD patients, liver biopsy was performed twice within 3 days, and 4 to 8 weeks after abstinence when serum levels of AST and ALT normalized. HA in biopsy specimens was stained histochemically with biotinylated HA binding protein. Staining intensity of HA in liver tissue was also determined by computer-assisted imaging analyzer. HA staining was clearly observed in sinusoidal wall and fibrous regions around the portal tract and central vein in liver diseases. HA staining intensities in patients actively drinking with ALD increased markedly, compared with those in patients with non-ALD, and these intensities decreased with abstinence. These results clearly suggest that hepatic HA contents in ALD may be increased by alcohol in addition to hepatic fibrosis, and, therefore, increased HA deposition in the liver may be reversible by abstinence of alcohol.     

ApoB C7623T polymorphism predicts risk for steroid-induced osteonecrosis of the femoral head after renal transplantation

Background Nontraumatic osteonecrosis of the femoral head (ONFH) is caused by disruption of blood flow. This disease often occurs in association with steroid treatment. The pathology of steroid-induced ONFH remains unclear, although abnormalities in lipid metabolism have been reported to be involved. In this study, we examined the differences of gene polymorphism frequencies of apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1), which are important proteins for lipid transport, as well as of lipid parameters, between ONFH cases and referent patients among those who were subjected to renal transplantation. Methods Subjects were 158 cases who had undergone renal transplant, including 34 cases that were diagnosed as ONFH after renal transplantation and 124 cases that were not. Four single nucleotide polymorphisms including C7623T and G12619A for the ApoB gene and G75A and C83T for the ApoA1 gene were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Taqman real-time PCR chemistry. Also, serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), ApoB, and ApoA1 were measured. Their relationship to ONFH was statistically evaluated. Results A higher frequency of 7623TT or CT of the ApoB gene was observed in ONFH cases than in referent patients (P = 0.033), resulting in an elevated odds ratio that was statistically significant (adjusted odds ratio = 6.37, 95% CI = 1.53–26.5, P = 0.011). No significant relationship was observed between other genes and ONFH. Regarding lipid parameters, a higher value of ApoB/ApoA1 ratio was observed in cases (P = 0.045). Conclusion For the prediction of ONFH, it is useful to analyze ApoB C7623T and plasma ApoB/ApoA1 ratio before the administration of steroids.     

3D imaging of intraductal spread of breast cancer and its clinical application for navigation surgery

BACKGROUND: To perform optimal tumor resection of breast cancer, preoperative information concerning intraductal spread of cancer (ISC) is very important. METHODS: To detect ISC, three-dimensional (3D) imaging methods including helical CT, MRI, and ultrasound were examined in patients with primary breast cancer by comparison with multi-sliced pathological specimens. RESULTS: The sensitivity of each modality for detecting ISC was 64.7%, 90.2% and 78.6%, and the specificity was 97.1%, 62.9% and 100%, respectively. Subsequently, the potential of each modality for navigation in breast conserving surgery was assessed. Three-dimensional helical CT navigation could reduce the positive rate of the specimen margins, and 3D MRI navigation using a special mapping sheet enabled removal of non-palpable breast cancer without positive margins in 66.7% of patients preliminarily. Real-time 3D ultrasound images correlated with the resected tumor size, with the difference between the two less than 2 cm in 72.7 % of the patients with ISC. CONCLUSION: Three-dimensional images from each modality were reliable enough for diagnosis of tumor spread, and surgical navigation using these images seemed to have potential clinical application for breast conserving surgery. Prospective studies for navigation surgery with more patients are needed.     

A case of breast cancer with multiple bone metastases that responded remarkably to doxifluridine (5'-DFUR), cyclophosphamide (CPA), medroxyprogesterone acetate (MPA) and pamidronate disodium therapy

A 49-year-old female underwent bilateral breast preserving surgery for heterochronic breast cancers. She later developed a sternal metastasis and was recommended for intravenous chemotherapy. However, she refused such an intensive therapy and opted for immunotherapy. Afterward, she came to our hospital because of spinal metastases with back pain. She was treated with oral administration of 5'-DFUR and MPA 1,200 mg/day for 3 weeks, respectively, CPA 100 mg/day for 2 weeks, and pamidronate disodium 30 mg intravenously every 4 weeks. This combined chemotherapy relieved her pain after one course. After 5 courses, tumor markers were reduced to the normal range. After 14 courses, bone X-P revealed that the osteolytic bone showed sclerotic changes and bone scintigraphy showed a complete remission (CR). The adverse effects were not remarkable. This regimen is possible on an outpatient basis, and it may play an important role from the standpoint of treatment effectiveness and the quality of life of the patient.     

Blood flow and blood volume in the femoral head of healthy adults according to age: Measurement with positron emission tomography (PET)

OBJECTIVE: To deepen understanding of hemodynamics in the femoral head, i.e., the essential factor in clarifying pathogenesis of hip disorders, this study examined blood flow and blood volume in the femoral heads of healthy adults, and their changes with age, by using positron emission tomography (PET). METHODS: In 16 healthy adult males (age: 20-78 years old, mean age: 42 years), blood flow was measured by means of the H2(15)O dynamic study method, and blood volume was measured by means of the (15)O-labeled carbon monoxide bolus inhalation method. RESULTS: Blood flow was 1.68-6.47 ml/min/100 g (mean +/- SD: 3.52 +/- 1.2), and blood volume was 1.67-6.03 ml/100 g (mean +/- SD: 3.00 +/- 1.27). Blood flow significantly decreased (p < 0.01) with age, and blood volume significantly increased (p < 0.05). CONCLUSION: PET was useful in the measurement of blood flow and blood volume in the femoral heads. With age, physiological hemodynamic changes also increased in femoral heads.     

Immunohistochemical Study of Hyaluronate Receptor (CD44) in Alcoholic Liver Disease

Background: It has been suggested that the elevation of serum hyaluronate (HA) levels in liver diseases may be due to increased synthesis of HA by hepatic stellate cells or decreased degradation by sinusoidal endothelial cells. The increase in serum HA levels in patients with cirrhosis is thought to be a response to a reduction in HA receptors (CD44) in hepatic sinusoidal endothelial cells. To learn more about how alcohol affects the number and distribution of HA receptors of hepatic sinusoidal endothelial cells, we immunohistochemically studied CD44 levels in liver biopsy obtained from patients with alcoholic liver disease (ALD patients) and also from patients with nonalcoholic liver disease (non-ALD); ALD patients were evaluated when they were currently drinking and again after they became abstinent. Normal liver tissue obtained from three autopsy cases served as a control. Methods: Liver biopsy specimens were obtained from 18 ALD patients and 12 non-ALD patients. In ALD patients, liver biopsy was performed twice within 3 days and 4 to 8 weeks after abstinence when serum levels of aspartate aminotransferase and alanine aminotransferase became normal. CD44 in liver specimens was stained with anti-CD44 antibody by streptavidine-biotin-peroxidase complex. The intensity of the staining of CD44 in liver tissue was determined by a computer-assisted imaging analyzer. We also measured serum levels of CD44 in both ALD and non-ALD patients. Results: The intensity and the number of CD44 staining increased in both ALD and non-ALD patients compared with those in normal liver, which was negative. The staining intensity of CD44 in liver specimens obtained from patients with ALD who were active in alcohol consumption were significantly higher when compared with patients with ALD after abstinence. Serum levels of CD44 in patients with liver disease increased compared with those of healthy subjects. Conclusions: The results suggest that HA receptors may increase to degrade the increased HA in serum and/or liver.