Intraperitoneal and intrathoracic administration of hydroxyapatite-carboplatin (HAp-CBDCA)

We have investigated the efficacy of intraperitoneal or intrathoracic administration of hydroxyapatite particles (HAp) loaded carboplatin (CBDCA). HAp-CBDCA (HAp; 200 mg, CBDCA; 4 mg) was administered intraperitoneally to rats with peritoneal carcinomatosis. The area under the curve of the ascitic platinum (Pt) increased significantly with rats given HAp-CBDCA, and the omental Pt levels in the HAp-CBDCA group remained higher and longer. Additionally, the HAp-CBDCA group showed a trend toward longer survival when compared with the CBDCA alone group. In clinical use, HAp-CBDCA (HAp; 5 g, CBDCA; 150 mg) was administered intrathoracically to a patient who had undergone esophagectomy. The Pt in serum was detected until 7 days after administration of HAp-CBDCA.     

Suppression of growth and dissemination in human pre-B leukemia cells by tumor necrosis factor-alpha in scid mice

Tumor necrosis factor (TNF) has been shown to inhibit the growth of ALL cells. Since the systemic administration of TNF for malignancy results in poor response and severe toxicity, future efforts should concentrate on local treatment. Here we examined the suppressive effect of TNF alpha on leukemic cells engrafted in scid mice. NALM6 cells derived from pre-B ALL were injected in scid mice subcutaneously with or without Matrigel. In mice with Matrigel, subcutaneous tumors rapidly increased with time, whereas none of the mice without Matrigel showed any obvious signs of disease or apparent tumors. High levels of leukemic infiltration were observed in peripheral organs in mice with Matrigel by flow cytometry and PCR for human beta-actin mRNA expression, while mice without Matrigel showed low or undetectable infiltration in these organs. Human TNF alpha was also coinjected subcutaneously with NALM6 cells and Matrigel into scid mice. Mice with 10 ng of TNF alpha showed small subcutaneous tumors at 8 weeks, which slowly increased. They were found to have a small number of leukemic cells in peripheral organs by flow cytometry. By PCR, all organs with the exception of lung and brain showed low or undetectable expression of beta-actin. However, a large dose of TNF alpha (100 ng) had no suppressive effect on tumor growth and leukemic infiltration in mouse organs. Similar results were obtained in colony formation of leukemic cells in vitro. To examine the mechanism of the suppressive effect of TNF alpha, the expression of TNF receptors in tumor cells was analyzed by flow cytometry. Parental NALM6 expressed both TNF alpha receptors I (TNFR60) and II (TNFR80), but these expressions were suppressed in tumor cells from mice with Matrigel. Only TNFR80 expression was induced in tumor cells of mice with 10 ng of TNF alpha. The induction of Fas expression was also detected, whereas neither DNA fragmentation nor apoptotic change in histology was observed in tumor cells of mice with TNF alpha. These results suggest that the suppressive effect of TNF alpha on the growth of leukemic cells in scid mice is mediated through the activation of TNFR80 without apoptotic signal.     

Flavonol glycosides from Epimedium sagittatum and their neurite outgrowth activity on PC12h cells

The MeOH extract of Epimedium sagittatum was found to show neurite outgrowth activity on cultured PC12h cells. Bioassay-guided fractionation of the MeOH extract yielded six prenylated flavonol glycosides, ikarisoside A (1), icarisid II (2), epimedoside A (3), icariin (4), epimedin B (5), and epimedokoreanoside-I (6) as the active ingredients.     

An arginine esterase in the human sperm

Human sperm was highly purified by the use of a discontinuous Percoll density gradient placed in an innercolumn of a centrifugation tube. Seminal plasma contamination was only 0.0008 percent in the purified sperm. A new basic arginine ester hydrolyzing enzyme with a weak affinity for lima bean trypsin inhibitor (LBTI) Cellulofine column was found in the purified human sperm, and the characteristics of this enzyme were found to be different from those of human acrosin.     

Successful emergency operation for subdural hematoma and acute epidural hematoma in a patient with acute promyelocytic leukemia]

A 22-year-old woman was admitted with purpura. Acute promyelocytic leukemia (APL) with disseminated intravascular coagulation (DIC) was diagnosed. On the 17th day after treatment with all-trans retinoic acid (ATRA), left subdural hematoma developed. Although coagulation abnormalities were still observed, emergency surgery was performed. Acute epidural hematoma was confirmed by computed tomographic scan after the operation. A second operation for drainage was successful. Post-operative intracranial hematoma may be caused by rapid decompression induced by surgery, but DIC could also be involved. This case underscored the need for careful consideration of the indications for surgical treatment of such DIC patients, with close follow-up monitoring for the postoperative development of neurological symptoms.     

Three cases of polymyositis/dermatomyositis complicated by pneumomediastinum.

Pneumomediastinum is a rare complication of dermatomyositis (DM) and Polymiositis (PM). We report here three cases of PM/DM who developed pneumomediastinum. First case was 61 years old woman with amyopathic dermatomyositis (aDM). Her aDM was complicated with skin ulceration due to vasculopathy, but complicated interstitial pneumonia was not severe. She developed subcutaneous emphysema and pneumomediastinum. Second case was 57 years old woman with DM, who had intractable skin phenomena and mild interstitial pneumonia. The patient became subcutaneous emphysema and pneumomediastinum following severe vasculopathy of skin. The last case was 63 years old man with PM. His PM was complicated with interstitial pneumonia. He had intractable respiratory symptom. Ten years later, he became subcutaneous emphysema and pneumomediastinum following pneumothorax. First and second cases suggest that their pneumomediastinum were due to vasculopathy. On the other hand, pneumomediastinum of the last patient seemed to be associated with interstitial pneumonia and steroid.     

Factors influencing vertebral bone density after renal transplantation

To improve our understanding of the mechanisms underlying osteoporosis following renal transplantation, we compared bone mineral density (BMD) in 158 transplant recipients and in 293 patients undergoing maintenance hemodialysis with age- and sex- matched normal controls. Observations in graft recipients were made up to several years following transplantation. Dual-energy X-ray absorptiometry was used to measure BMD. Correlations with clinical variables including serum concentration of parathyroid hormone (PTH) and steroid therapy were evaluated. Lumbar BMD was lower in transplant patients than in dialysis patients at all ages, and continued to decrease with increasing interval posttransplant until the second year after transplantation. Persistent hyperparathyroidism and daily prednisolone dosage were both associated with decreased BMD. Age and creatinine clearance were independent long-term predictors of BMD by multiple regression analysis. Treatment of renal graft recipients with calcium and vitamin D supplements or calcitonin may be indicated in the early months after transplantation.     

Coupling of resorption and formation on bone remodeling sequence in orthodontic tooth movement: A histochemical study

Rat's molars were submitted to orthodontic tooth movement. Bone formation areas were detected using lead-labeling technique. Osteoclasts and osteoblasts were detected by enzyme histochemistry using Tartrate resistant Acid phosphatase (TRACPase) and Alkaline phosphatase (ALPase) to determine simultaneously and mark the 2 types of cells on a same section. The sites selected for study were pressure/distal, tension/mesial and transitional areas of second molars. The results showed that: orthodontic force activated bone remodeling sequence throughout the alveolar bone; slight new bone formation was observed on the cement line on the pressure side. ALPase-positive cells were detected on the pressure side neighboring osteoclasts. On the tension side, bone formation was enhanced in the protrusions whereas both resorption and formation were observed in the depressions. In the transitional area, cellular sequence from osteoclastic bone resorption to bone formation was revealed over the cement line. These findings demonstrated that: coupling phenomena occur on the pressure side but with inhibited osteoblast activity. Bone formation on the tension side involves both promotion of bone formation by the traction force; bone remodeling sequence is established on the tension side by the interaction between osteoclastic bone resorption and bone formation that takes place in the depressions; Coupling phenomena occur in the transitional area as well. Our findings on the pressure side led to the consideration that osteoblastic cells in periodontal ligament would be involved in the regulation of osteoclastic bone resorption. Thus, there appears to be an interaction between osteoclastic and osteoblastic cells and an activated bone remodeling sequence involving the coupling phenomena as a mechanical adaptation to orthodontic force.     

Accumulation of L-type Bovine Prions in Peripheral Nerve Tissues

We recently reported the intraspecies transmission of L-type atypical bovine spongiform encephalopathy (BSE). To clarify the peripheral pathogenesis of L-type BSE, we studied prion distribution in nerve and lymphoid tissues obtained from experimentally challenged cattle. As with classical BSE prions, L-type BSE prions accumulated in central and peripheral nerve tissues.