Anemia in new congenital adult type polycystic kidney mice

Mechanisms for the development of anemia and the effects of recombinant human erythropoietin (r-HuEPO) on hematological parameters were studied in new congenital adult type polycystic kidney (DBA/2FG-pcy) mice. The majority of DBA/2FG-pcy mice showed progressive anemia and an elevation of blood urea nitrogen, while a minority showed progressive anemia following polycythemia. Kidneys with numerous cysts in the cortex and medulla occupied virtually the entire abdominal cavity, and the combined kidney weight taken as a percentage of body weight reached 13.5% in the DBA/2FG-pcy mouse. The osmotic fragility of DBA/2FG-pcy mice erythrocytes was significantly increased compared with that of normal control mice. In addition, two-fold increases in serum EPO levels, determined by radioimmunoassay, and a decreased number of colony forming unit-erythroid (CFU-E) were observed in the DBA/2FG-pcy mice. The administration of r-HuEPO during anemia significantly increased the red blood cell count, hemoglobin concentration, hematocrit and reticulocyte percentage in a dose-dependent manner. These findings indicate that anemia in the DBA/2FG-pcy mouse is due to increased fragility of erythrocytes, a deficiency in EPO for the degree of anemia and a decreased number or a decreased response of erythroid progenitor cells. We suggest that the DBA/2FG-pcy mouse is a useful spontaneous model of chronic progressive renal failure.     

Clinical significances of auditory brainstem responses (ABRS) in cases with intracranial lesion

In 47 cases with intracranial lesions, auditory brainstem responses (ABRS) were studied. From a detailed analysis of these data, the following results were concluded: In some cases, the intramedullary and extramedullary pontine tumor could be differentiated by ABR, A very small cerebello-pontine angle tumor was detected by ABR, ABR monitering was useful to evaluate brainstem function during the surgical operation, and ABRS were clinically very useful methods for predicting the outcome of a severe head injury and diagnosis of brain death. These results indicate that ABRS contribute to functional diagnosis of various diseases of the central nervous system.     

Establishment of a combined strategy of genetic and mass spectrometric analyses for characterizing hemoglobin mutations. An example of Hb Hoshida (beta43Glu-->Gln).

Structural analysis of mutant hemoglobins has been efficiently accomplished by a consecutive mass spectrometric strategy: molecular mass measurement of the protein to detect mutation and to determine the molecular mass change, and fragmentation analysis with collision-induced dissociation to determine the site and type of mutation. A flaw of this method is an inherent inability to detect a mutation associated with no or little change of the molecular mass. In the present study, the strategy was improved by incorporating genetic analysis prior to mass spectrometry, which confirms the resulting amino acid change and searches for possible post-translational modifications. The method was applied to an unknown mutant, and elucidated a substitution of glutamine for glutamic acid at position 43 of beta-globin subunit, the mutation of Hb Hoshida.     

Results of combined radiochemotherapy of intracranial ependymoma

Thirty patients with intracranial ependymoma were treated in our clinic from 1965 through 1984. They were 13 children and 17 adults. As for the location of tumor, 9 were in the lateral ventricle, 8 in the cerebral hemisphere, 12 in the fourth ventricle and one in the third ventricle. Histologically, 18 were benign and 12 were anaplastic. The clinical course was analyzed in 24 cases. Out of the 24 cases, surgical treatment with postoperative radiation therapy was done in 16 cases, surgical treatment with postoperative radiochemotherapy in 6, and radiochemotherapy alone in two. Five-year survival rate of patients treated by surgery with radiation therapy and with radiochemotherapy was 35.7% and 66.7%, respectively. Patients treated by surgery not only with radiation therapy but also with chemotherapy took a better outcome. Recurrence was observed in 9 cases. Four cases of the 9 were benign ependymoma. The recurrence was observed within 3 years after the initial treatment in all cases. Even if histologically benign, the recurrence occurred in a relatively high rate as reported in the past literature. It should, therefore, be stressed that the initial treatment is important not only for a malignant ependymoma but also for a benign one, and the postoperative radiochemotherapy is useful for the improvement of the results.     

Long-term survival after brain metastasis from endometrial cancer

A case is reported of prolonged survival after radical hysterectomy for poorly differentiated adenocarcinoma of the endometrium and resection of metastatic carcinoma of the brain followed by radiation therapy. The 43-year-old patient has survived for seven years after hysterectomy and six years 10 months after excision of the brain metastasis. Our results show that the surgical excision of a single metastatic lesion of the brain with postoperative irradiation offers hope of prolonged survival in patients with a solitary brain metastasis and no evident systemic disease.     

Sensitivity test for anti-tumor agents. 1. Application of human cord serum--as cellular growth factor

For the purpose to establish a rapid, accurate, in vitro drug sensitivity test, we have been working on surgical specimens and malignant effusions. For the primary cultures, we used cellular medium PRMI-1640 with 10% fetal calf serum (FCS). For the successful tissue culture, human cord serum (HCS) was in stead of FCS in this study. For the preparation of HCS, human cord blood was obtained aseptically just after the second stage of labor from the uncomplicated pregnant women. The serum was separated, filtrated, being confirmed negative Mycoplasma contamination, and inactivated by keeping in a water bath at 56 degrees C for 30 min. The experimental materials were T-24, HeLa and Vero cells. These cellular suspension samples in RPMI1640 with FCS or HCS were kept in 5% CO2 incubator at 37 degrees C for 120 hours. Estimation and evaluation of this test in comparison of FCS with HCS were made on the following points. 1. Cellular proliferation on the crystal violet staining. 2. Cellular function test by MTT assay. 3. Cellular morphologic changes on microscopic examination. Conclusions: 1. HCS, as well as FCS, seemed to be a good cellular growth factor. 2. 5% HCS is compatible with 10% FCS for good cellular development.     

ABC transporters of pathogenic fungi: recent advances in functional analyses]

ABC (ATP binding cassette) transporters consist of transmembrane domains which confer specificity, and structurally conserved nucleotide binding domains that contain highly conserved amino acid motifs. They act not only as transporters but also as receptors or channels that use energy generated by ATP hydrolysis. ABC transporters are widely dispersed in nature. They are found in cells ranging from prokaryotes (bacteria) to eukaryotes (including humans) and several are considered to play crucial roles in cellular homeostasis. Defects in ABC transporters in humans are associated with severe diseases such as type 2 diabetes and cystic fibrosis. Some ABC transporters extrude xenobiotics and confer resistance to chemotherapeutics on microbial pathogens and cancer cells. Thus ABC transporters are of considerable medical importance. Structure-function analysis of ABC transporters has begun to elucidate their mechanisms of substrate recognition, the functional regulation of ATP-binding and hydrolysis and to identify intrinsic physiological functions. In pathogenic fungi, ABC transporters contribute to the clinical problem of drug resistance. The application of new technologies to the examination of fungal ABC transporter function is providing new insights into the use of antifungal drugs in medical mycology and contributing to a better understanding of these important membrane proteins.