Biomedical subjects

Y Kohno

Publications and source records attributed to Y Kohno.

At least 181 records · Page 10Linked to original sources

PubMed1994

[Chemical iodination of hormonogenic tyrosine residues of human thyroglobulin is critical for the production of anti-thyroglobulin autoantibody and for the induction of experimental autoimmune thyroiditis in mice].

There is evidence from animal models that the iodine content of thyroglobulin (Tg) may influence its antigenicity in thyroid autoimmunity. To elucidate the effect of iodination of hormonogenic sites of human Tg (hTg) on its autoantigenicity, a synthetic peptide (TB: hTg 2546-2571), containing two hormonogenic tyrosine residues of hTg, and a chemically-iodinated peptide (TB-I) were prepared. We immunized C3H/He (H-2k) mice, a high responder strain to Tg, and BALB/c (H-2d), a low responder strain, with TB or TB-I plus lipopolysaccharide. Lymph node cells from the two strains immunized with TB or TB-I proliferated in response to both TB and TB-I. Anti-Tg autoantibodies were detected in both strains when immunized with TB-I, while immunization with TB failed to produce anti-Tg antibodies. Furthermore, one of the C3H/He mice immunized with TB-I developed diffuse thyroiditis, but BALB/c mice did not. These findings indicate that the iodination of the hormonogenic tyrosine residues of hTg, in other words, the synthesis of mono- and di-iodotyrosine (MIT and DIT) residues, is necessary for the production of anti-Tg autoantibodies in high and low responder mice and for the induction of autoimmune thyroiditis in high responder mice.

Amino Acid Sequence↗

PubMed1994

[Identification and immunopathogenicity of a common T cell epitope between human thyroglobulin and human thyroid peroxidase].

Human thyroglobulin (hTg) and human thyroid peroxidase (hTPO) share common B cell epitopes recognized by autoantibodies in patients with chronic autoimmune thyroiditis. Furthermore, we have demonstrated a functional common T cell epitope between hTg and hTPO in mice. Four hTg peptides in which 5 amino acid residues were identical to those of hTPO, and one hTPO peptide were prepared. Among these peptides, Tg-P4 (residues 2730-2743) and TPO-P4 (residues 118-131) shared the common T cell epitope and both peptides were highly antigenic. In addition, when the spleen cells from mice immunized with mouse Tg (mTg) were restimulated in vitro by Tg-P4 or TPO-P4, as well as by mTg, these cells transferred thyroiditis to naive recipient mice. These findings indicate that this common T cell epitope is immunogenic and related to the development of murine experimental autoimmune thyroiditis. The common T cell epitope between hTg and hTPO may play a role in the pathogenesis of human autoimmune thyroid disease.

Amino Acid Sequence↗

PubMed1994

[The clinical manifestations of Sjögren's syndrome in children].

Sjögren's syndrome (SS) is thought to be uncommon in children. We studied the clinical manifestations and laboratory findings of 12 pediatric patients with SS, all of children did not have sicca symptoms but have lymphocytic infiltration of salivary glands, abnormal sialograms or abnormal results of scintigraphy compatible with typical SS. Seven cases had primary SS and five were secondary SS and had other autoimmune disorders (three cases with systemic lupus erythematosus, one case with dermatomyositis, and the other with mixed connective tissue disease). All patients were female. The mean age at onset of symptoms, including other autoimmune manifestations, was 12.2 years (range 9-15 years). The initial symptoms were some systemic manifestations (fever, exanthema, arthralgia, etc.) and various autoimmune phenomena (butterfly rash, Raynaud's phenomenon, proteinuria, weakness of muscles, etc.). On the other hand, no patients complained sicca symptoms. Laboratory studies in our patients revealed elevated levels of IgG (92%), antinuclear antibody (92%), rheumatoid factor (58%), anti-SS-A antibody (75%). These findings were similar to those found in adult patients with sicca symptoms previously reported in literature. From these studies, we suggest that lip biopsy, sialography and/or salivary gland's scintigraphy should be carried out in patients who had abnormal laboratory findings as mentioned above, irrespective of absence of sicca symptoms, in order to diagnose SS at early period.

Adolescent↗

PubMed1994

Increase of acetylcholine release by nebracetam in dog cardiac sympathetic ganglion.

The effects of nebracetam (4-aminomethyl-1-benzylpyrrolidine-2-one hemifumarate, WEB 1881FU), a potential cognitive enhancer, on acetylcholine release from the preganglionic nerve terminals were investigated in the isolated dog stellate ganglia. Acetylcholine release from the isolated ganglia by preganglionic stimulation (5 Hz) was enhanced in the presence of nebracetam, 10(-7) to 10(-5) M. The release was decreased to a certain extent by bethanechol, 10(-5) M, and this decrease was completely antagonized by AFDX-116 (10(-5) M), a selective M2 muscarinic antagonist, but was unaffected by nebracetam (10(-6) M). Under the depleted condition of acetylcholine induced by pretreatment with hemicholinium-3 (10(-5) M) in combination with prolonged preganglionic stimulation, the release was increased to a degree by nebracetam or choline alone and was markedly increased in the presence of both nebracetam and choline. Nebracetam did not directly act on choline acetyltransferase activity, but acetylcholine formation was stimulated in the isolated ganglion incubated with the agent at 10(-6) M and in the ganglion isolated from the dog to which nebracetam, 5 mg/kg, was previously administered i.v. Uptake of choline in the isolated ganglia was not altered by nebracetam (10(-6) M) but was enhanced under the depleted conditions. These findings suggest that nebracetam enhances acetylcholine release from presynaptic sites of dog stellate ganglia not by blocking presynaptic M2 muscarinic autoreceptors but by accelerating acetylcholine formation, and by increasing choline uptake when acetylcholine is depleted.

Acetylcholine↗

PubMed1994

Preferential recognition of primary protein structures of alpha-casein by IgG and IgE antibodies of patients with milk allergy.

We studied the binding activities of IgE and IgG antibodies in patients with allergy to cow milk proteins, against different alpha-casein preparations: alpha-casein treated with urea, hydrochloric acid, sodium hydroxide, or sodium dodecyl sulfate (SDS); or heat-denatured alpha-casein. The binding activities of IgE and IgG antibodies to these denatured alpha-casein preparations were compared with those to native alpha-casein. The binding activities of IgE and IgG antibodies to these denatured alpha-casein preparations were similar to those to native alpha-casein although the binding activities of IgG antibodies to these denatured alpha-casein preparations were relatively heterogeneous compared with those of IgE antibodies. Since modifications of alpha-casein did not alter the ability of alpha-casein to react with these antibodies, IgE and IgG antibodies to alpha-casein in sera from patients with allergy preferentially bind to the antigenic determinants associated with primary protein structures.

Allergens↗

PubMed1994

[Detection of myocardial viability by delayed imaging after 201Tl reinjection].

Recent studies have demonstrated that some underestimation of myocardial viability remained to be not resolved even using reinjection method. So we devised a new technique of reinjection and reimaging, and using this we studied the detectability of myocardial viability in 32 patients of CAD. Exercise imaging (EX) was acquired after initial injection of thallium (111 MBq). Three hours after EX, the second dose thallium (37 MBq) was reinjected, and then the first reinjection image (Re1) was performed. Furthermore, the second reinjection image (Re2) was obtained at 3 hours after the second dose reinjection. SPECT images were divided in basal, mid and apical parts, and totally 13 segments were analyzed by visual scoring (0: severe, 1:moderate, 2:mild hypoperfusion and 3:normal). Twenty-seven (13.4%) of 202 segments of low score (0 to 2) shown in EX were improved in Re2, compared with Re1. Twenty-one (42.0%) of 50 segments of score 0 or 1 shown in Re1 were improved in Re2. These results showed that our devised new method of reimaging 3 hours after the second dose injection was useful to improve in detectability of myocardial viability.

Aged↗

PubMed1994

[Evaluation of myocardial perfusion and ventricular shape in hypertrophic cardiomyopathy using 99mTc-tetrofosmin scintigraphy: comparison with 201Tl myocardial scintigraphy].

Hypertrophic cardiomyopathy (HCM) is known to have the impairment of myocardial perfusion as well as irregularly hypertrophic myocardium. To evaluate myocardial perfusion and ventricular shape in HCM, 99mTc-Tetrofosmin scintigraphy was performed after exercise (Ex) and at resting state (Re) in 10 patients with HCM and was compared with early image (Ea) and delayed image (De) of 201Tl scintigraphy performed after exercise. SPECT images of both 99mTc-Tetrofosmin and 201Tl scintigraphy were analyzed with five scaled visual scores set in 18 segments. The complete concordance ratio between 99mTc-Tetrofosmin (Ex and Re) and 201Tl (Ea and De) images in segmental analysis was 75%. Image quality of 99mTc-Tetrofosmin was seemed to be superior to that of 201Tl scintigraphy. In 9 patients with HCM, 99mTc-Tetrofosmin scintigraphy was performed under the ECG gating and the thickness of septal and free wall was measured. Good correlation was observed with the data by ultrasound cardiography (r = 0.79, p < 0.002 in wall thickness, r = 0.84, p < 0.01 in the ratio of septal wall thickness to free wall thickness). Left ventricular shape (ventricular long axis) was closely resemble to that of left ventriculography by contrast medium. In conclusion, 99mTc-Tetrofosmin scintigraphy is useful for the evaluation of myocardial morphology as well as perfusion abnormality.

Adult↗

PubMed1993

Prognostic importance of histologic vascular density in cervical cancer treated with hypertensive intraarterial chemotherapy.

BACKGROUND: Over the past 20 years, various methods have been suggested to determine the histopathologic stage and grade of cervical cancer for predicting biologic behavior during chemotherapy. However, none of these complicated techniques have proved consistently accurate enough to predict chemotherapeutic effects on locally advanced cervical cancer. METHODS: Primary treatment with hypertensive intraarterial chemotherapy and, 4 weeks later, with radical hysterectomy were performed on 20 patients with locally advanced cancer of the uterine cervix (International Federation of Gynecology and Obstetrics [FIGO] Stages IIa-IVa). The vascular densities of biopsy specimens from pretreatment cancers stained by the Elastica-Goldner technique were measured semiquantitatively. Cytologic and histologic changes in the early stages after the intraarterial chemotherapy were simultaneously recorded. Patients were divided into two groups after analysis of the final histologic effects on operation materials in accordance with the criteria of the Japan Society for Cancer Therapy: (1) an effective group (> or = Grade 2; n = 7) or (2) a noneffective group (< Grade 2; n = 13). RESULTS: The vascular densities of the effective and noneffective groups were 6.91 plus or minus 4.51/mm2 and 1.94 plus or minus 1.21/mm2, respectively. The vascular densities of biopsy specimens were significantly higher in the effective group (P < 0.05). The early cytologic and histologic changes 1 week after chemotherapy were significantly greater in the effective group (P < 0.05). CONCLUSIONS: These results indicate that the efficacy of intraarterial chemotherapy for cervical cancers depends on their individual vascular densities, which can be detected beforehand through the study of biopsy specimens. Furthermore, cytologic and histologic changes in the early stages would seem to reflect the overall histologic effect of the treatment as a whole.

Adenocarcinoma↗

PubMed1993

Effect of a Ca2+ entry blocker, nilvadipine, on hearing disturbances and equilibrium dysfunction caused by microcirculatory disorders of the rat inner ear.

We evaluated the effects of Ca2+ entry blockers, nilvadipine and flunarizine, on microcirculatory disorders of the inner ear and on blood flow in the inner ear of rats. Under sodium pentobarbital anesthesia, the middle ear was opened by a ventrolateral approach. A green light (wave length 540 nm) was applied to the cochlea or the vestibule to induce a hearing disturbance or equilibrium dysfunction as a result of inner ear microcirculatory disorders, while rose bengal solution was infused intravenously. In a hearing disturbance model, a compound cochlear nerve action potential was recorded by electrocochleography every minute after the beginning of illumination. The sound stimulus was an 8 kHz sine wave 100 dB normal hearing level. The action potential was calculated 128 times. The action potential disappeared about 12 min after the beginning of illumination. In another model of equilibrium dysfunction, the photoillumination was applied for 40 min under the infusion of rose bengal. The behavior of rats was observed in the swimming test and nystagmus was recorded 24 h after the completion of photoillumination. In a separate experiment, blood flow in the inner ear was measured with a laser Doppler flowmeter under sodium pentobarbital anesthesia. In this study, both nilvadipine and flunarizine prolonged the time required for complete suppression of the action potential, prevented equilibrium dysfunction in the swimming test and reduced the occurrence of nystagmus. Flunarizine significantly increased inner ear blood flow and nilvadipine failed to decrease blood flow in the inner ear, despite a reduced systemic blood pressure. In conclusion, Ca2+ entry blockers may prevent microcirculatory disorders of the inner ear in rats.

Acoustic Stimulation↗

PubMed1993

A de novo deletion in the C1 inhibitor gene in a case of sporadic hereditary angioneurotic edema.

A sporadic case of hereditary angioneurotic edema (HANE) is reported here. The patient was a 15-year-old girl who for 4 years had suffered recurrent episodes of urticaria-like erythema, followed by vomiting with abdominal pain. She was diagnosed as having Sjögren syndrome by results of sialography and serological studies, and moreover, it was also observed that the C1 inhibitor (C1-INH) activity in her plasma was very low during these episodes of urticarial erythema. Diagnosis of acquired angioneurotic edema (AANE) was excluded because the patient's plasma had no inhibitory effect on the C1-INH activity of normal individuals. Although neither of her parents had a history of HANE, we were able to show that the patient had HANE by Southern blot analysis using C1-INH cDNA as a probe. One of the patient's C1-INH gene alleles was revealed to have at least a 17-kb-length deletion including exons 5-8. Neither her parents nor her healthy brother showed any abnormalities on Southern blot analysis. The parent-child relationship in this family was confirmed by an HLA-typing study of all family members.

Adolescent↗

PubMed1993

An animal model for hearing disturbance due to inner ear ischemia: photochemically induced thrombotic occlusion of the rat anterior inferior cerebellar artery.

A photochemical reaction between intravenous rose bengal and xenon light was used to induce a selective thrombus in the rat anterior inferior cerebellar artery (AICA). Compound action potentials (CAPs) were recorded by electrocochleography and cochlear blood flow (CBF) was monitored by laser Doppler flowmetry. Photothrombotic occlusion of the AICA caused inner ear ischemia to various degrees with or without alterations of the CAP. With use of this model we investigated the critical range of the CBF for preserving cochlear function, represented by the CAPs induced with 8 kHz half-wave of sinusoid at 100 dB SPL. Results then showed that a CBF range between 26.7% and 42.9% of baseline was somewhat critical for maintenance of cochlear function in an acute phase of ischemia. Pretreatment with heparin significantly delayed thrombotic occlusion of the AICA in a dose-dependent manner. Further use of our model for inner ear ischemia may be useful for studying pathophysiology and pharmacological therapy of cochlear disturbances subsequent to circulatory disorders.

Action Potentials↗

PubMed1993

Ultrastructural characteristics of intercellular contacts and bile canaliculi in neonatal rat hepatocytes in primary culture.

The ultrastructure of the cellular contacts and bile canaliculi was examined in cultured neonatal (day 5) rat hepatocytes to elucidate the development of cellular polarity. A new scanning electron microscopic technique for cultured hepatocytes allowed a view of cell-cell attachment and the entire cell surface, including the underside on plastic dishes. At 3 h after plating, neonatal hepatocytes were shown to be round, with loss of the preferential localization of cell organelles. After 6 h of culture, the cells had become oblong; they were aggregated in groups of several cells and the cellular contacts were not as rigid or as straight as those in adult hepatocytes. Transmission electron microscopy showed the biliary functional polarity to be like that in vivo. On the undersurfaces of adjacent neonatal hepatocytes a hemicanalicular structure lined with microvilli was found, which probably corresponds to the ultrastructure of bile canaliculi in vivo. However, no canaliculi or orifices of bile channels were found in adult hepatocytes. These results suggest that in neonatal rat hepatocytes the formation of tight rigid cellular contacts was suppressed. Modulation of cell membranes appeared on the undersurfaces of neonatal hepatocytes in early culture stages. The differences in the development of cellular polarity could be caused by the proliferating activity of neonatal hepatocytes.

Animals↗

PubMed1993

Effects of human epidermal growth factor on the development of bile canaliculi in neonatal rat hepatocytes in primary culture.

We have examined the effects of human epidermal growth factor (hEGF), a growth-promoting factor for hepatocytes, on the cytoskeletal structure and intercellular contacts in neonatal hepatocytes in primary culture. The ultrastructural characteristics of cellular contacts and bile canaliculi (BC) were examined using a newly developed technique of scanning electron microscopy for cultured hepatocytes. The neonatal hepatocytes incubated with hEGF plus insulin for 3 h showed more variety in shape than controls, and their cellular contacts were very loose with many long fibers. At this time, there were no changes in the distribution of microtubules or microfilaments. After treatment with hEGF plus insulin for 21 h, the distribution of microfilaments was altered. Actin filaments no longer surrounded BC, but were observed near the cell periphery; in addition, DNA synthesis was increased to 3.9 times the rate in controls. Treatment with dexamethasone for 3 h caused tight straight cellular contacts, and after 21 h actin filaments appeared around slightly dilated BC, but there was no increase in DNA synthesis. Transmission electron microscopy showed that the transport and secretion of horseradish peroxidase in BC was inhibited after 3-h incubation with hEGF. These results suggested that hEGF first affected the cellular contacts of hepatocytes necessary for the development of cellular polarity, and then affected the distribution of actin filaments, the development of functioning BC being suppressed.

Actin Cytoskeleton↗

PubMed1993

A common T-cell epitope between human thyroglobulin and human thyroid peroxidase is related to murine experimental autoimmune thyroiditis.

We have investigated functional common T-cell epitopes between human thyroglobulin (hTg) and human thyroid peroxidase (hTPO) in mice. Four hTg peptides, Tg-P1, Tg-P2, Tg-P3 and Tg-P4, in which 5 amino acid residues are identical to those of hTPO, and 1 hTPO peptide, TPO-P4 relevant to Tg-P4, were prepared. Among these peptides, only Tg-P4 (residues 2730-2743) and TPO-P4 (residues 118-131) were highly antigenic and both peptides shared the common T-cell epitope. In addition, when the spleen cells from mice immunized with mouse Tg (mTg) were restimulated in vitro by Tg-P4 or TPO-P4 as well as by mTg, these cells transferred thyroiditis to naive recipient mice. These findings indicate that this common T-cell epitope between hTg and hTPO is immunogenic and related to the development of murine experimental autoimmune thyroiditis.

Amino Acid Sequence↗

PubMed1993

Differentiation-associated localization of nPKC eta, a Ca(++)-independent protein kinase C, in normal human skin and skin diseases.

The expression of nPKC eta, a Ca(++)-independent isoform of protein kinase C in normal human skin, and skin from patients with psoriasis, squamous cell carcinoma, basal cell epithelioma, nevus pigmentosus, and seborrheic keratosis, were examined by immunohistochemical staining using a polyclonal antibody raised against a synthetic peptide at a diverse region of the nPKC eta molecule. In normal epidermis, the strongest staining was observed in the uppermost granular layer with no staining of the spinous or basal layers. The inner layer of the intra-epidermal eccrine duct was also strongly stained. Weak staining was observed in several layers of the outer root sheath of the follicular infundibulum. No staining was detected in the inner root sheath of the hair follicles, hair matrix, sebaceous gland, eccrine gland, intradermal eccrine duct, arrectores pilorum, melanocytes, Langerhans cells, fibroblasts, or blood vessels. In psoriatic skin, stained keratinocytes were distributed in the suprabasal layers with the most being observed in the uppermost layer and the least in layers closed to the basal layer. In squamous cell carcinoma, weak staining was observed in the keratotic cells around horny pearls. In the basal cell epithelioma and nevus pigmentosus, the cells were not stained, whereas in seborrheic keratosis, cells that stained were located in the granular layer. We conclude from the evidence presented above that nPKC eta is expressed in close association with epidermal differentiation in normal skin and skin diseases.

Adult↗

PubMed1993

Long QT syndrome with insulin-dependent diabetes mellitus: contiguous gene syndrome on chromosome 11p.

Long QT syndrome (Romano-Ward syndrome) and insulin-dependent diabetes mellitus (IDDM) have been documented as being linked with gene(s) on chromosome 11p although concurrence of the two disorders has not been reported. Our case is a 13-year-old boy with Romano-Ward syndrome accompanied by IDDM. The long QT syndrome seemed to be transmitted in an autosomal-dominant mode because the Q-T intervals of his father and paternal grandfather were longer than normal. There was no family member with an abnormally high level of blood glucose except the patient. The human leucocyte antigen (HLA) haplotypes of the patient and the father were DR4/DR9 and DR2/DR9, respectively. This study suggests that in our patient IDDM, as well as Romano-Ward syndrome, is linked with chromosome 11p in the presence of HLA-DR4. The results support the previous study that chromosome 11p encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility.

Child↗

PubMed1993

Iron-saturated lactoferrin as a co-mitogenic substance for neonatal rat hepatocytes in primary culture.

We studied the effect of lactoferrin on DNA synthesis in neonatal rat hepatocytes in primary culture to determine if this agent acts as a mitogen in human milk. Thymidine incorporation into the DNA of cultured hepatocytes stimulated by lactoferrin in the presence of insulin and human epidermal growth factor was examined. Iron-saturated lactoferrin increased DNA synthesis of neonatal hepatocytes by 1.5 times and this potency was the same as that of insulin. It significantly enhanced the stimulatory effect of human epidermal growth factor plus insulin; DNA synthesis under these conditions was seven times that of control. Iron-free lactoferrin did not affect DNA synthesis, nor did the exogenous addition of ferric ions. The enhancement of DNA synthesis by iron-saturated lactoferrin was significant for neonatal hepatocytes, but not for adult hepatocytes. These results suggest that iron-saturated lactoferrin, which itself had low mitogenic activity, is a co-mitogenic substance for neonatal hepatocytes in vitro.

Animals↗

PubMed1993

Comparison of the IgG subclass distribution of anti-thyroid peroxidase antibodies in healthy subjects with that in patients with chronic thyroiditis.

The IgG subclass distribution of anti-thyroid peroxidase (TPO) antibodies in patients with chronic thyroiditis and in healthy subjects has been investigated. Anti-TPO antibodies in sera of patients with chronic thyroiditis were predominantly associated with IgG1, with a lesser contribution by IgG4 and IgG3. In contrast, anti-TPO antibodies of healthy subjects were exclusively associated with IgG4. Since structural differences in IgG subclasses reflect differences in their biological roles, these findings suggest that the role of anti-TPO antibodies in patients may differ from that in healthy subjects.

Adolescent↗