PubMed Health⌕ Search

Biomedical subjects

K Horikawa

Publications and source records attributed to K Horikawa.

At least 19 recordsLinked to original sources
PubMed1998

The localization of the site of arylalkylamine N-acetyltransferase circadian expression in the photoreceptor cells of mammalian retina.

To investigate the molecular mechanism of the melatonin rhythm in the mammalian retina, we examined the temporal mRNA expression pattern of arylalkylamine (serotonin) N-acetyltransferase (AA-NAT), the rate-limiting enzyme in melatonin synthesis in the rat retina. Rat AA-NAT mRNA was detected exclusively in the retinal photoreceptors in the outer nuclear layer--low during the day and increased more than threefold at night. The nocturnal AA-NAT expression in rat retina was also confirmed by RNase protection and the AA-NAT enzymatic activity. This is the first report to localize the site of AA-NAT mRNA circadian expression in mammalian photoreceptor cells.

Animals↗
PubMed1998

A double-edged kinase Lyn: a positive and negative regulator for antigen receptor-mediated signals.

B cells from young lyn-/- mice are hyperresponsive to anti-IgM-induced proliferation, suggesting involvement of Lyn in negative regulation of B cell antigen receptor (BCR)-mediated signaling. Here we show that tyrosine phosphorylation of FcgammaRIIB and CD22 coreceptors, which are important for feedback suppression of BCR-induced signaling, was severely impaired in lyn-/- B cells upon their coligation with the BCR. Hypophosphorylation on tyrosine residues of these molecules resulted in failure of recruiting the tyrosine phosphatase SHP-1 and inositol phosphatase SHIP, SH2-containing potent inhibitors of BCR-induced B cell activation, to the coreceptors. Consequently, lyn-/- B cells exhibited defects in suppressing BCR-induced Ca2+ influx and proliferation. Thus, Lyn is critically important in tyrosine phosphorylation of the coreceptors, which is required for feedback suppression of B cell activation.

Animals↗
PubMed1997

Apoptosis resistance of blood cells from patients with paroxysmal nocturnal hemoglobinuria, aplastic anemia, and myelodysplastic syndrome.

Bone marrow (BM) hypoplasia is a major cause of death in paroxysmal nocturnal hemoglobinuria (PNH). However, little is known about the molecular events leading to the hypoplasia. Considering the close pathologic association between PNH and aplastic anemia (AA), it is suggested that a similar mechanism operates in the development of their BM failure. Recent reports have indicated apoptosis-mediated BM suppression in AA. It is thus conceivable that apoptosis also operates to cause BM hypoplasia in PNH. If this is the case, PNH clones need to survive apoptosis and show considerable expansion leading to clinical manifestations. We report here that granulocytes obtained from 11 patients with PNH were apparently less susceptible than those from 20 healthy individuals to both spontaneous apoptosis without any ligands and that induced by anti-FAS (CD95) antibody in vitro. The patients' BM CD34+ cells were also resistant to apoptosis induced by treatment with tumor necrosis factor-alpha, interferon-gamma, and subsequently with anti-FAS antibody. In lymphocytes, the pathologic resistance was not discriminated from inherent resistance to apoptosis. Granulocytes from 13 patients with AA and 12 patients with myelodysplastic syndrome (MDS) exhibited similar resistance to apoptosis. CD34+ cells from MDS-BM also showed similar tendency. Thus, the comparative resistance to apoptosis supports the pathogenic implication of apoptosis in marrow injury of PNH and related stem cell disorders.

Adult↗
PubMed1997

Differential glycosylation of Bence Jones protein and kidney impairment in patients with plasma cell dyscrasia.

Although Bence Jones protein (BJP) is generally accepted to be critically involved in the pathogenic process of kidney impairment in patients with myeloma, patients with BJP do not always have kidney dysfunction. As proteins often undergo glycosylation and alter their molecular nature, it is expected that the heterogeneity in kidney dysfunction can be explained at least partly by the differential affinity to the kidneys of BJP dependent on its glycosylation. Accordingly, we analyzed the structures of carbohydrates of urine BJP biochemically to correlate the structure with kidney function. BJP was obtained from 16 patients with myeloma, 2 patients with light chain amyloidosis, a patient with plasma cell leukemia, and a patient with Waldenstrom's macroglobulinemia. All BJP had five forms of oligosaccharides: three forms of biantennary oligosaccharides and two forms of triantennaries. The three biantennaries correspond to previously reported oligosaccharides on only lambda-type BJP, whereas the triantennaries are novel oligosaccharides found on BJP. Among the five oligosaccharides, the triantennary oligosaccharide Gal(beta)1-4GlcNAc(beta)1-2Man(alpha)1-6 [Gal(beta)1-GlcNA(beta)1-4(Gal(beta)1-4GlcNAc(beta) 1-2)Man(alpha)1-3]Man(beta)1-4GlcNAc(beta)1-4GlcNAc showed a significant negative correlation with the serum creatinine level (p = 0.015 by Spearman's correlation test, R = 0.744). Thus determination of BJP glycosylation may be useful for the evaluation of kidney impairment in patients with BJP.

Bence Jones Protein↗
PubMed1997

Markedly high plasma erythropoietin and granulocyte-colony stimulating factor levels in patients with paroxysmal nocturnal hemoglobinuria.

In patients with paroxysmal nocturnal hemoglobinuria (PNH), we measured plasma concentrations of endogenous hematopoiesis-regulatory cytokines to characterize bone marrow (BM) hypoplasia which is a major cause of death. Contrary to 10 healthy individuals, all 14 patients with PNH showed increases of erythropoietin (Epo) and granulocyte-colony stimulating factor (G-CSF). There were no signs of infection, renal dysfunction or hypoxia. The lower the hemoglobin level and granulocyte count, the higher the plasma Epo and G-CSF levels. In contrast, marked differences were not found in the levels of interleukin-3 (IL-3), tumor necrosis factor-alpha (TNF-alpha), stem cell factor (SCF), granulocyte/macrophage-colony stimulating factor (GM-CSF), or interferon-gamma) (IF-gamma). The cytokine profiles of PNH patients were quite similar to those of patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). The cytokine profiles may support a pathological relationship between PNH and these stem cell disorders.

Adolescent↗
PubMed1997

[A study for serodiagnosis of verotoxin-producing Escherichia coli (enterohemorrhagic E. coli) O157 by the bacterial agglutination technique].

We evaluated the usefulness of bacterial agglutination antibodies for serodiagnosis of verotoxin-producing Escherichia coli (enterohemorrhagic E. coli) O157 infections. We examined 50 serum samples from 50 control children (whiout diarrhea 31, with diarrhea 19), 24 samples from 8 diarrhea cases due to O157:H7, 37 samples from 14 cases of hemolytic uremic syndrome (HUS) for antibodies to heat-killed E. coli E32511 (O157:H.-) strain using the bacterial agglutination technique. Of the control sera all but one (x80) showed 20 > or = in the antibody. All the diarrhea patients due to O157:H7 showed a significant rise (x160-x5120) of the titers in the sera at 5-7 days on illness, after that the titers fell rapidly. Significant antibody rise (x160-x5120) was detected in twelve out of 14 HUS patients at the early stage of the illness which fell in the convalescent phase. The assay appeared to be a useful serodiagnostic technique because of its easiness and simplicity as well as because of its high sensitivity and specificity.

Agglutination Tests↗
PubMed1997

[Transarterial platinum coil embolization for direct carotid-cavernous fistula].

Two cases of direct carotid-cavernous fistula (CCF) were treated by transarterial platinum coil embolization (TACE) following unsuccessful transarterial balloon embolization (TABE). Case 1 was a 47-year-old man who complained of pulsatile left exophthalmos, chemosis and bruit. Left carotid angiograms showed a CCF with anterior, posterior and cortical venous drainage. Near total obliteration of the CCF was achieved by TABE, but it showed recurrence in the next morning. At this time, left carotid angiograms showed a CCF which drained only into the cortical veins via the enlarged sphenoparietal sinus. Because of high risk of intracranial hemorrhage, TACE was performed immediately. The result was successful. Case 2 was an 82-year-old woman who suffered from traumatic subarachnoid hemorrhage. First right carotid angiograms showed a small CCF which drained only into the inferior petrosal sinus. Right exophthalmos, swelling of the eyelids, severe eye pain and bruit appeared gradually. The second right CAG performed three months after the head trauma showed markedly dilated superior ophthalmic vein which was the new main draining root of the CCF. Because of progressive symptoms, TACE was performed immediately after the angiography, which proved successful. Direct CCFs must be treated aggressively because they don't cure by spontaneous obstruction of fistula. Although TABE is the first choice for direct CCF, complete occlusion of CCF in difficult in some cases. Those cases have; 1) small fistula of CCF for balloon insertion, 2) large fistula for occlusion by balloons, 3) not enough space for inserting a balloon after recurrence of CCF, and 4) sharp objects (bone fracture fragments, foreign objects) may puncture the balloon. If TABE couldn't provide successful treatments, TACE should be considered as an alternative treatment for direct CCF after angiography without delay because it is less complex compared with TABE.

Aged↗
PubMed1997

[Echocardiographic evaluation of cardiotoxicity induced by anthracycline therapy].

Echocardiographic reports on 144 adults receiving anthracycline therapy and 18 controls were reviewed for the possible relationship between dosage and ejection fractions. The cardiotoxicity of each anthracycline drug was evaluated as follows: Pirarubicin = 0.8, Mitoxantrone = 3.4, Daunorubicin = 0.5, Aclarubicin = 0, and Epirubicin = 0.6 with Doxorubicin = 1 as a control. As a whole, the ejection fractions, which decreased subsequently compared with increasing amount of dosage, showed a remarkable decrease at the dosage level of 600 mg/m2. However, the ejection fractions differed among individual patients. It was predicted that heart failure would not develop when the ejection fractions exceeded 55%. It is desirable to stop anthracycline therapy when the ejection fractions drop to 55%.

Aclarubicin↗
PubMed1997

[Investigation of doxorubicin cardiotoxicity by echocardiogram and the appropriate method of using doxorubicin].

For a sample of 136 adults on whom Doxorubicin (DXR) had been used, we looked for the ejection fraction (EF) by echocardiography and examined its relationship with the amount of DXR. Our results showed that as the amount of DXR increased the EF decreased significantly, particularly with aging. The use of previous mediastinal radiation and 5-FU, etc. on breast cancer patients had no effect on the EF. From our examination of patients developing congestive heart failure, we repeatedly performed echocardiography and found that DXR can be safely used until the EF decreases to 55 percent. In this way, we can find many patients with whom it is possible to use DXR in larger amounts than 550 mg/m2. In general, large quantities of DXR can be used on young people, but for elderly people, large quantities of DXR should be used with caution.

Adult↗
PubMed1996

Preferential hematopoiesis by paroxysmal nocturnal hemoglobinuria clone engrafted in SCID mice.

In paroxysmal nocturnal hemoglobinuria (PNH), little is known about the molecular events leading to the clinical manifestations except for the hemolysis. To unfold the complex pathophysiology, it is necessary to elucidate the nature of the PNH clone. PNH exhibits an acquired stem cell disorder, a clonal expansion of affected cells, concomitant depression of normal hematopoiesis in bone marrow (BM), and, although infrequently, the development of leukemia. The PNH clone is thus expected to exhibit some neoplastic features. We report here that CD34+ hematopoietic progenitor cells of PNH-BM yielded blood cells of three lineages with PNH phenotype alone when transplanted into sublethally irradiated severe combined immunedeficient mice. The hematopoiesis persisted for more than 10 months and did not always need human cytokines. In contrast, the hematopoiesis by control grafts obtained from healthy volunteers required an intense cytokine treatment. This in vivo model defines the preferential hematopoiesis of pluripotent PNH progenitor cells, indicating the intrinsic growth abnormality of PNH clone.

Adult↗
PubMed1995

Markedly high population of affected reticulocytes negative for decay-accelerating factor and CD59 in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) blood cells lack glycosylphosphatidylinositol-anchored membrane proteins such as decay-accelerating factor (DAF) and CD59. This lack is of diagnostic value in PNH. Because reticulocytes in PNH are not yet well characterized, we analyzed reticulocytes obtained from 12 patients with PNH and from 5 healthy volunteers by two-color flow cytometry with a membrane-permeable fluorescent dye, thiazole orange, to identify reticulocytes and monoclonal antibodies to DAF and CD59. Healthy individuals had no affected cells. In all patients, the population of affected reticulocytes negative for DAF and CD59 was markedly higher than the population of affected erythrocytes. Moreover, the population of affected erythrocytes became obviously low in patients who received transfusions and suffered from hemolytic precipitation, whereas the population of affected reticulocytes was unchanged. The persistently high population of affected reticulocytes, despite cytolytic exclusion and an inherently short lifetime, might possibly be explained by relative reticulocytosis caused by an anemia-induced feedback stimulation of erythropoiesis in PNH. Thus, affected reticulocytes could be a reliable marker for the diagnosis of PNH and for the evaluation of erythropoiesis by PNH stem cell.

Adolescent↗
PubMed1995

Paroxysmal nocturnal hemoglobinuria clone in bone marrow of patients with pancytopenia.

The lack of glycosylphosphatidylinositol (GPI)-anchored membrane proteins such as decay-accelerating factor (DAF) and CD59 on blood cells has a diagnostic value in paroxysmal nocturnal hemoglobinuria (PNH). Because PNH often develops in patients with aplastic anemia (AA), we attempted to detect a PNH clone in the bone marrow (BM) of patients with AA and pancytopenia before affected cells were evident in the peripheral blood (PB). We used flow cytometry with monoclonal antibodies against DAF and CD59 for the detection of the clone. Affected cells were observed in the BM of 3 of 7 patients with AA and 1 of 3 patients with pancytopenia of unknown origin, but not in their PB. All 8 patients with apparent PNH had affected cells in their BM and PB. On the basis of the early appearance of the PNH clone in the BM, a prospective 4-month follow-up study of the PB cells was performed. The study showed the release of affected mature cells first in granulocytes, then in monocytes, and finally in lymphocytes. Ham's test was positive before affected erythrocytes were detected by flow cytometry. Our findings indicate that detection of the PNH clone in BM could be predictive of the development of PNH in patients with AA and pancytopenia.

Anemia, Aplastic↗
PubMed1995

Astrocytoma linked to familial ataxia-telangiectasia.

A 7-year and 11 month-old girl with cerebellar astrocytoma linked to familial ataxia-telangiectasia (AT) is presented. She was born as the 7th girl of a woman with aortic arch syndrome. Two elder sisters of the patient have ataxia telangiectasia. She had immunodeficiency, and cerebellar ataxia, but had no oculocutaneous telangiectasia. The risk of cancer developing in AT patients is about 1,200 times greater than that in age-matched controls. With regard to central nervous system tumours, seven primary tumours have been reported, such as 3 cases of medulloblastoma and 4 cases of glioma. Members of AT families who were under the age of 45 had a risk of dying of a malignant neoplasm five times greater than in the general population. However, there were no reports of glioma in AT families. In this case, it is suggested that IgA deficiency linked to familial AT may have contributed to the development of astrocytoma.

Astrocytoma↗