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Biomedical subjects

M Kamiyama

Publications and source records attributed to M Kamiyama.

At least 37 records · Page 2Linked to original sources

Relationship between amount of beta-blockers permeating through the stratum corneum and skin irritation after application of beta-blocker adhesive patches to guinea pig skin.

We evaluated the relationship between the cumulative amounts of 5 kinds of beta-blockers (alprenolol, oxprenolol, timolol, acebutolol and atenolol) permeating through the stratum corneum and a* values obtained by measuring the formation of erythema, a skin irritation reaction, with a chromameter after transdermal application of adhesive patches containing 2 beta-blocker to the skin of guinea pigs. The cumulative amount of beta-blocker released from each adhesive patch to the skin increased with the increase in application time. The contents of alprenolol, oxprenolol and timolol in the stratum corneum and in the stripped skin increased markedly up to 4 h after application and thereafter were maintained at high levels up to 24 h. The contents of acebutolol and atenolol, on the other hand, increased up to 24 h, but these values were low. a* values of all adhesive patches 24 h after application were higher than those before application. The correlation coefficients between the cumulative amounts of alprenolol, oxprenolol, timolol, acebutolol or atenolol permeating through the stratum corneum and (delta a* -delta a*Placebo) values were 0.739, 0.717, 0.722, 0.551 and 0.633, respectively. The correlation coefficient calculated by averaging the cumulative amounts of 6 kinds of beta-blockers permeating through the stratum corneum [including propranolol which was reported previously (Kobayashi I., et al., Biol. Pharm. Bull., 19, 839-844 (1996))] was 0.731, higher than the correlation coefficient between contents of these beta-blockers in the stripped skin and (delta a* -delta a*Placebo) values (r = 0.552). This suggests that there was a high correlation between the cumulative amounts of beta-blockers permeating through the stratum corneum and (delta a* -delta a*Placebo) values.

Acebutolol↗

Menstrual stage influences postoperative nausea and vomiting following epidural buprenorphine.

BACKGROUND: Although buprenorphine sometimes causes severe emesis, its relation to the menstrual cycle has not been reported. METHODS: We conducted a prospective study on 68 reproductive-age women following lower extremity surgery under epidural anesthesia plus buprenorphine, to assess the effect of the day of the menstrual cycle on the incidence of postoperative nausea and vomiting. The patients were divided according to the phase of the menstrual cycle into four groups: day 1-7 group, day 8-14 group, day 15-24 group and day 25 to end of the cycle group. RESULTS: Nausea and vomiting were reported in 46 patients (67.6%), and the incidence was higher in the day 25 to end of the cycle group than in the day 8-14 or day 15-24 groups, and higher in the day 1-7 group than in the day 8-14 group. CONCLUSION: We conclude that emesis after epidural buprenorphine is related to the menstrual cycle.

Adult↗

Selective reduction of the S cone electroretinogram in diabetes.

AIMS: To determine whether the short wavelength sensitive (S) cone electroretinogram (ERG) is selectively altered in diabetic patients with and without retinopathy. METHODS: Ganzfeld spectral flashes in the presence of bright white background illumination were used to elicit S cone ERGs is 15 non-retinopathic diabetics, 16 background retinopathic diabetics, and 16 age matched normal controls. RESULTS: The amplitude of the S cone ERG b-wave was significantly reduced in both non-retinopathic and retinopathic diabetics. An action spectrum based on equal response criteria revealed a selective loss of S cone sensitivity in diabetics. However, no significant difference was observed in the long and middle wavelength sensitive cone ERG. CONCLUSIONS: Diabetic patients showed selective reduction of the S cone ERG, which is thought to reflect changes in the outer retina.

Adult↗

Undetectable S cone electroretinogram b-wave in complete congenital stationary night blindness.

AIMS: The short wavelength sensitive (S) cone electroretinograms (ERGs) were examined in two patients with the complete type of congenital stationary night blindness (CSNB). METHODS: Ganzfeld spectral flashes in the presence of strong white adapting fields were used to elicit the S cone ERGs. RESULTS: The S cone ERG b-wave was not detectable to short wavelength stimuli, while the mixed long (L) and middle (M) wavelength sensitive cone responses appeared normal in waveforms with normal amplitude in both patients. Both patients had normal colour vision on the Farnsworth Panel D-15. CONCLUSIONS: These ERG results indicated that the S cone system as well as rod system is more impaired in complete CSNB than the L and M cone system and that normal colour vision may not depend on a normal S cone ERG to full field stimuli.

Child↗

Relationship between the amount of propranolol permeating through the stratum corneum of guinea pig skin after application of propranolol adhesive patches and skin irritation.

In the present study we evaluated the relationship between the cumulative amount of propranolol permeating through the stratum corneum and the formation of erythema, a skin irritation reaction, after transdermal application of adhesive patches containing propranolol to the skin of guinea pigs. The intensity of erythema was expressed in terms of a* values measured with a chromameter. The a* values increased in guinea pigs after application of the adhesive patches containing 0.4 mg/cm2 of propranolol to the skin. Since the adhesive patches showed good adhesion to the skin (propranolol content is less than the saturated concentration in the adhesive base) and the cumulative amount of propranolol permeating through the stratum corneum is small, the development of erythema was considered to be mainly due to physical factors such as peeling. Even in adhesive patches containing 0.8 mg/cm2 or 1.2 mg/cm2 of propranolol, a* values increased, although adhesion to the skin is low because of crystallization of propranolol in the adhesive base. On the other hand, in these two adhesive patches, the cumulative amount of propranolol permeating through the stratum corneum increased up to 24 h after application. These findings suggest that the skin irritation reaction is due to propranolol mainly absorbed transdermally, because there is a high correlation between the cumulative amount of propranolol permeating through the stratum corneum and the a* values (r = 0.928).

Administration, Cutaneous↗

Nondetectable S-cone electroretinogram in a patient with crystalline retinopathy.

We examined cone and rod electroretinograms to ganzfeld stimuli in a patient with crystalline retinopathy. The 54-year-old man complained of night blindness, blurred vision, and metamorphopsia in both eyes. His visual acuity was 10/200 in the right eye and 10/20 in the left eye; his subjective dark-adaptation threshold was elevated 1 log unit, and he made one tritan error on the Farnsworth Panel D-15. Specular microscopic examinations revealed tiny crystalline deposits in the limbal cornea bilaterally. Ophthalmoscopically, crystalline deposits were found in the posterior fundi. His light-adapted cone electroretinograms to white stimuli were diminished (about 30% of those of normal controls), with normal implicit times. His dark-adapted rod electroretinogram amplitudes were 10% of those of normal controls. The S-cone electroretinogram was not detectable to different spectral stimuli with strong white background, while the L-M-cone responses appeared normal in waveforms with reduced amplitude. These ERG results indicated that the patient's S-cone system is more highly impaired than the L-M-cone system, supporting the psychophysical evidence that the S-cone system is more vulnerable than other cone systems in retinal diseases.

Dark Adaptation↗

[The clinical usefulness and problem of combined spinal epidural needle].

The clinical usefulness of combined spinal-epidural needles, Portex Spinal/Epidural set (Pencil point tip type and Lancet point tip type), was evaluated on 30 patients undergoing orthopedic lower limb surgeries, hysterectomies or transurethral surgeries. In all the patients, the spinal-epidural needles were successfully inserted with paramedian approach without any problem. The time to appearance of cerebrospinal fluid in the spinal needle hub after removal of the stylet was 15-40 seconds, and no patient in both groups had postspinal headache. Following spinal anesthesia, the local anesthetics injected through the epidural catheter extended the analgesia in the range of 1-2 dermatomes higher in the Lancet point type group in comparison with Pencil point type group. It is possible that the hole in the dura may allow a transfer of local anesthetics into the subarachnoid space. The present study shows that combined spinal-epidural block is clinically useful, and the Pencil point type is safer than the Lancet point type.

Adult↗

Characterization of human platelet IgG Fc receptor associated with membrane glycoprotein.

Human platelets express IgG Fc receptors (Fc gamma R). Previously we reported that circulating immune complexes (CIC) inhibited fibrinogen binding to platelet glycoprotein IIb/IIIa complex (GPIIb/IIIa) and that isolated Fc gamma R were recognized by monoclonal antibodies (mAb's) to GPIIb and GPIIIa (J.Lab. Clin. Med. 117:209-217, 1991). In this study, we further characterized the properties of the Fc gamma R and the activity associated with GPIIb/IIIa. Binding of Fc portion of human IgG (Fc) to the platelet Fc gamma R associated with GPIIb/IIIa complex, unlike fibrinogen receptor, did not require divalent cations. The Fc gamma R bound to immobilized immune complex were recognized by mAb's to GPIIb, GPIIIa, GPIIb/IIIa. Preincubation of platelet extract with fibrinogen inhibited the binding of heat-aggregated IgG (HAG) to the extract. Flow cytometry of whole platelets revealed inhibition of mAb binding to GPIIb/IIIa, when platelets were incubated with Fc fragments or HAG. Using platelet extract coated to microtiter plates, similar findings were noted with Fc and HAG. The dissociation of GPIIb/IIIa complex by incubating platelet extract at 37 degrees C in the presence of EDTA caused a marked decrease in the binding of GPIIb and GPIIIa to the immobilized immune complex. Activation of intact platelets with ADP resulted in an increased binding of HAG to the platelets, indicating that an augmented Fc gamma R activity is associated with the activation of GPIIb/IIIa. These results suggest a close relationship of the Fc gamma R activity to the fibrinogen binding site (GPIIb/IIIa complex).

Adenosine Diphosphate↗

Human platelet Fc receptors: binding kinetics of Fc derivatives to the receptors.

Human platelets are known to carry Fc receptors (Fc R), but the binding characteristics between ligands and Fc gamma R has not been well elucidated. In this study, we investigated the binding kinetics of IgG Fc fragments (Fc) to Fc R, the association and dissociation characteristics of the ligands to and from Fc gamma R using enzymatically modified Fc fragment derivatives. Approximately 60 minutes and 90 minutes were needed at 37 degrees C and 22 degrees C, respectively, for complete saturation of the Fc binding sites with horseradish peroxidase-conjugated Fc (HPO-Fc). Heat aggregated IgG (HAG) had a greater affinity for the Fc gamma R than Fc monomers. Additional binding of HAG was observed even after the binding sites were saturated with Fc monomers. This could be explained by different binding sites available only for immune complexes or by the partial dissociation of binding sites saturated with Fc by HAG. Further, we noted partial dissociation of HPO-Fc, when HAG was added after saturation of the binding sites with HPO-Fc. In a subsequent experiment, we compared the relative affinities of chemically or enzymatically modified Fc derivatives for Fc gamma R. HAG, which was used as a model for CIC, had a greater affinity for platelet Fc gamma R than IgG monomer and Fc derivatives. Pepsin-digestion of Fc caused a total loss of its affinity for the Fc gamma R, whereas b-mercaptoethanol-treated Fc fragments demonstrated substantial binding to the Fc gamma R. These results indicate that the pepsin digestion affects the Fc portion and causes a disruption in the area of the Fc which is essential for the recognition by the platelet Fc gamma R. On the other hand, cleavage of disulfide bridges by beta-mercaptoethanol resulted in a marked increase in affinity for the Fc gamma R. On the other hand, enzymatic cleavage of the carbohydrate moieties of Fc did not alter the affinity of Fc fragments for the Fc gamma R, indicating that the carbohydrates play an insignificant role or are not involved in their binding to the Fc gamma R.

Binding Sites↗

Acquired von Willebrand's syndrome in association with a lupus-like anticoagulant corrected by intravenous immunoglobulin.

We are reporting on a 47-year-old man who presented with a prolongation of the activated partial thromboplastin time (APTT) prior to orthopedic surgery. An evaluation suggested an inhibitor when his plasma prolonged a normal control APTT upon 50:50 solution of patients with normal plasma. The platelet-neutralizing procedure (PNP), anticardiolipin antibody, and antinuclear antibody (ANA) were positive. Further studies revealed decreased von Willebrand factor ristocetin cofactor (vWF:RCoF), von Willebrand factor antigen (vWF:Ag), an inhibitor to vWF, and absent high-molecular-weight vWF multimeters. Assays of FVIII:C, FIX, and FXI were nonparallel to the standard curve. Intravenous immunoglobulin (IVIG) corrected the APTT, multimeric pattern, and FVIII:C by the 7th day postinfusion. This case demonstrates the efficacy of IVIG for acquired von Willebrand's syndrome (vWS) and also represents a unique combination of a lupus-like anticoagulant and acquired vWS in a patient without the full serological requirement for systemic lupus erythematosus (SLE). Whether patients with acquired vWS and lupus inhibitors are more or less susceptible to either a thrombotic complication or hemorrhage is not established. Prospective studies for the incidence of lupus inhibitor/antiphospholipid syndromes and vWF deficiencies are needed to assess this question.

Blood Coagulation↗

Host factors required for internal initiation of translation on poliovirus RNA.

Translation of poliovirus RNA is initiated by entry of ribosomes into the nucleotide sequence (internal ribosomal entry site; IRES) within the 5'-untranslated region (5'-UTR). Efficiency of this translation initiation in rabbit reticulocyte lysates (RRL) was very low and was greatly enhanced by addition of the ribosomal salt-wash fraction (RSW) prepared from HeLa cells. This stimulating activity in the RSW was partially purified by gel-filtration column chromatography and its molecular weight was estimated to be higher than 240,000. Several proteins that bind specifically to the poliovirus IRES were detected in the active fraction. Among those, a 57 kDa protein, recognized by antibodies against polypyrimidide tract-binding protein (PTB), was found. In addition, La protein (52 kDa) which is a human antigen recognized by antibodies from patients with autoimmune disorders was also detected. Further purification on a hydroxylapatite column resulted in considerable loss of the stimulatory activity, accompanied by a reduction of the apparent molecular weight of active component(s). These results suggest that fully active HeLa cell stimulatory factors for the translation initiation on poliovirus RNA function in RRL as a large complex consisted of several components including PTB and La protein.

Acrylic Resins↗

Inhibition of human platelet glycoprotein IIB/IIIA binding to fibrinogen by tumor cell membrane proteins.

Immunochemical and functional characteristics of tumor cell membrane proteins and human platelet glycoproteins were studied. Immunoblotting revealed that membrane proteins of a cultured breast tumor cell line (BT-20) had three protein bands, which were each recognized by monoclonal antibodies to human platelet glycoprotein Ib, IIb, and IIIa, suggesting some immunochemical similarities between the tumor cell membrane proteins and platelet glycoproteins. The monoclonal antibodies failed to bind to an extract of a lung tumor cell line (A549). Neither tumor extract induced platelet aggregation. However, tumor-associated antigens isolated from the breast tumor cells markedly inhibited platelet glycoprotein IIb/IIIa binding to fibrinogen. In contrast, tumor-associated antigens from the lung tumor cells had no effect. These results suggest that tumor cells which have immunological and/or structural similarities to platelets may affect hemostasis and coagulation in vivo.

Binding, Competitive↗

Dysfunctional platelet glycoprotein IIb/IIIa associated with a platelet release defect: a family study.

We are reporting on a 36-year-old white female with a bleeding history attributed to dysfunctional platelet glycoprotein IIb/IIIa (GPIIb/IIIa) and a coexisting platelet release defect. Platelet aggregation studies (PAS) revealed markedly diminished to absent responses to ADP, epinephrine, collagen and arachidonic acid; the ristocetin response was normal. ATP content was normal with poor release to the agonists as measured by luminescent technique. DDAVP infusion shortened bleeding time from 13.5 min to 8.0 and 12 min (at 1 and 2 hours). Flow cytometry and immunoblotting revealed normal amounts of GPIIb and diminished GPIIIa (50% of control). Using a previously reported ELISA which measures the binding of GPIIb/IIIa to immobilized fibrinogen, the patient's platelet extract showed no binding to fibrinogen. Both the father and mother were found to have decreased PAS responses and normal amounts of GPIIb/IIIa determined by both Western blot and flow cytometry. However, the ELISA showed decreased binding of their GPIIb/IIIa to fibrinogen (71% and 62% as compared to controls, respectively). The patient's dysfunctional fibrinogen receptor was clearly demonstrated by the ELISA. The parents had moderately reduced GPIIb/IIIa function in this assay, but they did not demonstrate a reduced GPIIIa as was noted in the patient. The parents' PAS indicated a platelet release defect. These findings suggest an inherited platelet release defect and a dysfunctional GPIIIa. The partial response to DDAVP would be compatible with the presence of a platelet release defect.

Adult↗

Effect of intravenous immunoglobulin on inhibition of fibrinogen binding to platelets by sera from patients with immune thrombocytopenia.

We previously described an ELISA to measure the inhibition of platelet glycoprotein IIb/IIIa (GPIIb/IIIa) binding to fibrinogen due to immune complexes and/or anti-platelet antibodies from patients with immune thrombocytopenia (ITP) or HIV-related ITP. Circulating immune complexes (CIC) were the main factor in the inhibition of GPIIb/IIIa binding to fibrinogen in HIV-related ITP, whereas in non-HIV ITP, inhibition was only partially due to CIC; anti-platelet antibodies specific to GPIIIa were also shown to play a role. In this study, we correlated the rise in the platelet count after intravenous immunoglobulin (IVIG) infusion with the decrease in inhibition of fibrinogen binding to GPIIb/IIIa by the sera of patients with ITP and HIV-related ITP. In the majority of the patients' sera tested, as the platelet count increased following the administration of IVIG, the degree of inhibition of GPIIb/IIIa binding to fibrinogen decreased. We also observed a decrease and/or disappearance of the antibodies specific to GPIIb and/or GPIIIa after IVIG administration. In HIV-seronegative ITP patients, the decrease or disappearance of anti-platelet antibodies directly correlated with the decreased inhibition of GPIIb/IIIa binding to fibrinogen by the 2% PEG supernatants of sera which contained anti-platelet antibodies. These findings suggest that IVIG directly affects the binding of CIC and anti-platelet antibodies to platelets and thereby improves platelet survival. Our results also suggest that the anti-idiotypic effect may contribute to IVIG's therapeutic action. In contrast, in the HIV-seropositive group, the decreased inhibition by PEG precipitates after IVIG administration was more strongly associated with an increase in the platelet count.

Antibodies↗

Inhibition of platelet GPIIb/IIIa binding to fibrinogen by serum factors: studies of circulating immune complexes and platelet antibodies in patients with hemophilia, immune thrombocytopenic purpura, human immunodeficiency virus-related immune thrombocytopenic purpura, and systemic lupus erythematosus.

We have studied the conditions of in vitro binding of platelet glycoprotein IIb/IIIa (GPIIb/IIIa) to fibrinogen and applied the results to identify and measure the serum inhibitors to the binding. For the enzyme-linked immunosorbent assay, platelet extract was delivered to a fibrinogen-coated microtiter plate that was incubated for 2 hours, followed by incubation with anti-GPIIb/IIIa monoclonal antibody for another 2 hours. The plate was then incubated with peroxidase-conjugated anti-mouse IgG for color development. The binding was shown to be calcium-dependent. The binding was partially blocked by treating the coated fibrinogen with anti-fibrinogen antibody. Reduction or dissociation of GPIIb/IIIa resulted in the total loss of its ability to bind to fibrinogen. Platelet extracts of patients with hemophilia showed decreased binding (25% and 14%, compared with control platelet extract), and an extract from a patient with Glanzmann's thrombasthenia showed no binding. With the enzyme-linked immunosorbent assay we have measured serum inhibitors to GPIIb/IIIa binding to fibrinogen in 35 hemophilia A, 17 immune thrombocytopenic purpura, 22 human immunodeficiency virus-related immune thrombocytopenic purpura, and 29 systemic lupus erythematosus serum samples. In those patients with inhibition by serum, polyethylene glycol precipitation of circulating immune complexes (CICs) decreased the inhibition by the supernatants, and all the resolubilized CIC precipitates demonstrated inhibition, which indicates that CICs play a major role in the inhibition of GPIIb/IIIa binding to fibrinogen. This, then, provides evidence of CIC-mediated impaired GPIIb/IIIa binding to fibrinogen in hemophilia A, HIV-ITP, and SLE.

Antibodies↗

Computer-assisted linearization of the von Krogh Curve for the measurement of serum complement titre.

Computer simulations of complement titre measurement in sera by linearizing the sigmoidal curve of complement dose response were performed, to simplify the logarithmic calculations of CH50 values. CH50 titres of large variety of human sera including healthy donors and immune deficiency patients were estimated. The values obtained were compared with the hand-simulated results using the Y/(1-Y) conversion table and a log-log graphic paper. Using computer simulation, CH50 can be determined with great ease.

Complement Hemolytic Activity Assay↗