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Biomedical subjects

N Shimojo

Publications and source records attributed to N Shimojo.

At least 109 records · Page 6Linked to original sources
PubMed1990

The effect of non-insulin-dependent diabetes on serum concentrations of tumor-associated carbohydrate antigens of CA19-9, CA-50, and sialyl SSEA-1 in association with the Lewis blood phenotype.

Serum concentrations of the tumor-associated carbohydrate antigens CA19-9, CA-50, and sialyl SSEA-1 were measured in non-insulin-dependent diabetic patients without diseases causing the elevation of those antigens, and the relationship to diabetic conditions was studied. The patients of the Lewis blood group phenotype of Lea (23%) had higher serum CA19-9, CA-50, and sialyl SSEA-1 than those of Leb (67%) and Le(-) (10%). Lea patients with high HbA1c (greater than 10%) had significantly higher serum CA19-9 and CA-50 than those with low HbA1c (less than or equal to 7%). Leb patients with high HbA1c also had elevated CA19-9 and sialyl SSEA-1. In Leb patients, diabetic nephropathy was associated with increased CA19-9 levels. Diabetic retinopathy was also accompanied by high carbohydrate antigens in Leb patients, but the difference was not significant. Leb patients treated with sulfonylurea or insulin had increased CA19-9 and CA-50. The changes in serum concentrations of these carbohydrate antigens might have some relationship not only to the Lewis blood phenotype, but also to diabetes.

Aged↗
PubMed1990

Efflux of endogenous zinc liberated from metallothionein and alcohol dehydrogenase in the liver by replacement with cadmium.

Efflux of endogenous zinc (Zn) from the liver was examined to aid elucidation of the mechanisms of the discriminative uptake between the essential heavy metal Zn and the nonessential heavy metal cadmium (Cd). Cd was injected intravenously into rats with or without pretreatment of a small dose of Cd 6 or 24 hr earlier. The concentration of Zn in the whole liver decreased with time after Cd injection and the extent of the decrease was more apparent in the liver that contained the Zn bound to metallothionein (MT) by pretreatment. Time course curves of Cd and Zn in liver supernatants were identical to those of the corresponding whole livers, indicating that the changes observed in the whole livers were due to the changes in the supernatants. Distribution profiles of Cd and Zn by gel filtration chromatography indicated that Cd replaced Zn bound to both alcohol dehydrogenase (ADH) and MT. The decrease of Zn in the liver caused by Cd injection was explained by the efflux of the Zn liberated from ADH and MT, which suggests that efflux of Zn ions but not Cd ions occurs from the liver. The results are discussed from the viewpoint of discriminative uptake between Cd and Zn by the liver.

Alcohol Dehydrogenase↗
PubMed1990

Pregnancy-induced mobilization of copper and zinc bound to renal metallothionein in cadmium-loaded rats.

Our investigations undertook to examine whether copper (Cu) and zinc (Zn) bound to renal metallothionein (MT) along with cadmium (Cd) in Cd-loaded rats can be mobilized during pregnancy and lactation. Rats of the Wistar strain were injected with Cd. Synthesis of MT containing Cd, Cu and Zn was induced in the kidneys. Concentrations of Cd and essential elements in blood plasma and organs (liver and kidneys) were compared among non-pregnant and pregnant, and Cd-loaded and non-loaded rats at middle and late gestational days and after delivery. Cu bound to renal MT was decreased with gestational age, while Zn was slightly increased. The results indicate that Cu was mobilized and utilized even when the metal was bound to MT in the kidneys of dams. On the other hand, Zn bound to renal MT in Cd-loaded rats was retained and not mobilized during pregnancy. The elution profile of renal MT on an SW column was changed from a typical renal to a mixed profile of renal and hepatic MTs as a result of decreased Cu content in MT. Plasma essential elements changed similarly with gestational age in both concentrations and distributions in non-loaded and Cd-loaded rats. These results indicate that the 3 metals bound to renal MT are dealt with differently during gestation and lactation, and Cu but not Zn is transferred to the fetus, independently of the Cd status of the dam.

Animals↗
PubMed1990

Discriminative uptake of metals by the liver and its relation to induction of metallothionein by cadmium, copper and zinc.

1. Disappearance from plasma and uptake by the liver of cadmium (Cd), copper (Cu) and zinc (Zn) were examined with a view to studying the biological discrimination between essential and non-essential heavy metals. 2. Cd injected intravenously at a single dose of 0.8 mg/kg body wt disappeared from rat plasma rapidly within about 10 min, while Cu and Zn injected at the same dose disappeared slowly in plasma and decreased to the control level after about 3 hr. 3. Uptake of Cd by the liver corresponded well with the rapid disappearance from plasma, while Cu and Zn accumulated slowly in the liver and their concentrations started to increase after their plasma concentrations had decreased. 4. Metallothionein was induced in the liver at a similar time course for the three metals, suggesting the presence of discriminative uptake processes by the liver with similar or the same detoxification mechanisms through induction of metallothionein.

Animals↗
PubMed1990

Effects of pretreatment with cadmium on the discriminative uptake of subsequent cadmium, copper or zinc by the liver.

1. Effects of pretreatment with cadmium (Cd) on the uptake by the liver of subsequent Cd, copper (Cu) and zinc (Zn) were examined at two different time intervals to elucidate the biological discrimination mechanism among metals of similar chemical properties. 2. Pretreatment with 0.3 mg Cd/kg body wt 6 hr but not 24 hr before a subsequent dose of 0.8 mg metal/kg body wt enhanced the disappearance rate from plasma and accumulation rate in the liver of Cu (and Zn) but not of Cd. 3. Synthesis of metallothionein was induced with different time-courses depending on the time interval between the pretreatment and subsequent treatment, which coincided with the accumulation curves for Cu (and Zn) but not for Cd. 4. Although uptake of Cd was not enhanced by any pretreatment, metallothionein synthesis was enhanced depending on the timing of pretreatment.

Animals↗
PubMed1990

The kinetics of peptide binding to HLA-A2 and the conformation of the peptide-A2 complex can be determined by amino acid side chains on the floor of the peptide binding groove.

The ability of amino acid side chains in the floor of the peptide binding groove of HLA-A2 to affect the presentation of a viral peptide to peptide-specific cytotoxic T lymphocytes (CTL) has been examined. HLA-A2 molecules with naturally occurring single amino acid substitutions of Phe to Tyr at position 9 (HLA-A2.4a, Tyr9) and Tyr to Cys at position 99 (HLA-A2.4b, Cys99) and a site directed mutant with a Val to Leu substitution at position 95 (Leu95) were examined for their ability to present the influenza virus matrix M1 55-73 peptide and several sequence variants of the M1 peptide to a panel of 36 M1 55-73-specific HLA-A2.1-restricted CTL lines. The Leu95 molecule demonstrated enhanced kinetics of M1 peptide presentation and the ability to be sensitized by lower concentrations of the M1 peptide than the A2.1 molecule. The Tyr9 and Cys99 molecules exposed to M1 peptide were not recognized by 33 out of 36 CTL lines. The Tyr9 and Cys99 HLA-A2 molecules could bind the M1 55-73 peptide because at least one CTL line was found that could recognize each of these molecules that were exposed to the M1 peptide. CTL recognition patterns of variant M1 peptides presented by the Tyr9 molecule demonstrated that the amino acid at position 9 can be a critical determinant of the conformation of the peptide-A2 complex, and indicated that a particular peptide can bind in the HLA-A2 peptide binding groove in more than one conformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

[Effects of methylmercury on ethanol-induced sleeping time of mice].

This study was carried out to clarify the effects of methylmercury intoxication on the ethanol-induced sleeping time of mice. The mice were injected with methylmercury chloride (MMC) (10 mgMMC/kg body weight) subcutaneously for 1, 5 and 10 successive days (1, 5 and 10 inj.), and control mice received only saline. Twenty-four hours, after the last injection, these mice were treated with ethanol (4.5 mgEtOH/kg body weight) intraperitoneally and subsequent sleeping time was observed. After 24 hours, mice were sacrificed to measure the concentration of MMC in various brain regions and liver. A similar experiment with ethanol treatment was also performed to assay the biogenic monoamines in various brain regions and alcohol dehydrogenase (ADH) activity in liver. The results can be summarized as follows: 1) Ethanol-induced sleeping time was 170 min. in the 10 inj. and it was significantly longer than saline, 1 and 5 inj. However, other experimental groups showed no change when compared with saline. 2) Norepinephrine levels increased in white matter and pons + medulla after 1 inj. 3) Dopamine levels increased only in white matter of the 10 inj. when compared with saline. No changes were shown in the other groups. 4) Serotonin levels increased in all the regions after 1 inj. 5) ADH activity in liver did not show any alteration during the experimental period when compared with saline.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Locomotor activity and urinary excretion of orthocresol in rats exposed to toluene].

To clarify the effect of toluene on behavior, and to evaluate urinary orthocresol excretion as an indicator of toluene exposure and locomotor activity, we have investigated the urinary orthocresol excretion and levels of locomotor activity in rats exposed to 0-3000 ppm of toluene intermittently for 2 hours. The levels of locomotor activity were measured by a laboratory animal activity measuring apparatus (ANIMEX-III). Exposure of adult male rats to more than 1000 ppm (v/v) of toluene caused an elevation of the urinary orthocresol excretion and a good correlation was noted between the amount of toluene in the air and the urinary orthocresol excretion. Exposure to over 2000 ppm of toluene suppressed the level of locomotor activity, and there was a good correlation between the level of locomotor activity and the urinary orthocresol excretion. Further, rats exposed to 3000 ppm toluene showed elevated levels of locomotor activity during a 10-hour period after exposure. These patterns of urinary orthocresol excretion and the levels of locomotor activity remained unchanged even when rats were exposed to 3000 ppm of toluene intermittently over a 4-day period.

Animals↗
PubMed1990

[Systemic lupus erythematosus accompanied by cutaneous vasculitis. Comparison of molecular size of circulating immune complexes].

Systemic lupus erythematosus (SLE) is a disease caused by immune complexes (IC) and is sometimes accompanied by cutaneous vasculitis at the time of onset or in case of relapse. Usually, however, this manifestation does not newly develop after the beginning of steroid treatment. Here we report on a 16-year-old boy with SLE who developed cutaneous vasculitis 10 days after starting systemic prednisolone treatment despite improvements in clinical and laboratory parameters. We examined the molecular sizes of circulating immune complexes (CIC) through the course of the disease. At the time of admission the CIC were 7S to 19S in size. When the patient developed cutaneous vasculitis, the large component of CIC decreased and the 7S CIC became the major component. Although definitive conclusions cannot be drawn, it is suggested that the shift to the smaller size of the CIC is related to the development of cutaneous vasculitis.

Adolescent↗
PubMed1989

Pregnancy-associated changes in renal metallothionein concentration and plasma distributions of metals.

Pregnancy-associated changes in concentrations and distributions of selected essential elements were examined in the blood and tissues of rats. Concentrations of copper (Cu) and zinc (Zn) in the kidneys of dams significantly decreased with gestational age and recovered after delivery. Distribution profiles of multi-elements in the supernatant of the kidneys indicated that Cu and Zn bound to metallothionein decreased with gestational age without affecting their distributions to other components. Although concentrations of Cu and Zn in the liver did not show significant changes during gestational period, Zn bound to metallothionein decreased with gestational age. Plasma concentrations of Cu, iron, phosphorus, sulfur, Zn and other elements were altered by the physiological change, some of those chemical forms being assigned.

Animals↗
PubMed1989

Specificity of peptide binding by the HLA-A2.1 molecule.

The HLA-A2 molecule contains a putative peptide binding site that is bounded by two alpha-helices and a beta-pleated sheet floor. Previous studies have demonstrated that the influenza virus matrix peptide M1 55-73 can sensitize target cells for lysis by HLA-A2.1-restricted virus-immune CTL and can induce CTL that can lyse virus-infected target cells. To assess the specificity of peptide binding by the HLA-A2.1 molecule, we examined the ability of seven variant M1 peptides to be recognized by a panel of M1 55-73 peptide-specific HLA-A2.1-restricted CTL lines. The results demonstrate that five out of the seven variant M1 55-73 peptides could be recognized by A2.1-restricted M1 55-73 peptide-specific CTL lines. The two variant peptides that were not recognized by any CTL could bind to HLA-A2.1 as indicated by their ability to compete for presentation of the M1 55-73 peptide. In addition, 5 of a panel of 24 unrelated peptides tested could also compete for M1 55-73 presentation by HLA-A2.1. One peptide derived from the sequence of a rotavirus protein could sensitize HLA-A2.1+ targets for lysis by M1 55-73 peptide-specific CTL. We conclude from these studies that: 1) the HLA-A2.1 molecule can bind a broad spectrum of peptides; 2) T cells selected for the ability to recognize one peptide plus a class I molecule can actually recognize an unrelated peptide presented by that same class I molecule; and 3) a stretch of three adjacent hydrophobic amino acids may be an important common feature of peptides that can bind to HLA-A2.1.

Amino Acid Sequence↗
PubMed1989

Differential effects of amino acid substitutions in the beta-sheet floor and alpha-2 helix of HLA-A2 on recognition by alloreactive viral peptide-specific cytotoxic T lymphocytes.

Crystallographic studies of the HLA-A2 molecule have led to the assignment of a putative peptide binding site that consists of a groove with a beta-pleated sheet floor bordered by two alpha-helices. A CTL-defined variant of HLA-A2, termed HLA-A2.2F, differs from the common A2.1 molecule by three amino acids: a Leu to Trp substitution at position 156 in the alpha-2 helix, a Val to Leu substitution at position 95 in the beta-sheet floor of the groove, and a Gln to Arg substitution at position 43 in a loop outside of the groove. Another HLA-A2 variant, termed CLA, has a single Phe to Tyr substitution at position 9 that is sterically located adjacent to position 95 in the beta-sheet floor of the groove. We have determined which of the amino acid substitutions at positions 9, 43, 95, or 156 could individually affect recognition by panels of A2.1 allospecific and A2.1-restricted influenza viral matrix peptide-specific CTL lines, using a panel of site-directed mutants and CLA. Recognition by allospecific CTL lines was generally unaffected by any one of the amino acid substitutions, but was eliminated by the double substitution at positions 95 and 156. Allorecognition by some CTL lines was eliminated by a single substitution at position 9 or 95. In contrast, recognition by A2.1-restricted matrix peptide specific CTL was totally eliminated by a single substitution at position 9 or 156. The substitution at position 43 in a loop away from the peptide binding groove had no effect on allorecognition or matrix peptide recognition. These results indicate that amino acid residues in the floor or alpha-2 helical wall of the peptide binding groove of the HLA-A2 molecule can differentially affect allorecognition and viral peptide recognition.

Amino Acid Sequence↗
PubMed1989

A single amino acid substitution in HLA-A2 can alter the selection of the cytotoxic T lymphocyte repertoire that responds to influenza virus matrix peptide 55-73.

Previous studies have demonstrated that certain amino acid substitutions in the alpha two domain at positions 152 and 156 in the alpha two helix of the HLA-A2 molecule can affect presentation of the influenza virus matrix peptide M1 55-73 without abolishing binding of the M1 peptide. HLA-A2.1-restricted M1 55-73 peptide-specific CTL lines obtained from almost all HLA-A2.1+ individuals fail to recognize the M1 peptide presented by site-directed mutants of HLA-A2 that have either a Val----Ala or Val----Gln substitution at position 152 or a Leu----Trp substitution at position 156. Only one HLA-A2+ individual (donor Q66, HLA-A2,-B53,-B63) has been found who is able to generate a unique repertoire of HLA-A2-restricted M1 peptide-specific CTL that can recognize peptide presented by HLA-A2 mutants with either an Ala or Gln substitution at position 152 or a Trp substitution at position 156. These Q66 M1 peptide-specific CTL could be selected by stimulation with M1 peptide-pulsed transfectants that express the mutant HLA-A2 gene with the Trp substitution at 156. To determine if the presence of the unique CTL repertoire could be attributed to a variant HLA-A2 molecule in Q66, sequences were determined from polymerase chain reaction-amplified segments of the HLA-A2 RNA. Two different HLA-A2 genes were found expressed in Q66 cells: one is identical to HLA-A2.1 and the other is identical to HLA-A2.2F (Gln----Arg at position 43, Val----Leu at position 95, and Leu----Trp at position 156). These results demonstrate that a different CTL repertoire specific for HLA-A2 plus the M1 55-73 peptide is generated in an individual that expresses both HLA-A2.1 and HLA-A2.2F compared to individuals who express HLA-A2.1 alone, and that the unique repertoire can be selected by the presence of an HLA-A2 molecule with a single amino acid substitution at position 156.

Adult↗
PubMed1989

Risk factors in chronic obstructive pulmonary malfunction and "chronic bronchitis" symptoms in Beijing district: a joint study between Japan and China.

A cross sectional study of risk factors in respiratory diseases was carried out in August 1986, in Beijing, China. Inhabitants greater than or equal to 40 years old were selected at random from a rural area, a residential area and an industrial area, using a two stage sampling method. The analysis presented here is based on the sample population of adults who (1) were prepared to be interviewed, using the British Medical Research Council's questionnaire translated into Chinese (n = 3423) and (2) had lung function measurements at the same time (n = 3373). Obstructive lung disease was defined as forced expiratory volume in 1s (FEV1) less than 68% of forced vital capacity (FVC). Seven variables were considered as potential risk factors or confounding factors: area of residence, sex, age, cigarette smoking, history of respiratory disease, socio-economic status and familial component. A modified binary variable regression method developed by Feldstein was used for the adjustment of rate ratios. The adjusted prevalence of obstructive lung disease was highest in the rural area and lowest in the residential area(s). An increase in age, cigarette smoking, low socio-economic status and positive history of respiratory diseases were associated with significantly higher rates of impaired pulmonary function. The other measured factors did not appear to be related to impaired pulmonary function.

Adult↗