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Biomedical subjects

Y Inagaki

Publications and source records attributed to Y Inagaki.

At least 271 records · Page 15Linked to original sources

Higher incidences of anti-SS-A/Ro and anti-SS-B/La autoantibodies in Japanese patients with autoimmune disorders--studies of antigens and antibodies using the immunoblotting method.

A specific and sensitive assay was performed to detect both anti-SS-A/Ro and anti-SS-B/La antibodies in sera of patients with autoimmune diseases, including systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS), Sjögren's syndrome (SS), discoid lupus erythematosus (DLE), mixed connective tissue disease (MCTD), generalized morphea (GM), and dermatomyositis (DM). The SS-A/Ro and SS-B/La antigens were prepared from human spleen (HSE) and cultured human cell line (KB cells, KBE), white rabbit thymus extract (RTE) was used as the SS-B/La antigen marker. The antigens were partially purified by DEAE cellulose column chromatography. Immunoblotting showed that the SS-A/Ro antibody reacts mainly with the 58-kDa peptide of the partially purified antigen. Sera containing both the SS-A/Ro and SS-B/La antibodies reacted with the 40-kDa peptide of RTE, and the 58-kDa, 42-kDa, and 40-kDa peptides of HSE and KBE. We found that some of the SS-A/Ro antisera could further react with the 64-kDa peptide of HSE and KBE. The 58-kDa peptide is rich in its cytoplasmic fraction of KB cells, and the 4-kDa peptide in nucleoplasmic fraction. The KB cell line is a better source of the antigens than human spleen extract. The immunoblotting method clearly showed that the positivity rates of SS-A/Ro and/or SS-B/La autoantibodies were higher in sera from Japanese patients with SLE compared with titers reported for Caucasians but not in sera from healthy volunteers.

Autoantibodies↗

Decrease of transplantability by the immunopotentiators, OK-432 and interleukin-2: experiments on a human hepatoma cell line in nude mice.

The relationship between nonspecific cytotoxic activity of spleen cells and the resistance against the graft challenge of a human hepatoma cell line (HCC-M) was investigated in nude mice. Two administrations of an immunopotentiator, OK-432 or human interleukin-2, prior to the subcutaneous inoculation of HCC-M cells, which was performed 24 h after the last administration, significantly inhibited the tumor development in terms of rate of tumor take and tumor size. This effect was abrogated by simultaneous administration of an anti-asialo GM1 (ASGM1) antiserum. There was a significant inverse correlation between tumor volume and spleen cell cytotoxicity which was determined at the time of HCC-M cell inoculation against a YAC-1 or HCC-M target. Spleen cell cytotoxicity enhanced by these immunopotentiators could not completely be abolished by in vitro treatment with ASGM1 and complement. This result suggests that effector cells of the enhanced cytotoxicity consist of heterogeneous cells including both ASGM1+ natural killer cells and other nonselective cytotoxic cells. These results suggest that nonspecific cytotoxic cells play crucial roles in the resistance against tumor cell challenge and that the total level of cytotoxic activity of these cells at the time of tumor cell challenge is a key factor which determines tumor development.

Animals↗

In-vitro activity of DR-3355, an optically active isomer of ofloxacin, against bacterial pathogens associated with travellers' diarrhoea.

The in-vitro activity of DR-3355, the S-(-)-isomer of ofloxacin, was determined against bacterial pathogens associated with travellers' diarrhoea. DR-3355 was highly active against isolates of enteropathogenic Escherichia coli (MIC90 0.05 mg/l), Salmonella spp. (MIC90 0.10 mg/l), Shigella spp. (MIC90 0.10 mg/l), Campylobacter jejuni (MIC90 0.39 mg/l) and Vibrio parahaemolyticus (MIC90 0.39 mg/l). The activity of DR-3355 against these bacteria was generally two- to eight-fold greater than that of ofloxacin and equal to, or only two-fold less than, that of ciprofloxacin with the exception of isolates of C. jejuni, which were two-fold less susceptible to ciprofloxacin than to DR-3355.

Anti-Bacterial Agents↗

[Serovars, antimicrobial resistance and conjugative R plasmids of Salmonella isolated from human during the period of 1966-1986 in Tokyo. Research Group for Infectious Enteric Diseases].

We examined 4,739 isolates of Salmonella isolated from patients with gastroenteritis during the period of 1966-1986 in Tokyo for the incidences of serovars, antibiotic resistance and conjugative R plasmids. The period of study was divided into three: 1966-73 (early period), 1974-79 (middle period), and 1980-86 (late period). The predominant serovars were S. typhimurium (34.3%), Infantis (5.6%), Panama (4.9%) in the middle period, S. typhimurium (31.7%), Paratyphi B (9.4%), Litchfield (7.3%) in the late period. These results were consistent with serovars of isolates from healthy citizens. The frequency of resistant isolates was as high as 86.9% in the early period, mostly streptomycin (SM)- and tetracycline (TC)-resistant isolates, but decreased significantly in the middle and the late periods, to 53.3 and 39.4%, respectively. The percentages of ampicillin (ABPC)-, chloramphenicol (CP)-, and kanamycin (KM)-resistant isolates increased in the late period. Strains carrying conjugative R plasmids were isolated as frequently as 57.8% of the total isolates in 1973, but as less frequently as 6.7% in 1981 indicating that the rate was roughly proportional to the incidence of the drug resistant isolates. The rate, however, increased gradually after 1981. The predominant resistance pattern of the R plasmids was TC-resistance in the early period, gradually changed into multiple and finally to AP-, CP-, KM-, SM-, TC- and sulfonamides-resistance in the late period.

Conjugation, Genetic↗

Sympathetic nervous function and erythrocyte cation transport systems in normotensive individuals with family history of hypertension.

To investigate the influence of heredity to the sympathetic nervous function and the cell membrane cation transport systems, we studied the blood pressure and plasma catecholamine response to supine exercise testings by bicycle ergometer, the pressure response to noradrenaline infusion tests and the heart rate response to isoproterenol infusion tests in 88 healthy Japanese sedentary normotensive men with and without a family history of essential hypertension [FHH(+) and FHH(-)]. Several erythrocyte monovalent cation transport parameters were also measured in 74 of these individuals. In the results, (1) the systolic blood pressure response to exercise testings and noradrenaline infusion tests were larger in FHH(+) than FHH(-): (2) there was no difference between FHH(+) and FHH(-) in the heart rate response to isoproterenol infusion tests: (3) there was no significant difference between FHH(+) and FHH(-) in the increased plasma catecholamine levels to exercise testings: (4) the intraerythrocytic sodium content was significantly higher in FHH(+) than in FHH(-): and (5) several erythrocyte monovalent cation transport systems (Li-Na countertransport, Na-K cotransport and Na-K pump activity) were clearly accelerated in FHH(+). We concluded that in spite of normotension there were abnormalities of sympathetic nervous function, intracellular sodium content and several cell membrane cation transport systems in individuals with a family history of essential hypertension.

Adult↗

[Treatment of mediastinal infection following cardiac surgery by continuous closed irrigation with povidone-iodine in early infancy].

Two patients aged 2 months and 9 days with postoperative mediastinal infection were treated by continuous closed irrigation with 0.5% povidone-iodine solution. Satisfactory eradication was achieved in both two patients. Although serum iodine level was elevated as high as 7,610 micrograms/dl in the neonatal patient, no disturbances of the thyroid function and the acid-base balance were seen. The usefulness of continuous closed irrigation in the neonatal or infantile period was suggested.

Cardiac Surgical Procedures↗

[Systolic time intervals in mitral valve prolapse syndrome].

Systolic time intervals (STI) were measured in 135 patients with mitral valve prolapse syndrome (MVP). These patients were categorized as Group II (no or trivial mitral regurgitation) and Group III (moderate or severe regurgitation). The controls consisted of 120 normal subjects (Group I). The Group II patients tended to have increased ETc and shortened PEP. The Group III patients tended to have prolonged Q-I and decreased QIIc and ETc, reflecting mitral regurgitation. It was suggested that autonomic nervous system, especially sympathetic nerve, may play a role in changes of STI of the Group II patients.

Adolescent↗

Measurement of regional myocardial blood flow in hypertrophic cardiomyopathy: application of the first-pass flow model using [13N]ammonia and PET.

Positron emission tomography (PET) has become an important tool in the study of regional myocardial blood flow. The purpose of the present study was to measure regional myocardial blood flow using dynamic [13N]ammonia PET and the first-pass flow model. Thirteen patients with hypertrophic cardiomyopathy, and with a considerably thickened ventricular wall (25 mm or greater), were selected for the study in order to minimize errors due to spillover of radioactivity from blood to the myocardium and to the underestimation of myocardial activity caused by the partial volume effect. Arterial input function was determined by assigning a region of interest to the left atrial cavity on the PET images. Using left atrial and myocardial time-activity curves, regional myocardial blood flow was calculated using the first-pass flow model. Mean myocardial blood flow ranged from 47.8 to 76.5 ml/min per 100 g (63.0 +/- 9.4). Regional myocardial blood flow in the septum was significantly lower than in the anterior and lateral walls of the left ventricle (P less than .01). These results indicate the potential usefulness of dynamic PET in the measurement of regional myocardial blood flow in man.

Adult↗

Peritoneal dialysis as therapy for electrolyte and acid base disorders.

Peritoneal dialysis (PD) does not demand special equipment and its fluid composition can be easily changed according to the individual condition. Nine patients with chronic or acute renal failure presented severe metabolic alkalosis (MA). Hemodialysis (HD) proved virtually ineffective and the MA persisted. Physiological saline solution was adopted as the main component of the PD fluid for the treatment of MA. By this method, Cl- can be shifted from PD fluid to extracellular fluid (ECF) and HCO3- from ECF to PD fluid by ionic gradient. Therefore, pH and base excess (BE) of these patients both improved to the normal range after several fluid exchanges. The lowering effect of BE (delta BE/L) ranged from 0.99 to 2.6. Hyposaline and normo-osmol solution (Na+ 70 mEq/L) were used for one patient with hypernatremia and consciousness disturbance. Serum (S)-Na decreased from 170 to 138 mEq/L, and consciousness became almost clear with the use of 15 L of PD fluid. Hypersaline solution (Na+ 190 mEq/L) was used for two patients with hyponatremia (S-Na 113 and 121 mEq/L). S-Na rose to within the normal range after 16 and 9 L in the two cases. A fluid mixed with distilled water, 10% NaCl and 7% NaHCO3 (HCO3 34-68 mEq/L) was used to treat lactic acidosis in two patients. By this method, HCO3- can be shifted from PD fluid to ECF and lactic acid from ECF to PD fluid. Two patients recovered from prolonged shock, and pH was corrected by 10 L and 4 L, respectively. PD should be considered for application in other diseases besides renal failure.

Acid-Base Imbalance↗

Sodium sensitivity of blood pressure and baroreceptor reflex function in patients with essential hypertension.

In order to define the role of the baroreceptor reflex function in the sodium sensitivity of blood pressure in patients with mild essential hypertension, 25 patients were classified into two groups, salt-sensitive and salt-insensitive, depending on the difference in the averages of the resting systolic blood pressure, taken hourly on the fifth day of 7 days of sodium depletion and on the fifth day of 7 days of repletion. Increases in urinary sodium excretion and body weight and a decrease in haemotocrit during the sodium repletion period were similar in both groups. Baroreceptor reflex function, estimated from the baroreceptor slope and the blood pressure change on a 70 degrees tilting test, was enhanced by the sodium repletion period in the sodium-insensitive group but not in the sodium-sensitive group. These results suggest that sodium sensitivity might be due to differences in the ability of the baroreceptor reflex function to become sensitized during a high sodium intake.

Blood Pressure↗

SSA/Ro antigen expression in simian virus 40-transformed human keratinocytes.

SSA/Ro antigen is a soluble cellular component to which antibodies are frequently produced in patients with Sjögren's syndrome and systemic lupus erythematosus. Its exact location within the cell has yet to be determined. In this study we report the expression of SSA/Ro antigen in simian virus 40 (SV40)-transformed keratinocytes. The locations of SSA/Ro, U1RNP, and DNA antigens were studied by indirect immunofluorescence using monospecific antibodies. SSA/Ro antigen was detected in both the nucleus and cytoplasm of SV40-transformed keratinocytes tested with three monospecific sera. Primary cultured keratinocytes derived from adult human skin showed localized immunofluorescent staining within the nucleus. When Ca++ concentration of the medium was switched to 0.05 mM, these cells expressed cytoplasmic SSA/Ro antigens within 48 h. Depletion of the antibody activity with insolubilized human spleen extract abolished the staining. Surface expression of this antigen could not be detected in either primary or transformed cells. Localization of U1RNP and DNA was not altered. These results indicate that expression of SSA/Ro antigen in human keratinocytes is modulated by SV40 infection and that this antigen is expressed to a greater degree in cells that are less differentiated, transformed, or proliferating.

Autoantigens↗

Structure-activity relationship of hylambatin and its fragments as studied in the guinea-pig ileum.

Hylambatin (Hyl), a dodecapeptide isolated from the skin of the African frog, Hylambates maculatus, belongs to the family of tachykinin or physalaemin-like peptides. Hylambatin and its 12 fragments were tested in the guinea-pig ileum preparation for contractile activities. All fragments except 3 had contractile activities. The C-terminal fragment as short as the octapeptide sequence was at least as active as the parent molecules. The heptapeptide fragment (Hyl6-12) and the hexapeptide fragment (Hyl7-12) were less active and the C-terminal pentapeptide fragment (Hyl8-12) and the N-terminal hexapeptide fragment (Hyl1-6) were much less active. The N-terminal pentapeptide fragment (Hyl1-5) and the N-terminal fragment from which the N-terminal Asp or Asp-Pro residues were removed (Hyl2-6, Hyl3-6), were inactive at doses used.

Animals↗

Nucleotide sequences of cDNAs for human papillomavirus type 18 transcripts in HeLa cells.

HeLa cells expressed 3.4- and 1.6-kilobase (kb) transcripts of the integrated human papillomavirus (HPV) type 18 genome. Two types of cDNA clones representing each size of HPV type 18 transcript were isolated. Sequence analysis of these two types of cDNA clones revealed that the 3.4-kb transcript contained E6, E7, the 5' portion of E1, and human sequence and that the 1.6-kb transcript contained spliced and frameshifted E6 (E6*), E7, and human sequence. There was a common human sequence containing a poly(A) addition signal in the 3' end portions of both transcripts, indicating that they were transcribed from the HPV genome at the same integration site with different splicing. Furthermore, the 1.6-kb transcript contained both of the two viral TATA boxes upstream of E6, strongly indicating that a cellular promoter was used for its transcription.

Amino Acid Sequence↗

Urapidil in patients with severe hypertension and in long-term treatment.

In order to evaluate the usefulness of urapidil in the treatment of severe hypertension and in the long-term treatment of essential hypertension, two open multicentre studies were performed. In one study, 34 outpatients with diastolic blood pressure exceeding 105 mmHg following treatment with a combination of a diuretic and a sympatholytic or a diuretic and a beta-blocker were additionally given 15-60 mg urapidil twice a day for 8 weeks or more. The responder rate was 73.5%. The pulse rate did not change throughout. Side effects such as dizziness and malaise were observed in five patients (14.7%), but they were slight and did not require withdrawal of treatment. The other study included 95 outpatients with essential hypertension (World Health Organization stages I or II), 15-60 mg urapidil twice a day for 1 year or more in monotherapy (n = 48) or in combined therapy with a thiazide (n = 47). Under both therapies, diastolic blood pressure was reduced significantly at week 4, further reduced at week 12 and remained stable until week 52. Responder rates were 82.9% in monotherapy and 78.4% in combined therapy. Two patients (4.2%) taking monotherapy and six patients (12.8%) taking combined therapy were withdrawn due to inadequate blood pressure control or to side effects. These results indicate that urapidil is useful in severe and in long-term hypertension.

Adrenergic beta-Antagonists↗