Biomedical subjects
Publications and source records attributed to H Mikawa.
The effect of disodium cromoglycate (DSCG) on human B cell lines (IM-9, GM-1056, and AF-10) was studied. DSCG inhibited immunoglobulin production by these B cell lines without affecting thymidine uptake or cell number. Thus, in addition to its antiallergic function, DSCG may also act as a B cell-modulating reagent in vitro.
Two patients with a marked hypointensity of the globus pallidus on magnetic resonance imaging (MRI), which is known to be diagnostic for Hallervorden-Spatz disease (HSD), are presented. Patient 1 fell ill at about 10 years of age with visual disturbance, spastic paraplegia and mild ataxia, while patient 2 was affected during the second year of life with clinical features compatible with infantile neuroaxonal dystrophy (INAD). The two patients had certain clinical features in common; upper and lower motor neuron involvement, visual disturbance secondary to optic nerve atrophy, and dorsal column dysfunction, the evidence of which was seen from abnormal somatosensory evoked potentials (SEPs) obtained after posterior tibial nerve stimulation. In both patients, electron microscopic examination of the biopsied skin or sural nerve showed dystrophic axons, spheroids, and involvement of the peripheral nerve was indicated. Sharing of these clinical, pathological and MRI characteristics by the two patients supports the view of Seitelberger, who regarded HSD and INAD as constituents of a single disease entity, therefore the two patients were described as belonging to a disease spectrum of "Hallervorden-Spatz-neuroaxonal-dystrophy complex (HS-ND)." Sensory impairment has been a rare clinical feature in "HS-ND" complex, although its existence is not inconceivable considering the usual affection of the dorsal column/lemniscal pathway with spheroids. SEP was considered very useful in disclosing this often unmanifested sensory disturbance in "HS-ND" complex.
We studied the neurohypophyseal function of 20 patients with complete GH deficiency owing to pituitary stalk transection by means of the water deprivation and the hypertonic saline infusion test. In T1-weighted magnetic resonance images, high-signal intensity of the posterior lobe of the hypophysis was missing in all the patients. An ectopic posterior lobe was observed at the proximal stump of the transected stalk in 17 patients, whereas the 3 patients without ectopic posterior lobe had overt diabetes insipidus or intractable nocturnal enuresis. After water deprivation, 3 patients with large ectopic posterior lobes (length along the pituitary stalk axis exceeding 5 mm) showed urinary osmolality and plasma AVP levels as high as those of 13 patients with partial GH deficiency in whom magnetic resonance images revealed no abnormalities. On the other hand, 14 patients with small ectopic posterior lobes (length less than 5 mm) showed significantly lower urinary osmolality and plasma AVP levels than the patients with large ectopic posterior lobes (p less than 0.01 and p less than 0.01, respectively) and the patients with partial GH deficiency (p less than 0.01 and p less than 0.01, respectively). Urinary osmolality in the patients with small ectopic posterior lobes, however, was higher than that in 3 patients without ectopic posterior lobes (p less than 0.01). During the hypertonic saline infusion test, peak plasma AVP levels in the patients with small ectopic posterior lobes were significantly lower than those in the patients with partial GH deficiency (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
The inhibitory effect of ketotifen on platelet activating factor (PAF)-induced actin polymerization in a human eosinophilic leukaemia cell line, EoL-1, was examined by flow cytometry with the use of reagents specific for the filamentous form of actin (F-actin). Actin polymerization has been considered to be essential for locomotion of cells, chemotaxis and chemokinesis, and thus it reflects the chemotactic reaction of EoL-1 cells stimulated by PAF. Unstimulated EoL-1 cells showed little PAF-induced actin polymerization, whereas EoL-1 cells cultured for 9 days with the supernatant of a human ATL cell line, HIL-3 (HIL-3 sup), showed marked actin polymerization when stimulated with PAF. The actin polymerization in EoL-1 cells induced by PAF was seen in a dose-dependent manner at concentrations of 10(-10) M to 10(-6) M of PAF, and the maximum effect was seen at 10(-7) M of PAF. CV-3988, a specific antagonist of PAF, inhibited 80% of the actin polymerization in EoL-1 cells induced by PAF at a concentration of 10(-5) M. Ketotifen inhibited up to 40% of the PAF-induced actin polymerization of EoL-1 cells in a dose-dependent manner at concentrations of 10(-9) M to 10(-5) M. These results suggest that ketotifen may play an important role in the prevention of eosinophil-induced inflammation in allergic disorders by inhibiting PAF-induced chemotaxis of eosinophils.
A 16-month-old girl was admitted because of bilateral ophthalmoplegia, left blepharoptosis, and disturbance of consciousness. Her symptoms resolved spontaneously within a week after admission, but mild left abducens palsy remained. The cranial computed tomography showed a mild non-specific brain atrophy. The auditory brain stem response was normal. Visual evoked potentials (VEPs) to flash stimuli were repeated serially after the onset. No significative patterns of VEP were evoked during the acute stage. However, three months after the onset, an asymmetrical pattern, namely left-sided abnormalities (not-identified P 100 wave, etc.), was observed. The asymmetrical pattern of VEP diminished six months after. And a bilaterally normal VEP pattern was found twelve months after.
We investigated the positive and negative effects of IFN-gamma, PMA, dibutyryl cAMP (Bt2cAMP), dexamethasone and transforming growth factor-beta (TGF-beta) on Fc gamma R subtype expression and phagocytosis of a human monoblast cell line, U937. IFN-gamma increased and Bt2cAMP decreased Fc gamma RI expression determined by a mAb 32.2, whereas PMA and Bt2cAMP increased Fc gamma RII expression determined by a mAb IV-3. Phagocytosis was measured microscopically by counting ingested aggregated human IgG- or BSA-treated ox E (Eo'-IgG or Eo'-BSA). IFN-gamma increased the phagocytosis of Eo'-IgG but not that of Eo'-BSA, and PMA increased the phagocytosis of both Eo'-IgG and Eo'-BSA. Bt2cAMP decreased both basal and IFN-gamma- and PMA-augmented phagocytosis of U937 cells. Dexamethasone also inhibited both basal and IFN-gamma-augmented Fc gamma RI expression and PMA-augmented Fc gamma RII expression and phagocytosis, but did not affect IFN-gamma-augmented phagocytosis of Eo'-IgG. The augmentation of phagocytosis of Eo'-IgG by IFN-gamma thus seems to be due mainly to the increased internalizing process rather than to increased Fc gamma RI expression. TGF-beta slightly decreased Fc gamma R expression. In a study of the participation of protein kinase C (PK-C), it was found that H-7, a PK-C inhibitor, did not inhibit either IFN-gamma- or PMA-enhanced Fc gamma RI and Fc gamma RII expression, respectively, and 1-oleoyl-2-acetylglycerol and N-(6-phenylhexyl)-5-chloro-1-naphthalenesulfonamide, both PK-C activators, did not show any apparent increase in Fc gamma R expression and phagocytosis. These results show that Fc gamma RI and Fc gamma RII expression on U937 cells is regulated by different mechanisms and that IFN-gamma and PMA play their roles in Fc gamma R expression and phagocytosis by different pathways. It is possible that cAMP but not PK-C plays an important role in the regulation of Fc gamma R expression and phagocytosis.
Using a promyelocytic leukemia cell line, HL-60, we studied the membrane transport of Ara-C before and after differentiation induced by retinoic acid (RA). In RA-treated cells, Ara-C transport was reduced and there was a concomitant increase of the ID50 values of Ara-C in comparison with the controls. By three different procedures to synchronize untreated cells, i.e. density arrest G1 phase enrichment, aphidicolin-induced S phase accumulation and the double isoleucine block method, we found that Ara-C transport was 30-50% higher in the S phase than in the G1 phase. Therefore, the observed decrease in Ara-C transport is, in part, due to the retarded growth accompanied by an accumulation of cells in the G1 phase after differentiation induction.
We synchronized thymidine kinase deficient mouse Ltk-cells by two different methods, hydroxyurea double-block treatment or aphidicolin single-block treatment and transformed them with the cloned herpes simplex virus thymidine kinase gene at various time intervals by the electroporation technique. Marked enhancement of stable transformation efficiency was observed at the time corresponding to the peak of G2/M phase. These results suggest that the G2/M phase is the most efficient period for stable gene transfer by electroporation.
Treatment of rat basophilic leukemia cell line (2H3) with interferon-alpha significantly increased intracellular histamine levels. On the other hand, the histidine content was decreased reciprocally by interferon in a dose-dependent manner. Concomitantly, the activity of histidine decarboxylase, the enzyme responsible for histamine synthesis, was augmented. The increase in histidine decarboxylase activity was partially abolished in co-incubation with inhibitors of ADP-ribosyltransferase, such as 3-aminobenzamide or nicotinamide. These results suggest the pivotal role of activation of histidine decarboxylase, presumably through ADP-ribosylation of the enzyme, in interferon-induced histamine synthesis.
A 20-month-old child was treated for acute nonlymphocytic leukemia (ANLL) with basophilic differentiation. His leukemic cells also had the cytogenetic abnormality of t(9,11)(p22,q23). Although immature blasts responded well to induction therapy with etoposide, the leukemic cells that were more differentiated toward basophils were quite refractory to the drug. However, complete remission was finally achieved with a conventional multidrug regimen.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A male infant with DiGeorge syndrome had hypogammaglobulinaemia with a normal number of B cells. CD3(+) T cells were reduced and the CD4(+)/CD8(+) ratio was reversed. Proliferative responses of T cells to mitogens and to allogeneic cells were low. The pokeweed mitogen (PWM)-induced B cell differentiation assay revealed a higher than normal suppressor T cell activity. This suggests that some T cells had differentiated into functionally mature cells resulting in an imbalance of regulatory T cell functions and that excess suppressor activity might play a role in hypogammaglobulinaemia. Fetal thymus transplantation improved both cellular and humoral immunity. The patient's susceptibility to viral and bacterial infections, proliferative response of T cells and serum Ig concentration returned to normal. The excess suppressor activity seen before transplantation disappeared. Hypocalcaemia did not improve. These results show that fetal thymus transplantation was effective not only in reconstituting cellular immunity but also in normalizing the imbalance of regulatory T cell functions in this patient with DiGeorge syndrome.
Wilms tumour was found in a Japanese boy aged 5 years 9 months with isolated growth hormone (GH) deficiency and some congenital anomalies. He had received pituitary GH replacement therapy from the age of 2 years 1 month to 4 years 7 months and after a 1 year interval he received biosynthetic GH for 2 months until the tumour became clinically apparent. This was the sixth known patient with GH deficiency to develop a malignant neoplasm during or after GH replacement therapy and the first with a solid tumour in Japan since 1975, when treatment with pituitary GH for patients with GH deficiency was introduced.
Regulation of low-affinity receptors for IgE (Fc epsilon R2/CD23) on a human eosinophilic cell line EoL3 and a human monocytic cell line U937 was studied using an anti-Fc,R2/CD23 monoclonal antibody H107 by flow cytometry. While platelet-activating factor, interleukin 4, and interferon gamma significantly augmented Fc epsilon R2/CD23 expression on both cell lines, transforming growth factor beta (TGF beta) inhibited both the basal level of Fc epsilon R2/CD23 expression and the enhanced Fc epsilon R2/CD23 expression induced by these reagents in dose- and time-dependent manners. However, TGF beta did not significantly suppress the high basal level of Fc epsilon R2/CD23 expression on RPMI 8866 cells. These results suggest that Fc epsilon R2/CD23 expression on EoL3 and U937 cells is regulated by various cytokines and growth factors, and that TGF beta plays an important regulatory role in IgE-mediated immune responses.
Exposure of human promyelocytic leukemia cell line (HL-60) to VP-16 resulted in accumulation of DNA strand breaks. Concomitantly, intracellular NAD levels fell at 1 h, followed by declines in ATP at 2 h and in GTP, CTP, and UTP at 3 h. Furthermore, marked morphological changes, such as loss of microvilli or bleb formation, appeared at 4 h and cell death by 8-10 h. The addition of an inhibitor of poly(ADP-ribose) polymerase, 3-aminobenzamide (5 mM), theophylline (2 mM), or thymidine (1 mM), prevented these sequential reductions of nucleotide pools and cell death. In fact, the activation of poly(ADP-ribose) synthesis was detectable within a few hours after treatment with VP-16, although it was smaller than that induced by N-methyl-N'-nitro-N-nitrosoguanidine. These results may suggest the possible role of activation of poly(ADP-ribosyl)ation in VP-16-induced nucleotide pool changes and subsequent interphase death.
We investigated the accumulation of DNA strand breaks in a human promyelocytic leukemia cell line, HL-60, treated with methotrexate (MTX) and 1-beta-D-arabinofuranosylcytosine (Ara-C). The sequential treatment with MTX then Ara-C had a synergistic effect on the formation of DNA strand breaks, which was dependent on MTX and Ara-C concentrations. On the other hand, when Ara-C preceded MTX, no such synergism was observed. The addition of both thymidine and hypoxanthine to this system, but not thymidine or hypoxanthine alone, abolished the synergism. Pretreatment with MTX augmented the generation of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate. However, this augmentation did not necessarily correlate with the amount of strand breaks. Whatever the underlying mechanism of this synergism is, our present data provide one possible biochemical basis for sequential MTX and Ara-C therapy.