Molecular targeting for epidermal growth factor receptor expressed on breast cancer cells by human fusion protein

Recombinant human ribonuclease 1 (RNasel) was chemically linked to recombinant human epidermal growth factor (EGF). The cytotoxicity of this conjugate was assayed using MTT assay. The EGF-RNase conjugate showed dose-dependent cytotoxicity against breast and squamous cell carcinomas overexpressing the EGF receptor (EGFR). The cytotoxicity of the conjugate correlated positively with the level of EGFR expression by each cell line. These results suggest that the EGF-RNase conjugate is a more effective anticancer agent with less immunogenicity and toxicity than conventional chimeric breast cancer toxins.     

A Simple and Rapid Fluorometric Determination Method of α1-Acid Glycoprotein in Serum Using Quinaldine Red

We examined different fluorescent probes suitable for fluorometric determination of ₁-acid glycoprotein (AGP) in serum. Quinaldine red (QR) was shown to bind strongly and selectively to AGP. Taking advantage of the enhanced fluorescence of QR in the presence of AGP, we developed a direct method for the determination of serum AGP without removal of other serum proteins such as albumin. AGP concentrations in serum of healthy volunteers and patients correlated well with results from the conventional single radial immunodiffusion (SRID) method (r = 0.93, slope = 1). The newly developed method is faster and has a larger analytical concentration range than the SRID method. This method can also be used to determine AGP in serum of experimental animals, and it can serve to monitor AGP serum concentrations for pharmacokinetic evaluation of basic drugs.     

Microanatomy of the rat diaphragm with special reference to the lymphatics and mesothelial stomata

The three-dimensional microstructure of the rat diaphragm was studied in order to reveal morphological bases which permit peritoneal fluids to pass across the diaphragm to enter the pleural cavity. The methods used include scanning electron microscopy of either intact or alkali-treated tissues, enzyme-histochemistry, and confocal laser scanning microscopy (CLSM). The peritoneal and pleural surfaces of the diaphragm are covered with mesothelial cells studded with numerous microvilli. There are many round gaps between mesothelial cells on the peritoneal side of the diaphragm. The subperitoneal connective tissue contains voluminous, irregularly shaped lymphatics which extended many funnel-shaped projections of the endothelia towards the pored region of the mesothelium. On coming into contact with the mesothelium, many of the lymphatic projections are perforated at their ends, thus giving rise to stomata connecting the peritoneal cavity and lymphatic lumen. Some projections ended blindly while plugging the mesothelial pores, thereby making visible some intercellular gaps in this contact. The subperitoneal sheet of collagen fiber network possesses clusters of pores which tightly fit the passage of the lymphatic projections. CLSM of the diaphragm after intraperitoneal injection of FITC-dextran has demonstrated the tracer both in the lymphatic lumen and in the connective tissue spaces. The tracer has also been detected in the lymphatics located in the subpleural connective tissue space. These results indicate that peritoneal fluid is allowed to flow into the lymphatics directly through the stomata and indirectly through the intercellular gaps between endothelia and mesothelial cells, and then drain into the subpleural lymphatics. Discussions were made on the probable mechanisms by which a hydrothorax may occur during continuous ambulatory peritoneal dialysis.     

Recent trends in radiation therapy for pediatric cancer

A recent strategy in the treatment of pediatric cancer is the "total cell kill", in which the main part of therapy depends on intensive, aggressive chemotherapy with or without bone marrow transplantation. Radiotherapy, like surgery, plays a role in local treatment. Recent progress in therapy has permitted cures even of patients with advanced cancer. Disease-free patients should have the same quality of life as that of healthy children of the same sex and age. Therefore, both saving the patient's life and providing him or her with a good quality of life are important in treatment policy. To obtain these goals, radiation therapy has been included in combined multi-modality therapy for the management of pediatric cancer. Other important concerns are to reduce the radiation dose and determine the timing of radiation therapy.     

Finger bougie method compared with pyloroplasty in the gastric replacement of the esophagus

To elucidate the necessity of pyloroplasty for the gastric tube through the posterior mediastinum in esophageal surgery, gastric emptying and duodenogastric reflux (DGR) were evaluated in 16 cases undergoing an anterior pylorectomy (group P) and in 16 cases treated by the finger bougie method (group F). First, the obstruction and reflux symptoms were examined based on a patient questionnaire using a brief scoring system. The median value of the symptom score showed the patients in P to have more symptoms than those in F; however, the difference was not significant (8.0 vs 6.0). Secondly, the swallowed Tc O₄ ⁻ (85 MBq) was counted using a gamma camera at three sites on the sternal bone in the upright position based on a gastric transit scintigram. Both the descending time of the RI peak and the clearance rates were similar between the two groups. Thirdly, intragastric 24-h pH monitoring was carried out. Antimony pH sensors were anchored 5 and 15 cm below the esophagogastrostomy. We could not find any difference between the two groups in both the % time pH>4 and %time pH>7. These findings thus revealed no big difference between groups P and F. The finger bougie method to drain the vagotomized posterior mediastinal stomach was found to achieve results similar to conventional pyloroplasty, while it was also simpler and safer.     

Longitudinal association of vascular and Alzheimer's dementias, diabetes, and glucose tolerance

OBJECTIVE: To assess the relationship between impaired glucose tolerance and both vascular dementia and AD. BACKGROUND: Diabetes and abnormalities of glucose metabolism have been associated with stroke and poor cognitive function. In addition, glycoproteins and glycosylation have been postulated to be associated with the development of neuritic plaques characteristic of AD. METHODS: A historical prospective cohort study of Japanese-American men (n = 3,774), who were examined at ages 45 to 68 (1965 through 1968) and again at ages 71 to 93 (1991 through 1993). Measurements were obtained by clinical and home examinations: assessment of glucose intolerance (nonfasting 1 hour after glucose load) from 1965 through 1968 and history of diabetes diagnosed by a physician at examinations given from 1965 through 1968 and from 1976 through 1978. At the 1991 through 1993 examinations, the Cognitive Assessment Screening Instrument (CASI)-an instrument designed for use in cross-cultural settings combining features of the Folstein Mini-Mental State Examination, the Modified Mini-Mental State Examination, and the Hasegawa Dementia Screening Scale-was used. Diagnosis and classification of AD and vascular dementia were made by a consensus panel using neuropsychologic assessment data, a neurologist's evaluation, and information from a family informant. Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised criteria were used to establish dementia, and subclassification by cause was based on other published criteria. RESULTS: No association between AD and diabetes, present either 25 or 15 years previously, was found after adjustment for age and education in a multiple regression model. A significant association was found between impaired glucose tolerance at baseline and vascular dementia (p < 0.01). CONCLUSIONS: These findings confirm expected relationships between impaired glucose tolerance and stroke-related dementia but do not support an association of disordered glucose metabolism with AD.     

22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis

22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis. BACKGROUND: 22-Oxacalcitriol (OCT) is a unique vitamin D analogue with less calcemic activity than calcitriol, and it effectively suppresses parathyroid hormone (PTH) secretion in uremic rats. This study was performed to examine the long-term effect of intravenously administered OCT on high-turnover bone disease in model rats of slowly progressive renal failure. METHODS: Slowly progressive renal failure rats were made by a single injection of glycopeptide isolated from rat renal cortical tissues. At 250 days, glycopeptide-induced nephritis (GN) rats were divided into three groups with the same levels of serum creatinine and PTH, and they received either OCT (0.03 or 0.15 microg/kg body wt) or vehicle given intravenously three times per week for 15 weeks. RESULTS: Renal function of GN rats deteriorated very slowly but progressively, as assessed by the increase of serum creatinine concentration. At sacrifice, serum PTH levels, bone formation markers, bone resorption markers, and fibrosis volume were significantly elevated in vehicle-treated GN rats compared with those of sham-operated rats, suggesting the development of high-turnover bone disease with osteitis fibrosa. In contrast, in the GN-OCT 0.15 microg/kg group, these high PTH levels and high-turnover bone and fibrosis were significantly decreased. Such amelioration of bone abnormalities by OCT was not accompanied by either hypercalcemia or further deterioration of renal function. CONCLUSIONS: These data indicate that OCT may be a useful and safe agent not only for the suppression of PTH, but also for the amelioration of osteitis fibrosa and high-turnover bone without causing hypercalcemia in chronic dialysis patients.