Showing papers by "Kumamoto University published in 1991"

Does superoxide underlie the pathogenesis of hypertension

Abstract: Although active oxygen species play important roles in the pathogenesis of various diseases, the molecular mechanism for oxygen toxicity in vascular diseases remains to be elucidated. Since endothelium-derived relaxing factor (EDRF) is inactivated by superoxide radicals in vitro, oxidative stress in and around vascular endothelial cells may affect the circulatory status of animals. To study the role of superoxide radicals and related enzymes, such as superoxide dismutase (SOD), in vascular diseases, we have developed a fusion protein (HB-SOD) consisting of human Cu/Zn-type SOD and a C-terminal basic peptide with high affinity for heparan sulfate on endothelial cells. When injected intravenously, HB-SOD bound to vascular endothelial cells, underwent transcellular transport, and localized within vascular walls by a heparin-inhibitable mechanism. The blood pressure of spontaneously hypertensive rats (SHR) but not normal animals was decreased significantly by HB-SOD. Heparin inhibited the depressor effect of HB-SOD. In contrast, native SOD had no effect on blood pressure of either SHR or normal rats. Neither H2O2-inactivated HB-SOD nor the C-terminal heparin-binding peptide showed such a depressor effect, suggesting that the catalytic function of HB-SOD is responsible for its depressor action. To know the source of superoxide radicals, we determined xanthine oxidase activity in the aorta and uric acid levels in the plasma. Although no appreciable difference in xanthine oxidase activity was found between the two animal groups, uric acid levels were significantly higher in SHR than in normal rats. Oxypurinol, a potent inhibitor of xanthine oxidase, also decreased the blood pressure of SHR but not of normal rats. These findings indicate that superoxide radicals in and around vascular endothelial cells play critical roles in the pathogenesis of hypertension of SHR.

Expression and function of c-kit in hemopoietic progenitor cells

Abstract: The expression and function of a receptor tyrosine kinase, c-kit, in the adult bone marrow of the mouse were investigated by using monoclonal antibodies (mAbs) against the extracellular domain of murine c-kit. In adult C57BL/6 mouse, 7.8% of total bone marrow cells express c-kit on their surface. Half of the c-kit+ cells do not express lineage markers including Mac-1, Gr-1, TER-119, and B220, while the remainder coexpress myeloid lineage markers such as Mac-1 and Gr-1. After c-kit+ cells were removed from the bone marrow cell preparation, hemopoietic progenitor cells reactive to IL-3, GM-CSF, or M-CSF and also those which give rise to spleen colonies in irradiated recipients disappeared almost completely. Thus, most hemopoietic progenitors in the adult bone marrow express c-kit. To investigate whether or not c-kit has any role in the hemopoiesis of adult bone marrow, we took the advantage of one of the anti-c-kit mAbs that can antagonize the function of c-kit. As early as two days after the injection of 1 milligram of an antagonistic antibody, ACK2, almost all hemopoietic progenitor cells disappeared from the bone marrow, which eventually resulted in the absence of mature myeloid and erythroid cells in the bone marrow. These results provide direct evidence that c-kit is an essential molecule for constitutive intramarrow hemopoiesis, especially for the self-renewal of hemopoietic progenitor cells at various stages of differentiation.

Role of c-kit in mouse spermatogenesis: identification of spermatogonia as a specific site of c-kit expression and function.

Abstract: Recent studies have shown that the dominant white spotting (W) locus encodes the proto-oncogene c-kit, a member of the tyrosine kinase receptor family. One symptom of mice bearing mutation within this gene is sterility due to developmental failure of the primordial germ cells during early embryogenesis. To elucidate the role of the c-kit in gametogenesis, we used an anti-c-kit monoclonal antibody, ACK2, as an antagonistic blocker for c-kit function to interfere with the development of male and female germ cells during postnatal life. ACK2 enabled us to detect the expression of c-kit in the gonadal tissue and also to determine the functional status of c-kit, which is expressed on the surface of a particular cell lineage. Consistent with our immunohistochemical findings, the intravenous injection of ACK2 into adult mice caused a depletion in the differentiating type A spermatogonia from the testis during 24-36 h, while the undifferentiated type A spermatogonia were basically unaffected. Intraperitoneal injections of ACK2 into prepuberal mice could completely block the mitosis of mature (differentiating) type A spermatogonia, but not the mitosis of the gonocytes and primitive type A spermatogonia, or the meiosis of spermatocytes. Our results indicate that the survival and/or proliferation of the differentiating type A spermatogonia requires c-kit, but the primitive (undifferentiated) type A spermatogonia or spermatogenic stem cells are independent from c-kit. Moreover, the antibody administration had no significant effect on oocyte maturation despite its intense expression of c-kit.

Effect of Steel factor and leukaemia inhibitory factor on murine primordial germ cells in culture

Abstract: Despite the importance of germ cells to the survival of species, surprisingly little is known about their embryological origin, proliferation, migration and entry into mitotic arrest or meiosis. Mutations in the murine Dominant White Spotting (W) and Steel genes, which respectively encode the c-kit tyrosine kinase receptor and the c-kit ligand (or Steel factor), impair the development of primordial germ cells (PGCs) in vivo, as well as haematopoietic stem cells and neural crest-derived melanoblasts. Here we use a monoclonal antibody against c-kit tyrosine kinase receptor and recombinant Steel factor to study the c-kit receptor-ligand system in cultured PGCs. In addition, we show that leukaemia inhibitory factor (also known as differentiation inhibitory activity), a factor secreted by STO fibroblasts, can stimulate proliferation of primordial germ cells in vitro.

In utero manipulation of coat color formation by a monoclonal anti-c-kit antibody: two distinct waves of c-kit-dependency during melanocyte development.

Abstract: Previous studies on mice bearing various mutations within the c-kit gene, dominant white spotting (W), indicate the functional role of this tyrosine kinase receptor in the development of melanocytes, germ cells and hematopoietic cells Despite the availability of mice defective in the c-kit gene and a respectable understanding of the molecular nature of c-kit, however, it is not clear at what stage of gestation c-kit is functionally required for the development of each of these cell lineages To address this question, we have used a monoclonal anti-c-kit antibody, ACK2, as an antagonistic blocker of c-kit function to interfere with the development of melanocytes during embryonic and postnatal life ACK2 injected intradermally into pregnant mice entered the embryos where it blocked the proper development of melanocytes This inhibitory effect was manifested as coat color alteration in the offspring Furthermore, ACK2 injection also altered the coat color of neonatal and adult mice Based on the coat color patterns produced by ACK2 administration at various stages before or after birth, the following conclusions are drawn: (i) during mid-gestation, c-kit is functionally required during a restricted period around day 145 post-coitum when a sequence of events leading to melanocyte entry into the epidermal layer occurs; (ii) during postnatal life, c-kit is required for melanocyte activation which occurs concomitantly with the hair cycle which continues throughout life after neonatal development of the first hair

Hemodynamic, renal, and hormonal responses to brain natriuretic peptide infusion in patients with congestive heart failure

Abstract: BACKGROUNDThis study was designed to examine the hemodynamic, renal, and hormonal effects of brain natriuretic peptide (BNP) infusion in patients with congestive heart failure (CHF) and in control subjects.METHODS AND RESULTSWe infused synthetic human BNP at a rate of 0.1 micrograms/kg/min. BNP infusion decreased pulmonary capillary wedge pressure (control, from 5 +/- 1 to 2 +/- 1 mm Hg, p less than 0.01; CHF, from 21 +/- 3 to 14 +/- 4 mm Hg, p less than 0.05) and systemic vascular resistance (control, from 1,264 +/- 75 to 934 +/- 52 dyne.sec.cm-5; CHF, from 2,485 +/- 379 to 1,771 +/- 195 dyne.sec.cm-5; p less than 0.01, respectively) and increased stroke volume index (control, from 49.9 +/- 2.7 to 51.5 +/- 2.3 ml/m2, p = NS; CHF, from 25.6 +/- 3.8 to 32.0 +/- 3.9 ml/m2, p less than 0.01). BNP infusion significantly increased urine volume (control, from 2.3 +/- 0.7 to 7.5 +/- 1.9 ml/min; CHF, from 0.8 +/- 0.2 to 5.3 +/- 1.0 ml/min; p less than 0.01, respectively), excretion of sodium (control, from 79.2 +...

The new gene mukB codes for a 177 kd protein with coiled-coil domains involved in chromosome partitioning of E. coli.

Abstract: An Escherichia coli temperature sensitive mutant which produces spontaneously normal size anucleate cells at low temperature was isolated. The mutant is defective in a previously undescribed gene, named mukB, located at 21 min on the chromosome. The mukB gene codes for a large protein (approximately 180 kd). A 1534 amino acid protein (176,826 daltons) was deduced from the nucleotide sequence of the mukB gene. Computer analysis revealed that the predicted MukB protein has distinct domains: an amino-terminal globular domain containing a nucleotide binding sequence, a central region containing two alpha-helical coiled-coil domains and one globular domain, and a carboxyl-terminal globular domain which is rich in Cys, Arg and Lys. A 180 kd protein detected in wild-type cell extracts by electrophoresis is absent in mukB null mutants. Although the null mutants are not lethal at low temperature, the absence of MukB leads to aberrant chromosome partitioning. At high temperature the mukB null mutants cannot form colonies and many nucleoids are distributed irregularly along elongated cells. We conclude that the MukB protein is required for chromosome partitioning in E. coli.

Histopathologic pulmonary changes from mechanical ventilation at high peak airway pressures

Abstract: We investigated the histopathologic pulmonary changes induced by mechanical pulmonary ventilation (MV) with a high peak airway pressure and a large tidal volume in healthy baby pigs. Eleven animals were mechanically ventilated at a peak inspiratory pressure (PIP) of 40 cm H2O, a respiratory rate (RR) of 20 min-1, a positive end-expiratory pressure (PEEP) of 3 to 5 cm H2O, and an FIO2 of 0.4. High airway pressure MV was terminated in 22 +/- 11 h because of severe hypoxemia in the animals. Five of the baby pigs were killed for gross and light microscope studies. The pulmonary changes consisted of alveolar hemorrhage, alveolar neutrophil infiltration, alveolar macrophage and type II pneumocyte proliferation, interstitial congestion and thickening, interstitial lymphocyte infiltration, emphysematous change, and hyaline membrane formation. Those lesions were similar to that seen in the early stage of the adult respiratory distress syndrome (ARDS). The remaining six animals were treated for 3 to 6 days with conventional respiratory care with appropriate ventilator settings. Prominent organized alveolar exudate in addition to lesions was also found in the five animals. These findings were indistinguishable from the clinical late stage of ARDS. Six control animals were mechanically ventilated at a PIP of less than 18 cm H2O, a RR of 20 min-1, a PEEP of 3 to 5 cm H2O, and an FIO2 of 0.4 for 48 h. They showed no notable changes in lung functions and histopathologic findings. Aggressive MV with a high PIP is often applied to patients with respiratory distress to attain adequate pulmonary gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Transgenic mice expressing a B cell growth and differentiation factor gene (interleukin 5) develop eosinophilia and autoantibody production.

Abstract: Interleukin 5 (IL-5) has been suggested to be involved in the growth and differentiation of B cells and eosinophils. Especially, Ly-1+ B cells, which have been considered to produce autoantibodies, are selectively developed by this lymphokine in long-term bone marrow culture. To envisage the possible engagement of IL-5 in the development of these cells in vivo, transgenic mice carrying the mouse IL-5 gene ligated with a metallothionein promoter were generated. Transgenic mice carrying the IL-5 gene exhibited elevated levels of IL-5 in the serum and an increase in the levels of serum IgM and IgA. A massive eosinophilia in peripheral blood, bone marrow, and spleen, and an infiltration of muscle and liver with eosinophils, were observed. When cadmium-containing saline was injected intraperitoneally into transgenic mice, IL-5 production was augmented about five times within 24 h, and a distinctive Ly-1+ B cell population became apparent in the spleen after 5 d. IL-5 receptors were detected on those cells by monoclonal antibodies against IL-5 receptors. Another interesting finding in these transgenic mice was an increase in polyreactive anti-DNA antibodies of IgM class. It is suggested, therefore, that aberrant expression of the IL-5 gene may induce accumulation of Ly-1+ B cells and eosinophils. Furthermore, this IL-5 transgenic mouse can be a model mouse for eosinophilia, and we can determine the role of IL-5 in the differentiation of Ly-1+ B cells and eosinophils by using this mouse.

Expression of brain natriuretic peptide gene in human heart. Production in the ventricle.

Abstract: To elucidate the expression of the brain natriuretic peptide gene in the human heart, we have measured brain natriuretic peptide mRNA levels in hearts using the Northern blot hybridization method. Brain natriuretic peptide mRNA was present with a size of approximately 0.9 kb in the ventricle as well as in the atrium. The brain natriuretic peptide mRNA level in the ventricle was 52% of that in the atrium, whereas the atrial natriuretic peptide mRNA level in the ventricle was approximately two orders of magnitude lower than that in the atrium. Taking atrial and ventricular weights into account, the total amount of brain natriuretic peptide mRNA in the ventricle represented 77% of that in the whole heart. These results demonstrate that most of brain natriuretic peptide mRNA occurs in the ventricle, in contrast with atrial natriuretic peptide mRNA, which is present mainly in the atrium, indicating that the ventricle is a major production site of brain natriuretic peptide.

Predominant recognition of human T cell leukemia virus type I (HTLV-I) pX gene products by human CD8+ cytotoxic T cells directed against HTLV-I-infected cells.

Abstract: We established long-term cell lines of cytotoxic T lymphocytes (CTL) specific for human T cell leukemia virus type I (HTLV-I) from peripheral blood lymphocytes (PBL) of a patient with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), an HTLV-I-carrier with Sjogren syndrome, and an asymptomatic HTLV-I-carrier, by repeated stimulation with autologous HTLV-I-infected T cells in vitro. CTL derived from the patient with HAM/TSP expressed CD8 antigen, and their function was restricted by HLA-A2. They showed cytotoxic effects predominantly against the target cells expressing HTLV-I p40tax among the autologous B cell lines infected with vaccinia recombinants containing various HTLV-I genes which served as targets. These data are consistent with the previously reported findings that fresh PBL of HAM/TSP patients contain p40tax-specific CTL activity. Furthermore, CTL derived from the patient with Sjogren syndrome without neurological involvement also demonstrated cytotoxicity predominantly to p40tax. The cytotoxicity to the target cells experimentally expressing p40tax was blocked by unlabeled HTLV-I-infected cells possessing HLA-A2. HTLV-I-specific cytotoxicity was also inhibited by unlabeled B cells bearing p40tax. Thus, HTLV-I p40tax-specific cytotoxicity is mediated by the major CTL population activated by native HTLV-I antigens in patients with HAM/TSP or Sjogren syndrome. In contrast to the CTL of these patients, CTL similarly induced from the asymptomatic HTLV-I-carrier, which were highly cytotoxic to autologous HTLV-I-infected T cells, did not show significant levels of cytotoxicity to autologous B cells expressing p40tax.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal differentiation of tissue macrophage populations in 'osteopetrosis' (op) mice defective in the production of macrophage colony-stimulating factor.

Abstract: Examination of the op/op mouse disclosed marked reduction and abnormal differentiation of osteoclasts in the bones and of tissue-specific macrophages in various visceral organs and tissues. Most of these macrophages were immature as judged by ultrastructural criteria. In co-cultures of normal mouse bone marrow cells with fibroblast cell lines prepared from the lungs of the op/op mice, a defective differentiation of monocytes into macrophages was confirmed, supporting previous evidence that the fibroblast cell lines of the mutant mouse failed to produce functional macrophage colony-stimulating factor (M-CSF/CSF-1). In such co-cultures, however, a small number of macrophages apparently mature under the influence of granulocyte/macrophage colony-stimulating factor (GM-CSF) produced by the op/op fibroblast cell lines. In the mutant mice, the numbers of macrophages in the uterine wall and ovaries were severely reduced. Compared with the tissues of normal littermates, those of the mutants contained about 60% fewer macrophages in many tissues. This suggests that an M-CSF-independent population of macrophages is derived from granulocyte/macrophage-colony-forming cells (GM-CFC) or earlier hematopoietic progenitors.

The expression of c-kit protein during oogenesis and early embryonic development.

Abstract: The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor and was shown to be allelic with the white-spotting locus (W) of the mouse. Mutations at the W locus have pleiotropic effects on the development of hematopoietic stem cells, melanoblasts, and primordial germ cells. In order to elucidate the role of c-kit protein in gametogenesis and oocyte maturation, we have examined immunohistochemically the expression of c-kit in the ovaries of mice at late fetal and postnatal stages, and in early embryos. By the avidin-biotin-peroxidase (ABC) method using rat anti-mouse c-kit monoclonal antibody, the c-kit protein was detected in ovaries after the time of birth, but not before. The expression of c-kit was observed mainly on the surface of oocytes, but not in granulosa cells nor in interstitial regions. Oocytes of primordial to fully grown Graafian follicles showed the c-kit protein. When ovulation was induced by hCG, the expression of c-kit in ovulated unfertilized oocytes was weaker than in oocytes of Graafian follicles. In 1-cell embryos the c-kit protein was still observed, but with cell division its expression further decreased, and it was not detected in embryos of 4-cell, 8-cell, and morula stages. In summary, the highest expression of c-kit was observed on the surface of oocytes arrested in the diplotene stage of meiotic prophase. With ovulation and the resumption of meiotic maturation, its expression declined. These results suggest that the c-kit protein may play some role in meiotic arrest, oocyte growth, and oocyte maturation.

Staurosporine: an effective inhibitor for Ca2+/calmodulin-dependent protein kinase II.

Abstract: We investigated the effect of staurosporine on Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) purified from rat brain. (a) Staurosporine (10-100 nM) inhibited the activity of CaM kinase II. The half-maximal and maximal inhibitory concentrations were 20 and 100 nM, respectively. (b) The inhibition with staurosporine was of the noncompetitive type with respect to ATP, calmodulin, and phosphate acceptor (beta-casein). (c) Staurosporine suppressed the auto-phosphorylation of alpha- and beta-subunits of CaM kinase II at concentrations similar to those at which the enzyme activity was inhibited. (d) Staurosporine also attenuated the Ca2+/calmodulin-independent activity of the autophosphorylated CaM kinase II. These results suggest that staurosporine inhibits CaM kinase II by interacting with the catalytic domain, distinct from the ATP-binding site or substrate-binding site, of the enzyme and that staurosporine is an effective inhibitor for CaM kinase II in the cell system.

Japanese summer-type hypersensitivity pneumonitis. Geographic distribution, home environment, and clinical characteristics of 621 cases.

Abstract: A survey of hypersensitivity pneumonitis in Japan was carried out by nationwide questionnaire. A total of 835 cases of hypersensitivity pneumonitis was recognized during the last decade from 1980 to 1989. Of the 835 cases, 621 (74.4%) were summer-type hypersensitivity pneumonitis. The number of cases diagnosed doubled in the latter half of the 10-yr period. The residence of the patients was mostly in the western and southern parts of the country; the northernmost incidence was in Akita Prefecture at a latitude of 40 degrees north. Of the patients 86% experienced initial symptoms from June to September with a peak in July. Female patients were 2.0 times as numerous as male patients, probably as a result of more exposure to the offending antigen at home since 39.8% of the patients were female homemakers without an outside occupation. The frequency of family occurrence was 23.8%. The mean age of the patients' houses was 20.5 yr after building, and more than half had unsanitary conditions, such as shady, damp, or poorly ventilated rooms. Serum anti-Trichosporon cutaneum antibody activities were positive in 260 (99.2%) of the 262 cases examined. We conclude that summer-type hypersensitivity pneumonitis occupies the majority of hypersensitivity pneumonitis in the country and that to prevent the disease concentrated attention should be given to the home environment from the viewpoint of environmental medicine.

Tissue distribution, intracellular localization, and in vitro expression of bovine macrophage scavenger receptors.

Abstract: Macrophage scavenger receptors are trimeric membrane proteins implicated in the pathologic deposition of cholesterol in atherogenesis. The authors have studied the tissue distribution and intracellular localization of bovine scavenger receptors using monoclonal antibovine receptor antibody IgG-D2. The receptor proteins were detectable in macrophages of various organs and tissues, particularly Kupffer cells, alveolar macrophages, and macrophages in the spleen and lymph nodes. In the brain, perivascular macrophages were immunoreactive with IgG-D2. Fibroblasts, endothelial cells, smooth muscle cells, and dendritic cells such as epidermal Langerhans cells, interdigitating cells, or follicular dendritic cells, however, showed no immunoreactivity to IgG-D2. Immunoelectron microscopy showed localization of reaction products for these receptors on the cell surface, vesicles, and endosomes of macrophages. Transient expression of bovine scavenger receptors on cultured cells shows that scavenger receptors are mainly expressed in the endoplasmic reticulum, nuclear envelope, and Golgi apparatus of nonmacrophage cells and moved to the cell surface and endosomes of macrophagelike cells. These results indicate that efficient intracellular transport of scavenger receptors in macrophages is mediated by a macrophage-specific transport system.

Charge measurements on particle fallout from a volcanic plume

Abstract: THE aggregation of fine ash particles has an important role in controlling the deposition of widely dispersed volcanic ash. Here we report measurements of electrical charge on ash particles falling from the eruption columns of Sakurajima volcano in Japan. Absolute charge to mass (q/m) ratios ranged from +3 to +6x10-4C kg-1 and from -2 to -5 x 10-4 C kg-1. The average q/m ratio ranged from +2 to +5x10-5 C kg-1. The generation of electrostatic charge may result from triboelectric effects in the plume, or from fracture-induced charging. Charge on ash particles provides attractive forces large enough to cause the aggregation of smaller particles and the adhesion of dust to larger particles. Particle aggregation may explain the polymodal grain-size distributions commonly found in ash-fall deposits, and the proximal deposition of fine ash, as well as the distal deposition of coarse particles in these deposits. Our data suggest that electrostatic effects greatly influence the dispersal and deposition of ash during explosive volcanic eruptions.

The role of interleukin-5 in protective immunity to Strongyloides venezuelensis infection in mice.

Abstract: We depleted or neutralized interleukin-5 (IL-5) and IL-5 receptor of C57BL/6 mice, using rat anti-murine IL-5 monoclonal antibody (NC17) and anti-murine IL-5 receptor monoclonal antibody (H7). Mice treated with these monoclonal antibodies were infected with Strongyloides venezuelensis larvae. The time-course of faecal egg output and peripheral eosinophilia were monitored. In a primary infection, anti-IL-5 treatment did not affect faecal egg output, although the eosinophil count in peripheral blood was markedly reduced. There was no difference in intestinal worm burden or faecal egg output between anti-IL-5 treated and non-treated mice. In a secondary infection, worms were expelled from the small intestine of anti-IL-5-treated mice as well as from non-treated mice. Worm recovery from the lungs of mice treated with either anti-IL-5 or anti-IL-5 receptor monoclonal antibody was the same as that of normal controls. However, a marked reduction in worm recovery was observed in re-infected mice that had not been treated with monoclonal antibodies. Treatment with anti-IL-5 or anti-IL-5 receptor monoclonal antibody suppressed blood and tissue eosinophilia. Thus the results suggested that the host's protective immunity against tissue-migrating larvae was IL-5-dependent but intestinal immunity was not.

Exon skipping by mutation of an authentic splice site of c-kit gene in W/W mouse

Abstract: The murine mutation dominant white spotting (W) is in the proto-oncogene, c-kit. The receptor tyrosine kinase encoded by this gene has pleiotropic effects on murine development including hemopoietic cells, pigment cells, and germ cells. In this study, mutation in W homozygous mouse was identified as a single base substitution (GT----AT) at the 5'-splice donor site of the exon which encodes the transmembrane domain. Two types of aberrant exon skipping resulted from this mutation, occurred in a tissue specific manner. Either transcript lost the exon coding for transmembrane region and therefore the product might not be functional for signal transduction. Any unusual cryptic splice sites were not activated by this mutation as beta-globin gene in beta-thalassaemia. In addition, twelve base pair sequence of the 3'-end of the exon prior to the exon coding for transmembrane domain was found to be alternatively spliced. These findings should provide the genetic base for not only the receptor function but the splicing mechanism.

An artificial endocrine pancreas--problems awaiting solution for long-term clinical applications of a glucose sensor.

Abstract: The artificial endocrine pancreas is a feedback controlled system regulating insulin delivery on a minute-by-minute basis according to measured blood glucose levels. The bedside-type artificial endocrine pancreas has been proven to be useful not only as a therapeutic tool for diabetic patients but also as an elegant research tool for investigating the pathophysiology of the disease. Recently, a wearable-type, closed-loop system has been developed, of which the breakthrough was the establishment of a needle-type glucose sensor. However, for the long-term clinical use of needle-type glucose sensors, several obstacles remain to be solved, such as oxygen dependency, biocompatibility of the membrane, etc. The most promising method for the non-invasive determination of blood glucose is infrared spectroscopy. The trend in the development of a closed-loop glycemic control system which enables perfectly physiological glycemic regulation on a long-term basis is directed to an implantable device. Much research is being conducted to realize such devices.

Identification of the second subunit of the murine interleukin-5 receptor: interleukin-3 receptor-like protein, AIC2B is a component of the high affinity interleukin-5 receptor.

Abstract: Murine interleukin-5 (IL-5) binds to its receptor with high and low affinity. It has been shown that the high affinity IL-5 receptor (IL-5-R) is composed of at least two membrane protein subunits and is responsible for IL-5-mediated signal transduction. One subunit of the high affinity IL-5-R is a 60 kDa membrane protein (p60 IL-5-R) whose cDNA was isolated using the anti-IL-5-R monoclonal antibody (mAb), H7. This subunit alone binds IL-5 with low affinity. The second subunit does not bind IL-5 by itself, and is expressed not only on IL-5-dependent cell lines but also on an IL-3-dependent cell line, FDC-P1. Expression of the p60 IL-5-R cDNA in FDC-P1 cells, which do not bind IL-5, reconstituted the high affinity IL-5-R. We have characterized the second subunit of the IL-5-R by using another anti-IL-5-R mAb, R52.120, and the anti-IL-3-R mAb, anti-Aic-2. The anti-Aic-2 mAb down-regulated binding of IL-5 to an IL-5-dependent cell line, Y16. Both R52.120 and anti-Aic-2 mAbs recognized membrane proteins of 130-140 kDa expressed on FDC-P1 and Y16 cells. The R52.120 mAb recognized both murine IL-3-R (AIC2A) and its homologue (AIC2B) expressed on L cells transfected with suitable cDNAs. The high affinity IL-5-R was reconstituted on an L cell transfectant co-expressing AIC2B and p60 IL-5-R, whereas only the low affinity IL-5-R was detected on a transfectant co-expressing AIC2A and p60 IL-5-R.(ABSTRACT TRUNCATED AT 250 WORDS)

Difference in the phenotypes of bronchoalveolar lavage lymphocytes in patients with summer-type hypersensitivity pneumonitis, farmer's lung, ventilation pneumonitis, and bird fancier's lung: Report of a nationwide epidemiologic study in Japan

Abstract: We performed a nationwide epidemiologic study of hypersensitivity pneumonitis (HP) in Japan by questionnaire and found that 835 cases of HP were recognized during the 1980s; 74.4% were summer-type HP, 8.1% farmer's lung, 4.3% ventilation pneumonitis, 4.1% bird fancier's lung, 2.3% other types, such as chemical worker's lung, and 6.8% of unknown causative agent. It was found that the CD4/CD8 ratios of bronchoalveolar lavage (BAL) lymphocytes were significantly different with the type of disease. The ratio was 0.6 +/- 0.1 (mean +/- SEM) in summer-type HP (N = 271), 4.4 +/- 0.7 in farmer's lung (N = 22), 1.6 +/- 0.3 in ventilation pneumonitis (N = 19), and 2.0 +/- 0.5 in bird fancier's lung (N = 19). In farmer's lung, the CD4/CD8 ratio in smokers was 6.2 +/- 1.9 (N = 6) in contrast with 3.4 +/- 0.7 for nonsmokers (N = 16) (p less than 0.05). It has been generally considered that the phenotypes of BAL lymphocytes in patients with HP are predominately CD8 cells. Our present results, however, indicate that the phenotypes of BAL lymphocytes vary with the type of HP, probably depending on factors such as causative agent, smoking, or staging of the disease.

Prognostic factors in the treatment of hepatocellular carcinoma with transcatheter arterial embolization and arterial infusion.

Abstract: From January 1986 to December 1988, a prospective trial of transcatheter arterial treatment was carried out for hepatocellular carcinoma (HCC). Two hundred seventy-five patients were included. Okuda's staging system was employed. Patients with Stage I and II HCC were treated by transcatheter arterial embolization (TAE) with a gelatin sponge containing an anti-cancer agent (protocol 1a); a gelatin sponge and iodized oil mixed with an anti-cancer agent (protocol 1b); or iodized oil mixed with an anti-cancer agent (protocol 2). Patients with Stage III HCC were treated with iodized oil with anti-cancer agent (protocol 2). As an exception, patients with an unsuccessful superselective catheterization into the proper hepatic artery by Seldinger technique or obstruction of the main trunk of the portal vein were treated with percutaneous transcatheter arterial infusion into the common hepatic artery regardless of stage (protocol 3). Tumor type and extension, area of tumor involvement, portal vein involvement, method of treatment, and presence of ascites and icterus were found to be the significant factors for an initial response to therapy. Treatment method was the most important factor. Respective survival rates at 1 and 2 years were 70.9% and 55.3% for protocol 1a; 62.3% and 43.8% for protocol 1b; 37.8% and 18.3% for protocol 2; and 16.5% and 0% for protocol 3. Many factors proved to significantly influenced prognosis; however, tumor type had the most important prognostic significance followed by AFP value, ascites, treatment protocol, and area of tumor involvement.

Normal and abnormal pituitary glands: gadopentetate dimeglumine-enhanced MR imaging.

Abstract: Dynamic magnetic resonance (MR) imaging with a 1.5-T superconductive unit was used in the evaluation of nine normal pituitary glands and 10 pituitary adenomas, including four microadenomas and six macroadenomas. Seven to 10 images were obtained every 20-30 seconds with use of the spin-echo technique after rapid injection of gadopentetate dimeglumine. The earliest contrast material enhancement of normal structures was seen in the infundibulum and posterior lobe of the pituitary gland at 20 seconds, followed by gradual contrast material enhancement of the anterior lobe of the pituitary gland from the junction of the infundibulum to the peripheral portion of the anterior lobe of the pituitary gland within 80 seconds after gadopentetate dimeglumine injection. The peak enhancement of pituitary adenomas occurred at 60-200 seconds, usually after the most marked enhancement of the normal pituitary gland. Microadenomas are best visualized at earlier phases of gadopentetate dimeglumine-enhanced dynamic imaging, with signal intensity lower than that seen on images of normal pituitary glands.