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Biomedical subjects

T Shibata

Publications and source records attributed to T Shibata.

At least 721 records · Page 40Linked to original sources
PubMed1990

Interleukin 3 perfusion prevents death due to acute anemia induced by monoclonal antierythrocyte autoantibody.

We have evaluated the therapeutic activity of rIL-3, in comparison with recombinant granulocyte-macrophage CSF (rGM-CSF) and recombinant erythropoietin (rEpo), on a lethal form of acute anemia induced by a single injection of a monoclonal IgG1 anti-mouse RBC (MRBC) autoantibody. Continuous perfusion of rIL-3 before the administration of anti-MRBC mAb prevented animals from the death due to anemia with a rapid recovery in greater than 90% of the cases, while only partial protection (one third of the cases) was obtained by rEpo perfusion, and no protection by rGM-CSF. Since the anti-MRBC mAb induced a marked agglutination of RBC in spleens and livers, and subsequent hemodynamic failure may be an additional contributing factor to the animals' death, the activation of Fc gamma receptor-dependent phagocytosis by rIL-3, as well as the increased number of monocytes/macrophages resulting from rIL-3 perfusion, may also facilitate rapid elimination of these agglutinated RBC, resulting in the further amelioration of the animals' survival. Our results suggest that the therapeutic effect of rIL-3 on anti-MRBC autoantibody-induced anemia is achieved by: (a) its activity to promote the growth and differentiation of erythroid progenitors responsive to Epo and of monocyte/macrophage lineage; and (b) its activity to enhance the phagocytic activity of macrophages to efficiently eliminate agglutinated RBC in spleens and livers.

Acute Disease↗
PubMed1990

Usefulness of a new tumor marker, Span-1, for the diagnosis of pancreatic cancer.

Levels of serum Span-1, a new tumor marker for pancreatic cancer, were assayed in 64 patients with pancreatic cancer, 90 with nonpancreatic cancer, and 254 with nonmalignancies, involving 55 healthy controls. Furthermore, Span-1 was compared with other tumor markers (CA19-9, carcinoembryonic antigen [CEA], and DU-PAN-2). Frequency of elevated Span-1 levels was 81.3% in pancreatic cancer. False-positive elevations of serum Span-1 levels were rather common in liver cirrhosis (53.8%) and chronic hepatitis (26.3%). The sensitivity, specificity, and efficiency of this assay for pancreatic cancer, was 81.3%, 75.6%, and 76.5% against all subjects without pancreatic cancer, respectively. In comparison with other markers, sensitivity of Span-1 tended to be highest with similar specificity to those of CA19-9 and CEA. The Span-1 assay has a high sensitivity and specificity for pancreatic cancer. It is almost equivalent to CA19-9 assay. However, this assay is not specific for chronic liver diseases.

Adult↗
PubMed1990

Characteristics and natural history of abnormal atrial rhythms in left isomerism.

The object of this study is to document variation in atrial pacemaker rate and P-wave axis, and to clarify the natural history of abnormally slow atrial rhythms in left isomerism. Standard 15-lead electrocardiograms of 50 patients with left isomerism were retrospectively studied. On the average, 9 electrocardiograms covering 7 years for each patient were available. For comparison, atrial rhythms in patients with right isomerism and in those with situs solitus and 5 representative congenital cardiac conditions were studied with the same study protocol. In left isomerism, atrial rhythm with constantly normal P-wave axis was exceptional and the presence of atrial rhythm with abnormal P-wave axis was the rule. The most frequent abnormal mean frontal P-wave axis was between -30 and -90 degrees, recorded in 70%. Slow atrial rates below the second percentile were observed in 50%, either transiently and recurrently (in 40%), or persistently (in 10%), and were associated with junctional escape in 42%. The number of patients with slow atrial rate increased with age. In right isomerism, multiple atrial rhythms were also frequent, but slow atrial rhythms was present in only 4%. Multiple atrial rhythms or bradycardia associated with junctional escape were rare in the group of patients with congenital heart disease and situs solitus. It is concluded that multiplicity and progressive slowing of the atrial rhythm are characteristic in patients with left isomerism.

Abnormalities, Multiple↗
PubMed1990

G-CSF enhanced granulocyte production in a child with severe neutropenia in the setting of fatal virus-associated hemophagocytic syndrome.

A 14-year-old boy with fatal varicella zoster virus-associated hemophagocytic syndrome (VAHS) was treated with recombinant human granulocyte colony-stimulating factor (G-CSF) based on the finding that the patient had severe neutropenia and possible bacterial superinfection. Support for the G-CSF therapy in VAHS is provided by the recent reports that G-CSF is relatively specific for the granulocyte lineage; it would not activate mature monocyte/macrophage/histiocyte lineage in VAHS, where the most striking morphologic feature is histiocytic hyperplasia with hemophagocytosis. He responded well to G-CSF with an elevation of neutrophil counts. There were no effects on other blood cells. The result indicates that G-CSF is useful to increase granulocyte production in severe neutropenia, even in the setting of fatal VAHS.

Adolescent↗
PubMed1990

Variable region sequences of pathogenic anti-mouse red blood cell autoantibodies from autoimmune NZB mice.

New Zealand Black (NZB) mice spontaneously develop a severe autoimmune hemolytic anemia due to the production of anti-mouse red blood cell (MRBC) autoantibodies. The contribution of variable region genes and somatic mutations in the pathogenicity of anti-MRBC autoantibodies was investigated by mRNA sequencing of eight NZB anti-MRBC monoclonal autoantibodies, among which five are capable of inducing anemia in BALB/c mice. Here we report that at least three VH gene families (J558, J606 and 3609) and five Vchi subgroups (V chi 8, 9, 19, 21 and 28), in combination with several D, JH and Jchi gene segments, encode anti-MRBC autoantibodies. Thus, the NZB anti-MRBC autoantibodies, whether pathogenic or not, are encoded by a large number of immunoglobulin gene elements and by members of known VH and Vchi gene families with preferential usage of VH gene families most distal to the D regions. The presence of several mutations in the JH gene segments of both IgM and IgG anti-MRBC autoantibodies, whether pathogenic or not, strongly suggests that their VH regions may be highly mutated and that the mechanism of somatic diversification might be important in the generation of anti-MRBC autoantibodies. Our results support the idea that anti-MRBC autoimmune responses are likely to be generated by an antigen-driven mechanism.

Amino Acid Sequence↗
PubMed1990

5-Azacytidine inhibits the lpr gene-induced lymphadenopathy and acceleration of lupus-like syndrome in MRL/MpJ-lpr/lpr mice.

MRL/MpJ-lpr/lpr mice spontaneously develop a lupus-like autoimmune disorder characterized by massive proliferation of T cells and rapidly fatal immune complex glomerulonephritis. We evaluated the therapeutic effect of 5-azacytidine (5AC), a cytidine analogue known as an inhibitor of DNA methylation, in MRL/MpJ-lpr/lpr mice. Intraperitoneal injection of 5AC (50 micrograms, twice a week) starting from 6 weeks of age retarded the development of lymphadenopathy and autoimmune syndrome. Its beneficial effects included: (a) increased life-span, (b) diminution of lymphadenopathy and splenomegaly, (c) reduction in circulating levels of autoantibodies such as anti-DNA and rheumatoid factors, and (d) suppression of lupus glomerulonephritis. However, similar treatment in BALB/c mice did not affect the development of IgG anti-human IgG antibody responses. These results suggest that the protective effect of 5AC is related to the inhibition of the lpr gene-induced T cell proliferation, thereby suppressing the autoimmunity-accelerating effect mediated by the lpr gene.

Animals↗
PubMed1990

Spontaneous production of anti-mouse red blood cell autoantibodies is independent of the polyclonal activation in NZB mice.

New Zealand Black (NZB) mice spontaneously develop an autoimmune hemolytic anemia together with a markedly increased production of polyclonal antibodies. The spontaneous generation of anti-mouse red blood cells (MRBC), anti-bromelain-treated MRBC (BrMRBC) and anti-DNA autoantibodies was compared to the polyclonal antibody formation in irradiated (800 rad) 2-month-old NZB mice reconstituted with bone marrow cells (BMC) from 2- or 10-month-old NZB mice. The injection of 10-month-old NZB BMC markedly accelerated the mortality rate in parallel with the progressive increase of anti-MRBC and anti-BrMRBC autoantibody production, but the spontaneous production of polyclonal IgM antibodies and anti-DNA autoantibodies was completely abolished down to the levels of non-autoimmune mice. In contrast, mice reconstituted with 2-month-old NZB BMC exhibited neither the acceleration of anemia nor the lack of polyclonal antibody production. These results strongly suggest that the spontaneous production of anti-MRBC autoantibodies, including anti-BrMRBC autoantibodies, in the NZB mouse occurs independently of the polyclonal B cell activation, and that they result from a specific immune stimulation, while the anti-DNA autoantibody production is a consequence of polyclonal antibody formation.

Anemia, Hemolytic, Autoimmune↗
PubMed1990

Aged-onset Kienböck's disease.

Kienböck's disease with onset after 50 years of age was studied. Of 127 patients with Kineböck's disease seen over the past 30 years, the cases of 15 (12 female, 3 male) were analyzed. The average age of onset was 58.3 years. Five specimens were obtained operatively in which necrosis of the lunate bone mixed with empty lacunae was identified, as was bony remodelling. Ulnar variance in the aged diseased group (group A) was smaller than that of the aged control group (group C). Moreover, it was noteworthy that the variance among aged controls (group C) was higher than among the young controls (group D). The metacarpal index of the patients with aged-onset Kienböck's disease was markedly lower than that of the young. Considering the increase of ulnar variance with age, the persistence of minus variance and the presence of osteoporosis might make the lunate bone susceptible to injury.

Age Factors↗
PubMed1990

Prevention of experimental acute pancreatitis by intraduodenal trypsin inhibitor in rat.

To confirm that trypsin activity is a most important initiating factor in closed duodenal loop pancreatitis in rats, we observed the course of acute pancreatitis when trypsinogen activation was inhibited by intraduodenal infusion of a potent synthetic trypsin inhibitor (TI, nafamostat mesilate) but the other conditions were left unchanged. Intraduodenal and intrapancreatic trypsinogen activation was inhibited for 16 hr after the intraduodenal infusion of the inhibitor, although elevation of serum amylase and immunoreactive trypsin and pancreatic trypsinogen remained similar both in the TI and control groups. The mortality decreased from 44% (control) to 4% (TI) at 48 hr after establishing the model. Active trypsin in duodenal reflux is an initiating factor for further development of acute pancreatitis in the closed loop model, and inhibition of the initial activation of trypsinogen has a favorable effect on acute pancreatitis even if other deleterious factors remain unchanged.

Acute Disease↗
PubMed1990

Pathomorphological changes in rat brain choroid plexus due to administration of the amine-curing agent, bis(4-amino-3-methylcyclohexyl)methane.

Repeated oral administration of an amine-curing agent for epoxy resin, bis(4-amino-3-methylcyclohexyl)methane, gave rise to severe damage in the choroid plexus of rat brain. The damaged epithelium presented varying degrees of swelling and hydropic vacuolation on light microscopy, and varying numbers of vacuoles and inclusion bodies, frequently with lamellar structure, on transmission electron microscopy. Scanning electron microscopy of the choroid plexus disclosed some irregularity in the size of epithelial cells and occasional loss of microvilli. These changes in the choroid plexus were closely correlated with the dosage of the agent administered and the period of administration. In spite of the severe changes in the choroid plexus, no neurological abnormalities were observed in the animals during the experimental period.

Animals↗
PubMed1990

Prospective trial for early detection of pancreatic cancer by elevated serum immunoreactive elastase.

Early detection of pancreatic cancer was prospectively evaluated by measuring serum immunoreactive elastase (IRE) in 722 patients in two hospitals during the past 18 months. Patients included in the study were over 40 years of age and had symptoms suggestive of pancreatic disease such as upper abdominal pain, discomfort or mass, jaundice, weight loss, or diabetes. Among the 722 patients, 171 exhibited elevation of serum IRE. Pancreatic diseases were subsequently found in 42% of the 171 patients. Pancreatic cancer was found in 22 patients, among which 17 had elevated serum IRE. Among the 17 pancreatic cancer patients with elevated IRE, 10 underwent radical resection of the cancer but in none of the five patients with normal serum IRE could radical resection be carried out. Three of the 10 patients had a small cancer less than 2 cm in diameter and two of them survived for more than three years. Patients over 40 or 45 years of age complaining of upper abdominal pain of recent onset that cannot be explained by diseases other than that of the pancreas would be candidates for measurement of serum elastase, and this is an effective way to detect pancreatic cancer at an early stages.

Adult↗
PubMed1990

KIH-802, an acetohydroxamic acid derivative of 2-nitroimidazole, as a new potent hypoxic cell radiosensitizer: radiosensitizing activity, acute toxicity, and pharmacokinetics.

The radiosensitizing activity, acute toxicity, and pharmacokinetics of a new hypoxic cell radiosensitizer, potassium 2-nitroimidazole-1-acetohydroxamate (KIH-802), were compared with those of misonidazole (MISO) and etanidazole (SR-2508). The radiosensitizing activity of KIH-802 was slightly higher than that of MISO and SR-2508 in vitro and was similar to or slightly higher than that of MISO or SR-2508 in vivo. The acute toxicity of KIH-802 was slightly higher than that of MISO. The concentrations of KIH-802 in the brains and peripheral nerves of mice were as low as those of SR-2508 and lower than those of MISO.

Animals↗
PubMed1990

Plasma osmolality and exocrine pancreatic secretion.

To confirm the influence of plasma osmolality on exocrine pancreatic secretion, hypertonic saline (4% saline) was given intravenously to dogs with gastric and pancreatic fistulae. Intravenous administration of hypertonic saline caused a reduction of pancreatic juice flow and bicarbonate output, but did not alter protein output stimulated by secretin and cerulein. The changes of pancreatic juice flow(X) exhibited negative correlations with the changes in plasma osmolality(Y) (Y = -2.2X + 6.4, r = -0.74, p less than 0.01). Plasma osmolality and plasma vasopressin level were measured simultaneously. Plasma osmolality was elevated from 292 to 315 mOsm/kg with concurrent increase of plasma vasopressin level from 2.4 to 19.6 pg/mL. On the other hand, exogenous administration of vasopressin inhibited pancreatic juice flow and bicarbonate output dose-dependently. In conclusion, elevation of plasma osmolality decreased exocrine pancreatic secretion stimulated by secretin and cerulein, and vasopressin may play an important role in its mechanism.

Animals↗
PubMed1990

Pulse NMR study of the interaction of calcium ion with dipalmitoylphosphatidylcholine lamellae.

Molecular motion of dipalmitoylphosphatidylcholine (DPPC)/CaCl2 lamellae in a gel phase was studied by pulse NMR. Proton 1/T1 for DPPC in a gel phase showed that the rate of reorientation about the long axis of the lipid molecule decreased gradually from 0 to 500 mM CaCl2. At 10-50 mM CaCl2 the correlation time reached the value of the inverse Larmor frequency (approx. 2.6 ns). A proton NMR absorption spectrum and a spin-pair-dipolar-echo (SPDE) decay showed that the second moment in the hydrocarbon chain region decreased below about 1 mM CaCl2 and increased from 1 to 500 mM CaCl2. The second moment in the polar head group increased gradually with an increase in the CaCl2 concentration. The increase in the second moment at the high CaCl2 concentrations was attributed to an increase in the order parameters of the segments both in the polar head group and in the hydrocarbon chain region. At the lower CaCl2 concentrations, however, calcium ion possibly induced disorder in the lamellae which led to a decrease in the order parameter in the hydrocarbon chain region.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1990

Adrenaline increases the rate of cross-bridge cycling in rat cardiac muscle.

To characterize the myocardial cross-bridge dynamics in catecholamine-induced positive inotropic state, we studied the effects of adrenaline (6 X 10(-6) M) on the transient central segment length (SL) response to step decrease in tension in rat right ventricular papillary muscle in barium contracture. The time course of this response is thought to reflect the kinetics of actin-myosin interaction. The muscle was released stepwise from the steady contracture tension (Tc) to new steady tension levels (Tr) of varying magnitudes at 22 degrees C. When the tension decrease was less than 0.7 Tc, the SL transient responses comprised, in most cases, four phases. The first phase was a rapid and minute shortening during tension reduction; the second was a slow further shortening; the third, a slow lengthening; and the fourth, an extremely slow shortening toward a new steady length under the new tension. Adrenaline showed almost no effect on Tc and the amplitude of SL transients, but markedly reduced the duration of the second (D2) and third (D3) phases of SL transient regardless of the amplitude of tension reduction. The reduction of duration was 14 +/- 3% in D2 and 26 +/- 5% in D3 at Tr/Tc of 0.84 +/- 0.03 on the average (mean +/- S.D.) in nine preparations. The velocity measured from the quasi-steady SL shortening in the second phase increased with the addition of adrenaline, regardless of the amplitude of tension reduction. The increase in the shortening velocity was 16 +/- 6% (mean +/- S.D., n = 9) at Tr/Tc of 0.18 +/- 0.04. These results suggest that adrenaline increases the rate of cross-bridge cycling in cardiac muscle independent of activation level.

Animals↗
PubMed1990

Cryoglobulinemia induced by a murine IgG3 rheumatoid factor: skin vasculitis and glomerulonephritis arise from distinct pathogenic mechanisms.

MRL-lpr/lpr mice spontaneously develop a lupus-like syndrome characterized by immunopathological manifestations such as necrotizing vascular lesions of ear tips and severe glomerulonephritis. Similar skin vascular and glomerular lesions associated with cryoglobulinemia can be induced in normal mice by injection of a monoclonal antibody (mAb)--6-19 (gamma 3 heavy chain and kappa light chain), exhibiting both cryoglobulin and anti-IgG2a rheumatoid factor (RF) activities--derived from the MRL-lpr/lpr autoimmune mouse. To determine the role of RF and/or IgG3 Fc fragment-associated cryoglobulin activities in 6-19 mAb-induced tissue lesions, a 6-19-J558L hybrid mAb (gamma 3 heavy chain and lambda 1 light chain) was produced by fusion between the 6-19 hybridoma and the J558L myeloma. Here we report that the 6-19-J558L hybrid mAb, which loses the RF activity but retains the cryoglobulin activity, fails to induce skin vascular lesions. However, it is still able to provoke glomerular lesions identical to those caused by the 6-19 mAb. Further, we have observed that the depletion of the corresponding autoantigen, IgG2a, in mice by treatment with anti-IgM antisera from birth also prevents the development of skin but not glomerular lesions. Our results indicate that both RF and cryoglobulin activities of the 6-19 mAb are required for the development of skin vasculitis, but its cryoglobulin activity alone is sufficient to cause glomerular lesions. In addition, cDNA cloning and sequencing of the 6-19 mAb has revealed that the 6-19 kappa light chain variable region amino acid sequence is encoded in a germ-line configuration, suggesting that immunoglobulin variable region germ-line genes could contribute to the generation of pathogenic autoantibodies.

Animals↗
PubMed1990

Monoclonal anti-erythrocyte autoantibodies derived from NZB mice cause autoimmune hemolytic anemia by two distinct pathogenic mechanisms.

In vivo pathological manifestations of eight monoclonal anti-mouse red blood cell (MRBC) autoantibodies obtained from unmanipulated NZB mice were determined in BALB/c mice. Three (two IgG1 and one IgG2a) of four IgG monoclonal antibodies (mAb) and two of four IgM mAb were able to induce anemia following their i.p. injection. All five pathogenic anti-MRBC mAbs reacted only with MRBC, whereas non-pathogenic anti-MRBC mAbs showed binding to different species of RBC. Competition studies suggested the presence of at least two distinct epitopes recognized by our pathogenic anti-MRBC mAb. Histological examinations revealed that anemia resulted from either marked sequestration of agglutinated MRBC in spleens and livers or erythrophagocytosis, most remarkably by Kupffer cells in livers. This difference was correlated with the ability of each mAb to mediate Fc receptor-dependent phagocytosis by macrophages. The absence of complement-mediated hemolysis in vitro and the development of anemia in C5-deficient or C3-depleted mice indicated a minor role, if any, for complement-mediated lysis in the anemia induced by our anti-MRBC mAb. Our results suggest that (i) at least two different pathogenic epitopes are implicated in autoimmune hemolytic anemia; and (ii) sequestration of agglutinated MRBC in spleens and livers and Fc receptor-dependent phagocytosis, but not complement-mediated hemolysis, are the major mechanisms for the development of autoimmune hemolytic anemia.

Anemia, Hemolytic, Autoimmune↗