Biomedical subjects

Y Kakinoki

Publications and source records attributed to Y Kakinoki.

At least 55 records · Page 3Linked to original sources

PubMed1997

Natural course of serum-specific immunoglobulin E and immunoglobulin G4 for a span of eight years in untreated patients with perennial allergic rhinitis.

During the past two decades, considerable attention has been devoted to the clinical role of serum-specific IgE and IgG4 following immunotherapy. To definitely discuss the clinical role of serum-specific IgG4, we should know the natural course of serum-specific IgG4 in the untreated patient with allergic rhinitis. To our knowledge, however, no such kind of study can be found in the literature. Our present study focused on the long-term follow-up of serum-specific IgE and IgG4 in patients who were not treated with immunotherapy for perennial allergic rhinitis. They were scheduled to take no medication for their perennial nasal symptoms for 8 years. Serum-specific IgE and IgG4 in untreated patients with perennial allergic rhinitis never significantly change during the observation period. These data will be of great value for studies in serologic changes following active treatment for atopic diseases. Additionally, our study suggests that a reduction in serum-specific IgE and an increase in serum-specific IgG4 following immunotherapy are not the result of an immunotherapy-independent and age-related phenomenon but the result of active immunologic modulation by immunotherapy.

Adjuvants, Immunologic↗

PubMed1997

Soluble intercellular adhesion molecule-1 level in sera is elevated in perennial allergic rhinitis.

Soluble intercellular adhesion molecule-1 (sICAM-1) in sera was measured in some allergic disorders, but serum sICAM-1 levels in perennial allergic rhinitis remain to be determined. Our study was aimed at elucidating whether the serum sICAM-1 levels in patients with perennial allergic rhinitis are different from those in nonatopic healthy volunteers and whether immunotherapy can modulate sICAM-1 levels. Serum sICAM-1 was determined in 20 nonallergic volunteers and 137 patients with perennial allergic rhinitis by a sandwich enzyme-linked immunosorbent assay. Our study demonstrated that the level of sICAM-1 in untreated patients is significantly elevated, as compared with nonatopic subjects. Immunotherapy could decrease sICAM-1 in perennial allergic rhinitis, but this suppressive effect became apparent only after many years of immunotherapy. In patients on immunotherapy, a close correlation was observed between sICAM-1 and nasal symptom scores. To take these lines of evidence together, a decrease in sICAM-1 might be related to the working mechanism of immunotherapy, and serum sICAM-1 could be used to monitor the effect of immunotherapy.

Adult↗

PubMed1997

Effect of immunotherapy on seasonal changes in serum-specific IgE and IgG4 in patients with pollen allergic rhinitis.

Serum specific IgE and IgG4 in 70 patients with seasonal rhinitis caused by Japanese cedar pollens were determined before and during the pollen season. Seasonal increase rate in specific IgE was significantly smaller in the immunotherapy patients than the pharmacotherapy patients, and seasonal increase in specific IgG4 was significant in the immunotherapy patients only. Seasonal increase rate in specific IgE was not significantly different between the patients who responded markedly to short-term immunotherapy and those who did not. On the other hand, seasonal increase rate in specific IgG4 was significantly different between them. In contrast, seasonal increase rate in specific IgE was significantly smaller in the patients who showed marked response to the long-term immunotherapy than those who did not show marked response to the long-term immunotherapy, but seasonal increase rate in specific IgG4 was not significantly different between them. In conclusion, our results suggest that modulation of specific IgG4 response and specific IgE response might be involved in the early and late symptom relief during immunotherapy, respectively. However, further studies might be necessary to definitively establish the clinical roles of specific IgE and specific IgG4 in immunotherapy.

Adolescent↗

PubMed1997

Significant correlation between symptom score and IgG4 antibody titer following long-term immunotherapy for perennial allergic rhinitis.

Although there is evidence of some measure of clinical benefit as well as immunologic change during the early phase of immunotherapy, a sustained clinical response is only possible with prolonged therapy. Immunotherapy has to be administered for about 3 to 5 years for such sustained clinical efficacy. This study aimed at investigating the dynamics of IgE and IgG4 antibodies after more than 5 years of immunotherapy, to examine the statistical correlation between these antibodies and symptom scores. Our study demonstrated that the allergen-specific IgE antibody level significantly decreases and the IgG4 antibody level significantly increases following immunotherapy. However, the percent decrease in IgE antibodies did not correlate with the percent decrease in symptom scores. On the other hand, the percent increase in IgG4 antibodies correlated with the percent decrease in symptom scores. We infer that an elevation of IgG4 antibodies is not simply an epiphenomenon unrelated to the underlying working mechanism of clinically successful immunotherapy, but probably makes an active contribution to symptom relief.

Adolescent↗

PubMed1997

Effect of immunotherapy on serum levels of eosinophil cationic protein in perennial allergic rhinitis.

Eosinophil cationic protein (ECP) levels in the serum of clotted blood could reflect the rate of activation of circulating eosinophils. We investigated the serum ECP levels in patients with perennial allergic rhinitis, with special reference to the effect of immunotherapy on the serum ECP levels. Serum ECP levels in untreated patients with perennial allergic rhinitis are significantly higher than those of nonatopic volunteers. Therefore, this elevation in the untreated patients represents an ongoing inflammation occurring in allergic rhinitis. The mean serum ECP level of a 1-year immunotherapy group was significantly higher than that of the nonatopic group, and was not different from that of the untreated group. In contrast, the mean serum ECP level in patients who had more than 2 years of immunotherapy was significantly lower than that of the untreated group, and was not different from that of the nonatopic group. Additionally, serum ECP levels were significantly correlated with the duration of immunotherapy. These findings suggest that activation of circulating eosinophils decreases gradually during immunotherapy, but this inhibition becomes apparent only after 2 years of immunotherapy. The control of circulating eosinophil activation might be one of the important working mechanisms behind the clinical effect of immunotherapy.

Adolescent↗

PubMed1997

Gene expressions and activities of protein phosphatases 1 alpha, 2A and 2C in hepatocarcinogenesis and regeneration after partial hepatectomy.

The mRNA levels of protein phosphatases (PP) 1 alpha, 2A, and 2C were determined both in hepatocarcinogenesis and in liver regeneration. In the precancerous stage and during regeneration, the mRNA levels of PP1 alpha, PP2A, and PP2C were markedly increased compared with those in normal livers. In primary hepatomas, all three of these mRNA levels were decreased to the control levels. In poorly differentiated hepatomas, however, only PP1 alpha mRNA was specifically increased, in contrast to PP2A and PP2C, which were at the control levels or below. While PP1 activity in the non-nuclear fraction of partially hepatectomized livers was nearly constant, the activity in nuclei was increased about 2.5-fold over control levels at 12 h after partial hepatectomy, the time that corresponds to the G1 to S transition in the cell cycle of hepatocytes. On the other hand, PP2A activity in both fractions was nearly constant throughout. These results appear to suggest some involvement of protein phosphatases in regulation of hepatocyte proliferation.

3T3 Cells↗

PubMed1996

Serum levels of soluble interleukin-2 receptor in patients with perennial allergic rhinitis before and after immunotherapy.

BACKGROUND: Interleukin-2 receptor (IL-2R) exists in soluble form in sera, and the rate of release of the soluble form of IL-2R (soluble IL-2R) reflects T cell activation in vivo. Since T lymphocytes play a central role in respiratory allergic disorders, the measurement of serum levels of soluble IL-2R may be useful in analyzing the disease state of allergic disorders. OBJECTIVE: To investigate the serum concentrations of soluble IL-2R in 48 patients with perennial allergic rhinitis and 14 nonatopic healthy controls, with special reference to the possible changes following long-term immunotherapy. METHODS: This retrospective study included 48 patients who had had variable periods of long-term immunotherapy with Dermatophagoides farinae extracts. The duration of immunotherapy ranged from 5 to 15 years. Serum samples were collected twice from each patient, before the initiation of immunotherapy and at the time of clinical assessment of immunotherapy. All the serum samples were simultaneously used for determination of soluble IL-2R concentrations, by the use of an enzyme-linked immunosorbent assay. To serve as controls, 14 nonallergic subjects of the same age range and sex were chosen. RESULTS: Patients with allergic rhinitis before immunotherapy had significantly higher serum levels of soluble IL-2R than nonatopic subjects. Elevated serum levels of soluble IL-2R decreased significantly following immunotherapy and the serum levels of soluble IL-2R in patients with allergic rhinitis after immunotherapy were not statistically different from those of nonatopic subjects. In addition, the percent decrease in serum soluble IL-2R correlated significantly with the duration of immunotherapy. CONCLUSIONS: Hyperactivity of helper T cells of atopic patients is altered after long-term immunotherapy, and such immunoregulatory changes could be theoretically involved in the mechanisms of immunotherapy.

Adolescent↗

PubMed1996

Serum level of interleukin-4 in patients with perennial allergic rhinitis during allergen-specific immunotherapy.

Interleukin-4 (IL-4) may play a central role in the IgE synthesis system, the development of Th-2-like cells, and co-ordination as well as the persistence of airway inflammatory process in allergic disorders. Therefore, IL-4 plays a key role in airway allergic disorders. This study aimed at investigating the serum concentrations of IL-4 in patients with perennial allergic rhinitis, with special reference to the possible changes and the clinical relevance following long-term immunotherapy. The study has demonstrated that the serum level of IL-4 in allergic rhinitis patients before immunotherapy is significantly higher than that in non-atopic individuals. However, the serum IL-4 level in allergic rhinitis patients did not decrease following anti-allergic medications but significantly decreased following immunotherapy. The percentage decrease in IL-4 was correlated significantly with the percentage decrease in specific IgE antibodies following long-term immunotherapy. Immunotherapy also significantly decreased specific IgE anti-bodies, but this reduction in specific IgE antibodies was not significantly correlated with the clinical improvement. In contrast, the percentage decrease in serum IL-4 was significantly correlated with the percentage decrease in symptomatic scores. The authors interpret these data to mean that immunotherapy alters T-cell cytokine profiles in the long-term, and a decline of IL-4 following immunotherapy could modulate not only production of specific IgE antibodies but also inflammatory cellular events, leading to symptomatic relief in allergic rhinitis.

Adolescent↗

PubMed1995

Neoplastic alterations in subcellular distribution of type 1 alpha protein phosphatase in rat ascites hepatoma cells.

Neoplastic alterations of type 1 alpha protein phosphatase (PP1 alpha) have been studied in rat ascites hepatoma cells, using regenerating liver after partial hepatectomy and normal rat liver as controls. In the particulate fraction of hepatomas, potential PP1 activity and the amount of PP1 alpha were remarkably increased compared with either regenerating or normal livers. In the nuclear fraction, PP1 activity and the amount of PP1 alpha were increased in hepatoma compared with the controls. The nuclear PP1 activity in hepatomas was activated by treatment with CO2+/trypsin, whereas that of normal or regenerating liver was not activated. These characteristic alterations of PP1 alpha in its amount and subcellular distribution may be implicated in malignant phenotype(s) such as uncontrolled cell growth.

Animals↗

PubMed1994

TGF beta 1 suppresses EGF-induced increase in nuclear type 1 protein phosphatase activity at the G1/S transition of hepatocyte proliferation.

Nuclear type 1 protein phosphatase (PP1) activity in primary culture of EGF-stimulated hepatocytes was significantly and transiently increased at the G1/S transition, being about 2.5-fold, while that in non-stimulated hepatocytes showed almost no change. On the other hand, non-nuclear PP1 activity was gradually increased until the G1/S transition, but the activity showed no difference between EGF-stimulated and non-stimulated hepatocytes. Under growth-inhibited conditions in the presence of TGF beta 1, the increase in nuclear PP1 activity was completely suppressed, whereas non-nuclear PP1 activity was little affected. Such close correlation between nuclear PP1 activity and growth factor-induced positive or negative growth signaling strongly suggests an involvement of PP1 in progression from G1 to S phase of hepatocytes. On Western immunoblotting using antisera for PP1 alpha, PP1 gamma 1, and PP1 delta, no isoform showed any change in amount under these conditions. Mechanism(s) of growth-associated alterations in nuclear PP1 activity is discussed.

Animals↗

PubMed1994

Reversibility of cerebral ischaemia. Dynamic and xenon computed tomography study on ischaemic cerebrovascular disease.

Flow studies using dynamic CT and xenon (Xe) CT were carried out in 25 patients with ischaemic stroke in the territory of the middle cerebral artery to define the clinical characteristics of cerebral ischaemia at a chronic stage. The parameter of peak height/mean transit time (PH/MTT) obtained from dynamic CT can provide an accurate index for blood circulation in the cerebral vascular bed. Xe CT measurements revealed various kinds of ischaemia around the infarction even in the chronic stages. In mild ischaemia of more than 30 ml/100 g/min, reduction of cerebral blood flow (CBF) was well correlated to the PH/MTT. However, in severe ischaemia between 20 and 30 ml/100 g/min, changes of CBF were no longer correlated with the PH/MTT. There were cases showing severe reduction of CBF but which showed sufficient blood circulation (moderate value of PH/MTT). Mild reductions of CBF in parallel with decreased blood supply were often found in the peri-infarct area of infarctions in the centrum semiovale. On the other hand, infarctions in the cortico-subcortical region showed severe ischaemia, in even where blood circulation was relatively well sustained.

Adult↗

PubMed1994

Presence of bronchoalveolar lavage fluid necessary for platelet activating factor-induced ciliary depression.

Many different mediators have been implicated in allergic responses and allergic diseases of the respiratory tract. The influence of several allergic inflammatory mediators on the ciliary activity has been well studied. However, ciliary responsiveness to platelet-activating factor (PAF) is yet to be established conclusively. Our study concerns the response of normal tracheal cilia from the guinea pig during an in vitro contact with PAF. PAF at concentrations between 10(-10) and 10(-8) M never affected the ciliary activity. On the other hand, such concentrations of PAF inhibited the ciliary activity in a dose-response fashion within 5 min in the presence of alveolar macrophages. Such a ciliary dysfunction should allow allergens and other molecules to easily invade epithelium and submucosa of the airway, resulting in an increased epithelial permeability which might be a mild manifestation of airway hyperresponsiveness and make a significant contribution to further airway hyperresponsiveness.

Animals↗

PubMed1994

Chromosomal localization of human, rat, and mouse protein phosphatase type 1 beta catalytic subunit genes (PPP1CB) by fluorescence in situ hybridization.

Using fluorescent in situ hybridization (FISH) method, gene encoding the catalytic subunit of protein phosphatase type 1 beta (PPP1CB) in human and its corresponding gene in rat (PP1 delta) and mouse (dis2m2) were mapped to human 2p23, rat 6q21-q23, and mouse 12D, respectively. These results indicate that PPP1CB is a member of conserved syntenic group. It is shown that the genes encoding catalytic subunit of protein phosphatase type 1 family (PP1 alpha, PP1 beta, and PP1 gamma in human and those corresponding genes in rat and mouse), in spite of their high identity, are located to different chromosomes in these three species.

Animals↗

PubMed1994

Nitrogen dioxide-induced eosinophilia and mucosal injury in the nose of the guinea pig.

Nitrogen dioxide exposure-induced mucosal pathology of the guinea pig nose was studied. Guinea pigs were exposed to 3 ppm or 9 ppm of nitrogen dioxide for 6 h a day, 6 times weekly for 2 weeks, and sacrificed 24 h after the final exposure. Exposure to 3 ppm of nitrogen dioxide resulted in decreased ciliary activity and slight eosinophil accumulation on the epithelium and submucosal layer. More serious pathologies were observed in the nose of guinea pigs exposed to 9 ppm of nitrogen dioxide, including a more prominent eosinophil influx to the epithelium and epithelial injury due to activation of eosinophils. Epithelial damage induced by nitrogen dioxide could lead to hyperresponsiveness and may result in a prolonged allergic inflammation. Our study suggests that environmental nitrogen dioxide may contribute to hyperresponsiveness and thus be involved in the increased morbidity of allergic rhinitis.

Animals↗

PubMed1992

Gene expressions and activities of protein phosphatases PP1 and PP2A in rat liver regeneration after partial hepatectomy.

We have examined the levels of gene expressions and activities of protein phosphatases, PP1 and PP2A, in rat regenerating livers. PP1 alpha mRNA started to increase from 6 h after partial hepatectomy (PH) and showed two peaks at 12 and 48 h. PP2A mRNA level showed two peaks at 6 and 10-12 h. Protein phosphatase activities were determined both in non-nuclear fraction and in nuclei. While spontaneous PP1 activity in non-nuclear fraction was nearly constant, potential PP1 activity revealed by Co(2+)-trypsin treatment showed a small peak between 7 and 12 h. In nuclei, both spontaneous and potential PP1 activity began to increase from 4-7 h after PH, reached a maximum (about 2.5-fold over control levels) at 12 h, the time which corresponds to the G1 to S transition in the cell cycle, and then declined back to control levels by 7 days. PP2A activity in non-nuclear fraction was nearly constant in both spontaneous and potential forms. PP2A activity in both forms in nuclei was very low throughout. These results suggest the possibility that PP1 in nuclei plays some role in the G1 to S transition in the cell cycle of hepatocyte proliferation.

Animals↗

PubMed1991

[Torsade de pointes ventricular tachycardia in a patient with acute myelocytic leukemia].

The anti-leukemic antibiotics, anthracyclines, are most effective agents in the treatment of acute leukemia. However, they have severe cardiac toxicities, which ordinarily shows dose-dependency, but sometimes produce acute cardiomyopathy. We experienced Torsade-de-pointes arrhythmia during the treatment of acute myelocytic leukemia (AML); The patient was a 28 year old woman and had an AML-M1. After the short course administration of daunorubicin (total 90 mg/m2) and aclarubicin (total 219 mg/m2), she suffered from an attack of Torsade-de-pointes ventricular tachycardia and passed away, since any treatment against ventricular arrhythmia was not effective. Autopsy studies revealed degeneration and atrophy of cardiac muscle in the area around His's bundle, which suggested an anthracycline-induced cardiac toxicity.

Aclarubicin↗

PubMed1990

[Wide-spread spontaneous spinal subarachnoid hematoma. Case report].

A 56-year-old female experienced sudden excruciating pain extending from the upper neck to the lower back. She had mild disturbance of consciousness, and a lumbar puncture revealed bloody cerebrospinal fluid. The positive neurological findings were meningitis, spastic paraparesis, hyperesthesia of the left L3 dermatome, bilateral Babinski, disappearance of anal reflex, and urinary retention. Computed tomography scans, myelography, and magnetic resonance images revealed diffuse subarachnoid hematoma and hematomyelia from Th12 to L3. Spinal angiography was tried twice before surgery but no origin of this diffuse hematoma could be found. Laminectomy was performed from Th12 to L1 and organized hematoma was found in the subarachnoid space. After the hematoma removal, non-pulsating tortuous vessels were observed on the surface of the spinal cord at the L1 level which ran into the intramedullary region. However, there was no further abnormality to define spinal arteriovenous malformation or fistula within the limits of exposure. The postoperative course was uneventful and about 2 months later she was able to walk by herself.

Female↗

PubMed1990

Clivus epidural hematoma. Case report.

A rare case of epidural hematoma of the clivus is reported in an 11-year-old girl involved in a traffic accident which caused a severe hyperextension injury. Only one similar case has been reported in the literature. The mechanism for the formation of the hematoma of this region is discussed.

Child↗