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Biomedical subjects

T Shinohara

Publications and source records attributed to T Shinohara.

At least 289 records · Page 16Linked to original sources
PubMed1989

[Chronic myelogenous leukemia characterized by successive lymphoid and myelomonocytic blast crises].

We report a 25 year-old male of CML, who repeated lymphoid blast crises twice and finally experienced a myelomonocytic blast crisis. In the first and the second crises, after 2 years of chronic phase, the blasts were only weakly positive or negative for terminal deoxynucleotidyl transferase. Based on other morphological features of the blasts, however, lymphoid blast crisis was strongly suspected. Actually, he responded well to the vincristine and prednisolone therapy. In the third crisis, the blasts showed myelomonocytic features. He did not respond to the same regimen, and died of intracranial infiltration during daunorubicin and cytosine arabinoside therapy after one year from the first crisis. Chromosomal analysis showed the karyotypes of 46, XY, t(9:22) (q34:q11) in the chronic phase, 45, XY, -7, -9, +der(9) t(7;9) (q11;p11), t(9:22) (q34:q11) in the lymphoid blast crisis, and 46, XY, t(9:22) (q34:q11), t(11:17) (q23:q25) in the myelomonocytic blast crisis.

Adult↗
PubMed1989

[Clinical evaluation of surgical treatment of children with Kawasaki disease].

Clinical problems in the surgical treatment for the vascular lesion after Kawasaki disease were evaluated in five patients who underwent myocardial revascularization. Each patient had significant stenosis or complete occlusion with aneurysmal formation. Four patients received single aortocoronary bypass and one patient received double bypass. Three saphenous veins and three internal mammary arteries were used for bypass grafting. There were no operative or late deaths. Three saphenous vein grafts and two internal mammary artery grafts were patent both in the early postoperative and in the late postoperative studies. Progression of the obstructive lesions at other coronary arteries which were not bypassed at the operation were found in two patients. One patient revealed bilateral common iliac aneurysms associated with progressive obstruction of urinary tract followed by renal dysfunction. It appears that even the patient who had satisfactory surgical results in late studies are required to be followed up with utmost care to other coronary lesions or other vascular lesions in addition to the lesions bypassed.

Child↗
PubMed1989

[Successful treatment of secondary erythroleukemia with androgen].

A case of secondary erythroleukemia treated with apparent success with androgen is reported. The patient is 63-year-old Japanese female. She had a history of multiple myeloma and had been treated with melphalan, vincristine and prednisolone. She developed erythroleukemia 88 months after the initiation of chemotherapy, while her myeloma was a complete remission. She was treated first with vitamin D3 with no beneficial effect and subsequently with 0.5 mg/kg of mepitiostane. A hematologic improvement began two months from the initiation of androgen therapy, and a complete remission of erythroleukemia was attained thereafter. A chromosomal abnormality of bone marrow cells, which was observed at the time of developing erythroleukemia, also disappeared after the treatment. She remained in good condition and hematologic remission under the androgen therapy at the latest follow-up, 1-year after the development of erythroleukemia. Androgen therapy may be considered as a useful treatment for secondary erythroleukemia.

Androstanols↗
PubMed1988

Scale-up methodology for the preparative purification of peptide M.

An octadecapeptide, peptide M, the epitope of a retinal protein that induces experimental autoimmune uveitis, was synthesized and purified by preparative reversed-phase chromatography. The flow-rate and gradient conditions for maximum separation of impurities were determined on a 30 x 0.39 cm I.D. column of Delta Pak (15-microns spherical C18-bonded silica with 300-A pores). The maximum amount of peptide that was resolved under these conditions was then determined experimentally. Using a scale factor dependent on the square of the column diameters, the flow-rate and amount loaded were increased 164 times on a 30 x 5 cm I.D. column of the same packing. The same resolution was achieved. Batches of 200-342 mg were chromatographed with reproducible results, providing a total yield of 394 mg of pure peptide.

Chromatography, High Pressure Liquid↗
PubMed1988

Structural analysis of mouse S-antigen.

Mouse S-antigen clones were isolated from a mouse retinal cDNA library using a bovine S-antigen cDNA probe. The largest clone (MSC-242) comprised 1532 bp and contained the entire coding sequence. The nucleotide sequence homology between the mouse and bovine coding regions was 84%, while non-coding regions appeared to be more divergent. The deduced amino acid sequence indicated that the mouse S-antigen had 403 residues and its molecular ratio was 44,930. An overall amino acid sequence similarity of 84% was observed between the mouse and bovine proteins. This degree of similarity dropped to 60% and 47% at the N and the C termini, respectively. The local homology with alpha-transducin observed in the bovine proteins, including the putative phosphoryl and rhodopsin binding sites, was conserved in the mouse as well. There was no overall sequence similarity with other proteins listed in the National Biomedical Research Foundation (NBRF) protein sequence database. Among the uveitopathogenic sites for experimental autoimmune uveitis (EAU), peptides N and M were identical to their bovine counterparts. Peptides 3 and K, however, were more divergent. The short repeats within these peptides were conserved.

Amino Acid Sequence↗
PubMed1988

The sequence of human retinal S-antigen reveals similarities with alpha-transducin.

The complete amino acid sequence of human retinal S-antigen (48 kDa protein), a retinal protein involved in the visual process has been determined by cDNA sequencing. The largest cDNA was 1590 base pairs (bp) and it contained an entire coding sequence. The similarity of nucleotide sequence between the human and bovine is approximately 80%. The predicted amino acid sequence indicates that human S-antigen has 405 residues and its molecular mass is 45050 Da. The amino acid sequence homology between human and bovine is 81%. There is no overall sequence similarity between S-antigen and other proteins listed in the National Biomedical Research Foundation (NBRF) protein data base. However, local regions of sequence homology with alpha-transducin (T alpha) are apparent including the putative rhodopsin binding and phosphoryl binding sites. In addition, human S-antigen has sequences identical to bovine uveitopathogenic sites, indicating that some types of human uveitis may in part be related to the animal model of experimental autoimmune uveitis (EAU).

Amino Acid Sequence↗
PubMed1988

Structure-activity relationship of reversible cholinesterase inhibitors including paraquat.

The inhibitory effect of paraquat on cholinesterase activity was investigated in comparison with four paraquat derivatives, six monoquaternary ammoniums and six anticholinergic drugs. Inhibitor concentrations to cause 50% inhibition (I50) and Hill coefficients for three enzymes, human erythrocyte acetylcholinesterase (AChE), Electrophorus electricus AChE and human plasma butyrylcholinesterase (BuChE) were measured. The results obtained were as follows. The I50 for erythrocyte AChE was similar to the I50 for eel AChE. Secondary to edrophonium, diethylparaquat, paraquat, morfamquat and monoquat showed lower I50 for AChE, and possessed higher inhibition selectivity (IS), expressed as the ratio of I50 for BuChE to I50 for erythrocyte AChE. However, diquat showed higher I50 for AChE and lower IS, similar to the other monoquaternary ammoniums. A negative correlation was observed between log [I50 for erythrocyte AChE] and log [IS], among paraquat and its derivatives, monoquaternary ammoniums and anticholinergic drugs, respectively. With respect to Hill coefficients, these inhibitors could be classified into four groups, [1] competitive inhibitors: diquat, edrophonium, choline, tetramethylammonium and trimethylphenylammonium, [2] inhibitors showing negative cooperativity: paraquat, diethylparaquat, morfamquat, d-tubocurarine, atropine, gallamine and nicotine, [3] moderate type inhibitors: monoquat, hexamethonium and decamethonium. [4] the other type inhibitors showing positive cooperativity for erythrocyte AChE: tetraethylammonium and ethyltrimethylammonium.

Animals↗
PubMed1988

Imaging local cerebral blood flow by Xenon-enhanced computed tomography--technical optimization procedures.

Methods are described for non-invasive, computer-assisted serial scanning throughout the human brain during eight minutes of inhalation of 27%-30% Xenon gas in order to measure local cerebral blood flow (LCBF). Optimized Xenon-enhanced computed tomography (XeCT) was achieved by 5-second scanning at one-minute intervals utilizing a state-of-the-art CT scanner and rapid delivery of Xenon gas via a face mask. Values for local brain-blood partition coefficients (L lambda) measured in vivo were utilized to calculate LCBF values. Previous methods assumed L lambda values to be normal, introducing the risk of systematic errors, because L lambda values differ throughout normal brain and may be altered by disease. Color-coded maps of L lambda and LCBF values were formatted directly onto CT images for exact correlation of function with anatomic and pathologic observations (spatial resolution: 26.5 cubic mm). Results were compared among eight normal volunteers, aged between 50 and 88 years. Mean cortical gray matter blood flow was 46.3 +/- 7.7, for subcortical gray matter was 50.3 +/- 13.2 and for white matter was 18.8 +/- 3.2. Modern CT scanners provide stability, improved signal to noise ratio and minimal radiation scatter. Combining these advantages with rapid Xenon saturation of the blood provides correlations of L lambda and LCBF with images of normal and abnormal brain in a safe, useful and non-invasive manner.

Aged↗
PubMed1988

LCBF values decline while L lambda values increase during normal human aging measured by stable xenon-enhanced computed tomography.

Results of measurements of LCBF and L lambda values utilizing optimal CT-CBF methods under resting conditions are reported among thirty-two neurologically normal volunteers aged between 20 and 88 years. Measurements were made during inhalation of 26-30% stable xenon gas for 8 min and serial scanning utilizing a state-of the-art CT scanner with both eyes closed and ears unplugged. LCBF values for cortical gray matter were lowest in occipital cortex and highest in frontal cortex. Gray matter flow values were also high in subcortical structures with highest values measured in the thalamus. For white matter, highest flow values were measured in the internal capsule. Changes in LCBF and L lambda values were analyzed with respect to advancing age. Significant age-related declines in LCBF values were observed in occipital cortex and frontal white matter. Significant age-related increases in L lambda values were measured in frontal and temporal cortex, caudate nucleus and thalamus. Possible explanations are offered for these age-related increases in L lambda values for gray matter, such as accumulation of lipofuscin in neurons and relative compacting of gray matter with advancing age. The latter increases the numbers of nerve cells sampled per volume of gray matter measured.

Administration, Inhalation↗
PubMed1988

Identification of a uveitopathogenic and lymphocyte proliferation site in bovine S-antigen.

S-antigen is a well-characterized retinal protein that is highly pathogenic for the induction of experimental autoimmune uveitis (EAU), a severe inflammatory disease of the eye and the pineal gland. EAU was observed following the immunization of Lewis rats with various doses (50 to 200 micrograms) of a small synthetic peptide, peptide N (22 amino acids in length), which corresponds to amino acid positions 281 to 302 in bovine S-antigen. Peptide N consistently induced an EAU that was identical to the disease caused by native S-antigen. Clinically, the disease that developed in the eye was characterized by iris and pericorneal hyperemia, followed by inflammatory exudates in the anterior chamber and vitreous. Histopathologically, a severe inflammatory response was observed that resulted in the complete destruction of the photoreceptor cell layer of the retina. In addition, animals with ocular inflammatory disease had an associated pinealitis characterized by a lymphocytic infiltration of the pineal gland. Furthermore, draining lymph node cells of rats immunized with peptide N showed strong in vitro proliferative responses toward peptide N as measured by [3H]thymidine uptake. Our results indicate that several synthetic peptides, which correspond to the amino acid sequence of bovine S-antigen, are capable of inducing an EAU and, as such, suggest that multiple uveitopathogenic sites may be present in the molecule.

Animals↗
PubMed1988

Cytogenetic study of chronic lymphocytic leukemia in ten Japanese patients with a case of the same chromosome abnormality both in T and B cells.

Peripheral blood lymphocytes from ten patients with chronic lymphocytic leukemia (CLL) stimulated with phytohemagglutinin (PHA), pokeweed mitogen (PWM), Epstein-Barr virus (EBV), and T-cell growth factor were studied cytogenetically. Eight of ten cases were clinically and immunologically B-cell CLL, and two cases were T-cell CLL. Chromosome analysis revealed that one patient, diagnosed as B-cell CLL, had a clonal abnormality in the leukemic cells. The abnormal karyotype was 46,XY,+3,-15,t(10;19)(q22;p13),t(11;14) (q13;q32),13q+,17q-. The frequencies of the abnormal cell stimulated with PHA, PWM, and EBV were 50%, 13%, and 100%, respectively. Finding the same clonal abnormality after stimulation with three different mitogens suggests that the factor responsible for the development of CLL might affect the stem cell common to T-cell and B-cell lymphocytes. In cells with this abnormal karyotype, chromosome 13q+ seems to have a homogeneous staining region. In the present series of B-cell CLL, no trisomy 12 known to be the specific chromosome abnormality was observed.

Adult↗
PubMed1988

Distal trisomy of chromosome 17q due to inverted tandem duplication.

A female infant with distal trisomy 17q is described. The anomaly resulted from a de novo inverted duplication of the 17q2405----q25.3 region as defined by high-resolution banding. The proband's overall clinical picture was in good agreement with those of previously reported cases of partial trisomy 17q. The phenotypic features relatively common to our and other reported cases, included mental and growth retardation, microcephaly, temporal retraction, blepharophimosis, saddle nose, thin upper lip, down-turned corner of the mouth, high-arched palate, low-set and deformed ears, webbed neck and lowered posterior hairline. A unique feature of the present case was systemic hirsutism.

Abnormalities, Multiple↗
PubMed1988

Bilateral hemispheric reduction of cerebral blood volume and blood flow immediately after experimental cerebral hemorrhage in cats.

Acute cerebral circulatory changes following experimental cerebral hemorrhage were investigated in eight cats. The cerebral hemorrhage was produced in the right basal ganglia by introducing arterial blood via a thin catheter, using the systemic arterial blood pressure of the cat as a driving force. Local cerebral blood volume was measured continuously in the bilateral parietotemporal cortexes employing photoelectric apparatuses. Carbon black dilution curves were recorded from the regions, and the mean transit time of blood was calculated. Local cerebral blood flow was estimated from mean transit time and cerebral blood volume. Intracranial pressure was monitored continuously in the right parietal epidural space. Five minutes after cerebral hemorrhage, intracranial pressure increased by 24.0 +/- 6.1 mm Hg, while mean arterial blood pressure increased by only 2.9 +/- 2.0 mm Hg. Cerebral blood volume decreased by 1.60 +/- 0.24 vol% in the hemorrhagic and 1.14 +/- 0.30 vol% in the nonhemorrhagic hemisphere. Cerebral blood flow decreased by 30.0 +/- 4.5 ml/100 g brain/min in the hemorrhagic (initially 64.5 +/- 13.6) and by 30.3 +/- 7.5 ml/100 g brain/min in the nonhemorrhagic (initially 60.9 +/- 6.9) hemisphere. Increased intracranial pressure appeared to be the main cause of the observed cerebral blood volume/flow reduction shortly after experimental hemorrhage in the basal ganglia. Several other factors and mechanisms involved are discussed.

Animals↗
PubMed1988

Human S-antigen: characterization of uveitopathogenic sites.

Human S-antigen (HSA) is a 50,000 molecular weight photoreceptor cell protein capable of inducing an experimental autoimmune uveitis (EAU) in susceptible animal strains. In order to determine specific sites responsible for its uveitopathogenicity, we synthesized 39 overlapping peptides corresponding to its entire 404 amino acid sequence and tested each peptide for its ability to induce an EAU in Lewis rats. Two synthetic peptides designated peptide HSA 319 (amino acid positions 286 to 305) and peptide HSA 320 (amino acid positions 306 to 325) were uveitopathogenic when used at 50 and 100 micrograms immunizing doses. Smaller peptides corresponding to the amino, mid, and carboxy terminal portions of each peptide further refined each uveitopathogenic site to 12 amino acids. A computerized analysis of the amino acid sequence of S-antigen indicates that these uveitopathogenic sites are complex and may be related to a two-fold symmetry in the molecule. Our present and previous studies provide a basis for the uveitopathogenicity of human and bovine S-antigen in the pathogenesis of EAU as well as the pathogenesis of certain forms of uveitis in humans.

Amino Acid Sequence↗
PubMed1988

S-antigen: experimental autoimmune uveitis induced in guinea pigs with two synthetic peptides.

Experimental autoimmune uveitis (EAU) was observed in Hartley guinea pigs following immunization with two small synthetic peptides, peptide M and peptide M15L, which correspond to the amino acid sequence of a well-characterized region of bovine S-antigen. Groups of guinea pigs were immunized with 100 micrograms of each peptide in complete Freund's adjuvant and examined at regular intervals for the development of disease. Approximately two weeks later, an EAU was present which was characterized clinically by iris and pericorneal hyperemia. Histopathologically, a severe inflammatory response involving the uveal tract and retina was observed. In these eyes the photoreceptor cell layer of the retina was destroyed. A subretinal exudate containing mononuclear cells and polymorphonuclear leukocytes was also present. In addition, animals with EAU showed an associated pinealitis characterized by a lymphocytic infiltration of the subcapsular and central area of the pineal gland. Furthermore, draining lymph node cells of guinea pigs immunized with peptide M showed strong in vitro proliferative responses towards peptide M as measured by 3H thymidine uptake. These results demonstrate the existence of at least one common pathogenic epitope in bovine S-antigen for the induction of EAU in Hartley guinea pigs and Lewis rats.

Animals↗
PubMed1988

A cell line and clones of lymphocytes from a healthy donor, with specificity to S-antigen.

Retinal-specific antigens can induce autoimmune diseases in eyes of immunized experimental animals and are thought to be involved in certain uveitic conditions in man. We have recently found that peripheral blood lymphocytes from a large proportion of healthy donors react in culture against the retinal S-antigen (S-Ag), when tested by a modified sensitive assay. The investigation of this responsiveness was extended by isolation and characterization of a cell line and clones specific to S-Ag from the blood of a healthy donor. Characterization of the cell line and clones by flow cytometry showed that these lymphocytes carried antigens specific for helper/inducer T cells (CD3 and CD4). The response of the cell line and clones to S-Ag depended completely on added antigen-presenting cells (APC), and was MHC-restricted; no response was observed in cultures with APC carrying incompatible MHC antigens. The cell line and clones reacted to S-Ag considerably more vigorously than the freshly collected blood lymphocytes from the same donor. These data thus provide additional support to the notion that lymphocytes with reactivity toward retinal specific antigens are present in the circulation of normal donors. The possibility that such cells could be involved in pathogenic autoimmune processes in the eye is discussed.

Antigens↗
PubMed1988

[Uptake of anticancer drugs by target organs and the usefulness of adjuvant chemotherapy].

Forty-one patients with advanced gastric cancer underwent gastrectomy, and the correlation between tissue uptake of the adjuvant drug and the prognosis were studied. The patients were preoperatively administered Tegafur and samples of tissue were obtained intraoperatively. 5-FU levels in the tumor and lymphnodes were measured by gas chromato-mass fragmentography (GCMF). The patients measured for 5-FU tissue uptake were given more than 60 g of tegafur as postoperative adjuvant chemotherapy, and divided into two groups; one in which the 5-FU uptake by tumor tissue and lymphnode was over 0.05 microgram/g and the other lower than 0.05 microgram/g. In both groups there were no significant differences in background factors. Each survival rate was calculated by the Kaplan-Meier method, and the generalized Wilcoxon method was used for statistical analysis. There was no statistically significant correlation between 5-FU uptake by the tumor and the prognosis, but the 5-year survival rate in the group with over 0.05 microgram/g uptake by lymphnodes was statistically significant (p = 0.018).

Adult↗