Biomedical subjects

K Kitano

Publications and source records attributed to K Kitano.

At least 109 records · Page 6Linked to original sources

PubMed1993

Tumor necrosis factor-dependent production of human immunodeficiency virus 1 in chronically infected HL-60 cells.

Tumor necrosis factor (TNF) may play a central role in proviral activation and release from latency in cells infected with the human immunodeficiency virus (HIV). We studied viral production and its relation to TNF in a HL-60 cell line (J22-HL-60) infected with a monocytotropic strain of HIV-1JR-FL. Viral production was stimulated to similar levels by TNF, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Production of the virus was not suppressed by 3'-azido-3'-deoxythymidine (AZT), indicating that viral production was not caused by superinfection. Low concentrations of TNF (0.1 ng/mL) induced viral production with a short lag period of 8 hours, and this proviral activation was specifically suppressed by anti-TNF antibodies. However, induction of virus production by 1,25(OH)2D3 showed an extended lag period of 2 to 3 days. The effect of 1,25(OH)2D3 on virus production was also blocked by anti-TNF antibodies, which suggests the direct participation of TNF in this process. TNF accumulated in the culture supernatant of cells stimulated with 1,25(OH)2D3 with a kinetics consistent with its involvement in the action of 1,25(OH)2D3 on viral production. The J22-HL-60 cell line produced low levels of virus when cultured in the absence of an external stimulus; however, this basal viral production was suppressed greater than 80% in the presence of anti-TNF antibodies. Corresponding low levels of TNF were detected in the culture supernatants. Viral production decreased slowly with increasing passage of the cells, and no virus was detected in the supernatants of cells maintained in culture for several months. Concomitantly, TNF was no longer detected in the supernatant of these cells, which suggests that endogenous autocrine production of TNF drives viral production in the unstimulated cells. However, viral production was stimulated in these cells by low concentrations (0.1 ng/mL) of added TNF. These results argue for a central role for TNF in HIV proviral activation in chronically infected myeloid cells.

Calcitriol↗

PubMed1993

Eosinophilia in myelodysplastic syndrome with a (12;21)(q23;q22) translocation.

Cytogenetic analysis of bone marrow (BM) cells from a patient with myelodysplastic syndrome (MDS) associated with eosinophilia showed a 45,XY,t(12;21)(q23;q22), -17 karyotype. We performed clonal and suspension cultures using the patient's BM mononuclear cells to clarify the mechanism of eosinophilia. Eosinophil colonies formed in the presence of interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF), but not in the presence of IL-3. When BM cells were cultured in suspension in the presence of IL-5, they differentiated to mature eosinophils, and chromosome analysis identified the 45,XY,t(12;21)(q23;q22), -17 karyotype in all metaphases. The patient's serum did not stimulate eosinophil proliferation or differentiation in comparison with normal serum, however, these data suggest that the abnormal clone with 45,XY,t(12;21)(q23;q22), -17 karyotype may have an increased responsiveness to IL-5 and GM-CSF, resulting in eosinophilia.

Aged↗

PubMed1993

Transfusion-associated graft-versus-host disease in an immunocompetent patient following accidental injury.

We report a case of transfusion-associated graft-vs.-host disease (TA-GVHD) in a previously healthy, 58 year old Japanese man following an accidental injury. Despite intensive treatment, the patient died 22 days after the transfusion. Although many cases of fatal TA-GVHD have been reported in immunocompetent patients, only two are known to have developed this disorder unrelated to a surgical procedure. This is the first such case to be confirmed by HLA typing. Our report suggests that TA-GVHD can occur even in a healthy, immunocompetent recipient. Thus, it seems necessary to establish guidelines for the irradiation of cellular blood products before transfusion.

Accidental Falls↗

PubMed1993

cAMP stimulates human immunodeficiency virus (HIV-1) from latently infected cells of monocyte-macrophage lineage: synergism with TNF-alpha.

The present experiments were designed to study whether GTP binding protein activation and the resulting cAMP plays any role in HIV replication. The results showed that cholera toxin (CT) enhanced HIV replication dose dependently in myelo-monocytic cell lines latently infected with HIV-1, U1 and J22HL-60. Three- to 4-fold enhancement of virus production was observed in U1 cells and 4- to 11-fold enhancement in J22HL-60 cells 4 days after treatment with 100 ng/ml of CT. The increment of intracellular cAMP accumulation was parallel with HIV augmentation by CT in both cells. Even at the low concentration 0.1 ng/ml, TNF enhanced virus production to about an 80-fold higher level than the untreated U1 control cells as described previously (11). However, a synergistic effect (80- to 238-fold enhancement) was observed, when TNF-alpha and CT were added together to U1 cells. Similar synergism was seen in J22HL-60 cells. HIV antigen positive cells and gp120 expression were also increased to a similar degree. Phosphodiesterase inhibitor IBMX had no effect on HIV production alone, but potentiated HIV induction by CT and TNF. Adenylate cyclase activator, forskolin (FK), at 100 microM also significantly augmented HIV production (> 4-fold) and potentiated TNF induction in J22HL-60 and U1 cells. On the other hand, CT did not show any effect on HIV replication as well as TNF induction in HIV-1-infected T cell line. Northern blot experiment confirmed that this enhancement was mediated through the activation of HIV transcription. These data suggest that cAMP augments HIV replication and potentiates TNF induction in a particular monocyte-macrophage system.

1-Methyl-3-isobutylxanthine↗

PubMed1993

Establishment of Epstein-Barr virus-associated lymphoma cell line SUBL with t(2;3)(p11;q27) from a liver transplant patient.

A new lymphoma cell line, designated SUBL, was established from a Japanese patient with Epstein-Barr virus (EBV)-associated lymphoma, which developed during FK 506 therapy after liver transplantation. This cell line has undergone 80 passages over a period of 22 months. The cultured cells were positive for CD19, CD20, CD21, CD22, CD23, and HLA-DR, and negative for CD10 and surface immunoglobulins. Immunoglobulin gene analysis revealed rearrangements of JH and JK. T-cell antigens or T-cell receptor gene rearrangements were not observed on the cell line. The SUBL cells were positive for Epstein-Barr virus nuclear antigen (EBNA). The EBV genome was detected in the original tissue and the cell line by the in situ hybridization method. These data indicate that this cell line represents the B-cell lineage at a pre-B-cell stage. SUBL cells showed successful heterotransplantation to mice with severe combined immunodeficiency (SCID). Chromosomal analysis revealed the karyotype 46,XY,t(2;3)(p11;q27). Molecular studies showed that c-myc, N-myc, and bcl-2 were not rearranged. This cell line will provide a useful in vitro system to study the relationship between chromosomal abnormalities and the activation of cellular oncogenes.

Animals↗

PubMed1993

Treatment of acute monoblastic leukaemia by combination of recombinant human macrophage colony-stimulating factor and low dose of ara-C.

We present a patient with acute monoblastic leukaemia (AMoL) who achieved a complete remission on combination therapy with macrophage colony-stimulating factor (M-CSF) and low dose of cytosine arabinoside (ara-C). This 26-year-old man was admitted with a relapse of AMoL which proved refractory to several chemotherapeutic regimens. To kill dormant leukaemic cells, we administered 20 mg/m2 ara-C by continuous intravenous infusion and 800 x 10(4) unit M-CSF by 30 min drip intravenous infusion together for 14 d. The blasts disappeared, followed by a recovery of normal blood cells. The patient continued the complete remission for 5 months. This observation suggests that a combination M-CSF and a low dose of ara-C may be useful in treating some patients with AMoL.

Adult↗

PubMed1993

Aplastic anemia and idiopathic thrombocytopenic purpura with antibody to platelet glycoprotein IIb/IIIa following resection of malignant thymoma.

A case of a 64-year-old Japanese woman who developed aplastic anemia and idiopathic thrombocytopenic purpura with antibody to platelet glycoprotein IIb/IIIa 4 years following a resection of malignant thymoma is reported. Bone marrow was hypocellular and ferrokinetics revealed the prolongation of the half-time of plasma iron disappearance and a decrease in red cell utilization, findings compatible with a diagnosis of aplastic anemia. The life span of platelets was markedly decreased to 3.07 h, and the test for antiplatelet glycoprotein IIb/IIIa antibody was positive. The patient's serum had a suppressive effect on the formation of colonies of burst-forming unit-erythroid and colony-forming unit-granulocyte using normal bone marrow cells. These results suggest that the aplastic anemia in this patient may have been induced by some suppressive activity in the serum. Splenectomy followed by an administration of cyclosporine effectively restored the peripheral blood count.

Anemia, Aplastic↗

PubMed1993

Lethal posttransfusion graft-versus-host disease. Report of four cases.

Four cases of posttransfusion graft-versus-host disease are reported. Three were caused by high-dose transfusion of non-irradiated fresh blood during open-heart surgery and 1 by the contaminated lymphocytes in packed red blood cells transfused for renal injury. In 1 patient, change of HLA type of peripheral lymphocytes was demonstrated.

Aged↗

PubMed1993

T-cell non-Hodgkin's lymphoma of the lung.

We report a case of primary T-cell non-Hodgkin's lymphoma of the lung. A definite diagnosis was made histologically at open lung biopsy. Atypical cells in the biopsy specimen reacted with monoclonal T-cell markers. Transbronchial lung biopsy and bronchoalveolar lavage fluid were useful in the diagnosis. Primary T-cell lymphoma of the lung is rare and is reviewed in this report.

Adult↗

PubMed1993

Aggressive granular lymphocyte leukemia of natural killer cell type in an elderly patient.

A 75-year-old man was admitted to our hospital because of intermittent fever. His peripheral blood picture showed granular lymphocyte (GL) proliferation. The GLs were immunologically and functionally phenotyped as natural killer cells. Chromosomal analysis of peripheral lymphocytes with interleukin-2 stimulation revealed an inversion of chromosome 9 with an unusual breakpoint, showing abnormal monoclonal proliferation of the GLs. Progressive increase of GL count and hepatosplenomegaly necessitated the start of combined chemotherapy. His condition was complicated by icterus and renal failure, and he died finally of respiratory failure. Autopsy revealed disseminated intravascular coagulation and infiltration of GLs in the bone marrow, spleen, and liver.

Aged↗

PubMed1993

[B cell malignant lymphoma complicated with partial Addison's disease, report of a case].

A 58-year-old man was admitted in May 1988, because of high fever, skin, pigmentation and body weight loss. Abdominal ultrasonography and generalized computed tomography examinations showed swelling of general lymph nodes and bilateral adrenal glands, splenomegaly, and lesion in the liver. Serum cortisol, urinary 17-OHCS and 17-KS level were within the normal range, while the ACTH level was elevated (189.9 pg/ml). ACTH overload test showed a non-reactive pattern, leading to a diagnosis of partial Addison's disease. He was also diagnosed as non-Hodgkin lymphoma, diffuse, large cell type (B) by a biopsy of the left supraclavicular lymph node. After combination chemotherapy, swelling of the supraclavicular lymph node diminished, followed by normalization of ACTH level and improvement of symptoms. Abdominal lymphadenopathy, hepatosplenomegaly and swelling of adrenal glands also decreased in size. Although involvement of tumor cells in adrenal glands sometimes occurs in malignant lymphoma, it is reported that more than 90% destruction of adrenal gland tissue is necessary to develop Addison's disease. It was suggested that the involvement of many lymphoma cells in both adrenal glands resulted in the development of partial Addison's disease in this case.

Addison Disease↗

PubMed1993

[Ring eosinophils in patients with lowered eosinophil peroxidase activity].

Leucocyte cytograms were obtained by using a Technicon H6000 (Technicon Instrument Corporation, Tarrytown, NY, USA) in conjunction with an automated flow-cytochemical analyser by which leucocytes can be differentiated by cytochemical (peroxidase activity) and optical (cell size) methods. By analysis of cytograms obtained in this way, we found twelve cases of lowered eosinophil peroxidase activity among approximately 600,000 blood samples-days between 1984 and 1989. Ring eosinophils were observed on the peripheral blood smears in 2 out of 12 cases. The first case was a 41-year-old female confined to hospital with Hashimoto's disease, and the other a 54-year-old female hospitalized for trauma. In both cases, the percentage of eosinophils was normal, although some had ring-shaped nuclei with a large central nuclear hole and a nuclear ring formed with a thin nuclear chromatin bridge. Ring eosinophils previously have been described in patients with hematological malignancy, hypereosinophilic syndrome or severe alcoholism. Recently we observed ring eosinophils in a healthy individual for the first time. Although ring eosinophils may not have specific diagnostic significance, these cases are reported because they displayed a rare phenomenon.

Adolescent↗

PubMed1992

Intravenous recombinant tissue plasminogen activator in acute carotid artery territory stroke.

To determine the effect of intravenous recombinant tissue plasminogen activator (rt-PA) on vascular and neurologic outcomes, we enrolled 31 patients with acute carotid artery-territory ischemic stroke within 6 hours from symptom onset in a randomized, double-blind, placebo-controlled study. We gave either rt-PA (duteplase at the dose of 20 or 30 mega-international units [MIU]) or placebo intravenously for 60 minutes in patients randomly assigned to the three groups. A comparison between the baseline and postinfusion angiograms showed that complete or partial reperfusion occurred in 50% (5/10) of patients treated with 30 MIU rt-PA, 44% (4/9) of those treated with 20 MIU rt-PA, and 17% (2/12) in the control group. In patients with middle cerebral artery occlusions, reperfusion occurred in 71% (5/7) of the 30-MIU group, in 67% (4/6) of the 20-MIU group, and in 13% (1/8) of the control group. Patients treated with 30 MIU rt-PA showed a significantly early and better clinical improvement, as measured by the neurologic scale, than did those treated with placebo. Parenchymal hemorrhage occurred in one patient in each group, and frequency of clinically insignificant hemorrhagic infarction was comparable among the treatment groups. No major systemic complications occurred in any group. These results support the efficacy of intravenous infusion of rt-PA soon after the onset of stroke in producing rapid thrombolysis and neurologic recovery; it may be of particular value in patients with thromboembolic occlusion in the middle cerebral artery.

Acute Disease↗

PubMed1992

High pressure mediated Diels-Alder reaction using 2-iminomalonates as dienophiles: novel synthesis of carbocyclic nucleosides.

9-[c-4-(1,2-Dihydroxyethyl)cyclopent-2-en-r-1-yl]-9H-adenine , an isomer of BCA, has been synthesized from Diels-Alder adducts prepared by the reaction of 2-iminomalonates with cyclopentadiene under high pressure. The synthetic method involves a novel C-N bond cleavage reaction by NaBH4-K2CO3 (RRA reaction conditions) and has wide applicability for the synthesis of various carbocyclic nucleosides.

Adenine↗

PubMed1992

[Rhythmic skeletal myoclonus without palatal myoclonus].

We reported a case of 89-year-old woman showing rhythmic skeletal myoclonus mainly on the right upper limb. This myoclonus appeared five days after the cerebral infarction. It was seen constantly both at rest and in posture, and decreased during voluntary movement. When the patient was under emotional stress, it spread to the submandibular, neck and trunks of upper limb. During sleep, this movement completely disappeared. There was no myoclonus in palato-pharyngo-laryngo-oculo-diaphragmatic muscle group. In the examination of the surface electromyography, the movement was not reciprocal between extensor and flexor muscles, and its cycle was about 3.5 Hz. It was different from the intention tremor because it did not increase during the movement phase on the finger nose test. The examination of MRI revealed a small infarction including right dentate nucleus and right superior cerebellar peduncle, and from which an infarction of the superior cerebellar artery territory was considered. Only a few cases of rhythmic skeletal myoclonus without palatal myoclonus have been reported in the literature. All of these cases had small infarction of the same region as the above case. Their myoclonus began 5 to 15 days after the onset of cerebral infarction. These periods were markedly shorter than that of intention tremor and palatal myoclonus. This fact suggest that the rhythmic skeletal myoclonus has a different mechanism from that of the palatal myoclonus.

Aged↗

PubMed1992

[Shy-Drager syndrome and the syndrome of inappropriate secretion of antidiuretic hormone].

We report a 52-year-old male patient with Shy-Drager syndrome (SDS) complicated by an occurrence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The patient first developed impotence at the age of 48, accompanied by urinary incontinence, and episodes of dizziness while standing. The following year, the patient had developed a staggering gait and speech became monotonous. At age 52, the patient was admitted to the hospital after experiencing frequent episodes of syncope associated with complete loss of consciousness. Upon examination, blood pressure was 100/70 in a recumbent position, and 80/60 when standing. The pulse rate varied from 60 per minute to 62. The patient was alert. The alternating Horner sign was observed, and a paucity of facial movements was visible. His speech was slow and monotonous. Muscle tone was increased bilaterally. There was incoordination. A laboratory examination revealed reduced serum sodium levels of 127 mEq/L and increased sodium excretion with plasma hypoosmolality (262 mOsm/kg/H), urine hyperosmolality and low serum renin activity (0.2 ng/ml/h). Renal functions were normal and the levels of adrenocortical and thyroid hormones were normal. There were no abnormalities observed in the chest roentgenogram taken. The level of antidiuretic hormone (ADH) was unreasonably high (5.74 pg/ml). A water-load test demonstrated failure of both water diuresis and inhibition of ADH secretion. These data suggested that hyponatremia in this case was caused by SIADH. The correlation between plasma osmolality and the concentration of ADH suggested that osmolality that initiates ADH release appeared to have been reset to around 230 mOsm/kg lower than normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1991

Macrophage-active colony-stimulating factors enhance human immunodeficiency virus type 1 infection in bone marrow stem cells.

To define the relationship between human immunodeficiency virus type 1 (HIV-1) infection in hematopoietic stem cells and virus production by their progeny, we performed kinetic studies infecting bone marrow (BM) stem cells and culturing them in the presence of hematopoietic growth factors. CD34-positive (CD34+), CD4-negative (CD4-) BM cells were isolated and infected in vitro with the monocytotropic HIV-1JR-FL strain or the laboratory-maintained HTLV-IIIB strain at a high multiplicity of infection. The cells were susceptible to productive infection only with HIV-1JR-FL, and virus production as measured by p24 protein release was markedly increased (more than fivefold) in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3). Macrophage CSF (M-CSF) was less stimulatory and granulocyte CSF (G-CSF) had no effect on virus production. Virus production coincided with proliferation of mononuclear phagocytes but was not related to granulocytic proliferation in G-CSF-treated BM cultures. Although peak virus production from GM-CSF-treated macrophages occurred 2 to 3 weeks after infection, peak virus production in infected stem cells was observed 5 to 6 weeks after. Enhancement in virus production had a more rapid onset when CD34+/CD4- cells were cultured in the presence of both GM-CSF and IL-3 for 7 or 14 days. Under these conditions there was a 10-fold enhancement in virus production after 7 days of preincubation and a 50-fold enhancement after 14 days. These data indicate that while the stem cell compartment may be susceptible to infection with a monocytotropic HIV-1 strain, productive and sustained infection is realized only after macrophage differentiation. The lack of effect of G-CSF on virus production is likely because of the limited effect of this hematopoietin on mononuclear phagocyte generation and function.

Antigens, CD↗

PubMed1991

Improvement in the proliferative activity of human-human hybridomas at low cell density by transfection with bFGF gene.

Highly purified recombinant basic fibroblast growth factor (rbFGF) and acidic FGF (aFGF) stimulated the proliferation of human-human (h-h) hybridomas to the extent of over four-fold from a low cell density such as 1 x 10(3) cells per ml in a serum-free medium in 24-well plates. The stimulatory effect of rbFGF was also observed in various lymphoid cell lines. Expecting that FGF could be an autocrine growth factor, we introduced bFGF gene into a h-h hybridoma using an expression plasmid induced by dexamethasone. The transformed cells thus obtained, HPO-75.11 bFGF-7, were able to grow well from a low inoculum density in a serum-free medium and antibody production was also increased when bFGF gene expression was induced. The transformed cells could grow at clonal density in a serum-free medium in 96-well plates, though the original cells could not. We also obtained a more practical transfectant, HPO-75.29-H74, using a high-shear stress adapted clone as the recipient and an expression plasmid having bFGF gene under the control of metallothionein-I promoter. The HPO-75.29-H74 cells were capable of growing and producing human monoclonal antibody against hepatitis B virus surface antigen from an inoculum density of 1 x 10(3) cells per ml in an agitation vessel without addition of an inducer.

Animals↗