Accelerated declining tendency of human T-cell leukemia virus type I carrier rates among younger blood donors in Kumamoto, Japan.

The annual age- and sex-specific human T-cell leukemia virus type I carrier rate of blood donors in Kumamoto, Kyushu, Japan from 1986 to 1990 revealed that the carrier rates of all the age groups below 50 years declined linearly in both sexes (P less than 0.005). Furthermore, the annual declining rates relative to the carrier rates of 16-19-year-old and 20-29-year-old males were higher than those of all of the older males (P less than 0.02), and all female age groups below 50 years had higher relative declining rates than 50-64-year-old females (P less than 0.05). Although several factors, such as a notification program at obstetric clinics, methodological and technical improvement of the assays, wider knowledge of human T-cell leukemia virus type I infection in the latter years, and immigration of individuals from a nonendemic area, might cause an absolute decline of the carrier rate of the blood donors, these factors could not explain the acceleration of the relative declining rate among younger donors. Therefore, this acceleration represents the tendency of the general population.     

MRI findings in the mild type of mucopolysaccharidosis II (Hunter's syndrome)

Summary Neuroradiological findings in a 44-year-old male with the typical mild type of Hunter's disease are reported. Cranial MRI revealed patchy areas of increased and decreased signals in T1- and T2-weighted images in the thalamus and the basal ganglia giving rise to a honey comb-like appearance as a whole. The deep white matter showed high signals in the T2-weighted image. To our knowledge, the honey comb-like appearance has never been reported in this disorder. Deposition of mucopolysaccharides and/or glycolipids and increase in fluid content seem to be responsible for these changes.     

Types of nuclear endonuclease activity capable of inducing internucleosomal DNA fragmentation are completely different between human CD34+ cells and their granulocytic descendants

A hallmark of apoptosis is internucleosomal DNA fragmentation resulting from the activation of endonucleases. We characterized the endonuclease activity of human myeloid cell nuclei that cleaved their own nuclear chromatin to oligonucleosomal length fragments. Polymorphonuclear leukocytes (PMNs) of normal peripheral blood contained both Ca2+/Mg(2+)- dependent and DNase II-like acidic endonuclease activities in their nuclei. Immature myeloid cells of normal bone marrow at various stages of granulocytic maturation had similar nuclease activities. In contrast, a clear difference was shown in the circulating CD34+ cells, in that only Mg(2+)-dependent, Ca(2+)-independent endonuclease activity was detected. Consistent with these findings is the emergence of the Ca2+/Mg(2+)-dependent and acidic endonuclease concomitantly with the disappearance of the Mg(2+)-dependent endonuclease when CD34+ cells were induced to differentiate in vitro toward granulocytes. Leukemic cell lines of all lineages also had Mg(2+)-dependent nuclease activity. Our results suggest an association of the Mg(2+)-dependent endonuclease with hematopoietic progenitor cells and that the relative activities of the nuclear nuclease in human myeloid cells change substantially during granulocytic differentiation.     

Photodynamic therapy using pheophorbide-a and Q-switched Nd:YAG laser on implanted human hepatocellular carcinoma.

To evaluate whether administration of pheophorbide-a, a new photosensitizer, followed by use of Q-switched Nd:YAG laser produces a photodynamic reaction, we administered pheophorbide-a to female nude mice (BALB/c-nu) that had been implanted with human hepatocellular carcinoma. Intra-tumoral concentrations of pheophorbide-a were measured by high-performance liquid chromatography. 3 hours after peroral administration of 1 mg/kg body weight, the intra-tumoral concentration was too low to reveal photodynamic effects. Peroral administration of 250 mg/kg body weight, intra-peritoneal administration of 5 mg/kg body weight, and intra-tumoral injection of 200 micrograms yielded 0.24 micrograms/g, 0.83 micrograms/g and 3.68-108 micrograms/g tumor concentrations, respectively. All tumors were irradiated interstitially using a Q-switched Nd:YAG laser at 1064 nm. Only tumors that had been intra-tumorally injected had areas of necrosis larger than those in control tumors. The results suggest that the injection of pheophorbide-a followed by interstitial irradiation using a Q-switched Nd:YAG laser does not induce sufficient photodynamic reaction if the intra-tumoral pheophorbide-a concentration is less than 0.83 micrograms/g tumor tissue, and that photodynamic therapy may be useful if the pheophorbide-a tumor concentration is within the range of 0.83-108 micrograms/g.     

Deficiency of P62, a putative collagen receptor, in platelets from a patient with defective collagen-induced platelet aggregation.

Recently, we described a platelet antibody against a putative collagen receptor (P62), which was found in a patient with idiopathic thrombocytopenic purpura (ITP) (Blood 69:1712). We now report a deficiency of the P62 receptor in a young man whose platelets showed defective collagen-induced platelet aggregation. He had a mild bleeding tendency and slight thrombocytopenia. The results of coagulation and fibrinolysis studies were normal. The patient's platelets were partially unresponsive to collagen, although aggregation in response to ADP, thrombin, ristocetin, and calcium ionophore (A23187) was almost normal. Adhesion of his platelets to bovine collagen was markedly reduced. Addition of collagen caused no synthesis of thromboxane (TX)B2 in platelet rich plasma (PRP) from this patient. Furthermore, collagen produced no rise of cytosolic free calcium ([Ca2+]i) in fura2-loaded platelets. In contrast, thrombin caused TXB2 formation and an increase of [Ca2+]i in his platelets. These results suggest defective interaction between the platelets and collagen. The IgG from the ITP-patient induced irreversible aggregation in normal PRP, but caused no aggregation of the young man's platelets. Immunoblot studies showed that normal platelets had antigens with a molecular weight of 62 KDa under reducing conditions and of 57 KDa under nonreducing conditions. In contrast, the young man's platelets had no P62 band, although GPIa/IIa and thrombospondin were normally present. These results indicate that impaired collagen-induced aggregation in the patient's platelets was due to a deficiency of P62 and confirm that P62 may play a crucial role as a collagen receptor in platelet activation.